VA20E • Virginia Nurses 2020

Table of Contents

VA20E • Virginia Nurses 2020

How to Receive Credit

NetCE 10 Hour Course #94672 • Pneumonia

94672 • Pneumonia

1. HISTORICAL BACKGROUND

2. DEFINITIONS

3. EPIDEMIOLOGY AND SCOPE

4. GUIDELINE-DIRECTED MANAGEMENT AND PREVENTION OF PNEUMONIA

5. PATHOGENESIS AND CLASSIFICATION OF PNEUMONIA

6. COMMUNITY-ACQUIRED PNEUMONIA

7. PREVENTION OF PNEUMONIA

8. PNEUMONIA ASSOCIATED WITH HEALTHCARE FACILITIES

9. SUMMARY

Works Cited

Evidence-Based Practice Recommendations Citations

NetCE 3 Hour Course #39100 • Caring for the Geriatric Patient

39100 • Caring for the Geriatric Patient

1. INTRODUCTION

2. AGE-RELATED DISEASE

3. THE AGING BRAIN

4. ELDER ABUSE

5. END-OF-LIFE CONSIDERATIONS

Works Cited

Evidence-Based Practice Recommendations Citations

NetCE 2 Hour Course #96101 • Frontotemporal Degeneration

96101 • Frontotemporal Degeneration

1. INTRODUCTION

2. EPIDEMIOLOGY OF FTD

3. PATHOGENESIS AND PATHOPHYSIOLOGY OF FTD

4. CLINICAL PRESENTATION

5. CLINICAL DIAGNOSIS OF FTD

6. GENETICS AND FTD

7. MANAGEMENT OF FTD

8. PROGRESSION OF FTD

9. RESEARCH RELATED TO FTD

10. CASE STUDY

11. CONCLUSION

12. RESOURCES

Works Cited

Evidence-Based Practice Recommendations Citations

VA20E • Virginia Nurses 2020

Lori L. Alexander, MTPW, ELS, MWC

Carol Whelan, APRN

Alice Yick Flanagan, PhD, MSW

Allan G. Hedberg, PhD

www.netce.com

Copyright © 2026 NetCE, All rights reserved.

VA20E • Virginia Nurses 2020

Expiration Date: 01/31/2021

How to Receive Credit

To complete this Special Offer for continuing education credit please go to http://www.netce.com/specials in your browser.

For assistance with receiving continuing education credit, please contact us at help@netce.com.

94672 • Pneumonia

Lori L. Alexander, MTPW, ELS, MWC

Carol Whelan, APRN

www.netce.com

Copyright © 2018 NetCE, All rights reserved.

Pneumonia is a substantial healthcare concern, ranking among the most common reasons for emergency department and outpatient visits, hospitalizations, and deaths among both adults and children. Decreasing the incidence of pneumonia and its associated morbidity and mortality requires a multifaceted approach and a strategy that includes: a concerted effort to improve rates of pneumococcal and influenza vaccinations, especially among high-risk populations; better adherence to guideline-recommended treatment; systems-level approaches to improve the appropriate use of antibiotics; and performance improvement initiatives to reduce healthcare-associated infections.

Table of Contents

94672 • Pneumonia

Course Overview

Audience

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planners

Division Planners Disclosure

About the Sponsor

Disclosure Statement

1. HISTORICAL BACKGROUND

2. DEFINITIONS

3. EPIDEMIOLOGY AND SCOPE

4. GUIDELINE-DIRECTED MANAGEMENT AND PREVENTION OF PNEUMONIA

5. PATHOGENESIS AND CLASSIFICATION OF PNEUMONIA

6. COMMUNITY-ACQUIRED PNEUMONIA

EPIDEMIOLOGY

RISK FACTORS

ETIOLOGY

DIAGNOSIS IN ADULT PATIENTS

MANAGEMENT OF COMMUNITY-ACQUIRED PNEUMONIA IN ADULTS

ILLUSTRATIVE CASE

PNEUMONIA IN THE PEDIATRIC PATIENT

7. PREVENTION OF PNEUMONIA

IMMUNIZATION

8. PNEUMONIA ASSOCIATED WITH HEALTHCARE FACILITIES

EPIDEMIOLOGY

RISK FACTORS

ETIOLOGY

DIAGNOSIS

TREATMENT

PREVENTION

ILLUSTRATIVE CASE

9. SUMMARY

Works Cited

Evidence-Based Practice Recommendations Citations

94672 • Pneumonia

Education Category. Infection Control / Internal Medicine

Release Date. 09/01/2018

Expiration Date. 08/31/2021

Course Overview

Pneumonia is a substantial healthcare concern, ranking among the most common reasons for emergency department and outpatient visits, hospitalizations, and deaths among both adults and children. Decreasing the incidence of pneumonia and its associated morbidity and mortality requires a multifaceted approach and a strategy that includes: a concerted effort to improve rates of pneumococcal and influenza vaccinations, especially among high-risk populations; better adherence to guideline-recommended treatment; systems-level approaches to improve the appropriate use of antibiotics; and performance improvement initiatives to reduce healthcare-associated infections.

Audience

This course is designed for all physicians, physician assistants, and nurses, especially those working in the emergency department, outpatient settings, pediatrics, nursing homes, and intensive care units.

Course Objective

The purpose of this course is to provide primary care clinicians and other members of the healthcare team with the knowledge and skills necessary to appropriately diagnose, treat, and prevent pneumonia. It is designed to enhance clinical skills, improve outcomes, and foster an interprofessional collaborative practice consistent with published guidelines.

Learning Objectives

Upon completion of this course, you should be able to:

1. Discuss the epidemiology, scope, and classification of pneumonias.

2. Predict the likely etiology (pathogens) in a given case of pneumonia, based on epidemiologic features, clinical setting, and risk factor assessment

3. Assess the diagnostic probability of pneumonia in a given patient, using careful history and clinical examination findings.

4. Determine, by clinical criteria and severity of illness score, which patients with pneumonia require hospitalization or admission to an intensive care unit.

5. Develop a management plan for community-acquired pneumonia, including selection of initial antibiotic therapy appropriate to clinical context and site of care, in accordance with established guidelines.

6. Outline the diagnosis and management of community-acquired pneumonia in pediatric patients.

7. Devise a strategy for prevention of community-acquired pneumonia, including risk factor reduction and recommended immunization protocols.

8. Identify the epidemiology and risk factors of hospital-acquired, ventilator-associated, and nursing home-acquired pneumonia.

9. Anticipate the likely pathogens and antibiotic-sensitivity patterns associated with pneumonia that arises in healthcare facilities.

10. Initiate the management of patients with hospital-acquired or ventilator-associated pneumonia, including guideline-adherent selection of empiric antibiotic therapy.

11. Develop a strategy to reduce the risk of pneumonia for patients in healthcare facilities.

Faculty

Carol Whelan, APRN, has been working in nursing education since 2000. She received her Master's degree in psychiatric/mental health nursing from St. Joseph College in West Hartford, Connecticut, and completed post-graduate nurse practitioner training at Yale University. Ms. Whelan is an Associate Clinical Professor and Lecturer at Yale University and works as an APRN at the Department of Veterans' Affairs in Connecticut, where she also serves as the Vice President of Medical Staff. She has authored many articles, textbook chapters, and books.

Lori L. Alexander, MTPW, ELS, MWC, is President of Editorial Rx, Inc., which provides medical writing and editing services on a wide variety of clinical topics and in a range of media. A medical writer and editor for more than 30 years, Ms. Alexander has written for both professional and lay audiences, with a focus on continuing education materials, medical meeting coverage, and educational resources for patients. She is the Editor Emeritus of the American Medical Writers Association (AMWA) Journal, the peer-review journal representing the largest association of medical communicators in the United States. Ms. Alexander earned a Master’s degree in technical and professional writing, with a concentration in medical writing, at Northeastern University, Boston. She has also earned certification as a life sciences editor and as a medical writer.

Faculty Disclosure

Contributing faculty, Carol Whelan, APRN, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Contributing faculty, Lori L. Alexander, MTPW, ELS, MWC, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planners

John V. Jurica, MD, MPH

John M. Leonard, MD

Jane C. Norman, RN, MSN, CNE, PhD

Division Planners Disclosure

The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

1. HISTORICAL BACKGROUND

Hippocrates first described the clinical picture of pneumonia in 400 B.C.E., including the presence of fever, chest pain, productive cough, rales, and dyspnea [1]. However, the disease was recognized even before Hippocrates' time. The disease has resulted in a serious public health and mortality burden over the years, with Osler referring to pneumonia as the "captain of the men of death" in the early 1900s. During this same period, pneumonia surpassed tuberculosis as a leading cause of death.

However, dramatic changes in the past century, namely the introduction of effective antibiotics and vaccinations and improved medical and surgical techniques, have changed the clinical picture of pneumonia dramatically. These developments have resulted in vast improvements in morbidity and mortality from pneumonia in developed countries. Despite these advances, pneumonia remains a major health concern, and the emergence of multidrug-resistant organisms has led to renewed interest and research on this ancient disease.

2. DEFINITIONS

Pneumonia is defined as a lower respiratory tract, parenchymal infection of the lung. The usual clinical presentation is that of acute- or subacute-onset fever, productive cough, pleuritic chest pain, localized rales and signs of consolidation, and a new pulmonary opacification on chest radiograph. For clinical purposes, acute pneumonia that develops in the nonhospitalized patient is designated as either community-acquired (CAP) or healthcare-associated (HCAP) depending on whether there has been significant exposure to a healthcare environment (e.g., hospital, nursing home, dialysis clinic) within the previous 90 days. Pneumonias that develop as a complication of hospitalization are termed "nosocomial" and are further divided into hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). These are important distinctions, as HCAP and nosocomial pneumonias carry a greater risk for less common, multidrug-resistant bacterial infection.

The term "pneumonia" is sometimes used in reference to other inflammatory conditions of the lung when a component of infection is known or suspected. An example is "aspiration pneumonia," whereby a focal chemical pneumonitis (lung injury) is followed rapidly by bacterial overgrowth and incipient infection (pneumonia).

3. EPIDEMIOLOGY AND SCOPE

Pneumonia is a substantial healthcare concern, ranking among the most common reasons for emergency department and outpatient visits, hospitalizations, and deaths among both adults and children [2,3,4,5,6]. The World Health Organization (WHO) estimates that 57 million people die from pneumonia every year [228]. Collected data consistently demonstrate a bimodal distribution of mortality, with peaks in children younger than 5 years of age and adults older than 75 years of age. Worldwide, pneumonia was responsible for an estimated 920,000 deaths in children younger than 5 years of age in 2015, mainly in developing countries [228]. In the United States, pneumonia is the leading cause of death from infectious disease and the eighth most common cause of death overall. There is seasonal variation in the incidence of pneumonia, with most cases occurring in the winter months.

U.S. hospital discharge statistics show that the rate of hospitalization for pneumonia varies with age, being highest among adults 75 to 84 years of age. In recent decades, the rate of hospitalization for pneumonia has been relatively stable for adults younger than 65 years of age and has declined somewhat for adults older than 65 years (Table 1) [6]. In 2010, there were 1.1 million U.S. hospital discharges for which the leading discharge diagnosis was pneumonia, and the average length of stay for these patients was 5.2 days [2].

Table 1: DISCHARGES FROM HOSPITAL WITH A FIRST-LISTED DIAGNOSIS OF PNEUMONIA, BY AGE

Age

Rate (per 10,000)

1990

2000

2009–2010

18 to 44 years

12.5

10.9

9.5

45 to 64 years

33.5

35.3

32.6

65 to 74 years

98.1

121.3

83.8

75 to 84 years

224.6

263.5

179.3

85 years and older

501.0

514.9

355.3

Source: [6]

The mortality rate for pneumonia and influenza combined has decreased substantially in the United States over the past 20 years, falling from 36.8 per 100,000 in 1990 to 16.1 per 100,000 in 2016 [6]. Two important public health factors, which may account for this trend, are the increased utilization of pneumococcal and influenza vaccines among adults and children and the decline in cigarette smoking [220,221].

Despite advances made in prevention, treatment, and clinical outcomes, the impact on healthcare delivery systems and the aggregate cost of caring for patients with pneumonia are expected to increase in years to come. This is because of an aging U.S. population, the very group in whom the rate of pneumonia is highest. Using a decision analytic model that assumes no targeted intervention, a population medicine study group projected the incidence of pneumococcal pneumonia in the United States will increase by 38% between 2014 and 2040, with hospitalizations for pneumococcal pneumonia increasing by 96% (from 401,000 to 790,000) in that same period. As a result, healthcare costs associated with pneumonia are expected to increase by $2.5 billion and demand for healthcare services for pneumonia is expected to double [14].

4. GUIDELINE-DIRECTED MANAGEMENT AND PREVENTION OF PNEUMONIA

In the past two decades, clinical guidelines for the management of pneumonia have been developed by infectious disease and pulmonary medicine societies to improve outcomes and decrease the cost of care. Unfortunately, adherence to guideline-directed management protocols has been low, despite studies demonstrating that lack of adherence is associated with higher rates of adverse outcomes and inappropriate use of antimicrobials [15,16,17,18,20,21]. Attention to guidelines varies across hospitals, clinical settings, and specialty practices. Adherence rates tend to be lower among non-pulmonologists and in relation to patient variables such as presence or absence of comorbidities and recent use of antibiotics [20,22,23]. Several barriers to guideline adherence have been identified, including lack of familiarity, concern over the practicality and perceived cost of recommended antibiotics, limited documentation of improved outcomes, and potential conflict with other guidelines [23]. The time spent on continuing education activities appears to have a direct correlation with a positive attitude toward, and propensity to follow, published clinical guidelines.

Success in reducing the incidence of pneumonia relies on effective strategies to prevent disease. The primary preventive strategy for CAP is immunization with influenza and pneumococcal vaccines, especially for high-risk groups (i.e., young children, older individuals, and people with compromised immune systems). Targeted immunization has been shown to decrease the rate of hospitalization for pneumonia and influenza and to decrease the risk of long-term morbidity and mortality [7,9,10,218]. However, vaccine utilization rates are low, especially pneumococcal vaccination among high-risk groups and influenza vaccination among children [6,11].

Prevention of HCAP focuses on care measures to preserve healthy pulmonary defense mechanisms and to reduce transmission of healthcare-associated, often multidrug-resistant, bacterial pathogens. The adherence to guidelines for the prevention of pneumonia that arises in the hospital setting has also been low, with approximately 39% to 66% of hospitals reporting full compliance and up to one-half of nurses reporting that they do not routinely adhere to recommended prevention practices [12,13].

Decreasing the incidence of pneumonia and its associated morbidity and mortality requires a multifaceted approach and a strategy that includes a concerted effort to improve rates of pneumococcal and influenza vaccinations, especially among high-risk populations; better adherence to guideline-recommended treatment; systems-level approaches to improve the appropriate use of antibiotics; and performance improvement initiatives to reduce healthcare-associated infections. This course is designed to assist healthcare professionals provide better care to their patients by highlighting guideline-recommended diagnosis, treatment, and prevention of pneumonia.

5. PATHOGENESIS AND CLASSIFICATION OF PNEUMONIA

Pneumonia is an acute inflammatory condition within the parenchyma of the lung caused by infection that reaches the lower respiratory tract. In most cases, pneumonia develops as a consequence of bacterial colonization/infection of the upper respiratory tract, followed by microaspiration of infected secretions at a time of impaired host pulmonary defense mechanisms [217]. The prime host defenses against foreign particulate matter that reaches the lower respiratory tract are the cough reflex, tracheobronchial (mucociliary) clearance, and alveolar macrophage phagocytosis. Activation of the humeral (antibody) immune response provides augmentation of phagocytosis and the acute cellular response. One or more of these defense mechanisms may be impaired by a variety of factors, including underlying cardiopulmonary and neurologic disease, sedative medication, bronchial obstruction, concurrent active viral and mycoplasma bronchitis, and toxic/metabolic conditions such as alcohol excess, acidosis, and hypoxia. Individuals with an impaired immune system, such as occurs from immunosuppressive drugs, human immunodeficiency virus (HIV), chronic disease, or old age, are more susceptible to infection [4].

Clinically, pneumonia is often described in reference to suspected or established causative pathogens (i.e., viral, bacterial, fungal, or parasitic); however, the specific etiology cannot be identified in more than half of cases in which testing is done [9,24,25]. Classifying pneumonia according to the setting in which it develops is more useful for clinical purposes because the most common pathogens, as well as the outcomes, are similar within distinct clinical settings [26,27]. Pneumonia was once broadly classified as either community-acquired (developing outside of a hospital or other healthcare facility) or nosocomial (developing 48 hours or more after hospital admission, usually postoperatively). In its 2005 guideline, the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) noted three distinct categories within the broader classification of pneumonia associated with healthcare facilities: HAP, VAP, and HCAP (Table 2) [3,28]. These three categories of pneumonia are similar in that they often result from colonization, then infection, by resistant gram-negative bacilli and methicillin-resistant Staphylococcus aureus (MRSA), necessitating broader empiric antibiotic therapy than that commonly used for CAP [27].

Table 2: TYPES OF PNEUMONIA

Type

Definition

Community-acquired

New infection in a patient residing in the community, with no recent exposure to a healthcare setting or antibiotics

Hospital-acquired

New infection occurring more than 48 hours after hospital admission

Ventilator-associated

New infection occurring more than 48 to 72 hours after endotracheal intubation

Healthcare-associated

Infection developing within 90 days after hospitalization in an acute care facility for 2 days or more

Infection in a resident of a nursing home or long-term care facility

Infection after receiving care in an outpatient setting (e.g., hemodialysis or intravenous therapy clinic)

Infection occurring with 30 days after home care (e.g., intravenous antibiotic therapy, chemotherapy, or wound care)

Source: [28]

As noted, the cause of pneumonia varies according to setting and patient age. Viruses are the most common cause in young children, whereas bacteria are the more frequent cause among older children and adults [29,30,31]. Studies have shown that respiratory viral pathogens play a greater role in the pathogenesis of pneumonia than once thought; many cases of pneumonia, both pediatric and adult, involve a combination of bacterial and viral pathogens or two or more viral pathogens [9,24,30,32]. The increase in the number of viral infections is thought to be related, in part, to better diagnostic testing methods, most notably, polymerase chain reaction (PCR)-based techniques [24,33,34].

Pyogenic bacterial infection is the cause of nearly all cases of HAP and VAP, and the distribution of pathogens varies among institutions [26,28,29]. Mixed infection appears to be common, as more than one pathogen is frequently isolated from sputum cultures in these cases [28]. Bacteria isolated from cases of early-onset HAP (within four days after admission) are usually sensitive to available drugs [28]. In contrast, late-onset HAP (i.e., more than five days after admission) is likely to be caused by multidrug-resistant pathogens, such as Pseudomonas spp., MRSA, and Acinetobacter spp. [26,35]. Viral and fungal pathogens rarely cause HAP or VAP [28].

6. COMMUNITY-ACQUIRED PNEUMONIA

EPIDEMIOLOGY

Determining accurate incidence rates for CAP is challenging for a variety of reasons, including the facts that "pneumonia" is not a reportable disease, case definition varies across studies, and national databases often link pneumonia with influenza. The epidemiology relies primarily on estimates derived from community-based cohort studies and surveillance networks. Approximately 5 to 6 million cases of pneumonia are diagnosed annually, with about 1 million occurring in older adults [36]. Approximately 4.2 million adult outpatient visits are related to CAP every year, and the mortality rate is less than 1% for adults treated on an outpatient basis [37].

The burden of disease is considerably greater for patients hospitalized with pneumonia. A prospective cohort study of adult residents living in Louisville, Kentucky (population 587,000 adults), recorded 7,449 unique patients hospitalized with CAP between June 2014 and June 2016 [232]. The annual age-adjusted incidence was 649 patients hospitalized with CAP per 100,000 adults, which extrapolates to nearly 1.6 million annual adult CAP hospitalizations in the United States. The observed mortality during hospitalization was 6.5%. An earlier report placed the average overall mortality rate for hospitalized adults at 12%, but the rate is higher—about 30% to 40%—for adults who require admission to an intensive care unit (ICU) [37]. The estimated direct and indirect financial costs are $3.7 billion and $1.8 billion, respectively [38].

The burden of pneumonia is greatest among the elderly (65 years of age and older). In one study of 46,237 people 65 years of age and older, the overall rate of CAP was 18.2 cases per 1,000 person-years for people 65 to 69 years of age, increasing to 52.3 cases per 1,000 person-years for those 85 years of age or older [39].

The mortality rate for adults with pneumonia has decreased substantially over the past two decades. In a review of more than 2.6 million Medicare claims for pneumonia between 1987 and 2005, the age- and sex-adjusted mortality rate dropped from 13.5% to 9.7% [40].

The rate of pediatric outpatient visits for CAP has been reported to be 35 to 52 per 1,000 children 3 to 6 years of age and 74 to 92 per 1,000 children 2 years of age and younger [10]. The hospitalization rate for children up to 18 years of age is 201.1 per 100,000; the highest rate is for infants younger than 1 year of age (912.9 per 100,000) and lowest for teenagers (62.8 per 100,000) [4]. According to data from the Centers for Disease Control and Prevention (CDC), 525 infants and children (up to 15 years of age) in the United States died as a result of pneumonia (or another lower respiratory tract infection) in 2006 [30].

RISK FACTORS

The primary risk factors for CAP are age, smoking history, and chronic lung disease (e.g., chronic obstructive pulmonary disease [COPD]) and other comorbidities. Occupational dust exposure and history of childhood pneumonia have also been associated with an increased risk, as has male gender, unemployment, and single marital status [39,41]. As noted earlier, the risk for pneumonia is higher for individuals 65 years or older compared with younger adults, with the risk further increasing for those 85 years and older [39]. Alcoholism and chronic diseases, such as respiratory disease, cardiovascular disease, or kidney disease, also increase the risk for pneumonia, especially in the older population [3,42,43]. In the pediatric population, very young children are at increased risk because their immune systems have not fully developed. Conditions of frailty, dementia, alcohol use, and sedative medication all lead to diminished or ineffectual cough and the propensity for aspiration, thereby increasing the risk for pneumonia. Diseases or medications that suppress the immune system increase the risk among all ages [39,42].

The airways of normal lungs are sterile, and pulmonary defense mechanisms (e.g., mucociliary clearance, alveolar macrophage phagocytosis) work in concert to maintain this sterility. Smoking cigarettes eventually leads to bronchial inflammation and disrupts host defense mechanisms to such an extent that "colonization" of the airways by microbial pathogens is established early in the course of many persons with COPD [44]. The pathogens most commonly implicated are adenovirus, Chlamydophila pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Bacterial colonization in this setting represents low-grade chronic infection, which, in combination with clinical exacerbations, augments airway inflammation, and contributes to pathogenesis and disease progression.

Proton pump inhibitors (PPIs) may increase the risk of pneumonia, but the data are somewhat unclear. One study found that only treatment with PPIs within the past 30 days (and not long-term use) was associated with increased risk, but a later meta-analysis showed that the risk was increased among people taking PPIs or histamine2 receptor antagonists [44,45].

Among the nursing home population, older age and male gender are risk factors for pneumonia. Other risk factors for this population include swallowing difficulty, inability to take oral medications, profound disability, bedridden state, and urinary incontinence [42].

ETIOLOGY

Given the right conditions, a great many micro-organisms are capable of infecting the lung. In general, however, a relatively small collection of viruses and bacteria account for most cases of CAP in adults and children. For a given case, the clinical setting and the patient's age, comorbidity, and risk factors are useful predictors of causation. Viral pneumonia (e.g., influenza) is most commonly linked to community outbreaks.

The most common cause of CAP is S. pneumoniae, accounting for approximately one-third of all cases and 40% to 50% of all culture-confirmed bacterial pneumonia cases that require hospitalization [9,29,30,46]. The most common causative pathogen varies in relation to the patient's age, illness severity, and clinical context (Table 3) [29,30,47].

Table 3: MOST LIKELY ETIOLOGIES OF COMMUNITY-ACQUIRED PNEUMONIA ACCORDING TO PATIENT AGE AND SETTING

Age and/or Setting

Most Likely Pathogens

Adults

Outpatient

Streptococcus pneumoniae

Mycoplasma pneumoniae

Chlamydophila pneumoniae

Haemophilus influenzae

Respiratory viruses

Legionella spp.

Inpatient, not intensive care unit

S. pneumoniae

M. pneumoniae

C. pneumoniae

H. influenzae

Legionella spp.

Respiratory viruses

Intensive care unit

S. pneumoniae

Staphylococcus aureus

Legionella spp.

Gram-negative bacilli

H. influenzae

Children

Birth to 3 weeks

Group B streptococci

Listeria monocytogenes

Gram-negative bacilli

Cytomegalovirus

3 weeks to 3 months

S. pneumoniae

Respiratory viruses

Bordetella pertussis

S. aureus

Chlamydia trachomatis (transnatal exposure)

4 months to 4 years

S. pneumoniae

Respiratory viruses

M. pneumoniae (in older children)

Group A streptococci

5 to 15 years

S. pneumoniae

M. pneumoniae

C. pneumoniae

Source: [29,47]

Clues to the etiology of the pneumonia can often be found in the patient's past medical or social history (Table 4). Persons with chronic bronchitis/COPD frequently have tracheobronchial colonization with S. pneumoniae, H. influenzae, or M. catarrhalis, and when pneumonia supervenes, it is usually with one of these pathogens. Heavy alcohol use carries the risk for anaerobic pleuropulmonary infection (e.g., lung abscess, empyema) and pneumococcal or gram-negative bacillary (e.g., Klebsiella pneumoniae, Proteus spp.) pneumonia.

Table 4: COMORBIDITY AND EXPOSURE IN RELATION TO AT-RISK PATHOGENS

Patient Characteristic

Suspect Pathogen(s)

Alcoholism

Oral anaerobes

Streptococcus pneumoniae

Gram-negative bacilli

COPD, tobacco use

Haemophilus influenzae

S. pneumoniae

Moraxella catarrhalis

Nursing home resident

S. pneumoniae

Gram-negative bacilli

H. influenzae

Staphylococcus aureus

Poor dental hygiene

Oral anaerobes

Recent exposure to contaminated plumbing or water

Legionellaorganisms

Exposure to exotic birds and/or decaying bird nesting sites

Chlamydia psittaci

Histoplasma capsulatum (histoplasmosis)

HIV infection

Pneumocystis carinii

S. pneumoniae

H. influenzae

Mycobacterium tuberculosis

Exposure to excreta of wild rodents

Sin nombre virus (hantavirus pulmonary syndrome)

COPD = chronic obstructive pulmonary disease.

Source: Adapted with permission from File TM, Tan JS, Plouffe JF. Community-acquired pneumonia: what's needed for accurate diagnosis. Postgrad Med. 1996;99(1):102. ©1996 McGraw-Hill.

Other epidemiologic clues to the etiology of pneumonias include seasonal and geographic considerations. Influenza outbreaks are associated with a seasonal increase in secondary S. pneumoniae, S. aureus, and H. influenzae pneumonias. Legionellosis is acquired through inhalation of an aerosol arising from contaminated water; cases present sporadically or as cluster outbreaks related to a point source exposure such as a reservoir, water tower, or air conditioning system [229].

Bacterial Pathogens

Bacterial causes of CAP predominate, accounting for at least half of all adult cases, including older individuals [9,42]. S. pneumoniae is the leading cause of CAP in any adult age-group, with or without comorbid conditions [6,7,10]. It is estimated that pneumococcal infection accounts for 20% to 60% of all hospitalized patients with pneumonia [6]. Common bacterial pathogens other than S. pneumoniae include H. influenzae type b, S. aureus, and gram-negative bacilli [25,26,29,48]. H. influenzae type b is a small, pleomorphic gram-negative rod known for causing pneumonia in older adults and patients with underlying lung disease.

Atypical pneumonia (and the pathogens associated with this syndrome) is so labeled because the onset of illness tends to be subacute and the clinical exam and radiographic features lack the classical findings seen with typical cases of pneumonia. The most common atypical pathogens are Mycoplasma pneumoniae and C. pneumoniae, followed by Legionella spp. [9]. M. pneumoniae is a tiny bacterium that lacks a rigid cell wall. It is spread by droplet nuclei, and transmission within a community proceeds slowly over many weeks. Mycoplasma infection is a disease of adolescence and young adulthood, and it is the most common cause of atypical pneumonia in those younger than 40 years of age [66]. Small cluster outbreaks of pneumonia have been observed in large families, schools, nursing homes, and other closed population. There are about 60 different species of Legionella, but most disease is caused by Legionella pneumophila, a gram-negative rod usually transmitted via inhalation of aerosolized water contaminated with the bacteria [229].

The distribution of etiologic agents accounting for pneumonia varies in relation to illness severity and management setting. In cases of relatively mild illness that permit treatment as an outpatient, blood cultures are rarely positive and the diagnosis is usually made by sputum culture and/or serial serology. In a Canadian study of CAP in the ambulatory setting, designed to determine the frequency of usual and atypical bacterial pathogens, an etiologic diagnosis was established in 48% of patients examined [222]. Of the 419 patients who had blood cultures, 7 (1.4%) were positive, all for S. pneumoniae. The atypical pathogen group (M. pneumoniae or C. pneumoniae) accounted for 29% of cases, S. pneumoniae for 6%, and Haemophilus spp. for 5%. The etiologic role of viruses was not studied [222].

A similar distribution and frequency was observed in a well-studied series from Spain, comparing pneumonia microbial etiology in three clinical management settings: outpatient, inpatient on the general care ward, and inpatient admissions to the ICU [29]. Among outpatients with CAP, the most frequently identified etiology was the atypical pathogen group (36%), followed by S. pneumoniae (35%), viruses (9%), and mixed etiologies (9%). As the severity of illness increased, marked by admission to the hospital general ward and ICU, the likelihood of mycoplasma or chlamydia etiology decreased substantially (14%) and the frequency of S. pneumoniae (43%), mixed bacterial pathogens (22%), S. aureus, Pseudomonas, and other gram-negative bacteria infection increased.

In general, S. aureus is an uncommon cause of CAP but should be suspected during influenza outbreaks and in any patient with sepsis syndrome and multifocal pulmonary infiltrates. The role of S. aureus, and MRSA specifically, was examined in an observational study of 627 CAP cases admitted to 12 university-affiliated hospitals during the winter months (influenza season) of 2006–2007 [49]. Of the 595 patients from whom blood and sputum cultures were collected, a bacterial pathogen was identified in 107 (17%). The most common pathogen identified was S. pneumoniae (57 cases), followed by S. aureus (23 cases, 14 of which were MRSA). Thus, S. aureus accounted for 5% of the total and 22% of the cases in which the etiology was identified. Of the 23 patients with staphylococcal pneumonia, blood cultures were positive in 39% and sputum culture in 89%. Clinical features observed to be highly associated with S. aureus infection were multiple pulmonary infiltrates, altered mental status, illness severity requiring ICU admission, and intubation [49].

Viral Pathogens

Studies have indicated that 5% to 20% of adult CAP may be caused by a viral pathogen [50]. However, as noted earlier, the role of respiratory tract viral infection in pneumonia is complex and perhaps underestimated. Studies utilizing newer diagnostic methods such as PCR have demonstrated rates of viral infection as high as 39% in patients presenting with pneumonia [9,34]. Because these studies rely on specimens and washings taken from the nasopharynx, rather than directly from the lung, it is not clear to what extent viral isolates in this setting represent primary pneumonia pathogens or concomitant viral upper respiratory infection that may impair pulmonary defense mechanisms and thus predispose to bacterial pneumonia.

Clinical and pathologic studies of pneumonia during influenza seasons have demonstrated clearly that influenza virus (types A and B) is an important cause of primary viral CAP [25,47]. Other common respiratory viruses associated with pneumonia in adults are respiratory syncytial virus (RSV), rhinovirus, adenovirus, and parainfluenza virus [31,34,47]. RSV and rhinovirus are especially common among older adults and nursing home residents [31]. Clinical studies that utilize viral culture for case definition have demonstrated that RSV can be recovered from 3% to 10% of older adults with pneumonia [30]. The paramyxovirus hMPV, first isolated in 2001 from children hospitalized with acute respiratory infection, has now been reported in all age groups and with varying stages of disease, from asymptomatic carrier states to severe bronchitis and pneumonia [30].

Mixed Pathogens

Mixed viral-bacterial infection has been observed in 30% of adult cases of CAP in some studies [9,31,34]. Most commonly, S. pneumoniae is identified in combination with rhinovirus, influenza A, or RSV [34]. On rare occasions fungal and parasitic pathogens are isolated in association with CAP syndrome.

DIAGNOSIS IN ADULT PATIENTS

Clinical Features

The diagnosis of CAP in adults is challenging because its presentation is similar to other acute respiratory illnesses such as pulmonary embolism/infarction and congestive heart failure [3,51,52]. Diagnosis relies primarily on clinical features combined with radiographic findings; however, both the clinical presentation and chest x-ray abnormalities are variable and in part nonspecific, particularly in the elderly [3,29]. Common presenting symptoms and signs are:

- Productive cough, purulent sputum

- Fever with rigors (shaking chills)

- Dyspnea

- Pleuritic chest pain

- Tachypnea

- Tachycardia

- Hypoxemia

- Signs of consolidation (e.g., crackles, bronchial breath sounds, egophony)

- Signs of pleural effusion (e.g., absent fremitus, dullness to percussion, decreased breath sounds)

Pneumonia in the elderly may present without a history of chills or fever, little cough, and a paucity of findings on exam and chest x-ray. Often in such cases, some combination of tachypnea, tachycardia, and altered mental status is the only sign [31,42].

Physical examination should focus on the chest, with auscultation to detect localized crackles (rales), bronchial breath sounds, and other signs of consolidation or pleural effusion [47]. Pulse oximetry should also be done. The most clinically significant individual findings are (in descending order) egophony, bronchial breath sounds, and dullness on percussion [53].

Chest Radiography

Evidence Based Practice Recommendation

The American College of Radiology asserts chest x-ray is the imaging modality of choice for complicated pneumonia.

https://acsearch.acr.org/docs/69446/Narrative

Last Accessed: August 22, 2018

Strength of Recommendation: 9

When pneumonia is suspected on the basis of these clinical features, chest radiography is the standard for confirming the diagnosis, and posteroanterior and lateral radiographs are recommended [3,29]. The IDSA/ATS guideline notes that evidence of an infiltrate on chest radiograph or other imaging study is required for a diagnosis of pneumonia [47]. In addition to establishing the diagnosis, the chest radiograph can help differentiate pneumonia from other conditions with similar signs and symptoms. Some degree of infiltrate is almost always demonstrated on chest radiographs of patients who have been ill longer than 24 to 48 hours, although the appearance may be subtle or absent on initial presentation [29,47]. Pneumonia is described according to its anatomic distribution on chest radiographs as either lobar, multifocal/lobar, bronchopneumonic, or interstitial.

The characteristic symptoms and signs, combined with radiographic findings of an infiltrate, establish the clinical diagnosis of pneumonia. One validated prediction tool commonly used assigns 1 point for each of five clinical features present in conjunction with an infiltrate on chest radiography [54]:

- Temperature >37.8°C (100.04°F)

- Heart rate >100 beats per minute

- Crackles on auscultation

- Decreased breath sounds

- Absence of asthma

A score of 4 or 5 indicates a 25% to 50% probability of pneumonia; a score of 2 or 3 indicates a probability of 3% to 10%; and a score of 0 or 1 represents a probability of l% or less [29,54]. Neither clinical nor radiographic features can reliably differentiate primary viral from bacterial or combined viral-bacterial pneumonia [9,31,32]. There are some features that, if present, aid in making the distinction. The presence of a viral epidemic in the community, such as influenza or RSV, increases the likelihood of a viral etiology [32]. The patient's age can also help identify the most probable cause; as noted previously, viral infections have been found more often in young children and adults older than 60 years of age compared with younger adults [9,24]. Chest pain is significantly more frequent in adults with bacterial pneumonia than in those with viral pneumonia [9]. Radiographic findings are generally not useful in identifying a specific pathogen, although multilobar infiltrates suggest infection with S. pneumoniae, S. aureus, or L. pneumophila, and patchy, interstitial infiltrates suggest a viral or mycoplasmal etiology [47,49].

Atypical Pneumonia

The first use of the term atypical pneumonia was in 1938 to describe a series of seven patients who had developed an unusual form of tracheobronchitis [65]. There had also been descriptions of outbreaks of pneumonia that behaved atypically in Europe in the 1920s. In general, these outbreaks were milder and had higher recovery rates than expected for the typical case of pneumonia.

At the present time, atypical pneumonia is encountered, and managed, primarily in the outpatient setting. The causative pathogen most commonly identified in such cases is M. pneumoniae. According to CDC estimates, Mycoplasma infections occur at the rate of 2 million cases each year and are responsible for between 1 and 10 of every 50 cases of CAP [66].

Atypical pneumonia syndrome, best represented by mycoplasma infection, presents with a subacute prodrome of malaise, low-grade fever, headache, myalgia, and non-productive cough. Symptoms progress slowly over days to weeks; often patients are thought to have an upper respiratory infection or bronchitis and appear less ill than those with typical bacterial pneumonia [65,66]. The physical examination usually reveals fine rales but no signs of lung consolidation. In the early stage, there may be a maculopapular skin eruptions and, on examination of the ear canal, bullous myringitis of the tympanic membrane. Chest x-ray reveals patchy alveolar densities or inhomogeneous segmental infiltrates, often bilateral involving the middle lobe and lingual. The white blood cell count may be normal or only slightly elevated. Full recovery is expected with no residual effects in a previously healthy individual. However, the disease can be severe in those with sickle cell anemia, older adults, and those with immunosuppression [65].

In younger patients, C. pneumoniae (TWAR strain) infection may present as atypical pneumonia. Outbreaks tend to occur in communal settings such as military units and college dormitories [231]. The illness is similar to that seen with mycoplasma infection, except that laryngitis is a prominent feature and nonexudative pharyngitis is common [26]. Chest x-ray may show patchy consolidation, interstitial infiltrates, or funnel-shaped lesions. The white blood cell count is usually normal.

Legionellosis

The first recorded outbreak of legionellosis occurred in 1976 at an annual convention of the American Legion in Philadelphia. A total of 182 of the delegates (many of whom were elderly) became ill, and 146 were hospitalized. The mortality rate was 16%. Because the conference ended prior to the development of significant symptoms in many patients, hospitals all over the United States admitted one or more of the patients who had attended the convention. Despite an outpouring of resources, it took six months to isolate the organism, later named L. pneumophila. The pneumonia caused by the organism is commonly known as Legionnaires' disease [65].

L. pneumophila is a small gram-negative bacillus, atypical in its clinical presentation and for its lack of susceptibility to ß-lactam antibiotics. There are about 60 identified species of Legionella, although L. pneumophila is the primary pulmonary pathogen [230]. Legionella accounts for an estimated 8,000 to 18,000 cases of pneumonia requiring hospitalization in the United States each year [229,230]. Suspicion for infection with Legionella organisms should be high in older adults, in those with chronic underlying disease, and in all patients with pneumonia severe enough to require hospitalization.

Legionella bacteria are found in common sources of freshwater but not usually in sufficient numbers to cause disease. However, in commercial water systems such as those found in large buildings, storage tanks, cooling towers, decorative fountains, or hot tubs, Legionella growth exceeds the threshold required for transmission to susceptible hosts via aerosolization [229]. Because hotels, resorts, and cruise ships often use large, complex water systems and other aerosol-generating devices, travel is a risk factor for disease. This is also true for hospitals and long-term care facilities.

The onset of infection is marked by dry cough, fever of 38.3°C–38.8°C (101°F–102°F), then progressive symptoms and signs of pneumonia accompanied by multi-organ involvement—vomiting, diarrhea, headache, and altered mental status. Chest x-ray reveals rapidly progressive, asymmetric infiltrates without signs of consolidation. Prompt diagnosis relies on clinical suspicion, urine antigen assay, and specialized culture techniques.

Laboratory Diagnosis

The challenge of diagnosis is complicated by the lack of cost-effective, reliable, and rapidly available tests to discriminate between viral and bacterial pneumonia [37]. The IDSA/ATS guideline notes that routine cultures of sputum and blood are not recommended for patients treated in the ambulatory setting, as results rarely impact management decisions [47]. The primary reason for cultures and serologic testing is to identify specific pathogens suspected on the basis of clinical and epidemiologic findings or cases in which the results of testing will substantially alter the empirical treatment of the patient [47]. Testing may be useful when evaluating a critically ill patient, a patient in whom a drug-resistant or unusual organism is suspected (e.g., Legionella), or a patient whose condition is deteriorating or who is not responding within 72 hours after treatment.

Blood Culture

Blood cultures are optional and not recommended as a routine diagnostic test for CAP managed in the ambulatory setting. The principle reason is that the yield is low, and studies show that a positive culture leading to a change in antimicrobial therapy occurs in about 3% or fewer cases [55,56,222]. The IDSA/ATS guideline recommends blood cultures before treatment only for patients hospitalized with one of the following conditions [47]:

- Cavitary infiltrates

- Leukopenia

- Active alcohol abuse

- Chronic severe liver disease

- Asplenia

- Positive test result for pneumococcal urinary antigen

- Pleural effusion

- Illness severity requiring admission to the ICU

Blood cultures are indicated for patients who have severe CAP, as they are more likely to have infection with a pathogen other than S. pneumoniae [47].

The ATS and the American College of Emergency Physicians (ACEP) also note that blood cultures need not be obtained routinely in all patients admitted with CAP [57]. Similarly to IDSA/ATS, ACEP adds that blood cultures should be considered for patients at higher risk, such as persons who have compromised immune systems, significant comorbidities, severe disease, or another risk factor for infection with resistant organisms [57].

Sputum Culture and Gram Stain

Sputum stain and culture are also considered optional, but are recommended when specific conditions are present [47]:

- Cavitary infiltrates

- Active alcohol abuse

- Severe obstructive/structural lung disease

- Positive result for urinary Legionella antigen test

- Positive result for urinary pneumococcal antigen test

- Pleural effusion

Sputum culture and Gram stain should also be performed for all hospitalized patients who are moderately ill or who warrant admission to an ICU [47]. The IDSA/ATS note that examination and culture of respiratory secretions should be performed only on specimens that meet quality performance measures for collection, transport, and processing of samples.

The diagnostic utility of sputum Gram stain and culture has been demonstrated in patients hospitalized with proven (bacteremic) pneumococcal pneumonia. In a series of 58 patients, from whom good quality sputum specimens (>10 inflammatory cells per epithelial cell) were submitted before or within six hours after initiation of antibiotic therapy, pneumococci were identified by Gram stain in 63% and by culture in 89% of cases [224].

Newer Diagnostic Techniques

Assays for the detection of antigen and other components of bacterial and viral pathogens have become a useful adjunct for establishing the etiology of pneumonia. Among these is the detection of bacterial antigen in the urine of patients with CAP. In a clinical series report, an assay for S. pneumoniae cell wall polysaccharide in urine was positive in 64% of patients with pneumococcal pneumonia; the sensitivity increased to 88% in patients who were bacteremic [225].

In a meta-analysis of published studies, the assay for detection of Legionella antigen in the urine of patients with pneumonia has been shown to have excellent specificity (99%) but only modest sensitivity (74%) [226]. Thus, a urine Legionella antigen assay is very useful to "rule in" the diagnosis but does not rule it out—a negative result should be interpreted with caution. Urine samples for Legionella antigen assay should be submitted in all cases of CAP with severe illness, suspicion of Legionella infection, or with risk factors such as COPD, HIV, immunosuppressive therapy, or organ transplantation. Isolation of Legionella from sputum can be accomplished on selective media. Serologic diagnosis requires acute and convalescent serum; it is useful to confirm a case, but of little value in early diagnosis.

Testing for Viruses

Viral culture remains the criterion standard for diagnosis of viral pneumonia, but because of limitations such as the need for prompt transportation, time needed for viral detection, and the lack of sensitivity for all viruses, rapid antigen testing is often done. In adults, rapid testing has a sensitivity of 50% to 60% and a specificity of at least 90% [31]. Testing of nasal swab specimens is slightly less sensitive than testing of wash specimens, but wash specimens can be difficult to obtain in frail or cognitively impaired adults. Rapid RSV tests are usually not useful for adults, as the level of virus titers shed is low [31].

Molecular diagnostic testing of sputum holds promise for providing a rapid and accurate etiologic diagnosis. Studies show that real-time PCR is significantly more sensitive and specific for the detection of the common respiratory viruses that cause CAP, as well as M. pneumoniae and C. pneumoniae [24,33]. However, molecular assays are expensive and not currently widely available [31].

Biomarkers

Over the past several years, researchers have been evaluating biomarkers for their utility in diagnosis and for determining duration of empirical therapy for presumed bacterial pneumonia. Procalcitonin has been shown to be superior to other commonly used markers for its specificity for bacterial infection and its ability to distinguish CAP from asthma and COPD [58,59]. This marker has predictive value; however, no biomarker should be used on its own and, if used, should be considered within the context of clinical and laboratory findings [59].

MANAGEMENT OF COMMUNITY-ACQUIRED PNEUMONIA IN ADULTS

Guidelines for the management of pneumonia in adults were first developed independently by the ATS and the IDSA, with each publishing guidelines in the 1990s and early 2000s [36,63,64]. The recommendations in each guideline differed somewhat, but the principles were the same [36]. To eliminate the confusion associated with separate guidelines, the IDSA and ATS jointly developed the current guideline for CAP, published in 2007 (update in progress as of 2018) [47]. The IDSA/ATS guideline focuses on decision making about site of care; the empirical selection of antibiotics; and issues in the delivery of antibiotics, such as the timing of the first dose of antibiotics, the timing of switch therapy (from parenteral to oral antibiotics), and the duration of therapy [47]. The treatment of symptoms associated with CAP is not addressed in the guideline. A systematic review published in 2012 found insufficient evidence to determine if there is benefit to over-the-counter medications (e.g., mucolytics, cough suppressants) for cough associated with acute pneumonia [67].

Site of Care

One of the most important decisions in the management of CAP is determining the site of care—that is, outpatient or inpatient and, if the latter, a general care floor or an ICU [68]. Many physicians admit patients to the hospital when they could be managed effectively on an outpatient basis [47]. This decision requires a careful evaluation of the severity of illness in the context of the personal and social well-being of the patient. Objective severity-of-illness scores and prognostic models can aid in identifying patients who may require hospitalization or admission to an ICU. The most widely used scales are the CRB-65 (confusion, respiratory rate, blood pressure, age 65 years or older) (Figure 1), the CURB-65 severity score (which adds urea level to the CRB-65 criteria), and the Pneumonia Severity Index (PSI) (Table 5). These assessment tools are recommended by the IDSA/ATS as an aid to clinical judgment in determining the site of care [47,69,70]. The scales have been compared, and they do not differ significantly in overall performance [71]. However, each scale has advantages and disadvantages, and none factor in all clinical considerations (such as comorbidities or social factors) [68]. CURB-65 and CRB-65 are easier to score as they have fewer variables and are more likely to correctly classify high-risk patients (i.e., high positive-predictive value) [72]. In contrast, the PSI is more sensitive and is better at determining which patients do not require hospitalization (i.e., low false-negative rate). About 30% to 60% of patients at low risk are unnecessarily admitted to the hospital according to the PSI score [68].

Figure 1: CLINICAL SEVERITY ASSESSMENT IN THE COMMUNITY SETTING: THE CRB-65 SCORE

aDefined as a Mental Test Score of 8 or less or new disorientation in person, place, or time.

Source: Reprinted with Permission from Lim W, van der Eerden MM, Laing R, et al. Defining community-acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003;58:377-382.

Table 5: PNEUMONIA SEVERITY INDEX: POINT SCORING SYSTEM FOR STEP 2 OF THE PREDICTION RULE FOR ASSIGNMENT TO RISK CLASSES II, III, IV, AND V

Characteristic

Points Assigneda

Nursing home resident

+10

Demographic factor (age)

Men

Age (yr)

Women

Age (yr)-10

Coexisting illnessesb

Neoplastic disease

+30

Liver disease

+20

Congestive heart failure

+10

Cerebrovascular disease

+10

Renal disease

+10

Physical-examination findings

Altered mental statusc

+20

Respiratory rate ≥30 breaths/min

+20

Systolic blood pressure <90 mm Hg

+20

Temperature <35°C or ≥40°C

+15

Pulse ≥125 beats/min

+10

Laboratory and radiographic findings

Arterial pH <7.35

+30

Blood urea nitrogen ≥30 mg/dL

+20

Sodium <130 mmol/L

+20

Glucose ≥250 mg/dL

+10

Hematocrit <30%

+10

Partial pressure of arterial oxygen <60 mm Hgd

+10

Pleural effusion

+10

aA total point score for a given patient is obtained by summing the patient's age in years (age minus 10 for women) and the points for each applicable characteristic. The points assigned to each predictor variable were based on coefficients obtained from the logistic-regression model used in step 2 of the prediction rule. A score <70 is risk class II, 71–90 is risk class III, 91–130 is risk class IV, and >130 is risk class V. Higher risk classes are associated with increased mortality.

bNeoplastic disease is defined as any cancer except basal or squamous cell cancer of the skin that was active at the time of presentation or diagnosed within one year of presentation. Liver disease is defined as a clinical or histologic diagnosis of cirrhosis or another form of chronic liver disease, such as chronic active hepatitis. Congestive heart failure is defined as systolic or diastolic ventricular dysfunction documented by history, physical examination, and chest radiograph, echocardiogram, multiple gated acquisition scan, or left ventriculogram. Cerebrovascular disease is defined as a clinical diagnosis of stroke or transient ischemic attack or stroke documented by magnetic resonance imaging or computed tomography. Renal disease is defined as a history of chronic renal disease or abnormal blood urea nitrogen and creatinine concentrations documented in the medical record.

cAltered mental status is defined as disorientation with respect to person, place, or time that is not known to be chronic, stupor, or coma.

dIn the Pneumonia PORT cohort study, an oxygen saturation of less than 90% on pulse oximetry or intubation before admission was also considered abnormal.

Source: Reprinted with permission from Fine M, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336:243-250.

The PSI, CURB-65, and CRB-65 were developed to predict the risk of death. Because this risk does not always equate to the need for hospitalization and/or ICU admission, other scales have been developed. For example, SMART-COP provides a score based on a composite of systolic blood pressure, multilobar involvement on chest radiograph, albumin level, respiratory rate, tachycardia, confusion, oxygenation, and arterial pH [73]. SMART-COP was found to accurately predict the need for intensive respiratory or vasopressor support. Another tool, the Severe Community-Acquired Pneumonia (SCAP) score, includes points assigned to eight variables: arterial pH, systolic pressure, confusion, blood urea nitrogen level, respiratory rate, chest radiograph findings, pulmonary arterial oxygen tension (PaO_2), and age (older than 80 years) [74]. SCAP has identified a larger proportion of patients as low risk compared with the PSI, CURB-65, and CRB-65, and is better than or as accurate as those scores at predicting adverse outcomes in hospitalized patients [74,75]. The IDSA/ATS guideline notes that the results of these objective criteria should always be accompanied by clinical judgment, including consideration of subjective factors, such as the availability of outpatient support resources and the patient's ability to safely and reliably take oral medication [47].

It is estimated that admission to an ICU is needed for 10% to 20% of patients hospitalized with CAP [76]. The IDSA/ATS guideline establishes major and minor criteria for direct admission to an ICU [47]. The major criteria are septic shock requiring vasopressors or acute respiratory failure requiring intubation and mechanical ventilation. The presence of at least three of the following minor criteria suggests the need for ICU admission [47]:

- Increased respiratory rate (≥30 breaths per minute)

- Low PaO_2/fraction of inspired oxygen ratio (≤250)

- Multilobar infiltrates

- Confusion/disorientation

- Uremia (blood urea nitrogen level ≥20 mg/dL)

- Leukopenia (white blood cell [WBC] count <4,000 cells/mm^3)

- Thrombocytopenia (platelet count <100,000 cells/mm^3)

- Hypothermia (core temperature <36°C [96.8°F])

- Hypotension requiring aggressive fluid resuscitation

These criteria were validated as being useful for predicting the severity of CAP [77,78].

Selection of Antibiotics

Evidence Based Practice Recommendation

The Infectious Diseases Society of America (IDSA) recommends empirical therapy for MRSA pending sputum and/or blood culture results for hospitalized patients with severe community-acquired pneumonia defined by any one of the following: a requirement for ICU admission, necrotizing or cavitary infiltrates, or empyema.

https://academic.oup.com/cid/article/52/3/e18/306145

Last Accessed: August 22, 2018

Level of Evidence: A-III (Good supporting evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees)

The goal of antibiotic treatment of pneumonia is to eradicate the infection or to reduce the bacterial load that the patient's own immune response is able to limit spread and speed recovery. The choice and duration of therapy is based on consideration of known or suspected etiology, age and severity of illness, comorbidities, and knowledge of resistance patterns in the community. One should strive to tailor therapy and avoid unnecessarily prolonged treatment so as to minimize the potential for the development of resistance [37].

Pending results of culture or serologic testing, the initial treatment is empirical and is selected according to patient variables and clinical setting (Table 6) [47]. Patients with mild illness and no serious coexisting disease may be managed as outpatients. The ATS/IDSA guideline recommends a macrolide for outpatient treatment of CAP, provided the patient has not received antimicrobials within the previous three months and the prevalence of macrolide resistance among pneumococci in the community is <25% [47]. S. pneumoniae resistance to macrolides is four times more likely in adult patients who have received this class of drug within the previous three months, in which case a fluoroquinolone or ß-lactam plus macrolide combination should be selected. A respiratory fluoroquinolone (levofloxacin or moxifloxacin) is recommended for adults who have comorbidities or a compromised immune system [47]. Fluoroquinolones should not be used routinely, as widespread use increases the possibility that resistance will develop. Alternatively, a ß-lactam plus a macrolide can be used.

Table 6: RECOMMENDED EMPIRICAL ANTIMICROBIAL THERAPY ACCORDING TO 2007 IDSA/ATS GUIDELINE FOR THE MANAGEMENT OF COMMUNITY-ACQUIRED PNEUMONIA

Site of Care and Patient Characteristics

Recommended Drug Class

Specific Drug Options

Level of Evidence

Previously healthy outpatient, no exposure to antibiotics within past three months

Macrolide

Azithromycin, clarithromycin, or erythromycin

Strong recommendation, level I evidence

Tetracycline

Doxycycline

Weak recommendation, level III evidence

Outpatients with comorbiditiesa or exposure to antibiotics within the previous three monthsb

Respiratory fluoroquinolone

Moxifloxacin, gemifloxacin, or levofloxacin

Strong recommendation, level I evidence

ß-lactam + macrolide

High-dose amoxicillin or amoxicillin-clavulanate

Strong recommendation, level I evidence

Alternatives: ceftriaxone, cefpodoxime, or cefuroxime

Level II evidence

ß-lactam + tetracycline

High-dose amoxicillin and doxycycline

Level II evidence

Inpatient (not ICU)

Respiratory fluoroquinolone

—

Strong recommendation, level I evidence

ß-lactam + macrolide

—

Strong recommendation, level I evidence

Inpatient (ICU)

ß-lactam + azithromycin

OR

ß-lactam + respiratory fluoroquinolone

Alternative for penicillin allergy: respiratory fluoroquinolone and aztreonam

Cefotaxime, ceftriaxone, or ampicillin-sulbactam

Strong recommendation, level I and II evidence

aComorbidities include chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignant disease; or asplenia or use of immunosuppressant drugs.

bIf patient has been exposed to antibiotics within previous three months, a different drug from a different class should be used.

Source: [47]

The selection of a respiratory fluoroquinolone or a ß-lactam plus macrolide combination is recommended also for patients with CAP who are hospitalized on a general floor [47]. Adults admitted to an ICU need empiric treatment for S. pneumoniae and Legionella spp., as well as consideration of coverage for S. aureus and gram-negative bacteria infection, pending sputum and blood culture results. This is achieved with a regimen that combines a broad-spectrum ß-lactam with either azithromycin or a respiratory fluoroquinolone, adding vancomycin or linezolid to cover MRSA if there is clinical suspicion of S. aureus infection. Aztreonam, a monobactam, may be substituted for gram-negative bacteria coverage in patients allergic to ß-lactams [47]. The IDSA/ATS guideline also specifies antibiotic selection in reference to specific pathogens (Table 7) [47].

Table 7: RECOMMENDED ANTIBIOTIC THERAPY FOR SPECIFIC PATHOGENS ACCORDING TO 2007 IDSA/ATS GUIDELINE FOR THE MANAGEMENT OF COMMUNITY-ACQUIRED PNEUMONIA

Pathogen

Preferred Antibiotic

Alternative Options

Streptococcus pneumoniae, not penicillin resistant

Penicillin G, amoxicillin

Macrolide, cephalosporins, clindamycin, doxycycline, respiratory fluoroquinolone

Streptococcus pneumoniae, penicillin resistant

Based on susceptibility (cefotaxime, ceftriaxone, fluoroquinolone)

Vancomycin, linezolid, high-dose amoxicillin

Haemophilus influenzae, non-ß-lactamase producing

Amoxicillin

Fluoroquinolone, doxycycline, azithromycin, clarithromycin

Haemophilus influenzae, ß-lactamase producing

Second- or third-generation cephalosporin, amoxicillin-clavulanate

Fluoroquinolone, doxycycline, azithromycin, clarithromycin

Mycoplasma pneumoniae/Chlamydophila pneumoniae

Macrolide, a tetracycline

Fluoroquinolone

Legionella spp.

Fluoroquinolone, azithromycin

Doxycycline

Pseudomonas aeruginosa

Antipseudomonal ß-lactam plus ciprofloxacin or levofloxacin or aminoglycoside

Aminoglycoside plus ciprofloxacin or levofloxacin

Acinetobacter spp.

Carbapenem

Cephalosporin-aminoglycoside, ampicillin-sulbactam, colistin

Staphylococcus aureus, methicillin susceptible

Antistaphylococcal penicillin

Cefazolin, clindamycin

Staphylococcus aureus, methicillin resistant

Vancomycin or linezolid

Trimethoprim/sulfamethoxazole

Source: [47]

For adults who present with presumed viral CAP, it is unclear whether antibiotic treatment is beneficial. When there is epidemiologic, clinical, or laboratory evidence of active influenza, a neuraminidase inhibitor should be administered [32].

Timing of Initial Antibiotic Therapy

The time to the first dose of antibiotics for adults with CAP has engendered debate. A 2003 guideline developed by the IDSA recommended initiation of antibiotic therapy within four hours after hospitalization. Quality measures linked to this timeframe were developed by the Joint Commission and the Centers for Medicare and Medicaid Services [2,66,79,80]. Experts have criticized the timeframe requirement, with some noting that it has the potential to result in less-than-optimal care and others adding that diagnosis of pneumonia in the emergency department is challenging, especially in older patients who have an atypical presentation [51,52,79,80]. In a survey of 121 emergency physicians, 55% of the respondents said they had prescribed antibiotics to patients they did not believe had pneumonia in an effort to comply with the Centers for Medicare and Medicaid Services quality measure; 42% of these respondents said they had prescribed as such more than three times a month [80]. Sixty percent of the respondents said they did not believe that the guideline improves patient care. The results of a systematic review and a large-scale study have shown no decrease in mortality with a first dose administered within four hours [57,81,82].

As emphasized by the IDSA/ATS guideline committee, the recommendation at present is to begin antibiotic treatment promptly, without delay, administering the initial dose at the site of care (e.g., emergency department, clinic, office) where the diagnosis is first made [47].

Duration of Therapy

With the availability of well-absorbed, effective oral antibiotics, hospitalized adults do not require intravenous antibiotics for the duration of treatment. Intravenous therapy can be changed to an oral regimen when the patient is hemodynamically stable, improving clinically, and able to take oral medications safely [47]. For patients on a general ward floor, this transition can often be made by the third hospital day; patients in the ICU usually reach this point within seven days. It is recommended that the oral antibiotic be either the same drug or within the same drug class as the intravenous antibiotic [47]. Patients can be discharged from the hospital as soon as clinical stability has been achieved, provided they have no comorbidities requiring inpatient care and have a safe home environment and reliable follow-up. The IDSA/ATS note the following criteria for determining clinical stability [47]:

- Temperature ≤37.8°C (100.04°F)

- Heart rate ≤100 beats per minute

- Respiratory rate ≤24 breaths per minute

- Systolic blood pressure ≥90 mm Hg

- Arterial oxygen saturation ≥90% or partial pressure of oxygen ≥60 mm Hg on room air

- Ability to maintain oral intake

- Normal mental status

The IDSA/ATS recommend that antibiotic therapy be given for a total of at least five days. The duration of therapy should be extended at least 48 to 72 hours beyond resolution of fever, assuming significant clinical improvement and no more than one pneumonia-associated active clinical sign [47]. A five- to seven-day course should suffice for most uncomplicated cases that show a prompt and satisfactory response to treatment.

The duration of treatment for gram-negative bacillary and staphylococcal pneumonia bears further comment. Unlike pneumococcal pulmonary infection, which usually heals without residual damage, these pathogens often cause destructive changes and small cavities in the lung, which clear slowly and heal by fibrosis. Thus, a more prolonged course of therapy (two to three weeks) should be considered, depending on severity of illness and response to therapy.

Treatment Failure

The clinical response to initial antibiotic therapy is unsatisfactory in approximately 15% of adults with CAP [47]. Failure to respond has no clear definition, and the IDSA/ATS guideline suggests using a systematic classification of cases, with attention to timing and character of response, as a guide to further evaluation and management. In general, treatment failures may be classified as persistent or non-responding, as a delay in achieving clinical stability, or as progressive pneumonia with clinical deterioration. Some clinical deterioration during therapy is not uncommon in the first 24 hours of treatment; as many as 45% of adults admitted to the hospital later require transfer to the ICU [47]. When the diagnosis of CAP is correct and guideline-recommended therapy has been used, the most common reason for treatment failure is an inadequate host response. For these patients, the appropriate management depends on individual case considerations, such as comorbidities, adequacy of pulmonary toilet, and whether the intravenous regimen has been reliably and consistently administered [47].

Benefits of Guideline-Adherent Antibiotic Therapy

Guideline-directed management of CAP has been associated with many benefits. In one study, use of guideline-recommended antibiotics was associated with a significantly shorter time to clinical stability; clinical stability was achieved by seven days in 71% of patients treated with guideline-recommended antibiotics and in 57% of those treated with nonadherent regimens [15]. Adherence to recommendations guiding the selection of antibiotics was also associated with a significantly shorter length of stay (8 vs. 10 days) and a significantly lower overall in-hospital mortality rate (8% vs. 17%) [15]. In a Canadian study of adults (mean age: 51 years) who, in the main, had mild pneumonia, guideline-adherent selection of antibiotic treatment was associated with a lower mortality rate (1%) than that found when treatment selection that was not adherent to guidelines (6%) [83]. The mortality rate associated with the use of macrolides was also significantly lower than that with the use of fluoroquinolones (0.2% vs. 3%) [83]. In a large study of 54,619 patients who were hospitalized at 113 community hospitals (not in the ICU), use of guideline-adherent treatment was associated with a lower in-hospital mortality rate, lower rate of sepsis and renal failure, and shorter length of stay and duration of parenteral therapy [17]. Decreased mortality has also carried over to populations with more severe disease, with nonadherent therapy being associated with an increase in inpatient mortality (25% vs. 11%) among older adults (median age: 71 years) who were admitted to an ICU [16]. In addition to the higher rates of adverse outcomes, the low rate of adherence has also resulted in the inappropriate use of antimicrobials in at least half of cases [21].

Despite the benefits of guideline-directed treatment and the wide dissemination of the guidelines for management of pneumonia in adults, adherence has been low, especially with regard to antibiotic selection, with rates ranging from 9% to 82% [15,16,17,18,20]. In a study of more than 34,000 patients in a managed care organization, adherence to the 2003 IDSA guidelines in ambulatory settings was 52% for patients who were previously healthy and had not had recent exposure to antibiotics [20]. The rate of adherence was better (82%) for patients who had comorbidities and no recent exposure to antibiotics [20]. One study found that most cases of guideline-discordant use of antibiotics for older adults represent undertreatment [15]. The use of recommended antibiotics in the emergency department significantly increased from 1993 through 2008, but the percentage of patients receiving these drugs is still not optimal, with 60% to 70% of patients not receiving recommended antibiotics [84].

Strategies to Enhance Adherence to Therapeutic Guidelines

As the low rate of guideline adherence demonstrates, disseminating clinical practice guidelines alone is not enough to change practice. Physician education should address barriers to guideline adherence, including lack of familiarity, concerns about the practicality of recommended antibiotics, increased cost, lack of documented improved outcomes, and potential conflict with other guidelines [23]. Physician practices and healthcare systems should implement strategies that have changed physician behavior in other health condition settings, such as face-to-face educational outreach, use of local opinion leaders, and individualized audit with peer-comparison feedback [85]. In a study of six Dutch hospitals, significant increases in adherence to guideline-recommended care were achieved with an intervention that included the establishment of a local committee, a lecture by a respected opinion leader, feedback on performance, and critical care pathway pocket cards [86]. The intervention also included a second phase that focused on aspects of treatment in most need of improvement. In another study, weekly e-mail reminders listing performance data on antibiotic administration recommendation for individual emergency physicians helped to increase guideline adherence [87]. The use of a standardized evidence-based order set was associated with a decrease in mortality and was also cost-effective [88].

Follow-Up Care

Evidence suggests that severe pneumonia is a cause of long-term morbidity and excess mortality among adults. In a population-based follow-up study of adults with CAP in Canada, conducted over a median of four years, the re-hospitalization rate for pneumonia was 16% to 72% for all causes [9].

The PSI classification and the time to clinical stability can both help predict adverse outcomes. Mortality has been reported to be higher for people originally classified as PSI class V than PSI classes I and II, with rates of 82% compared with 15% [9]. A time to clinical stability of more than 72 hours has been associated with a significantly higher rate of adverse outcomes than shorter times [90]. Overall, severe CAP has been associated with a 30-day re-hospitalization rate as high as 20%, a 30-day mortality rate as high as 23%, and all-cause mortality within one year as high as 28% [76].

These findings indicate that adults with severe pneumonia should be followed up closely to monitor for adverse events after discharge. The time to clinical stability is a useful guide for a follow-up plan; patients in whom clinical stability is not achieved until more than 72 hours after admission should be seen in follow-up soon after discharge [3,90]. Strategies to prevent influenza and pneumonia should also be emphasized for all hospitalized patients. When indicated, immunization against pneumococcal infection should be initiated before or shortly after discharge, as recommended by the Advisory Committee on Immunization Practices (ACIP) and others [47,91,94,227].

Patient and Family Education

After a diagnosis of pneumonia has been made, patient education should include directions for use of the antibiotic and information on potential untoward effects of the drug. Follow-up instructions, depending on the clinical situation, may include 24-hour telephone contact or follow-up in the office after 24 to 48 hours. This will improve adherence to the prescribed therapy, provide an opportunity to address side effects of drug therapy, and allow progress to be monitored. The need for hospitalization should be assessed throughout the course of the illness. Education should also include instructions to drink plenty of fluids and to use an antipyretic to control fever and myalgias when needed. Use of cough suppressants should be avoided, as the cough reflex and sputum expectoration enhance removal of thick secretions. However, in the event of a constant, nonproductive cough, as found especially with mycoplasmal infection, a narcotic such as codeine at night may allow for more restorative sleep.

Provisions for patients with limited English language proficiency are required under federal law, and the U.S. Department of Health and Human Services and the Office of Civil Rights view a lack of adequate interpretation as discrimination, based on the Civil Rights Act of 1964 [19]. According to U.S. Census Bureau data, more than 60 million Americans speak a language other than English at home, with more than 25 million (8.6% of the population) reporting that they speak English less than "very well" [127]. Immigrant patients with chronic illness may feel unable to return to their home countries due to a lack of available medical care. Changes in healthcare law restricting federal funding of services to only legal residents may cause significant problems for certain facilities, with conflicts arising from providing life-saving care for patients who have no means of reimbursement and no medical services waiting for them in their home countries.

ILLUSTRATIVE CASE

A semi-retired man, 68 years of age, presents one Sunday morning to the emergency department with malaise, fever, productive cough, and right pleuritic chest pain of less than 24 hours duration. He has been active, works as a custodian, has never been hospitalized, takes no medications, and does not regularly see a physician. On review of systems, the patient states that he gave up smoking years ago, has a mild chronic cough and morning sputum production, and has noted mild dyspnea on exertion for the past six months. He drinks only beer, never after work, but every Saturday afternoon he likes to take a six-pack out into the backyard, where he relaxes in his lounge chair. When asked whether there was anything different about the Saturday before the onset of the illness, his wife relates that he consumed two six-packs and failed to come in that evening. She found him later, after dark, asleep in his lounge chair, and helped him in to bed. He awoke this morning with fever and chills. On exam, the patient's temperature is 102.6°F, blood pressure 154/80 mm Hg, pulse 94 beats per minute, and respiration 20 breaths per minute. He is alert, with signs of mild emphysema and crackles audible over the right lower posterolateral chest. The chest x-ray shows patchy alveolar opacification in the right lower lobe and slight cardiomegaly.

The working diagnosis here is CAP, likely caused by S. pneumoniae or H. influenzae, as the patient has no prodromal upper respiratory symptoms to suggest viral or mycoplasma infection.

Why is this happening now? COPD/chronic bronchitis appears to have developed in recent years. Such patients have damaged, poorly functioning mucociliary epithelium and rely on compensatory cough to promote tracheobronchial clearance. Moreover, they often have colonization with pneumococcus and H. influenzae. An additional risk factor in this patient may be mild heart failure with ambient alveolar edema in the basal segments of the lower lungs. Excessive beer consumption the evening before onset of illness made him somnolent and suppressed his cough reflex, thus rendering him vulnerable to aspiration and retention of upper tract secretions (if not gastroesophageal reflux and aspiration). Encumbered by alveolar edema, and perhaps impaired by the metabolic effects of alcohol, pulmonary macrophages in the basal segment of the right lung were simply overwhelmed.

What is the best site of care and treatment for this patient? While he does not meet the criteria for ICU admission, his age, comorbidities, degree of illness, and social situation taken together suggest the need for hospital admission, parenteral antibiotic therapy, and close observation, anticipating a short hospital stay. He was treated with a ß-lactam and macrolide, improved rapidly, and was discharged day 3 on a matching oral regimen, to complete a 10-day course of therapy.

What preventive measures were taken to reduce the risk of this happening again? The 23-valent polysaccharide vaccine (PPSV23) (Pneumovax) was administered prior to discharge and arrangements were made for primary care follow-up. The patient and his wife were educated regarding the need for yearly influenza vaccination. The role of alcohol was discussed, as well as the importance of keeping the Saturday afternoon beer consumption within clearly defined limits.

PNEUMONIA IN THE PEDIATRIC PATIENT

Etiology

Viral pathogens are reported to be responsible for most cases of CAP in preschool-aged children and as many as 80% of cases in children younger than 2 years of age [30]. In children younger than 2 years of age, the most common viral pathogen, occurring in up to 40% of cases, is RSV; other viral pathogens include adenoviruses, bocavirus, human metapneumovirus, influenza A and B viruses, parainfluenza viruses, coronaviruses, and rhinovirus [9,29,30,32].

RSV infection is common in infants and young children; it is estimated that most children have had RSV by 2 years of age [31]. It is leading cause of pneumonia in infants younger than 1 year of age, with 25% to 40% of those infected developing signs of pneumonia or bronchiolitis [29]. Premature birth, very young age, compromised immune system, and impaired lung or heart function are all risk factors for RSV-related pneumonia in infants. In contrast to preschool-aged children, the percentage of viral cases is much lower among older children and adolescents (10 to 16 years of age), and pneumonia caused by RSV is rare in this population.

In older children, viral and atypical bacterial infection account for most mild CAP managed in the ambulatory setting, while pyogenic respiratory bacterial infection is responsible for the majority of CAP in seriously ill, hospitalized children [30]. S. pneumoniae is the most common bacterial pathogen in school-aged children. Studies show that atypical pathogens account for 3% to 23% of cases, most commonly mycoplasma in older children and chlamydia in infants and young children [30]. A 2009 European study examining causative agents in hospitalized pediatric patients with radiographic evidence of pneumonia found bacterial infection in 53% of patients and viral pathogens in 67% of patients, with 33% of children in the study showing evidence of both [63]. S. pneumoniae was the most common bacterial pathogen (46%), followed by M. pneumoniae and C. pneumoniae. The primary viral pathogens identified were influenza A or B, parainfluenza, rhinovirus, RSV and, human metapneumovirus [63].

As with adults, severe CAP caused by S. aureus is encountered during outbreaks of influenza [223]. Legionella spp. and fungal pathogens are uncommon in children. A combination of viral and bacterial pathogens occurs in up to half of children with CAP [30,32].

Clinical Features and Diagnosis

The clinical presentation of CAP in children is similar to that in adults, but can vary according to age and developmental stage. For example, cough productive of purulent sputum may be elicited in older children, but nonproductive cough is common in young children and infants [30,60]. Nonspecific irritability and restlessness may be the primary symptoms in infants.

During the physical examination of pediatric patients, the clinician should look for signs of hypoxia and dehydration, as well as retractions, tachypnea, and use of accessory muscles of respiration [60]. The clinician should also evaluate the upper respiratory tract for evidence of rhinorrhea, otitis media, and pharyngitis [60]. Auscultation of the chest should be carried out, and the Pediatric Infectious Diseases Society (PIDS)/IDSA guideline recommends pulse oximetry for children with suspected hypoxemia [30].

One of the most common reasons for pediatric emergency room visits is fever, and fever is present in 88% to 96% of identified pneumonia cases in developed countries [70]. However, children with fever and wheezing commonly have either upper respiratory disease or reactive airway disease. As with pneumonia in adults, the accuracy of any one sign or symptom in predicting the likelihood of pneumonia is limited [61]. Nonspecific symptoms such as vomiting and abdominal discomfort are common. Careful attention should be given to the chest exam, as diminished breath sounds and fine end-inspiratory crackles are subtle, important clues to the presence of pneumonia in the pediatric patient. In one study, non-specific crackles were present in more than 90% of children with pneumococcal or mycoplasma pneumonia [70]. Infants with pneumonia commonly present with poor feeding and irritability as well as tachypnea, retractions, grunting, and hypoxemia; cough is rare [64].

Several clinical rules have been developed for predicting the likelihood of pneumonia in children on the basis of discernable clinical signs. The presence of at least two of the following signs—fever, tachypnea, and reduced oxygen saturation—is associated with a high probability of the disease; the absence of all three indicates a low probability [61]. Other signs of respiratory distress, such as cough, nasal flaring (in infants), rales, and decreased breath sounds, have also been found to be independent predictors of pneumonia in infants and children [60,62]. Bronchial breath sounds, rales, and dullness to percussion are more likely to occur in older children and adolescents [60].

Unlike diagnosis in adults, a chest radiograph is not the diagnostic standard to be applied for all CAP in children. The PIDS/IDSA guideline notes that routine chest radiographs are not necessary for children who can be treated as outpatients [30]. However, postero-anterior and lateral chest radiographs should be obtained when there is fever and respiratory distress suspected or documented hypoxemia, or illness severe enough to warrant hospitalization [30]. In a study of 99 children hospitalized with what was later determined to be pneumonia, the most common abnormal finding was "diminished" breath sounds; only 21% were described as having "normal" breath sounds. Radiographic evidence of pulmonary consolidation was present in 79% of patients, and correlation between diminished breath sounds and a positive chest x-ray was 60.2% [63].

Laboratory Tests

Unlike the situation in adults, titers of shed virus in children are high [31]. Thus, rapid antigen testing of nasal or throat swabs for influenza and other respiratory viruses should be done for infants and young children [30]. However, it should be noted that negative results of influenza virus on rapid antigen tests do not conclusively rule out infection with influenza virus. Testing for C. pneumoniae is not recommended.

Blood cultures are not routinely needed but should be obtained in children hospitalized for moderate-to-severe pneumonia that is presumed to be bacterial [30]. Urinary antigen detection tests often have false-positive results in children and are therefore not recommended for the diagnosis of pneumococcal pneumonia.

Management of Community-Acquired Pneumonia in Children

The PIDS/IDSA guidelines, published in 2011, addresses the management of CAP in children 3 months of age and older who are otherwise healthy; the guideline does not provide guidance for neonates and infants younger than 3 months of age or children with comorbidities [30]. The guidelines were developed in an effort to decrease morbidity and mortality, as had been shown with the guideline for adults. Similar to the IDSA/ATS guideline, the management issues addressed in the PIDS/IDSA guidelines are site of care and selection and duration of antibiotic therapy, as well as adjunctive surgical and nonantibiotic treatment for complications. As with the guideline for adults, treatment of pneumonia-related symptoms is not included in the pediatric guideline. The discussion here is limited to site of care and antibiotic therapy.

Site of Care

To aid in making site-of-care decisions, the PIDS/IDSA guidelines recommend that a child or infant with CAP be hospitalized if any of the following factors are present [30]:

- Moderate-to-severe illness, as defined by several features, including respiratory distress and hypoxia

- Suspected or documented infection caused by a pathogen with increased virulence, such as community-associated MRSA

- Uncertainty about care at home or availability for follow-up

Most children with pneumonia do not require care in an ICU. The guideline states that a child should be admitted to an ICU or a unit with continuous cardiorespiratory monitoring capabilities if the child [30]:

- Requires invasive ventilation via a nonpermanent artificial airway (endotracheal tube)

- Has impending respiratory failure or sustained tachycardia, inadequate blood pressure, or need for pharmacologic support of blood pressure or perfusion

- Has altered mental status as a result of pneumonia

- Has a pulse oximetry measurement <92% on inspired oxygen of ≥0.50

- Requires acute use of noninvasive positive pressure ventilation

Selection of Antibiotics or Antivirals

Evidence Based Practice Recommendation

According to the Pediatric Infectious Diseases Society and the IDSA, influenza antiviral therapy should be administered as soon as possible to children with moderate-to-severe community-acquired pneumonia consistent with influenza virus infection during widespread local circulation of influenza viruses, particularly for those with clinically worsening disease documented at the time of an outpatient visit. Because early antiviral treatment has been shown to provide maximal benefit, treatment should not be delayed until confirmation of positive influenza test results.

https://academic.oup.com/cid/article/53/7/e25/424286

Last Accessed: August 22, 2018

Strength of Recommendation/Level of Evidence: Strong recommendation; moderate-quality evidence

The PIDS/IDSA guideline recommends empiric antibiotic therapy according to patient age, immunization status, and site of care. Among infants and children 3 months to 5 years of age, antibiotic therapy is not routinely recommended because viral infection is the predominate cause of CAP in this age group [30]. When the cause is thought to be an influenza virus, influenza antiviral therapy should be started as soon as possible, as maximal benefit has been found when treatment begins within 48 hours after symptomatic infection. (Treatment should not be delayed while waiting for the results of viral testing.) The PIDS/IDSA guideline recommends three U.S. Food and Drug Administration (FDA)-approved influenza antiviral therapies: oseltamivir (Tamiflu), zanamivir (Relenza), and amantadine (Symmetrel) [30]. A fourth antiviral therapy, rimantadine (Flumadine), is included in the guideline, with a note that the agent is FDA-approved for prophylaxis—not treatment—in children 1 year of age and older [30]. The guideline adds that data on the safety and efficacy of the agent for children 1 year of age and older have been published.

As in adults, S. pneumoniae is the most common bacterial cause of CAP in children; thus, if a bacterial pathogen is thought to be the cause, amoxicillin or amoxicillin/clavulanate is recommended as first-line therapy for mild-to-moderate illness in previously healthy children 3 months to 5 years of age who are up-to-date with immunization [30]. Several alternatives can be used for children who are allergic to amoxicillin (Table 8). Amoxicillin is also the preferred antibiotic for mild-to-moderate CAP in adolescents and children 5 years of age and older [30]. For children of all ages, especially children older than 5 years of age and adolescents, a macrolide is recommended if an atypical bacterial pathogen is thought (or documented) to be the cause.

Table 8: EMPIRIC ANTIBIOTIC THERAPY FOR COMMUNITY-ACQUIRED PNEUMONIA IN CHILDREN ACCORDING TO PIDS/IDSA GUIDELINE

Site of Care, Patient Characteristics

Presumed Bacterial Pneumonia

Presumed Atypical Pneumonia

Outpatient

<5 years

Amoxicillin

Alternative: amoxicillin clavulanate

Azithromycin

Alternatives: clarithromycin or erythromycin

≥5 years

Amoxicillina

Alternative: amoxicillin clavulanate

Azithromycin

Alternatives: clarithromycin, erythromycin, doxycycline (children >7 years)

Inpatient (all ages)

Fully immunizedb and minimal local penicillin resistance in invasive strains of pneumococcus

Ampicillin or penicillin G

Alternatives: ceftriaxone or cefotaxime (with vancomycin or clindamycin if MRSA suspected)

Azithromycin (with ß-lactam if atypical pneumonia is doubtful)

Alternatives: clarithromycin, erythromycin, doxycycline (children >7 years), or levofloxacin (children who have reached growth maturity or who cannot tolerate macrolides)

Not fully immunized and/or significant local penicillin resistance in invasive strains of pneumococcus

Ceftriaxone or cefotaxime (with vancomycin or clindamycin if MRSA suspected)

Alternative: levofloxacin (with vancomycin or clindamycin if MRSA suspected)

Azithromycin (with ß-lactam if atypical pneumonia is doubtful)

Alternatives: clarithromycin, erythromycin, doxycycline (children >7 years), or levofloxacin (children who have reached growth maturity or who cannot tolerate macrolides)

aA macrolide plus ß-lactam can be used for children 5 years of age and older with presumed bacterial pneumonia who have clinical, radiographic, or laboratory evidence to distinguish bacterial from atypical pneumonia.

bHas received conjugate vaccines for Haemophilus influenzae b and Streptococcus pneumoniae.

Source: [30]

For fully immunized infants and school-aged children who are hospitalized, treatment with ampicillin or penicillin G is recommended when local epidemiologic data show a low level of penicillin resistance to S. pneumoniae [30]. For children who are not fully immunized or are hospitalized in an area with a high level of penicillin-resistant S. pneumoniae, treatment with a third-generation cephalosporin (ceftriaxone or cefotaxime) should be given intravenously. If M. pneumoniae or C. pneumoniae is strongly suspected, treatment should include a macrolide (orally or intravenously) with a ß-lactam and diagnostic testing should be done as soon as possible [30]. The PIDS/IDSA guideline also recommends antimicrobial treatment for specific pathogens; however, a discussion of all possible pathogens is beyond the scope of this course.

According to a systematic review, zinc supplementation in addition to standard antibiotic therapy was not shown to have significant benefit on clinical recovery of severe or nonsevere pneumonia in children 2 to 59 months of age [89].

Duration of Therapy

Most studies have evaluated 10-day therapy, and this duration is associated with good outcomes. However, a shorter duration may be equally as effective, especially for mild disease treated on an outpatient basis [30].

Benefits of Guideline Adherence

Because the PIDS/IDSA guideline for management of CAP in children is relatively recent, data are lacking on the benefits of guideline-adherent treatment in the pediatric population. One study did show that more children received appropriate antibiotics after the development of a clinical practice guideline based on the PIDS/IDSA guideline and an antimicrobial stewardship program [14]. It is assumed that more data will become available over time.

Late Complications

Data on the long-term effects of pneumonia during childhood are lacking. A systematic review demonstrated that severe pneumonia in children younger than 5 years of age is associated with long-term sequelae, with restrictive lung disease being the most common sequela [95]. Overall, major respiratory sequelae (e.g., restrictive lung disease, obstructive lung disease, bronchiectasis) occurred in 5.5% of children treated on an outpatient basis and in 13.6% of children hospitalized for treatment [95]. Sequelae occurred in approximately 54% of children who had pneumonia caused by adenovirus.

7. PREVENTION OF PNEUMONIA

IMMUNIZATION

The primary preventive strategy for pneumonia is immunization with pneumococcal and influenza vaccines, especially for older individuals (older than 65 years of age), young children, and groups at high risk (Table 9) [91]. Other strategies include improved hand hygiene compliance and adherence to healthy lifestyle behaviors.

Table 9: HIGH-PRIORITY AND HIGH-RISK GROUPS FOR VACCINATION

Vaccination

Priority Groups

Annual influenza vaccination

Adults 65 years of age and older

Children 6 to 59 months of age

Residents of long-term care facilities

Adults and children with chronic medical conditions

Women who are pregnant during the influenza season

Pneumococcal vaccination

Adults 65 years of age and older with no history of pneumococcal vaccination

Adults younger than 65 years of age with at least one of the following:

- Chronic disease (e.g., lung, cardiovascular, or liver disease or diabetes)

- Compromised immune system

- Alcoholism

- Cochlear implants

- Cerebrospinal fluid leaks

- Functional or anatomic asplenia

- Resident of nursing home or long-term care facility

- Current or recent past history of smoking

Source: [28,91]

Pneumococcal Vaccination

Pneumococcal vaccines have been improved over time by broadening the coverage of serotypes in the vaccine to include those that are causing the most common invasive infections. In the past, a single agent, PPSV23, has been recommended for use in selected adults with conditions of impaired immunity, and for all adults older than 65 years of age [96]. This vaccine provides some protection against 85% to 90% of the pneumococcal serotypes that cause invasive disease in these populations [97]. Pneumococcal conjugate vaccines are used for younger children, as polysaccharide vaccines are not effective in children younger than 2 or 3 years of age. In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent vaccine (PCV7) previously in use since 2000 [97].

The use of pneumococcal conjugate vaccines in the pediatric age group has been followed by a reduction in the incidence of pneumococcal disease among children, and, indirectly, among adults as well. By 2013, the incidence of invasive pneumococcal disease caused by serotypes represented in the PCV13 vaccine had declined in the adult population older than 65 years of age by approximately 50% compared with 2010 [227]. In 2012, upon approval by the FDA, the ACIP recommended the use of PCV13 for adults with immune deficits and other conditions that impose a heightened risk for invasive pneumococcal infection. After reviewing additional data in 2014, the ACIP extended its recommendation for PCV13 use to all adults older than 65 years age [227].

The ACIP now recommends that both PCV13 and PPSV23 be administered routinely in series to all adults older than 65 years of age (Table 10) [227]. Only a single dose of PCV13 is recommended for adults. No additional dose of PPSV23 is indicated for adults who have previously received this vaccine at or after age 65 years. Pneumococcal vaccine-naïve older adults or those for whom the vaccine history is unknown should receive a dose of PCV13 first, followed by a dose of PPSV23 in 6 to 12 months. Current information, schedules, and guidance for adult immunizations is maintained at the CDC/ACIP website at https://www.cdc.gov/vaccines/schedules.

Table 10: IMMUNIZATION SCHEDULE RECOMMENDED BY THE ACIP

Vaccination

Recommended Recipients

Influenza vaccination (annually)a

Adults and children 6 months of age and older

Pneumococcal vaccination (PCV13 and PPSV23, in series 6 to 12 months apart)b

Adults 65 years of age and older

High-risk children and adults (2 to 64 years of age)

Haemophilus influenzae b (series of 4)

Infants at 2, 4, 6, and 12 to 15 months of age

Pneumococcal conjugate vaccine (series of 4)

Infants at 2, 4, 6, and 12 to 15 months of age

aIn its 2012 immunization schedule for adults, the ACIP notes that the trivalent inactivated vaccine (TIV) may be used for all adults, including pregnant women. Adults older than 65 years of age may receive either standard-dose or high-dose TIV. The live, attenuated influenza vaccine (LAIV) may be used in healthy, nonpregnant adults who are younger than 50 years of age and have no high-risk medical conditions. Healthcare staff who care for severely immunocompromised patients should receive TIV rather than LAIV.

bBoth the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) should be administered routinely in series to all adults older than 65 years of age. The dose of PPSV23 should be given 6 to 12 months after a dose of PCV13.

Source: [91,92,227]

Influenza Vaccination

The influenza vaccine is developed each year to contain the three virus strains that are expected in the upcoming influenza season. The vaccine has traditionally been a trivalent inactivated vaccine (TIV), but in 2003, a trivalent live, attenuated influenza vaccine (LAIV) was introduced in the United States [97]. In 2010, a new high-dose formulation of TIV became available. The LAIV, which contains four times the amount of influenza antigens as other TIVs, is designed to induce a higher immune response in older people [97]. The LAIV is administered as a nasal spray.

The ACIP once recommended a risk-stratified approach to influenza vaccination, but it updated its recommendations to universal vaccination beginning in the 2010–2011 influenza season (Table 10) [91]. The ACIP's immunization schedule also notes which types of vaccines should be used according to age and other factors. In their guideline for the management of CAP, the IDSA/ATS make the following strong recommendations for prevention based on the ACIP recommendations [47]:

- All persons 50 years of age and older, others at risk for influenza complications, household contacts of high-risk persons, and healthcare workers should receive inactivated influenza vaccine as recommended by the ACIP (level I evidence).

- The intranasally administered LAIV is an alternative vaccine formulation for some persons 5 to 49 years of age without chronic underlying diseases, including immunodeficiency, asthma, or chronic medical conditions (level I evidence).

- Pneumococcal vaccines are recommended for persons 65 years of age and older and for those with selected high-risk concurrent diseases, according to the current ACIP guideline (level II evidence).

The IDSA/ATS guideline for management of CAP also states that vaccination status should be assessed at the time of hospital admission for all patients, especially those with medical illnesses [47]. If vaccination is needed, it may be done either at hospital discharge or during outpatient treatment. The Joint Commission developed measures for influenza and pneumococcal vaccination, as appropriate, for inpatients, which became effective for discharges on and after January 1, 2012 [94].

The PIDS and the IDSA also echo the ACIP recommendations in their guideline [30]:

- Children should be immunized with vaccines for bacterial pathogens, including S. pneumoniae, H. influenzae type b, and pertussis (strong recommendation, high-quality evidence).

- All infants 6 months of age or older and all children and adolescents should be immunized annually with vaccines for influenza virus (strong recommendation, high-quality evidence).

- Parents and caretakers of infants younger than 6 months of age, including pregnant adolescents, should be immunized with vaccines for influenza virus and pertussis to protect the infants from exposure (strong recommendation, weak-quality evidence).

- High-risk infants should be provided immune prophylaxis with RSV-specific monoclonal antibody to decrease the risk of severe pneumonia and hospitalization caused by RSV (strong recommendation, high-quality evidence).

Vaccine Efficacy

Declining rates of pneumonia and pneumonia-related deaths are thought to represent the effectiveness of influenza and pneumococcal vaccination [40,98,99]. In a study of a community-dwelling older population, influenza vaccination decreased the risk of hospitalization for pneumonia or influenza, as well as the risk of death, across 10 influenza seasons [7]. Systematic reviews and meta-analyses have shown that pneumococcal vaccination reduces the incidence of invasive pneumococcal disease in both older adults and children, although the findings are unclear for adults with chronic illness [100,101]. Other studies of adults have shown that pneumococcal vaccination is associated with benefit in terms of a lower risk of adverse outcomes associated with the disease. For example, in a study of nearly 3,500 older people (median age: 75 years) who were hospitalized for CAP, the rate of mortality or ICU admission was 40% lower among those who had received prior PPSV23 vaccination [8].

Among children, the introduction of the PCV7, and later PCV13, has led to a substantial decrease in the rate of invasive pneumococcal disease, but the decrease in the rate of CAP has been less dramatic. Early studies showed substantial improvements in the hospitalization rate for CAP only among young children. In one study, the hospitalization rate decreased 39% for children younger than 2 years of age [98]. In another study, the decrease was substantial only for children younger than 1 year of age (22%) and was minimal for children 1 to 5 years of age; the rate increased for adolescents and children older than 5 years of age [4]. The rate of outpatient CAP visits has not changed significantly for this population [5,10].

Vaccination Rates

Despite the wide distribution of the ACIP immunization schedule and public campaigns about the importance of vaccination, rates of both pneumococcal and influenza vaccination remain relatively low. According to National Center for Health Statistics data collated for 2016, the estimated rate of influenza vaccination is 49.9% for children, 31.8% for adults 18 to 49 years of age, 45.2% for adults 50 to 64 years of age, and 67.2% for adults 65 years of age and older [103].

According to the CDC, influenza vaccination coverage for the 2014–2015 season among adults 19 years of age or older was 44.8%, an increase of 1.6% from the 2013–2014 season [102]. Coverage among white adults was higher (48.5%) than that for blacks (37.7%) and Hispanics (33.0%). Influenza coverage was 32.5% among adults 19 to 49 years of age and 48.7% among adults 50 to 64 years of age. Coverage among adults 65 years of age or older (73.5%) was higher compared with younger age groups. Among healthcare personnel , influenza vaccination coverage overall was 68.6%. Among healthcare personnel with and without direct patient care responsibilities, influenza vaccination coverage was 68.9% and 67.9%, respectively.

The national rate of influenza vaccination among all adults has improved over the past decade, yet racial disparities persist. Comparing rates at five-year intervals from 2005 to 2015, the rate of vaccination has more than doubled for adults younger than 65 years of age and for each ethnic category (Table 11) [113]. The rate disparity between white adults (44.2%) and that observed for black (36.7%) and Hispanics (31.2%) remains evident. Previous studies have also shown higher rates of vaccination for white older adults compared with black and Hispanic older adults [104,105,106,107]. Racial disparities have also been found when rates of pneumococcal and influenza vaccination for residents of long-term care facilities were compared, with substantially lower rates for black residents [108,109,110].

Table 11: RATE OF INFLUENZA VACCINATION AMONG ADULTS ACCORDING TO AGE AND RACE/ETHNICITY, FIVE-YEAR INTERVALS, 2005–2015

Age/Ethnicity

Rate

2005

2010

2015

18 to 44 years of age

10.1%

24.6%

30.9%

45 to 64 years of age

20.2%

37.8%

45.1%

65 years of age and older

59.7%

63.9%

69.1%

White

22.5%

36.9%

44.2%

Black

15.5%

28.1%

36.7%

Hispanic

12.0%

26.5%

31.2%

Source: [113]

Data on influenza vaccination readiness among children and adults comes from national survey for the 2017–2018 influenza season. Only approximately two of every five persons in the United States had received an influenza vaccination by early November 2017. The rate was 38.6% for all persons 6 months of age and older. Among children, influenza vaccination coverage was somewhat higher for Hispanic children (41.3%) than for non-Hispanic white (38.0%) and non-Hispanic black (34.6%) children.

According to national surveys, the overall rate of pneumococcal vaccination is approximately 64% for adults 65 years and older, and the rate is substantially lower (approximately 23%) for younger adults in high-risk groups. The CDC report on pneumococcal vaccination coverage (PPSV23 and PCV13) for 2015 is summarized in Table 12 [102].

Table 12: RATE OF PNEUMOCOCCAL VACCINATION AMONG ADULTS 19 YEARS OF AGE AND OLDER, 2015

Race/Ethnicity

High-Risk Adults 19 to 64 Years

Adults 65 Years and Older

All races

23.0%

63.6%

White (non-Hispanic)

24.0%

68.1%

Black (non-Hispanic)

24.0%

50.2%

Hispanic or Latino

19.4%

41.7%

Asian

24.0%

49.0%

Based on data from the National Health Interview Survey, United States, 2015.

Source: [102]

In addition, adherence to the recommendation for pneumococcal and influenza vaccinations for older adults admitted to the hospital has been low. In a study of nearly 105,000 patients 65 years of age and older who had not received either vaccination before admission to the hospital, 99.4% did not receive the pneumococcal vaccine and 97.3% did not receive the influenza vaccine before hospital discharge [111].

Rates of both pneumococcal and influenza vaccination are higher among children than adults. Overall, approximately 83% of children 19 to 35 months of age have received at least four PCV13 doses [112]. The rate varies according to race/ethnicity, with the lowest rates among Asian and black children (Table 13) [112].

Table 13: RATE OF VACCINATION WITH AT LEAST FOUR PCV DOSES AMONG CHILDREN 19 TO 35 MONTHS OF AGE

Race/Ethnicity

Rate

White (non-Hispanic)

84.1%

Black (non-Hispanic)

74.5%

Hispanic

81.4%

American Indian/Alaska Native

80.1%

Asian

81.0%

Multiracial

83.6%

Total

83.3%

PCV = pneumococcal conjugate vaccine.

Source: [112]

Barriers to Vaccine Use

In its Healthy People 2020 initiative, the U.S. Department of Health and Human Services has set objectives for improving pneumococcal and influenza vaccination rates among adults and children, with targets of 80% to 90% (Table 14) [114]. To reach these targets, healthcare providers must address documented barriers to recommended vaccinations and gain a better understanding of other challenges to vaccination. Unequal access to health care appears to account for a low percent of racial disparities [105]. Rather, lack of awareness of the need for vaccination and misconceptions about vaccines have been reported as the primary barriers in several studies [104,105,106,115,116,117].

Table 14: HEALTHY PEOPLE 2020 TARGETS FOR PNEUMOCOCCAL AND INFLUENZA VACCINATION RATES

Target Population

Target Rate

Baseline Rate for Improvement (Year)

Pneumococcal vaccination

Four doses of PCV by 19 to 35 months of age

90%

80% (2008)

Adults 65 years of age and older

90%

60% (2008)

High-risk adults 16 to 64 years of age

60%

17% (2008)

Institutionalized adults 18 years of age and oldera

90%

66% (2006)

Annual influenza vaccination

Three doses of Hib vaccine by 19 to 35 months of age

90%

57% (2009)

Children 2 to 4 years of age

80%

40% (2008)

Children 5 to 12 years of age

80%

26% (2008)

Children 13 to 17 years of age

80%

10% (2008)

Adults 18 to 64 years of age

80%

25% (2008)

Adults 65 years of age and older

90%

67% (2008)

High-risk adults 18 to 64 years of age

90%

39% (2008)

Institutionalized adults 18 years of age and older

90%

62% (2006)

aAdults residing in long-term care facilities and nursing homes.

PCV = pneumococcal conjugate vaccine; Hib = Haemophilus influenzae type b.

Source: [114]

Among adults, misconceptions about vaccines range from the belief that healthy people do not need vaccinations to a fear of side effects [104,106,116]. Beliefs about vaccines vary by race/ethnicity, age, education, and gender. For example, in a survey of more than 6,700 older adults, lack of awareness that influenza vaccination was needed was more common among Hispanic (33%) and black individuals (25%) than among white individuals (21%) [105]. In contrast, concern about side effects was more common among white individuals (15%) than among black and Hispanic individuals (10% and 6%, respectively) [105]. The belief that vaccination would not prevent illness was consistent across the racial/ethnic groups. In other studies, lower rates of influenza vaccination among older black adults have been significantly associated with lower rates of positive attitudes about vaccination [105,118]. It is unclear whether the negative attitude represents mistrust of the vaccine itself or of healthcare/healthcare providers in general [105]. The findings of one study showed that, compared with white adults, more black and Hispanic adults believed that they had become sick from a previous influenza vaccination [106]. Language proficiency and level of acculturation have been associated with lower vaccination rates among older Hispanic adults [107,119].

Parental attitudes about vaccines are an important factor in vaccination rates among children. The primary attitude is concern about the safety and efficacy of the vaccine, including fear of adverse events, the discomfort associated with vaccination, distrust of advocates of vaccination, and belief that the vaccine should not be given when a child has a minor illness [117,120,121,122]. Difficulty remembering or confusion about the vaccination schedule for children is also a major challenge [120,122]. Changes in access to health care have been noted as a factor in the low rate of influenza vaccination among teenagers [117].

Healthcare provider-related factors should also be addressed. Slightly more than half of older adults have said that their healthcare provider did not recommend influenza vaccination, and this percentage has been consistent across races/ethnicities [105,106]. The lack of provider recommendation may be a misperception or may be a reality. It has been noted that nearly half of providers do not follow the ACIP recommendations for vaccination [116]. Provider recommendation is essential, as it has been found to be the strongest predictor of whether a person will receive vaccination, even among those who have negative attitudes toward vaccines [104,106,115,116,123]. Providers have said that the lack of an effective reminder system is a factor in low vaccination rates [116,123].

Strategies to improve rates of vaccination and other preventive measures rely on effective patient-clinician communication. Among the most important factors for effective communication across all healthcare settings are knowledge of the language preference of the patient and family; an awareness of the patient's and family's health literacy levels; and an understanding of and respect for the patient's and family's cultural values, beliefs, and practices [124,125,126]. These issues are significant, given the growing percentages of racial/ethnic populations. According to U.S. Census Bureau data from 2013, more than 60.3 million Americans speak a language other than English in the home, with more than 25.1 million of them (8.6% of the population) reporting that they speak English less than "very well" [127]. Clinicians should ask their patients what language is spoken at home and what language they prefer for their medical care information, as some patients prefer their native language even though they have said they can understand and discuss medical information in English [128]. When the healthcare professional and the patient speak different languages, a professional interpreter should be used. Studies have demonstrated that the use of professional interpreters rather than "ad hoc" interpreters (e.g., untrained staff members, family members, friends) facilitates a broader understanding, leads to better outcomes, and is better aligned with patient preferences [129,130,131].

Studies have indicated that as many as 26% of patients have inadequate health literacy, which means they lack the ability to understand health information and make informed health decisions; an additional 20% have marginal health literacy [132,133,134]. Health literacy varies widely according to race/ethnicity, level of education, and gender. Clinicians are often unaware of the literacy level of their patients and family, but several instruments are available to test the health literacy level [126,135]. These instruments vary in the amount of time needed to administer and the reliability in identifying low literacy. Among the most recent tools is the Newest Vital Sign (NVS), an instrument named to promote the assessment of health literacy as part of the overall routine patient evaluation [136]. The NVS takes fewer than three minutes to administer, has correlated well with more extensive literacy tests, and has performed moderately well at identifying limited literacy [126,135]. Two questions have also been found to perform moderately well in identifying patients with inadequate or marginal literacy: "How confident are you in filling out medical forms by yourself?" and "How often do you have someone help you read health information?" [126]. Clinicians should adapt their discussions and educational resources to the patient's and family's identified health literacy level and degree of language proficiency and should also provide culturally appropriate and translated educational materials when possible.

Cultural competency is essential for addressing healthcare disparities among minority groups [124]. Clinicians should ask the patient about his or her cultural beliefs, especially those related to health, and should be sensitive to those beliefs.

Targeted evidence-based strategies can help clinicians improve vaccination rates (Table 15). Education about the importance of vaccination is the cornerstone of most strategies. Messages should be clear and emphasize the benefits of vaccination and the risks of not receiving vaccination. Acknowledging the risks of vaccines can help enhance patient trust [117]. Clinicians should give their patients a list of online resources that provide balanced information on vaccines (Table 16). Differences in beliefs about vaccines across racial/ethnic groups indicate that targeted messages developed for specific demographic subgroups may be useful [219]. In addition, language-specific educational resources may also help increase vaccination rates by enabling patients to better understand the need for vaccination and its safety.

Table 15: BARRIERS TO OPTIMAL VACCINATION AND POSSIBLE SOLUTIONS

Barriers

Solutions

Decreased knowledge about pneumonia and its seriousness

Provide education resources (language-specific, as appropriate) that highlight the potential severity of disease and the consequences of not receiving protection through vaccination.

Belief that vaccines are unsafe or will cause illness

Refer patient (or parent) to objective information about vaccines.

Lack of awareness for the need of vaccination

Take advantage of all visits (well and acute) to remind patients (or parents) about the need for vaccination, to administer vaccination, or to schedule appointment for vaccination.

Lack of provider recommendations

Identify high-risk patients and encourage them to receive vaccination.

Lack of effective practice systems

Implement effective reminder systems and standing orders.

Source: Compiled by Author

Table 16: RESOURCES ABOUT VACCINATIONS FOR PATIENTS AND PARENTS

American Academy of Pediatrics

https://www.aap.org

American Academy of Family Physicians

https://www.aafp.org

U.S. Department of Health and Human Services Vaccines

https://www.vaccines.gov

The History of Vaccines

https://www.historyofvaccines.org

Immunization Action Coalition

http://www.vaccineinformation.org

Centers for Disease Control and Prevention Vaccines for Children (VFC) Program

https://www.cdc.gov/vaccines/programs/vfc

Source: Compiled by Author

Education and provider recommendation are particularly important for high-risk people, as the lowest vaccination rates are reported for this population [102,103]. One survey showed that provider recommendations for pneumococcal and influenza vaccination were low for this population; the rate of recommendation was lowest for people with a weakened immune system and those receiving radiation therapy or chemotherapy (Table 17) [116]. Clinicians should identify high-risk patients in their practice and take special steps to ensure that these patients receive appropriate vaccinations.

Table 17: HEALTHCARE PROVIDER RECOMMENDATIONS FOR INFLUENZA AND PNEUMOCOCCAL VACCINATIONS BY PATIENT TYPE

Patient Type

Influenza Vaccine

Pneumococcal Vaccine

Physicians

PA/NP/RNs

Physicians

PA/NP/RNs

All adults

39%

59%a

—

—

Aged ≥50 years

28%a

15%

4%

18%a

Aged ≥65 years

37%

28%

65%

55%

Chronic lung disease

45%

40%

68%

55%

Diabetes mellitus

31%

25%

44%a

26%

Heart disease

20%

11%

29%a

12%

Chronic liver disease

22%

16%

27%

20%

Chronic kidney disease

22%

12%

25%

17%

Weak immune system

17%

20%

24%

29%

Radiation/chemotherapy

14%

9%

17%

10%

Asplenia

—

—

27%a

8%

Complications or risk from other illness

25%

17%

28%

23%

Smoker

—

—

13%

11%

Close contact with someone at high risk

24%

22%

11%

10%

aSignificantly greater (P <0.05) than other provider group.

NP = nurse practitioner; PA = physician assistant; RN = registered nurse.

Source: Reprinted with permission from Johnson D, Nichol KL, Lipczynski K. Barriers to adult immunization. Am J Med. 2008;121:S28-S35.

Missed opportunities represent another practice-related area in which clinicians can improve vaccination rates. Although many clinicians check immunization status during well visits, most do not check the status during acute visits, nor do they take advantage of the visit to administer the vaccination [105,115]. Healthcare providers can close the gap on missed opportunities for vaccination by taking advantage of every office visit to administer vaccinations, reminding their patients about the need for vaccination, or scheduling a future appointment for vaccination [105,115,117]. Educational fliers and pamphlets in the waiting room and examination rooms can engage patients and parents and help prompt discussions about vaccination [116].

Patient reminder and recall systems in primary care settings have been effective in improving vaccination rates. A meta-analysis found that rates among both children and adults increased up to 20% with several types of reminders, including postcards, letters, and phone calls [137]. The most effective reminder system was phone calls, but it was also the most expensive. Given that about 25% of primary care physicians currently use reminder systems, increasing the number of physicians who use such systems can in turn increase vaccination rates [123]. Standing orders for vaccinations have been shown to substantially increase vaccination rates, yet are used by only 20% to 33% of physicians [123,138]. Again, adopting this system results in improved vaccination rates.

Many people have turned to facilities outside of their primary healthcare provider to receive vaccinations. Health fairs, pharmacies, grocery stores, senior centers, and workplaces have become more common settings for vaccination because of their convenience and lower cost [123,138]. Clinicians can also help increase vaccination rates by participating in community events that provide vaccinations and by promoting these settings as alternative options.

Programs to provide vaccinations to high-risk patients in the emergency room have been successful at increasing vaccination rates [139,140]. In a three-week intervention program at one inner city emergency department, participants were provided appropriate immunizations when they were at high risk for specific diseases [139]. During the study period, rates of influenza and pneumococcal vaccinations increased from 16% to 83% and from 18% to 84%, respectively. Such programs can help healthcare systems adhere to guideline recommendations for vaccinating hospitalized patients.

8. PNEUMONIA ASSOCIATED WITH HEALTHCARE FACILITIES

Pneumonia associated with healthcare facilities encompasses the broad category of cases that arise in persons who reside in, or have had significant recent exposure to, facilities such as hospitals, nursing homes, dialysis clinics, and transfusion centers. Despite advances in clinical care and prevention, this category of pneumonia remains a serious cause of morbidity and mortality and a challenging, costly public health issue. The IDSA and the ATS subdivide and defines this category of pneumonia as follows:

- HAP is hospital-acquired pneumonia that occurs 48 hours or more after admission and did not appear to be incubating at the time of admission.

- VAP is a separate type of HAP that develops more than 48 hours after endotracheal intubation.

- HCAP is defined as pneumonia that occurs in a nonhospitalized patient with extensive healthcare contact, as defined by one or more of the following:

- Intravenous therapy/chemotherapy or wound care within the prior 30 days

- Residence in a nursing home or other long-term care facility

- Discharge from an acute care hospital or chronic care facility within the prior 90 days

- Attendance at a hospital or hemodialysis clinic within the prior 30 days

HAP and VAP have been studied most often, and the bulk of data on causative pathogens comes from studies of VAP. All three categories of pneumonia carry an increased risk for drug-resistant infection, though the risk of multidrug-resistant infection has been more consistently applicable to HAP and VAP [28]. Within the category of HCAP, nursing home-acquired pneumonia is the type with the most published data and will be discussed in this course. The ATS and the IDSA have collaborated to provide evidence-based recommendations, updated in 2016, for the diagnosis and treatment of HAP and VAP [28].

EPIDEMIOLOGY

Approximately 3 to 10 cases of HAP occur per 1,000 hospital admissions [26]. Pneumonia as a complication of hospitalization increases length of stay (by more than one week), increases mortality risk, and adds an additional cost of care that can reach $40,000 per case [26].

The rate of VAP is higher than that for HAP, with a reported rate of 1 to 4 cases per 1,000 ventilator-days, and rates as high as 10 cases per 1,000 in some neonatal and surgical populations [12,28,141]. An estimated 10% of patients requiring mechanical ventilation will develop VAP, and the mortality rate directly attributable to VAP is estimated at 13% [28]. Excess cost of care resulting from prolongation of hospital stay is estimated to be range from $30,000 to $40,000 per patient [28]. Pediatric VAP has not been as well studied as in adults. It occurs most commonly in children 2 to 12 months of age [142].

Pneumonia develops in approximately 2.3% of nursing home residents [1]. The mortality rate attributed to nursing home-acquired pneumonia is 10% to 30% [143].

RISK FACTORS

Illness and injury requiring admission to a healthcare facility often confers an increased risk for infection. Multiple factors account for this, including weakness and debility, use of indwelling catheters, compromised immune function, and poor nutrition [26,144]. To these may be added sedating medication intended to promote sleep or permit invasive procedures; this in turn increases the risk for aspiration of nasopharyngeal secretions colonized with nosocomial bacterial pathogens.

The nasopharynx tends to become colonized by enteric gram-negative bacilli within a few days after admission to a hospital. Risk factors for colonization by multidrug-resistant pathogens include exposure to critical care units, prolonged hospital stay, prior antibiotic therapy, history of cigarette smoking, major surgery, multiple organ-system failure, and foreign bodies such as nasogastric and endotracheal tubes [26,144].

Hospital-Acquired Pneumonia

In a systematic review, the American College of Physicians found several patient-related and surgery-related factors that increased the risk of postoperative pulmonary complications. The most common patient-related factors were the presence of COPD and an age older than 60 years [145]. Other significant factors were an American Society of Anesthesiologists (ASA) class of 2 (defined as a patient with mild systemic disease) or higher, functional dependence, and congestive heart failure. Cigarette use was associated with a modest increase in risk, and obesity and mild or moderate asthma were not found to increase risk [145]. Use of a PPI or histamine2 receptor antagonist is also thought to be a risk factor [45]. Surgery-related factors included prolonged duration of surgery (i.e., more than three to four hours), emergency surgery, and surgical site, with abdominal surgery, thoracic surgery, neurosurgery, head and neck surgery, vascular surgery, and aortic aneurysm repair being associated with the greatest risks [145].

Ventilator-Associated Pneumonia

The risk for VAP appears to be greatest during the first week after intubation. In one study, the risk was estimated to be 3% per day during the five-day period following intubation, decreasing to 2% per day for days 5 through 10, and to 1% per day for longer durations [147]. In a population of children who had cardiothoracic surgery, pneumonia risk correlated with mechanical ventilation for longer than three days [144]. Nearly half of all cases of VAP develop within the first four days of mechanical ventilation [148].

Other identified risk factors among adults include prolonged placement of the patient's head in the supine position; use of a nasogastric tube, paralytic agents, or PPI or histamine2 receptor antagonist; advanced age; chronic lung disease; and head trauma [45,149]. Among children, VAP has been significantly associated with subglottic/tracheal stenosis, trauma, and tracheostomy [150]. In one study, VAP was most frequently associated with ICU admission diagnoses of postoperative care, neurologic conditions, sepsis, and cardiac complications [151].

Nursing Home-Acquired Pneumonia

The risk factors reported to be associated with nursing home-acquired pneumonia include profound disability, immobility, urinary incontinence, deteriorating health status, difficulty swallowing, and inability to take oral medications [42]. Older age, male gender, and antipsychotic and anticholinergic medications have also been reported to increase risk [23,42].

ETIOLOGY

Gram-negative enteric bacilli and Pseudomonas spp. rarely colonize the upper respiratory tract of healthy individuals, but often do so in persons with an underlying disease, such as alcohol use disorder, and in those who are hospitalized or reside in nursing homes. Therefore, a history of recent hospitalization or nursing home residency should heighten suspicion for a gram-negative pathogen when such a patient presents with clinical signs of infection.

Most cases of pneumonia that develop in a healthcare facility are caused by aspiration of oropharyngeal or gastric secretions colonized with hospital bacterial flora [26,28]. Consequently, the prevalent causation as well as the antibiotic sensitivity pattern of resident pathogens will vary from region to region in relation to the type of facility and burden of antimicrobial usage. The selection of initial antibiotic therapy in these cases is based on the patient's risk factors for infection with a multidrug-resistant organism, such as MRSA, P. aeruginosa, K. pneumoniae, or Acinetobacter. The ATS/IDSA lists the following risk factors for multidrug-resistant pathogens in patients presenting with HAP or VAP [233,28]:

- Prior intravenous antibiotic use within 90 days

- Septic shock at time of VAP

- ARDS prior to onset of VAP

- High frequency of antibiotic resistance in the community of residence or the hospital unit of residence

- Five or more days of hospitalization prior to onset of pneumonia

- Home infusion therapy

- Chronic dialysis within 30 days

- Family member with multidrug-resistant infection

- Immunosuppression

Viral and fungal pathogens are rare causes of HAP, VAP, and nursing home-acquired pneumonia in immunocompetent adults. Outbreaks of viral pneumonia may occur during influenza season, and influenza, parainfluenza, adenovirus, and RSV are involved in about 70% of those cases [28]. Candida spp. and Aspergillus fumigatus may cause pneumonia in patients who have had organ transplantation or who have a compromised immune system and neutropenia.

Hospital-Acquired Pneumonia

Among adults with no previous antibiotic exposure, the most common bacterial causes of HAP are S. pneumoniae, H. influenzae, Escherichia coli, K. pneumoniae, and S. aureus [26,28,35,148]. Gram-negative bacilli resistant to first-generation cephalosporins also frequently develop in late-onset HAP. For up to 40% of adults with previous antibiotic exposure, late-onset HAP is caused by potentially multidrug-resistant pathogens, including Pseudomonas aeruginosa, Acinetobacter baumannii, and MRSA [26]. In a study of more than 3,600 patients admitted to an ICU, Pseudomonas spp. was the cause of pneumonia in 25% of patients; MRSA in 18%; and Acinetobacter spp. in 6% [35]. Other studies have shown that S. aureus is common among patients who are in a coma or have diabetes or renal failure. P. aeruginosa is common among patients who have had a prolonged stay in the ICU, have received prior antibiotics or corticosteroids, or who have structural lung disease. Legionella is usually found in patients who have compromised immune systems [35].

The causes of HAP in children have not been well studied. However, outbreaks of pneumonia caused by RSV have been common in pediatric wards [28].

Ventilator-Associated Pneumonia

The most common pathogens associated with VAP in adults are S. aureus and P. aeruginosa, followed by Enterobacter spp., A. baumannii, and K. pneumoniae[26,148,152,153]. These bacteria are among those that have become resistant to antibiotics, and the frequency of infection with MRSA is increasing. Almost half of all cases are caused by infection with more than one pathogen [148]. Although bacteria are the primary causative agents, viruses and saprophytic fungi have also been implicated as well [154].

As with HAP, few data are available on the etiology of VAP in children. In one report, P. aeruginosa was the most common cause, accounting for 22% of cases [142].

Nursing Home-Acquired Pneumonia

The bacterial pathogens that cause pneumonia in residents of nursing homes (and other long-term care facilities) differ according to the severity of disease. S. pneumoniae and H. influenzae are the most common causes of mild-to-moderate pneumonia in long-term care facilities [155]. In cases requiring hospitalization, C. pneumoniae, S. aureus, and influenza virus are frequently observed as well. Patients with severe illness commonly are infected with methicillin-sensitive S. aureus or MRSA, gram-negative enteric pathogens, or P. aeruginosa[23,155].

DIAGNOSIS

The difficulty in recognizing HAP, VAP, or nursing home-acquired pneumonia has been well documented [28,147,156]. The clinical signs often resemble other, noninfectious conditions, and the specificity of clinical criteria is low [148]. According to the CDC definition, the diagnosis in adults is made on the basis of clinical signs and results of laboratory testing or imaging and must meet one of two criteria [157].

Criterion 1 is rales or dullness to percussion on physical examination of the chest and at least one of the following:

- New onset of purulent sputum or change in character of sputum

- Organisms cultured from blood

- Isolation of an etiologic agent from a specimen obtained by transtracheal aspirate, bronchial brushing, or biopsy

Criterion 2 is chest radiograph that shows new or progressive infiltrate, consolidation, cavitation, or pleural effusion and at least one of the following:

- New onset of purulent sputum or change in character of sputum

- Organisms cultured from blood

- Isolation of an etiologic agent from a specimen obtained by transtracheal aspirate, bronchial brushing, or biopsy

- Isolation of virus from or detection of viral antigen in respiratory secretions

- Diagnostic single antibody titer immune globulin M or fourfold increase in paired sera immune globulin G for pathogen

- Histopathologic evidence of pneumonia

A set of clinical diagnostic criteria for HCAP includes the presence of a new and persistent (more than 48 hours) infiltrate in addition to one of the following [148]:

- Radiographic evidence of cavitation or necrosis

- Histopathologic evidence of pneumonia

- Positive pleural or blood culture for the same micro-organism as that found in respiratory secretions

Plus two of the following signs:

- Core temperature >38.3°C (100.94°F)

- WBC count >10,000 cells/mm^3

- Purulent tracheal secretions

There are no compelling data to recommend a specific approach to diagnosing HAP and VAP. For patients who are not receiving mechanical ventilation, collection of a sputum specimen should be attempted before antibiotic therapy is begun [35,158]. Specimens for culture can be obtained by bronchoscopy with a protected specimen brush to limit contamination or by bronchoalveolar lavage. The latter method has been found to lead to higher rates of treatment than diagnosis based on the CDC definition, and one study showed that preferential sampling of the right lung (rather than the left) improved the diagnostic accuracy of bronchoalveolar lavage [35,159,160]. However, the invasive procedure has disadvantages, including high cost, need for technical expertise, and the potential for false-negative results [35,159].

The ATS/IDSA guideline recommends collecting specimens from the lower respiratory tract for culture, preferably by noninvasive techniques, and reliance on semiquantitative culture technique [28]. Noninvasive methods to obtain respiratory samples in patients with HAP (non-VAP) include spontaneous expectoration, sputum induction, nasotracheal suctioning (in a patient unable to produce a sample), and endotracheal aspiration in a patient with HAP who subsequently requires mechanical ventilation [28]. A 2012 meta-analysis found no evidence that the use of quantitative cultures of respiratory secretions resulted in decreased mortality, reduced time in ICU and on mechanical ventilation, or higher rates of antibiotic change compared with qualitative cultures in patients with VAP [161]. In addition, there was no difference in mortality whether invasive or noninvasive methods were used to obtain specimens.

TREATMENT

The treatment of HAP and VAP is complicated by two divergent needs: the need for empiric therapy with a broad-spectrum antibiotic, to aid in reducing mortality rates, and the need to avoid the indiscriminate use of antibiotics, to avoid the development of resistance. To address this complex issue, the strategy of de-escalation therapy was developed. With this treatment approach, a broad-spectrum antibiotic targeted to likely pathogens is administered, and the antibiotic regimen is modified after the results of cultures are known [154,162]. This strategy has reduced the mortality rate while achieving an overall objective of a more judicious use of antibiotics [154,163]. In one study, de-escalation led to a significantly lower mortality rate compared with either escalation therapy or therapy that was neither escalated nor de-escalated (17% vs. 43% and 24%, respectively) [151].

The empiric treatment of nosocomial pneumonia in general, requires knowledge of the infection history (hospital flora) of the healthcare facility and of individual patient units [35,148,164]. The selection of an empiric antibiotic regimen for HAP and VAP should be guided by local antibiotic-resistance data. The ATS/IDSA recommend that all hospitals regularly generate and disseminate a local antibiogram, ideally one that is specific to their intensive care population(s), if possible [28].

In managing a case of HAP and VAP, the clinician should review in detail the guidance provided by the ATS/IDSA, and consider consultation with appropriate subspecialty colleagues [28]. Recommendations governing selected issues of initial management emphasize the following principles [28]:

- Obtain sputum samples from the lower respiratory tract for culture before beginning antibiotic therapy. Do not delay initiation of therapy for critically ill patients in order to obtain specimens.

- Begin treatment promptly, selecting an empiric antibiotic regimen that coversS. aureus, P. aeruginosa, and other gram-negative bacilli.

- In selecting coverage for S. aureus, choose an agent active against MRSA (vancomycin or linezolid) for patients with risk factor(s) for antimicrobial resistance, treatment in hospital or units where >10% of isolates are methicillin-resistant, and patients in settings where the prevalence of MRSA is unknown.

- In selecting coverage for P. aeruginosa, one antibiotic active against this pathogen is satisfactory if the patient has no risk factors for antimicrobial resistance and <10% of gram-negative isolates from the patient's unit are resistant to the agent chosen; otherwise, prescribe two antipseudomonal antibiotics from different classes.

- Consider de-escalation of antibiotics after the results of cultures and sensitivities are known and the clinical response is satisfactory.

- After an optimal antibiotic regimen is confirmed, a seven-day course of therapy is recommended, provided the rate of improvement of clinical, radiographic, and laboratory parameter is satisfactory.

- For patients with HAP/VAP, it is suggested to use serum procalcitonin levels plus clinical criteria to guide discontinuation of antibiotic therapy, rather than clinical criteria alone.

Selection of specific antimicrobial therapy is influenced by the timing of onset of clinical signs, as well as the presence or absence of risk factors for infection with multidrug-resistant organisms. For early-onset pneumonia and/or patients with no such risk factors, limited-spectrum antibiotic therapy is recommended (Table 18) [28]. For late-onset pneumonia and/or patients at increased risk for multidrug-resistant organisms, a broad-spectrum antibiotic regimen is recommended.

Table 18: RECOMMENDED ANTIBIOTIC THERAPY FOR HEALTH FACILITY-ASSOCIATED PNEUMONIA ACCORDING TO SITE OF CARE

Site of Care

Recommended Regimen

Nursing home

Antipneumococcal fluoroquinolone or either a high-dose ß-lactam/ß-lactamase inhibitor or a second- or third-generation cephalosporin in combination with azithromycin

Hospital

Antipseudomonal cephalosporin, antipseudomonal carbapenem, or extended-spectrum ß-lactam/ß-lactamase inhibitor and antipseudomonal fluoroquinolone or aminoglycoside and anti-MRSA agent (vancomycin or linezolid)

Intensive care unit

Empiric MRSA and double coverage of Pseudomonas pneumonia

Source: [28]

Ventilator-Associated Pneumonia and Multi-Drug Resistant Pathogens

Evidence Based Practice Recommendation

For healthcare-associated or community-acquired MRSA pneumonia, the IDSA recommends IV vancomycin or linezolid 600 mg PO/IV twice daily, if the strain is susceptible, for 7 to 21 days, depending on the extent of infection.

https://academic.oup.com/cid/article/52/3/e18/306145

Last Accessed: August 22, 2018

Level of Evidence: A-II (Good evidence from one or more 1 well-designed clinical trial, without randomization to support a recommendation for use)

VAP is often caused by MRSA and gram-negative bacilli such as Acinetobacter spp. and Pseudomonas. Vancomycin has been considered the first choice for treatment of MRSA infections [154]. However, the ATS/IDSA guidelines note that linezolid may have advantages over vancomycin for pneumonia caused by MRSA [28]. Linezolid has been compared with vancomycin for the treatment of pneumonia caused by MRSA in many studies, and linezolid has been found to improve survival and to be more cost-effective [147,165,166,167,168]. In a 2008 study, the rate of early microbiologic cure was not significantly higher for linezolid than for vancomycin, although there were trends favoring linezolid in several secondary clinical outcomes, such as clinical cure; duration of ventilation, hospitalization, and stay in ICU; survival time not on a ventilator; and overall survival [169]. The findings led the authors to suggest that the benefit of linezolid may be related to factors other than bacterial clearance.

Role of Inhaled Antibiotic Therapy

For cases of VAP caused by gram-negative bacilli that are susceptible only to aminoglycosides or polymyxins, the ATS/IDSA suggests both inhaled and systemic antibiotics, rather than systemic antibiotics alone [28]. It is also reasonable to consider adjunctive inhaled antibiotic treatment as a last resort for patients who are not responding to intravenous antibiotics alone, whether or not the infecting organism is multi-drug resistant.

According to a meta-analysis, a short fixed-course (7 or 8 days) of antibiotic therapy may be more appropriate than a prolonged course (10 to 15 days) for patients with VAP not caused by nonfermenting gram-negative bacilli [170]. The short course reduced recurrence of pneumonia caused by multiresistant organisms without adversely affecting other outcomes. Among patients with nonfermenting gram-negative bacilli, recurrence was greater after the short course.

Nursing Home-Acquired Pneumonia

The ATS/IDSA guideline provides some direction for choice of antibiotic therapy but do not specify a distinct management protocol for nursing home-acquired pneumonia. This is expected to be addressed in the forthcoming updated guidelines for management of CAP.

Adherence to Guideline-Directed Treatment

The lack of adherence to guideline-directed treatment of pneumonia cases associated with healthcare facilities is evidenced by wide variations in practice. For example, one study showed that more than 100 different antibiotic regimens had been prescribed as initial treatment and that de-escalation therapy was used for only 22% of patients [151]. Adherence rates for pneumonia associated with healthcare facilities have been reported to be lower than rates of adherence to guidelines for treatment of CAP. In one survey, guideline-recommended antibiotics were used 78% of the time for CAP, compared with 9% for HCAP [18]. This lack of adherence was not due to unfamiliarity or disagreement with the guidelines; 71% of the survey respondents said they were aware of the guidelines, and 79% said they agreed with and practiced according to them. In contrast, another survey showed that fewer than half of physicians were familiar with the ATS/IDSA guideline for treatment of nursing home-associated pneumonia [23]. It is reasonable to expect that strategies used to enhance adherence to guidelines in the setting of CAP would also be beneficial in the setting of pneumonia associated with healthcare facilities. Thus, feedback on performance, reminder systems, standardized order sets, and education emphasizing outcomes and cost-effectiveness would be valuable.

PREVENTION

The CDC has published a guideline for the prevention of HAP and VAP, with a focus on strategies to decrease or eliminate modifiable risk factors for pneumonia associated with healthcare facilities [93]. These strategies are related to preoperative and postoperative care and measures to reduce the risk of transmission of etiologic pathogens. In addition, steps to prevent the spread of influenza virus are essential, especially during influenza season.

Hospital-Acquired Pneumonia

The prevention of postoperative pneumonia has long been a part of initiatives to decrease complications among patients undergoing surgery. The Respiratory Risk Index was developed to classify patients as being at low, medium, or high risk for postoperative respiratory failure [26]. The factors in the index include the complexity of the surgery, the ASA status, and comorbidities.

Smoking triples the risk for pulmonary complications after surgery, and smoking cessation for at least eight weeks before surgery, when possible, is recommended for current smokers [26]. The risk for complications in patients with respiratory disease or congestive heart failure can be ameliorated by optimum treatment before surgery (e.g., treatment with steroids for patients with COPD or asthma) [26].

Effective pain management after surgery also helps to decrease the risk of pulmonary complications. For postoperative patients who are not mechanically intubated, the ability to cough and clear secretions is important for preventing pulmonary complications [26]. The use of incentive spirometry and deep breathing exercises are recommended, especially for people at high risk for pulmonary complications, as are frequent coughing and early movement (in bed and/or walking) [26,93,145]. Fair evidence supports the selective (rather than routine) use of a nasogastric tube after abdominal surgery [145].

Ventilator-Associated Pneumonia

Two guidelines were developed to focus specifically on the prevention of VAP; one was jointly developed by the Society for Healthcare Epidemiology of America (SHEA) and IDSA, and the other was jointly developed by the Canadian Critical Care Trials Group and the Canadian Critical Care Society [149,171]. In addition, the CDC guideline addresses the prevention of HAP and VAP [93]. All of these agencies suggest a multicomponent strategy for prevention of pneumonia. Compliance with guidelines, however, has been slow; nursing surveys demonstrate rates of adherence to specific preventive measures ranging from 15% to 50% [12,172]. Education is beneficial, and training sessions are a proven means to enhance knowledge and practice among healthcare professionals caring for intubated patients [173].

The Institute for Healthcare Improvement (IHI) found that implementation of its ventilator bundle, a collection of five prevention strategies drawn from these guidelines, led to a 45% reduction in the incidence of VAP [174]. The bundle includes the following interventions [174]:

- Assessment of readiness to extubate and daily interruptions of sedation

- Elevation of the head of the bed

- Daily oral care with chlorhexidine

- Prophylaxis of peptic ulcer disease

- Prophylaxis of deep venous thrombosis

The IHI how-to guide on preventing VAP provides several practical recommendations, and posting compliance with the ventilator bundle in a prominent place in the ICU can encourage and motivate staff (Table 19) [174].

Table 19: PRACTICAL STEPS IN FOLLOWING GUIDELINES TO PREVENT VENTILATOR-ASSOCIATED PNEUMONIA

Assessment of Readiness to Extubate and Sedative Interruptions

Implement a protocol to lighten sedation daily at an appropriate time to assess for neurologic readiness to extubate. Include precautions to prevent self-extubation, such as monitoring and vigilance, during the trial.

Include a sedative interruption strategy in the overall plan to wean the patient from the ventilator; add the strategy to the weaning protocol, if available.

Assess compliance each day on multidisciplinary rounds.

Consider implementation of a sedation scale, such as the Riker scale, to avoid oversedation.

Elevation of the Head of the Bed

Include the intervention on nursing flow sheets and discuss at multidisciplinary rounds.

Encourage respiratory therapy staff to notify nursing staff if the head of the bed is not elevated or empower respiratory therapy staff to place the bed in this position with the help of nursing staff.

Include the intervention on order sets for initiation and weaning of mechanical ventilation, delivery of tube feedings, and provision of oral care.

Oral Care with Chlorhexidine

Include the intervention as part of the intensive care unit admission order set and ventilator order set. Make application of prophylaxis the default value on the form.

Include intervention as an item for discussion on daily multidisciplinary rounds.

Post compliance with the intervention in a prominent place to encourage change and motivate staff.

Develop a comprehensive oral care process that includes the use of 0.12% chlorhexidine oral rinse.

Schedule chlorhexidine as a medication, which then provides a reminder for nursing staff and triggers the oral care process delivery.

Prophylaxis of Peptic Ulcer Disease

Include intervention as part of the intensive care unit admission order set and ventilation order set. Make application of prophylaxis the default value on the form.

Include intervention as an item for discussion on daily multidisciplinary rounds.

Empower pharmacy staff to review orders for patients in the intensive care unit to ensure that some form of prophylaxis is in place at all times for patients.

Prophylaxis of Deep Venous Thrombosis

Include intervention as part of the intensive care unit admission order set and ventilation order set. Make application of prophylaxis the default value on the form.

Include intervention as an item for discussion on daily multidisciplinary rounds.

Empower pharmacy staff to review orders for patients in the intensive care unit to ensure that some form of prophylaxis is in place at all times for patients.

Source: [174]

Assessment of Readiness to Extubate

Because of the increasing risk of infection as the duration of ventilation increases, the primary goal is to extubate patients as early as possible. Thus, assessment of the readiness for extubation and weaning protocols are key aspects in the preventive approach [28,35]. Daily interruption of sedation until the patient is awake has been shown to significantly decrease the number of days on mechanical ventilation, from 7.3 days to 4.9 days in one study [175]. There are risks to this approach, including the potential for increased pain, anxiety, and desaturation [174]. However, sedation interruption has been further demonstrated to reduce the complications of prolonged mechanical ventilation [176]. The SHEA/IDSA guideline recommends daily assessment of the readiness to wean and the use of weaning protocols [171]. For children, daily assessment of readiness to extubate should be carried out, but sedation interruption is not recommended because of the high risk of unplanned extubation [177].

Elevation of the Head of the Bed

Evidence Based Practice Recommendation

The Institute for Clinical Systems Improvement recommends that, in the absence of medical contraindications, the head of the bed should be elevated at an angle of 30–45 degrees for patients at high risk for aspiration.

https://www.icsi.org/_asset/y24ruh/VAP-Interactive1111.pdf

Last Accessed: August 22, 2018

Strength of Recommendation/Level of Evidence: A (Randomized, controlled trial) and R (Consensus statement)

Reducing the risk of aspiration and contamination with gastric secretions also helps to prevent the development of pneumonia. Positioning the head of the bed at an angle of 30 to 45 degrees reduces the risk of aspiration significantly [149,178,179]. In one randomized, controlled trial, there were 18% fewer cases of VAP among intubated patients in the group assigned to the recumbent position (45 degrees) compared with the group assigned to the supine position [179]. In another study, elevation of the head of the bed to 30 degrees was the most effective measure among a group of preventive interventions, resulting in a 52% variance in the rate of VAP [180]. Both the ATS/IDSA and SHEA/IDSA guidelines recommend maintaining the head of the bed at a 30- to 45-degree angle [28,171]. An angle of 30 to 45 degrees is also recommended for infants and children, but a lower angle (15 to 30 degrees) should be used for neonates [177].

Daily Oral Care with Chlorhexidine

Oral care interventions have been suggested by some, in part because of an association between a high level of dental plaque and a high rate of colonization with aerobic pathogens, including S. aureus, gram-negative bacilli, and P. aeruginosa [181]. Research has shown that oral decontamination with chlorhexidine leads to a significant reduction in the colonization of pathogens in the oropharynx. In most studies, the intervention has not had a significant effect on the rate of VAP or associated mortality, but more recent studies have shown a significant decrease in the rate of pneumonia [180,182,183,184,185,186]. Brushing the teeth with chlorhexidine does not seem to add benefit [183]. Regular oral care with an antiseptic solution or chlorhexidine is recommended in the ATS/IDSA and SHEA/IDSA guidelines [28,171].

Prophylaxis of Peptic Ulcer Disease

Prophylaxis of peptic ulcer disease has evolved with some conflicting views. Antacids, histamine2 receptor antagonists, and sucralfate have been traditionally given to patients receiving mechanical ventilation to prevent the formation of stress ulcers. However, reducing the amount of gastric acid can increase the risk of colonization of gram-negative bacilli in the stomach. As a result, the WHO recommends avoiding the use of these agents [187]. The CDC notes that there was insufficient evidence on the use of peptic ulcer prophylaxis and includes no recommendations in this regard in its guideline [93]. The ATS/IDSA guideline states that the risks and benefits of prophylaxis should be weighed carefully [28]. The most recent guideline, developed by SHEA/IDSA, notes that histamine2 receptor antagonists and PPIs should be avoided in patients who are not at high risk for developing a stress ulcer or stress gastritis [171]. However, peptic ulcer prophylaxis is recommended for children, as appropriate for age and health status [177].

Prophylaxis of Deep Venous Thrombosis

There is no clear relation between prophylaxis of deep vein thrombosis and VAP pneumonia, but the ACCP reported a decrease in the rate of VAP when such prophylaxis was implemented as part of a package of interventions and included this measure in its clinical practice guideline [188]. This recommendation also applies to children, as appropriate for age and health status [177].

Other Measures

In addition to the interventions in the ventilator bundle, other measures have been recommended to help prevent VAP. One such measure is selective decontamination of the digestive tract, which involves the use of either topical antiseptic, oral antibiotics, or a brief course of systemic antibiotics [26]. A meta-analysis of 28 studies showed that selective decontamination of the digestive or respiratory tract with use of topical antiseptic or antimicrobial agents helped reduce the frequency of VAP in the ICU [146]. The estimate of efficacy in prevention was 27% for antiseptics and 36% for antibiotics. Neither had an effect on mortality. This intervention is recommended in the SHEA/IDSA guideline [171].

Other preventive measures are targeted primarily to the care and use of ventilator equipment and practices in direct patient care. Meticulous attention to aseptic care of the equipment is necessary, and all reusable components, such as nebulizers, should be disinfected or sterilized. Tubing circuits should be replaced after 48 hours or earlier if there are signs of malfunction or contamination [93]. Changes in the design of the endotracheal tube have also been evaluated; for example, a tube with a suction port above the cuff allows for continuous aspiration of subglottic secretions. Use of this specially designed endotracheal tube has led to significantly lower rates of VAP as well as shorter durations of ventilation and shorter stays in the ICU [189,190]. Among patients who had major cardiac surgery, the greatest benefit was found for patients who received ventilation for more than 48 hours [190]. Although the cost of the tube is higher than traditional tubes, the overall cost savings in preventing VAP more than compensates [189]. In one meta-analysis, subglottic secretion drainage was significantly associated with a decreased incidence of VAP, shorter time on mechanical ventilation, and longer time to the development of pneumonia [191]. The CDC, the ATS/IDSA, and the SHEA/IDSA guidelines recommend subglottic secretion drainage with this tube when possible [28,93,171].

The use of noninvasive ventilation is another measure that has reduced the incidence of VAP [93,192,193,194]. In one study, the incidence decreased from 20% to 8% when noninvasive techniques were used routinely for critically ill patients with acute exacerbation of COPD or severe cardiogenic pulmonary edema [192]. Again, the CDC, the ATS/IDSA, and the SHEA/IDSA guidelines recommend the use of noninvasive ventilation when possible [28,93,171].

Quality Improvement Initiatives and Enhanced Infection Control Strategies

Quality improvement and infection control initiatives and strategies have led to a substantial decrease in the rates of VAP since the early 2000s [195]. The use of physician-led multidisciplinary rounds with team decision-making, checklists, and a focus on the ventilator bundle has led to significant reductions in the risk for pneumonia [196,197,198]. Strong downward trends were also found for the average length of stay in the ICU and the financial costs per patient [196].

Nursing Home-Acquired Pneumonia

As with HAP, strategies to decrease or eliminate modifiable risk factors for nursing home-acquired pneumonia should be implemented. In a guideline developed by a multidisciplinary panel, three recommendations were made for preventing pneumonia among nursing home residents [199]:

- Pneumococcal vaccination of patients at admission, if indicated

- Annual influenza vaccination for residents

- Annual influenza vaccination for nursing facility staff

Influenza Outbreaks

The vaccination status of healthcare workers has been found to have a direct effect on transmission of influenza virus to patients. Outbreaks of influenza in healthcare settings have been associated with low rates of vaccination among healthcare workers, and lower rates of nosocomial influenza have been related to higher vaccination rates among healthcare workers [200,201]. Because of these findings, the ACIP recommends annual influenza vaccination for all healthcare workers, and the IDSA/ATS guideline endorses this recommendation [47]. The ACIP notes that the TIV is preferred over LAIV for workers who are in close contact with severely immunosuppressed people requiring protective isolation [112]. In addition, the Joint Commission began including vaccination programs in its accreditation standards in 2007 [123].

Despite these recommendations, only 29% to 69% of healthcare workers receive the influenza vaccination each year [202,203,204]. Healthcare workers have given many reasons for not being vaccinated, and the reasons vary among professions. Across all categories, shortage of the vaccine is the primary reason for not being vaccinated; other reasons include concern about side effects, inconvenience, and forgetfulness [204].

Efforts to increase the vaccination rate among healthcare workers are ongoing. A CDC guideline includes four level I recommendations to help increase rates of vaccination [205]:

- Offer influenza vaccine annually to all eligible healthcare workers

- Provide influenza vaccination to healthcare workers at the work site and at no cost as one component of employee health programs. Use strategies that have been demonstrated to increase influenza vaccine acceptance, including vaccination clinics, mobile carts, vaccination access during all work shifts, and modeling and support by institutional leaders.

- Monitor influenza vaccination coverage and declination of healthcare workers at regular intervals during influenza season and provide feedback of ward-, unit-, and specialty-specific rates to staff and administration.

- Educate healthcare workers about the benefits of influenza vaccination and the potential health consequences of influenza illness for themselves and their patients, the epidemiology and modes of transmission, diagnosis, treatment, and non-vaccine infection control strategies, in accordance with their level of responsibility in preventing healthcare-associated influenza.

Hand Hygiene

Hand hygiene is the most important preventive measure in hospitals, and the Joint Commission mandates that hospitals and other healthcare facilities comply with the Level I recommendations in the CDC guideline for hand hygiene [206]. The CDC guideline states the specific indications for washing hands, the recommended hand hygiene techniques, and recommendations about fingernails and the use of gloves [207]. The guideline also provides recommendations for surgical hand antisepsis, selection of hand-hygiene agents, skin care, educational and motivational programs for healthcare workers, and administrative measures.

Despite the simplicity of the intervention, its substantial impact, and wide dissemination of the guideline, compliance with recommended hand hygiene has ranged from 16% to 81%, with an average of 30% to 50% [207,208,209,210,211,212]. Among the reasons given for the lack of compliance are inconvenience, understaffing, and damage to skin [207,210,213]. The development of effective alcohol-based handrub solutions addresses these concerns, and studies have demonstrated that these solutions have increased compliance [211,214,215]. The CDC guideline recommends the use of such solutions on the basis of several advantages, including [207]:

- Better efficacy against both gram-negative and gram-positive bacteria, mycobacteria, fungi, and viruses than either soap and water or antimicrobial soaps (such as chlorhexidine)

- More rapid disinfection than other hand-hygiene techniques

- Less damaging to skin

- Time savings (18 minutes compared with 56 minutes per eight-hour shift)

The guideline suggests that healthcare facilities promote compliance by making the handrub solution available in dispensers in convenient locations (such as the entrance to patients' room or at the bedside) and provide individual pocket-sized containers [207]. The handrub solution may be used in all clinical situations except for when hands are visibly dirty or are contaminated with blood or body fluids. In such instances, soap (either antimicrobial or nonantimicrobial) and water must be used.

However, there are many other reasons for lack of adherence to appropriate hand hygiene, including denial about risks, forgetfulness, and belief that gloves provide sufficient protection [207,210,213]. These reasons demand education for healthcare professionals to emphasize the importance of hand hygiene. Also necessary is research to determine which interventions are most likely to improve hand-hygiene practices, as no studies have demonstrated the superiority of any intervention [216]. Single interventions are unlikely to be effective.

ILLUSTRATIVE CASE

A man, 73 years of age, with a history of coronary disease, COPD, benign prostatic hyperplasia, and type 2 diabetes is hospitalized on transfer from an assisted-living facility because of weakness, loss of appetite, and low-grade fever. He had been admitted elsewhere for similar symptoms six months earlier and was diagnosed with urinary tract infection and treated with an unknown antibiotic. On evaluation, the patient's temperature is 37.6°C (99.8°F) and his other vital signs are stable; his exam is unremarkable. The WBC is normal, and the urinalysis shows pyuria. The admission chest x-ray shows hyperlucent lung fields and flattened diaphragms indicative of emphysema, but no infiltrate. Empiric treatment with a first-generation cephalosporin is begun for presumed urinary tract infection. The patient has no further fever, and his appetite and strength improve over the next 48 hours. He does have periods of mild agitation and insomnia, which are treated with a benzodiazepine at bedtime.

On the fourth day, as plans for discharge were in place, the patient appears worse, with a cough and a temperature of 38°C (100.4°F). A repeat chest x-ray shows a small focal opacity in the left upper lobe, thought to represent "aspiration." No change in antibiotics is made, and he is observed. Over the next 36 hours, the patient's condition worsens; he now has a cough productive of purulent sputum, fever (102°F to 103°F), shortness of breath, and tachypnea. A follow-up chest x-ray now shows an extensive opacification/infiltrate in the left upper lobe, with signs suggestive of either central cavitation or consolidation high-lighting emphysematous blebs.

In this elderly, somewhat debilitated man with chronic lung disease, who may be at risk of aspiration, a rapidly progressive, necrotizing (hospital-acquired) pneumonia developed while he was being treated with an oral cephalosporin for urinary tract infection, and receiving a nightly sedative medication for sleep.

What are the etiologic considerations and how should the patient be managed? Within days of admission to a hospital, and especially if treated with antibiotics, many patients develop nasopharyngeal colonization by hospital flora (e.g. gram-negative bacilli and occasionally S. aureus). When pneumonia supervenes, it reflects this colonization; moreover, prior antibiotic therapy tends to select out resistant pathogens. Therefore, the selection of empiric antibiotic treatment for this patient is based on the presumption of hospital-acquired bacterial infection in the lung caused by one or more pathogens resistant to first-generation cephalosporins. Cultures of blood and sputum should be obtained; gram stain of the sputum is often helpful in cases such as this, as it may demonstrate a predominate pathogen and whether it is gram-positive or gram-negative. Empiric antibiotic therapy, following ATS/IDSA recommendations for HAP, should be started promptly. A good choice here would be either an extended-spectrum ß-lactam/ß-lactamase inhibitor or a carbapenem with activity against Pseudomonas, combined with a fluoroquinolone and vancomycin, pending culture results.

Gram stain of the patient's sputum shows many polys and gram-negative bacilli; the culture is positive for K. pneumoniae and P. aeruginosa. His management, including empiric antibiotic therapy followed by de-escalation (of vancomycin) after culture data are available, conforms to ATS/IDSA recommendations. The patient is treated for 10 days and recovers following a brief period in the ICU.

This case illustrates that the pathogenesis of adult bacterial HAP is essentially the same as for CAP; namely, nasopharyngeal and upper respiratory colonization by virulent bacteria combined with aspiration of infected secretions during a period of impaired host pulmonary defenses. The difference lies in the burden of vulnerability imposed by hospitalization, including the propensity for colonization by gram-negative bacilli and the likelihood of antimicrobial resistance — so uncommon in healthy individuals outside of healthcare facilities, but so prevalent among patients hospitalized longer than 48 hours.

9. SUMMARY

Pneumonia-related mortality and morbidity have decreased since the late 1990s, but the disease still represents a substantial healthcare concern, especially for high-risk adults and children. Pneumonia is primarily classified according to the setting in which it develops, and the epidemiology, etiology, and risk factors vary according to setting. Diagnosis can be challenging because of differences in presentation and the lack of reliable, cost-effective, and rapidly available diagnostic testing methods. Specialty society guidelines for prevention, diagnosis, and treatment are available for CAP, HAP, and VAP. Guideline-directed treatment has been shown to improve the care of patients while promoting good antibiotic stewardship, minimizing exposure to inappropriate antibiotic treatment and reducing the emergence of antibiotic-resistant pathogens.

For CAP and nursing home-acquired pneumonia, determining the site of care is an important initial decision point. Guidelines from the IDSA/ATS, the PIDS/IDSA, and the ATS outline useful criteria for determining need for hospitalization and ICU care. These objective criteria are important factors in decision-making, but clinical judgment is also necessary for selecting the most appropriate site of care. Initial antibiotic treatment of all types of pneumonia is empirical. The selection is best made in relation to the most likely pathogens in a given clinical setting and to patient variables, such as comorbidities, recent exposure to antibiotics, and immunization status (for children). The timeliness of antibiotic treatment is also important; treatment should begin as soon as possible after diagnosis is made, administering the first dose promptly at the originating site of care.

Guideline-directed therapy of pneumonia has been shown to decrease morbidity and mortality, but adherence varies across settings and specialties and has been suboptimal. Physician practices and healthcare systems can improve adherence by implementing evidence-based strategies, such as standardized order sets, reminders, performance feedback, and easy-to-carry resources.

The incidence of pneumonia and its associated morbidity and mortality can be reduced further by adherence to effective preventive measures. Several guidelines are available for preventing specific types of pneumonia. The primary preventive strategy for CAP is immunization with influenza and pneumococcal vaccines, especially for individuals at high risk. These vaccinations have been shown to decrease the incidence and severity of pneumococcal pneumonia, as well as the risk of long-term morbidity and mortality. However, rates of vaccination vary across age, race/ethnicity, and risk. Two target populations with the lowest immunization rates are high-risk adults in need of pneumococcal vaccination and teenagers in need of influenza vaccination. Rates of vaccination among healthcare professionals are also low. Clinicians and healthcare systems should encourage vaccination and offer convenient access, especially during influenza season.

Lack of awareness about the need for vaccination, misconceptions about vaccines, and low level of knowledge about pneumonia have been reported to be the primary barriers to vaccination, especially among minority populations. Clinicians should promote practice strategies and public health efforts designed to target these barriers and address the populations in greatest need. Several strategies have been shown to increase vaccination rates, and education is the cornerstone. Clinicians should emphasize to patients the need and benefit of immunization, address concerns about the safety of vaccines, and incorporate routine immunization protocols into their practices. Provider recommendation is essential, as it is the strongest predictor of vaccination. System-related strategies such as automatic reminders and standing orders have also been effective.

Guidelines for prevention of HAP focus on measures to reduce pulmonary complications after surgery. Prevention of VAP relies on strategies to reduce the risk of transmission of etiologic agents. Use of a ventilator "bundle" (a set of interventions) has been shown to markedly reduce VAP. Although adherence to guidelines is suboptimal, healthcare facilities are increasingly implementing initiatives to help enhance adherence.

Works Cited

1. Hippocrates. On Regimen in Acute Disease. Available at http://classics.mit.edu/Hippocrates/acutedis.html. Last accessed August 14, 2018.

2. Centers for Disease Control and Prevention. Pneumonia. Available at https://www.cdc.gov/nchs/fastats/pneumonia.htm. Last accessed August 14, 2018.

3. Shorr A, Owens RC. Guidelines and quality for community-acquired pneumonia: measures from the Joint Commission and the Centers for Medicare and Medicaid Services. Am J Health Syst Pharm. 2009;66(12 Suppl 4):S2-S7.

4. Haessler S, Schimmel JS. Managing community-acquired pneumonia during flu season. Cleve Clin J Med. 2012;79(1):67-78.

5. Lee G, Lorch SA, Sheffler-Collins S, Kronman MP, Shah SS. National hospitalization trends for pediatric pneumonia and associated complications. Pediatrics. 2010;126(2):204-213.

6. National Center for Health Statistics. Health, United States, 2014. Hyattsville, MD: National Center for Health Statistics; 2015.

7. Nichol K, Nordin JD, Nelson DB, Mullooly JP, Hak E. Effectiveness of influenza vaccine in the community-dwelling elderly.N Engl J Med. 2007;357(14):1373-1381.

8. Johnstone J, Marrie TJ, Eurich DT, Majumdar SR. Effect of pneumococcal vaccination in hospitalized adults with community-acquired pneumonia. Arch Intern Med. 2007;167(18):1938-1943.

9. Johnstone J, Majumdar SR, Fox JD, Marrie TJ. Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation. Chest. 2008;134(6):1141-1148.

10. Grijalva C, Poehling KA, Nuorti JP, et al. National impact of universal childhood immunization with pneumococcal conjugate vaccine on outpatient medical care visits in the United States. Pediatrics. 2006;118(3):865-873.

11. O'Leary ST, Crane LA, Wortley P, et al. Adherence to expanded influenza immunization recommendations among primary care providers. J Pediatr. 2012;160(3):480-486.

12. Pogorzelska M, Stone PW, Furuya EY, et al. Impact of the ventilator bundle on ventilator-associated pneumonia in intensive care unit. Int J Qual Health Care. 2011;23(5):538-544.

13. Cason C, Tyner T, Saunders S, Broome L. Nurses' implementation of guidelines for ventilator-associated pneumonia from the Centers for Disease Control and Prevention. Am J Crit Care. 2007;16(1):28-37.

14. Wise PC, Finkelstein JA, Ray GT, et al. Aging population and future burden of pneumococcal pneumonia in the United States.J Infect Dis. 2012;205:1589-1592.

15. Arnold F, LaJoie S, Brock GN, et al. Improving outcomes in elderly patients with community-acquired pneumonia by adhering to national guidelines: Community-Acquired Pneumonia Organization International Cohort study results. Arch Intern Med. 2009;169(16):1515-1524.

16. Frei C, Attridge RT, Mortensen EM, et al. Guideline-concordant antibiotic use and survival among patients with community-acquired pneumonia admitted to the intensive care unit. Clin Ther. 2010;32(2):293-299.

17. McCabe C, Kirchner C, Zhang H, Daley J, Fisman DN. Guideline-concordant therapy and reduced mortality and length of stay in adults with community-acquired pneumonia. Arch Intern Med. 2009;169(16):1525-1531.

18. Seymann G, Di Francesco L, Sharpe B, et al. The HCAP gap: differences between self-reported practice patterns and published guidelines for health care-associated pneumonia. Clin Infect Dis. 2009;49(12):1868-1874.

19. Youdelman M, Perkins J. Providing Language Interpretation Services in Health Care Settings: Examples from the Field. Available at https://www.commonwealthfund.org/publications/fund-reports/2002/may/providing-language-interpretation-services-health-care-settings?redirect_source=/publications/fund-reports/2002/may/providing-language-interpretation-services-in-health-care-settings--examples-from-the-field. Last accessed August 14, 2018.

20. Wu J, Howard DH, McGowan JE Jr, Turpin RS, Henry Hu X. Adherence to Infectious Diseases Society of America guidelines for empiric therapy for patients with community-acquired pneumonia in a commercially insured cohort. Clin Ther. 2006;28(9):1451-1461.

21. Dellit T, Owens RC, McGowan JE Jr, et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44(2):159-177.

22. Menéndez R, Torres A, Zalacaín R, et al. Guidelines for the treatment of community-acquired pneumonia: predictors of adherence and outcome. Am J Respir Crit Care Med. 2005;172(6):757-762.

23. El-Solh A, Alhajhusain A, Saliba RG, Drinka P. Physicians' attitudes toward guidelines for the treatment of hospitalized nursing home-acquired pneumonia. J Am Med Dir Assoc. 2011;12(4):270-276.

24. Templeton K, Scheltinga SA, van den Eeden WCJFM, Graffelman AW, van den Broek PJ, Claas ECJ. Improved diagnosis of the etiology of community-acquired pneumonia with real-time polymerase chain reaction. Clin Infect Dis. 2005;41(3):345-351.

25. Davis B, Aiello AE, Dawid S, Rohani P, Shrestha S, Foxman B. Influenza and community-acquired pneumonia interactions: the impact of order and time of infection on population patterns. Am J Epidemiol. 2012;175(5):363-367.

26. Kieninger A, Lipsett PA. Hospital-acquired pneumonia: pathophysiology, diagnosis, and treatment. Surg Clin N Am. 2009;89(2):439-461.

27. Anand N, Kollef MH. The alphabet soup of pneumonia: CAP, HAP, HCAP, NHAP, and VAP. Semin Respir Crit Care Med. 2009;30(1):3-9.

28. American Thoracic Society, Infectious Diseases Society of America. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63:1-61.

29. Catia C, Santiago E, Eva P, et al. Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax. 2011;66:340-346.

30. Bradley J, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25-e76.

31. Falsey A, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006;42(4):518-524.

32. Ruuskanen O, Lahti E, Jennings LC, Murdoch DR. Viral pneumonia. Lancet. 2011;377(9773):1264-1275.

33. Johansson N, Kalin M, Tiveljung-Lindell A, Giske CG, Hedlund J. Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. Clin Infect Dis. 2010;50(2):202-209.

34. Jennings L, Anderson TP, Beynon KA, et al. Incidence and characteristics of viral community-acquired pneumonia in adults. Thorax. 2008;63(1):42-48.

35. Flanders S, Collard HR, Saint S. Nosocomial pneumonia: state of the science. Am J Infect Control. 2006;34(2):84-93.

36. Niederman M, Mandell LA, Anzueto A, et al. Guidelines for the management of adults with community-acquired pneumonia: diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med. 2001;163(7):1730-1754.

37. File TMJ. The science of selecting antimicrobials for community-acquired pneumonia (CAP). J Manag Care Pharm. 2009;15(2 Suppl):S5-S11.

38. Weycker D, Strutton D, Edesberg J, Sato R, Jackson LA. Clinical and economic burden of pneumococcal disease in older U.S. adults. Vaccine. 2010;28(31):4955-4960.

39. Jackson M, Neuzil KM, Thompson WW, et al. The burden of community-acquired pneumonia in seniors: results of a population-based study. Clin Infect Dis. 2004;39(11):1642-1650.

40. Ruhnke G, Coca-Perrallion M, Kitch BT, Cutler DM. Marked improvement in 30-day mortality among elderly inpatients and outpatients with community-acquired pneumonia. Am J Med. 2011;124(2):171-178.

41. Farr B, Bartlett CL, Wadsworth J, Miller DL. Risk factors for community-acquired pneumonia diagnosed upon hospital admission. Respir Med. 2000;94(10):954-963.

42. Marrie T. Community-acquired pneumonia in the elderly. Clin Infect Dis. 2000;31(4):1066-1078.

43. Müllerova H, Chigbo C, Hagan GW, et al. The natural history of community-acquired pneumonia in COPD patients: a population database analysis. Respir Med. 2012;106(8):1124-1133.

44. Sethi S, Maloney J, Grove L, Wrona C, Berenson CS. Airway inflammation and bronchial bacterial colonization in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;173:991-998.

45. Eom CS, Jeon CY, Lim J-W, Cho E-G, Park SM, Lee K-S. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ. 2011;183(3):310-319.

46. Jinno S, Jacobs MR. Pneumonia due to drug-resistant Streptococcus pneumoniae. Curr Infect Dis Rep. 2012;14(3):292-299.

47. Mandell L, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44:S27-S72.

48. Thiem U, Heppner HJ, Pientka L. Elderly patients with community-acquired pneumonia: optimal treatment strategies. Drugs Aging. 2011;28(7):519-537.

49. Moran G, Krishnadasan A, Gorwitz RJ, et al. Prevalence of methicillin-resistant Staphylococcus aureus as an etiology of community-acquired pneumonia. Clin Infect Dis. 2012;54(8):1126-1133.

50. File TM. Community-acquired pneumonia. Lancet. 2003;362(9400):1991-2001.

51. Metersky M, Sweeney TA, Getzow MB, Siddiqui F, Nsa W, Bratzler DW. Antibiotic timing and diagnostic uncertainty in Medicare patients with pneumonia: is it reasonable to expect all patients to receive antibiotics within 4 hours? Chest. 2006;130(1):16-21.

52. Fee C, Weber EJ. Identification of 90% of patients ultimately diagnosed with community-acquired pneumonia within four hours of emergency department arrival may not be feasible. Ann Emerg Med. 2007;49(5):553-559.

53. McGee SR (ed). Evidence-Based Physical Diagnosis. 3rd ed. Philadelphia, PA: Elsevier Inc.; 2012.

54. Heckerling P, Tape TG, Wigton RS, et al. Clinical prediction rule for pulmonary infiltrates. Ann Intern Med. 1990;113(9):664-670.

55. Campbell S, Marrie TJ, Anstey R, Ackroyd-Stolarz S, Dickinson G. Utility of blood cultures in the management of adults with community acquired pneumonia discharged from the emergency department. Emerg Med J. 2003;20(6):521-523.

56. Afshar N, Tabas J, Afshar K, Silbergleit R. Blood cultures for community-acquired pneumonia: are they worthy of two quality measures? A systematic review. J Hosp Med. 2009;4(2):112-123.

57. Nazarian D, Eddy OL, Lukens TW, et al. Clinical policy: critical issues in the management of adult patients presenting to the emergency department with community-acquired pneumonia. Ann Emerg Med. 2009;54(5):704-731.

58. Christ-Crain M, Opal SM. Clinical review: The role of biomarkers in the diagnosis and management of community-acquired pneumonia. Crit Care. 2010;14(1):203.

59. Berg P, Lindhardt BØ. The role of procalcitonin in adult patients with community-acquired pneumonia: a systematic review.Dan Med J. 2012;59(3):A4357.

60. Ostapchuk M, Roberts DM, Haddy R. Community-acquired pneumonia in infants and children. Am Fam Physician. 2004;70(5): 899-908.

61. Ebell M. Point-of-care guides: clinical diagnosis of pneumonia in children. Am Fam Physician. 2010;82(2):192-193.

62. Lynch T, Platt R, Gouin S, Larson C, Patenaude Y. Can we predict which children with clinically suspected pneumonia will have the presence of focal infiltrates on chest radiographs? Pediatrics. 2004;113(3 pt 1):e186-e189.

63. Cevey-Macherel M, Galetto-Lacour A, Gervaix A, et al. Etiology of community-acquired pneumonia in hospitalized children based on WHO clinical guidelines. Eur J Pediatr. 2009;168(12):1429-1436.

64. Mandell LA, Bartlett JG, Dowell SF, et al. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis. 2003;37(11):1405-1433.

65. Forgie S, Marrie TJ. Healthcare-associated atypical pneumonia. Semin Respir Crit Care Med. 2009;30(1):67-85.

66. Centers for Disease Control and Prevention. Mycoplasma pneumoniae Infection. Available at https://www.cdc.gov/pneumonia/atypical/mycoplasma/index.html. Last accessed August 14, 2018.

67. Chang C, Cheng AC, Chang AB. Over-the-counter (OTC) medications to reduce cough as an adjunct to antibiotics for acute pneumonia in children and adults. Cochrane Database Syst Rev. 2012;2:CD006088.

68. Niederman M. Making sense of scoring systems in community acquired pneumonia. Respirology. 2009;14(3):327-335.

69. Fine M, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336(4):243-250.

70. Lim W, van der Eerden MM, Laing R, et al. Defining community-acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003;58(5):377-382.

71. Chalmers J, Singanayagam A, Akram AR, et al. Severity assessment tools for predicting mortality in hospitalised patients with community-acquired pneumonia: systematic review and meta-analysis. Thorax. 2010;65(10):878-883.

72. Loke Y, Kwok CS, Niruban A, Myint PK. Value of severity scales in predicting mortality from community-acquired pneumonia: systematic review and meta-analysis. Thorax. 2010;65:884-890.

73. Charles P, Wolfe R, Whitby M, et al. SMART-COP: a tool for predicting the need for intensive respiratory or vasopressor support in community-acquired pneumonia. Clin Infect Dis. 2008;47(3):375-384.

74. Yandiola P, Capelastegui A, Quintana J, et al. Prospective comparison of severity scores for predicting clinically relevant outcomes for patients hospitalized with community-acquired pneumonia. Chest. 2009;135(6):1572-1579.

75. España P, Capelastegui A, Quintana, JM, et al. Validation and comparison of SCAP as a predictive score for identifying low-risk patients in community-acquired pneumonia. J Infect. 2010;60(2):106-113.

76. File TMJ, Marrie TJ. Burden of community-acquired pneumonia in North American adults. Postgrad Med. 2010;122(2):130-141.

77. Kontou P, Kuti JL, Nicolau DP. Validation of the Infectious Diseases of America/American Thoracic Society criteria to predict severe community-acquired pneumonia caused by Streptococcus pneumoniae. Am J Emerg Med. 2009;27(8):968-974.

78. Chalmers J, Taylor JK, Mandal P, et al. Validation of the Infectious Diseases Society of America/American Thoracic Society minor criteria for intensive care unit admission in community-acquired pneumonia patients without major criteria or contraindications to intensive care unit care. Clin Infect Dis. 2011;53(6):503-511.

79. Kanwar M, Brar N, Khatib R, Fakih MG. Misdiagnosis of community-acquired pneumonia and inappropriate utlization of antibiotics. Chest. 2007;131:1865-1869.

80. Nicks B, Manthey DE, Fitch MT. The Centers for Medicare and Medicaid Services (CMS) community-acquired pneumonia core measures lead to unnecessary antibiotic administration by emergency physicians. Acad Emerg Med. 2009;16(2):184-187.

81. Yu K, Wyer PC. Evidence behind the 4-hour rule for initiation of antibiotic therapy in community-acquired pneumonia. Ann Emerg Med. 2008;51(5):651-652.

82. Quattromani E, Powell ES, Khare RK, et al. Hospital-reported data on the pneumonia quality measure "time to first antibiotic dose" is not associated with inpatient mortality: results of a nationwide cross-sectional analysis. Acad Emerg Med. 2011;18(5):496-503.

83. Asadi L, Eurich DT, Gamble JM, Minhas-Sandhu JK, Marrie TJ, Majumdar SR. Guideline adherence and macrolides reduced mortality in outpatients with pneumonia. Respir Med. 2012;106(3):451-458.

84. Neuman M, Ting SA, Meydani A, Mansbach JM, Camargo CA Jr. National study of antibiotic use in emergency department visits for pneumonia, 1993 through 2008. Acad Emerg Med. 2012;19(5):562-568.

85. Simpson S, Marrie TJ, Majumdar SR. Do guidelines guide pneumonia practice? A systematic review of interventions and barriers to best practice in the management of community-acquired pneumonia. Respir Care Clin North Am. 2005;11(1):1-13.

86. Schouten JA, Hulscher ME, Trap-Liefers J, et al. Tailored interventions to improve antibiotic use for lower respiratory tract infections in hospitals: a cluster-randomized, controlled trial. Clin Infect Dis. 2007;44(7):931-941.

87. Weiner S, Brown SF, Goetz JD, Webber CA. Weekly e-mail reminders influence emergency physician behavior: a case study using the Joint Commission and Centers for Medicare and Medicaid Services Pneumonia Guidelines. Acad Emerg Med. 2009;16(7):626-631.

88. Fleming NS, Ogola G, Ballard DJ. Implementing a standardized order set for community-acquired pneumonia: impact on mortality and cost. Jt Comm J Qual Patient Saf. 2009;35(8):414-421.

89. Haider B, Lassi ZS, Ahmed A, Bhutta ZA. Zinc supplementation as an adjunct to antibiotics in the treatment of pneumonia in children 2 to 59 months of age. Cochrane Database Syst Rev. 2011;10:CD007368.

90. Aliberti S, Di Pasquale M, Zanaboni AM, et al. Stratifying risk factors for multidrug-resistant pathogens in hospitalized patients coming from the community with pneumonia. Clin Infect Dis. 2012;54(4):470-478.

91. Kroger AT, Sumaya CV, Pickering LK, Atkinson WL. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2011;60(RR2);1-60.

92. Centers for Disease Control and Prevention. Recommended adult immunization schedule—United States, 2012. MMWR. 2012;61(4):1-7.

93. Tablan O, Anderson LJ, Besser R, Bridges C, Hajjeh R. Guidelines for preventing health-care-asssociated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR. 2004;53(RR3):1-36.

94. The Joint Commission. Immunization. Available at https://www.jointcommission.org/immunization. Last accessed August 14, 2018.

95. Edmond K, Scott S, Korczak V, et al. Long term sequelae from childhood pneumonia: systematic review and meta-analysis. PLoS One. 2012;7(2):e31239.

96. Nuorti J, Whitney CG. Updated recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent pneumococcal polysaccharide vaccine (PPSV23). MMWR. 2010;59(34):1102-1106.

97. Immunization Action Coalition. Pneumococcal: PCV. Available at http://www.immunize.org/resources/pneumococcal-pcv.asp. Last accessed August 14, 2018.

98. Grijalva C, Nuorti JP, Arbogast PG, Martin SW, Edwards KM, Griffin MR. Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis. Lancet. 2007;369(9568):1179-1186.

99. Klugman K, Chien YW, Madhi SA. Pneumococcal pneumonia and influenza: a deadly combination. Vaccine. 2009;27(Suppl 3):C9-C14.

100. Moberley S, Holden J, Tatham DP, Andrews RM. Vaccines for preventing pneumococcal infection in adults. Cochrane Database Syst Rev. 2008;(1):CD000422.

101. Lucero M, Dulalia VE, Nillos LT, et al. Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and x-ray defined pneumonia in children less than two years of age. Cochrane Database Syst Rev. 2009;7(4):CD004977.

102. Williams WW, Lu PJ, O'Halloran A, et al. Surveillance of vaccination coverage among adult populations—United States, 2017. MMWR. 2012;66(11):1-28.

103. Clarke TC, Norris T, Shillar JS. Early Release of Selected Estimates Based on Data from 2016. Available at https://www.cdc.gov/nchs/data/nhis/earlyrelease/earlyrelease201705.pdf. Last accessed August 14, 2018.

104. Santibanez T, Nowalk MP, Zimmerman RK, et al. Knowledge and beliefs about influenza, pneumococcal disease, and immunizations among older people. J Am Geriatr Soc. 2002;50(10):1711-1716.

105. Hebert P, Frick KD, Kane RL, McBean AM. The causes of racial and ethnic differences in influenza vaccination rates among elderly Medicare beneficiaries. Health Serv Res. 2005;40(2):517-537.

106. Winston C, Wortley PM, Lees KA. Factors associated with vaccination of Medicare beneficiaries in five U.S. communities: results from the racial and ethnic adult disparities in immunization initiative survey, 2003. J Am Geriatr Soc. 2006;54(2):303-310.

107. Haviland A, Elliott MN, Hambarsoomian K, Lurie N. Immunization disparities by Hispanic ethnicity and language preference.Arch Intern Med. 2011;171(2):158-165.

108. Marsteller J, Tiggle RB, Remsburg RE, Bardenheier B, Shefer A, Han B. Pneumococcal vaccination in nursing homes: does race make a difference? J Am Med Dir Assoc. 2008;9(9):641-647.

109. Bardenheier B, Wortley P, Ahmed F, Gravenstein S, Hogue CJ. Racial inequities in receipt of influenza vaccination among long-term care residents within and between facilities in Michigan. Med Care. 2011;49(4):371-377.

110. Bardenheier B, Wortley P, Shefer A, McCauley MM, Gravenstein S. Racial inequities in receipt of influenza vaccination among nursing home residents in the United States, 2008—a pattern of low overall coverage in facilities in which most residents are black. J Am Med Dir Assoc. 2012;13(5):470-476.

111. Bratzler DW, Houck PM, Jiang H, et al. Failure to vaccinate Medicare inpatients: a missed opportunity. Arch Intern Med. 2002;162(20):2349-2356.

112. Hill HA, Elam-Evans LD, Yankey D, et al. Vaccination coverage among children aged 19–35 months—United States, 2016. MMWR. 2017;66(43):1171-1177.

113. National Center for Health Statistics. Health, United States, 2016. Available at https://www.cdc.gov/nchs/data/hus/hus16.pdf. Last accessed August 14, 2018.

114. U.S. Department of Health and Human Services. Immunization and infectious diseases. In: Healthy People 2020. Washington, DC: U.S. Department of Health and Human Services; 2010.

115. Burns I, Zimmerman RK. Immunization barriers and solutions. J Fam Pract. 2005;54(1):S58-S62.

116. Johnson D, Nichol KL, Lipczynski K. Barriers to adult immunization. Am J Med. 2008;121(7 Suppl 2):S28-S35.

117. Keeton V, Chen AK. Immunization updates and challenges. Curr Opin Pediatr. 2010;22(2):234-240.

118. Lindley M, Wortley PM, Winston CA, Bardenheier BH. The role of attitudes in understanding disparities in adult influenza vaccination. Am J Prev Med. 2006;31(4):281-285.

119. Pearson W, Zhao G, Ford ES. An analysis of language as a barrier to receiving influenza vaccinations among an elderly Hispanic population in the United States. Adv Prev Med. 2011:298787.

120. Mills E, Jadad AR, Ross C, Wilson K. Systematic review of qualitative studies exploring parental beliefs and attitudes toward childhood vaccination identifies common barriers to vaccination. J Clin Epidemiol. 2005;58(11):1081-1088.

121. Niederhauser V, Markowitz M. Barriers to immunizations: multiethnic parents of under- and unimmunized children speak. J Am Acad Nurse Pract. 2007;19(1):15-23.

122. Luthy K, Beckstrand RL, Peterson NE. Parental hesitation as a factor in delayed childhood immunization. J Pediatr Health Care. 2009;23(6):388-393.

123. Nichol K. Improving influenza vaccination rates among adults. Cleve Clin J Med. 2006;73(11):1009-1015.

124. Office of Minority Health. Cultural and Linguistic Competency. Available at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=1&lvlid=6. Last accessed August 14, 2018.

125. Paez K, Allen JK, Beach MC, Carson KA, Cooper LA. Physician cultural competence and patient ratings of the patient-physician relationship. J Gen Intern Med. 2009;24(4):495-498.

126. Powers B, Trinh JV, Bosworth HB. Can this patient read and understand written health information? JAMA. 2010;304(1):76-84.

127. U.S. Census Bureau. Selected Social Characteristics in the United States: 2013. Available at https://factfinder.census.gov/faces/tableservices/jsf/pages/productview.xhtml?pid=ACS_13_5YR_DP02&src=pt. Last accessed August 14, 2018.

128. Karliner L, Napoles-Springer AM, Schillinger D, Bibbins-Domingo K, Pérez-Stable EJ. Identification of limited English proficient patients in clinical care. J Gen Intern Med. 2008;23(10):1555-1560.

129. Karliner L, Jacobs EA, Chen AH, Mutha S. Do professional interpreters improve clinical care for patients with limited English proficiency? A systematic review of the literature. Health Serv Res. 2007;42(2):727-754.

130. Flores G. The impact of medical interpreter services on the quality of health care: a systematic review. Med Care Res Rev. 2005;62(3):255-299.

131. Ngo-Metzger Q, Massagli MP, Clarridge BR, et al. Linguistic and cultural barriers to care: perspectives of Chinese and Vietnamese immigrants. J Gen Intern Med. 2003;18(1):44-52.

132. Committee on Health Literacy Board on Neuroscience and Behavioral Health. Health Literacy: A Prescription to End Confusion. Washington, DC: The National Academies Press; 2004.

133. Paasche-Orlow M, Parker RM, Gazmararian JA, Nielsen-Bohlman LT, Rudd RR. The prevalence of limited health literacy. J Gen Intern Med. 2005;20(2):175-184.

134. Kutner M, Greenberg E, Jin,Y, Paulsen C, White S. The Health Literacy of America's Adults: Results from the 2003 National Assessment of Adult Literacy. Washington, DC: National Center for Education Statistics; 2006.

135. Shah L, West P, Bremmeyr K, Savoy-Moore RT. Health literacy instrument in family medicine: the "newest vital sign" ease of use and correlates. J Am Board Fam Med. 2010;23(2):195-203.

136. Weiss B, Mays MZ, Martz W, et al. Quick assessment of literacy in primary care: the newest vital sign. Ann Fam Med. 2005;3(6):514-522.

137. Jacobson V, Szilagyi P. Patient reminder and patient recall systems to improve immunization rates. Cochrane Database Syst Rev. 2005;(3):CD003941.

138. Traeger M, Say KR, Hastings V, Yost DA. Achievement of Healthy People 2010 objective for adult pneumococcal vaccination in an American Indian community. Pub Health Rep. 2010;125(3):448-456.

139. Rimple D, Weiss SJ, Brett M, Ernst AA. An emergency department-based vaccination program: overcoming the barriers for adults at high risk for vaccine-preventable diseases. Acad Emerg Med. 2006;13(9):922-930.

140. Martin D, Brauner ME, Plouffe JF. Influenza and pneumococcal vaccinations in the emergency department. Emerg Med Clin North Am. 2008;26(2):549-570.

141. Society of Healthcare Epidemiology of America Research Committee. Enhancing patient safety by reducing healthcare-associated infections: the role of discovery and dissemination. Infect Control Hosp Epidemiol. 2010;31(2):118-123.

142. Richards MJ, Edwards JR, Culver DH, Gaynes RP. Nosocomial infections in pediatric intensive care units in the United States: National Nosocomial Infections Surveillance System. Pediatrics. 1999;103(4):e39.

143. Mills K, Graham AC, Winslow BT, Springer KL. Treatment of nursing home-acquired pneumonia. Am Fam Physician. 2009;79(11):976-982.

144. Foglia E, Meier MD, Elward A. Ventilator-associated pneumonia in neonatal and pediatric intensive care unit patients. Clin Microbiol Rev. 2007;20(3):409-425.

145. Qaseem A, Snow V, Fitteman N, et al. Risk assessment for and strategies to reduce perioperative pulmonary complications for patients undergoing noncardiothoracic surgery: a guideline from the American College of Physicians. Ann Intern Med. 2006;144(8):575-580.

146. Pileggi C, Bianco A, Flotta D, Nobile CG, Pavia M. Prevention of ventilator-associated pneumonia, mortality and all intensive care unit acquired infections by topically applied antimicrobial or antiseptic agents: a meta-analysis of randomized controlled trials in intensive care units. Crit Care. 2011;15(3):R155.

147. Kollef MH. Antibiotic management of ventilator-associated pneumonia due to antibiotic-resistant gram-positive bacterial infection. Eur J Clin Microbiol Infect Dis. 2005;24(12):794-803.

148. Kollef MH. What is ventilator-associated pneumonia and why is it important? Respir Care. 2005;50(6):714-721.

149. Dodek P, Keenan S, Cook D, et al. Evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia. Ann Intern Med. 2004;141(4):305-313.

150. Bigham M, Amato R, Bondurrant P, et al. Ventilator-associated pneumonia in the pediatric intensive care unit: characterizing the problem and implementing a sustainable solution. J Pediatr. 2009;154(4):582-587.

151. Kollef MH, Morrow LE, Niederman MS, et al. Clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia. Chest. 2006;129(5):1210-1218.

152. Hidron A, Edwards JR, Patel J, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007. Infect Control Hosp Epidemiol. 2008;29(11):996-1011.

153. Kollef MH, Micek ST. Staphylococcus aureus pneumonia: a "superbug" infection in community and hospital settings. Chest. 2005;128(3):1093-1097.

154. Depuydt P, Myny D, Blot S. Nosocomial pneumonia: aetiology, diagnosis and treatment. Curr Opin Pulm Med. 2006;12(3):192-197.

155. El-Solh A, Niederman MS, Drinka P. Nursing home-acquired pneumonia: a review of risk factors and therapeutic approaches.Curr Med Res Opin. 2010;26(12):2707-2714.

156. Davis KA. Ventilator-associated pneumonia: a review. J Intensive Care Med. 2006;21(4):211-226.

157. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36(5):309-332.

158. Porzecanski I, Bowton DL. Diagnosis and treatment of ventilator-associated pneumonia. Chest. 2006;130(2):597-604.

159. Miller PR, Johnson JC 3rd, Karchmer T, Hoth JJ, Meredith JW, Chang MC. National nosocomial infection surveillance system: from benchmark to bedside in trauma patients. J Trauma. 2006;60(1):98-103.

160. Zaccard CR, Schell RF, Spiegel CA. Efficacy of bilateral bronchoalveolar lavage for diagnosis of ventilator-associated pneumonia.J Clin Microbiol. 2009;47(9):2918-2924.

161. Berton D, Kalil AC, Teixeira PJ. Quantitative versus qualitative cultures of respiratory secretions for clinical outcomes in patients with ventilator-associated pneumonia. Cochrane Database Syst Rev. 2012;1:CD006482.

162. Micek ST, Heuring TJ, Hollands JM, Shah RA, Kollef MH. Optimizing antibiotic treatment for ventilator-associated pneumonia. Pharmacotherapy. 2006;26(2):204-213.

163. Rello J, Vidaur L, Sandiumenge A, et al. De-escalation therapy in ventilator-associated pneumonia. Crit Care Med. 2004;32(11):2183-2190.

164. Sligl W, Taylor G, Brindley PG. Five years of nosocomial gram-negative bacteremia in a general intensive care unit: epidemiology, antimicrobial susceptibility patterns, and outcomes. Int J Infect Dis. 2006;10(4):320-325.

165. Mullins D, Kuznik C, Shaya FT, Obeidat NA, Levine AR, Liu LZ, Wong W. Cost-effectiveness analysis of linezolid compared with vancomycin for the treatment of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus. Clin Ther. 2006;28(8):1184-1198.

166. Shorr AF, Susla GM, Kollef MH. Linezolid for treatment of ventilator-associated pneumonia: a cost-effective alternative to vancomycin. Crit Care Med. 2004;32(1):137-143.

167. Grau S, Alvarez-Lerma F, del Castillo A, Neipp R, Rubio-Terres C. Cost-effectiveness analysis of the treatment of ventilator-associated pneumonia with linezolid or vancomycin in Spain. J Chemother. 2005;17(2):203-211.

168. Kollef MH, Rello J, Cammarata SK, Croos-Dabrera RV, Wunderink RG. Clinical cure and survival in gram-positive ventilator-associated pneumonia: retrospective analysis of two double-blind studies comparing linezolid with vancomycin. Intensive Care Med. 2004;30(3):388-394.

169. Wunderink RG, Mendelson MH, Somero MS, et al. Early microbiological response to linezolid vs vancomycin in ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus. Chest. 2008;134(6):1200-1207.

170. Pugh R, Grant C, Cooke RP, Dempsey G. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev. 2011;10:CD007577.

171. Coffin SE, Klompas M, Classen D, et al. Strategies to prevent ventilator-associated pneumonia in acute care hospitals. Infect Control Hosp Epidemiol. 2008;29:S31-S40.

172. van Nieuwenhoven CA, Vandenbroucke-Grauls C, van Tiel FH, et al. Feasibility and effects of the semirecumbent position to prevent ventilator-associated pneumonia: a randomized study. Crit Care Med. 2006;34(2):396-402.

173. Tolentino-Delos Reyes AF, Ruppert SD, Shiao SY. Evidence-based practice: use of the ventilator bundle to prevent ventilator-associated pneumonia. Am J Crit Care. 2007;16(1):20-27.

174. Institute for Healthcare Improvement. How-to Guide: Prevent Ventilator-Associated Pneumonia. Available at http://www.ihi.org/resources/Pages/Tools/HowtoGuidePreventVAP.aspx. Last accessed August 14, 2018.

175. Kress J, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342(20):1471-1477.

176. Schweickert W, Gehlbach BK, Pohlman AS, Hall JB, Kress JP. Daily interruption of sedative infusions and complications of critical illness in mechanically ventilated patients. Crit Care Med. 2004;32(6):1272-1276.

177. Institute for Healthcare Improvement. Ventilator-Associated Pneumonia: How-To Guide Pediatric Supplement. Available at http://www.ihi.org/resources/Pages/Tools/HowtoGuidePreventVAPPediatricSupplement.aspx. Last accessed August 14, 2018.

178. Bearman GM, Munro C, Sessler CN, Wenzel RP. Infection control and the prevention of nosocomial infections in the intensive care unit. Semin Respir Crit Care Med. 2006;27:310-324.

179. Drakulovic MB, Torres A, Bauer TT, Nicolar JM, Nogué S, Ferrer M. Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial. Lancet. 1999;354(9193):1851-1858.

180. Shay A, O'Malley P. Blue Ribbon Abstract Award: clinical outcomes of a ventilator associated pneumonia prevention program.Am J Infect Control. 2006;34(5):E19-E20.

181. El-Solh AA, Pietrantoni C, Bhat A, et al. Colonization of dental plaques: a reservoir of respiratory pathogens for hospital-acquired pneumonia in institutionalized elders. Chest. 2004;126(5):1575-1582.

182. Sona C, Zack JE, Schallom ME, et al. The impact of a simple, low-cost oral care protocol on ventilator-associated pneumonia rates in a surgical intensive care unit. J Intensive Care Med. 2009;24(1):54-62.

183. Munro C, Grap MJ, Jones DJ, McClish DK, Sessler CN. Chlorhexidine, toothbrushing, and preventing ventilator-associated pneumonia in critically ill adults. Am J Crit Care. 2009;18(5):428-437.

184. Fourrier F, Dubois D, Pronnier P, et al. Effect of gingival and dental plaque antiseptic decontamination on nosocomial infections acquired in the intensive care unit: a double-blind placebo-controlled multicenter study. Crit Care Med. 2005;33(8):1728-1735.

185. Pineda LA, Saliba RG, El Solh AA. Effect of oral decontamination with chlorhexidine on the incidence of nosocomial pneumonia: a meta-analysis. Crit Care. 2006;10(1):R35.

186. Bopp M, Darby M, Loftkin KC, Broscious S. Effects of daily oral care with 0.12% chlorhexidine gluconate and a standard oral care protocol on the development of nosocomial pneumonia in intubated patients: a pilot study. J Dent Hyg. 2006;80(3):9.

187. World Health Organization. Prevention of Hospital-Acquired Infections: A Practical Guide. 2nd ed. Geneva: WHO Press; 2002.

188. Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):338S-400S.

189. Dezfulian C, Shojania K, Collard HR, Kim HM, Matthay MA, Saint S. Subglottic secretion drainage for preventing ventilator-associated pneumonia: a meta-analysis. Am J Med. 2005;118(1):11-18.

190. Bouza E, Pérez MJ, Muñoz P, Rincón C, Barrio JM, Hortal J. Continuous aspiration of subglottic secretions in the prevention of ventilator-associated pneumonia in the postoperative period of major heart surgery. Chest. 2008;134(5):938-946.

191. Wang F, Bo L, Tang L, et al. Subglottic secretion drainage for preventing ventilator-associated pneumonia: an updated meta-analysis of randomized controlled trials. J Trauma Acute Care Surg. 2012;72(5):1276-1285.

192. Girou E, Brun-Buisson C, Taille S, Lemaire F, Brochard L. Secular trends in nosocomial infections and mortality associated with noninvasive ventilation in patients with exacerbation of COPD and pulmonary edema. JAMA. 2003;290(22):2985-2991.

193. Isakow W, Kollef MH. Preventing ventilator-associated pneumonia: an evidence-based approach of modifiable risk factors. Semin Respir Crit Care Med. 2006;27(1):5-17.

194. Osmon S, Kollef MH. Prevention of pneumonia in the hospital setting. Clin Chest Med. 2005;26(1):135-142.

195. Craven DE, Hjalmarson K. Prophylaxis of ventilator-associated pneumonia: changing culture and strategies to trump disease. Chest. 2008;134(5):898-900.

196. Jain M, Miller L, Belt D, King D, Berwick DM. Decline in ICU adverse events, nosocomial infections and cost through a quality improvement initiative focusing on teamwork and culture change. Qual Saf Health Care. 2006;15(4):235-239.

197. Stone MJ, Snetman D, O'Neill A, et al. Daily multidisciplinary rounds to implement the ventilator bundle decreases ventilator-associated pneumonia in trauma patients: but does it affect outcome? Surg Infect (Larchmt). 2011;12(5):373-378.

198. Cachecho R, Dobkin E. The application of human engineering interventions reduces ventilator-associated pneumonia in trauma patients. J Trauma Acute Care Surg. 2012;73(4):939-943.

199. Hutt E, Kramer AM. Evidence-based guidelines for management of nursing home-acquired pneumonia. J Fam Pract. 2002;51(8):709-716.

200. Salgado CD, Giannetta ET, Hayden FG, Farr BM. Preventing nosocomial influenza by improving the vaccine acceptance rate of clinicians. Infect Control Hosp Epidemiol. 2004;25(11):923-928

201. Carman WF, Elder AG, Wallace LA, et al. Effects of influenza vaccination on health-care workers on mortality of elderly people in long-term care: a randomized controlled trial. Lancet. 2000;355(9198):93-97.

202. Dash GP, Fauerbach L, Pfeiffer J, et al. APIC position paper: Improving health care worker influenza immunization rates. Am J Infect Control. 2004;32(3):123-125.

203. Centers for Disease Control and Prevention. Estimated influenza vaccination coverage among adults and children—United States, September 1, 2004–January 1, 2005. MMWR. 2005;54(12):304-307.

204. Christini AB, Shutt KA, Byers KE. Influenza vaccination rates and motivators among healthcare worker groups. Infect Control Hosp Epidemiol. 2007;28(2):171-177.

205. Pearson ML, Bridges CB, Harper SA. Influenza vaccination of health-care personnel. MMWR. 2006;55(RR02):1-16.

206. U.S. Food and Drug Administration. Reprocessing of Reusable Ultrasound Transducer Assemblies Used for Biopsy Procedures. Available at https://wayback.archive-it.org/7993/20170112170658/http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm151526.htm. Last accessed August 14, 2018.

207. Boyce JM, Pittet D. Guideline for hand hygiene in health-care settings. MMWR. 2002;51(RR16):1-44.

208. Burke JP. Infection control-a problem for patient safety. N Engl J Med. 2003;348(7):651-656.

209. Leapfrog Group. Press Release: Eighty-Seven Percent of U.S. Hospitals Do Not Take Recommended Steps to Prevent Avoidable Infections. Available at http://www.leapfroggroup.org/media/file/Leapfrog_hospital_acquired_infections_release.pdf. Last accessed August 20, 2015.

210. Clark AP, Houston S. Nosocomial infections: an issue of patient safety: part 2. Clin Nurse Spec. 2004;18(2):62-64.

211. Pittet D, Hugonnet S, Harbarth S, et al. Effectiveness of a hospital-wide programme to improve compliance with hand hygiene. Lancet. 2000;356(9238):1307-1312.

212. Larson EL, Quiros D, Lin SX. Dissemination of the CDC's hand hygiene guideline and impact on infection rates. Am J Infect Control. 2007;35(10):666-675.

213. Weinstein R. Hospital-acquired infections. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Isselbacher KJ (eds.) Harrison's Principles of Internal Medicine. 16th ed. New York, NY: McGraw Hill; 2004.

214. Johnson PDR, Rhea M, Burrell LJ, et al. Efficacy of an alcohol/chlorhexidine hand hygiene program in a hospital with high rates of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection. Med J Aust. 2005;183(10):509-514.

215. Gordin FM, Schultz ME, Huber RA, Gill JA. Reduction in nosocomial transmission of drug-resistant bacteria after introduction of an alcohol-based handrub. Infect Control Hosp Epidemiol. 2005;26(7):650-653.

216. Gould DJ, Chudleigh JH. Moralejo D, Drey N. Interventions to improve hand hygiene compliance in patient care. Cochrane Database Syst Rev. 2007;(2):CD005186.

217. Mason CM, Nelson S. Pulmonary host defenses and factors predisposing to lung infection. Clin Chest Med. 2005;26(1):11-17.

218. Johnstone J, Eurich DT, Jamumdar SR, Jin Y, Marrie TJ. Long-term morbidity and mortality after hospitalization with community-acquired pneumonia: a population-based cohort study. Medicine (Baltimore). 2008;87(6):329-334.

219. Santibanez T, Mootrey GT, Euler GL, Janssen AP. Behavior and beliefs about influenza vaccine among adults ages 50–64 years.Am J Health Behav. 2010;34(1):77-89.

220. Griffin M, Zhu Y, Moore M, Whitney C, Grijalva C. U.S. hospitalizations for pneumonia after a decade of pneumococcal vaccination. N Engl J Med. 2013;369:155-163.

221. Nuorti J, Butler J, Farley M, et al. Cigarette smoking and invasive pneumococcal disease. N Engl J Med. 2000;342:681-689.

222. Marrie T, Poulin-Costello M, Beecroft M, Herman-Gnjidic Z. Etiology of community-acquired pneumonia in the ambulatory setting. Respir Med. 205;99:60-65.

223. Kallen AJ, Reed C, Patton M, et al. Staphylococcus aureus community-onset pneumonia in patients admitted to children's hospitals during autumn and winter of 2006–2007. Epidemiol Infect. 2010;138:666-672.

224. Musher D, Montoya R, Wanahita A. Diagnostic value of microscopic examination of Gram-stained sputum and sputum cultures in patients with bacteremic pneumococcal pneumonia. Clin Infect Dis. 2004;39:165-169.

225. Gutiérrez F, Masiá M, Rodríguez JC, et al. Evaluation of the immunochromatographic Binax NOW Assay for detection of Streptococcus pneumoniae urinary antigen in a prospective study of community-acquired pneumonia in Spain. Clin Infect Dis. 2003;36(3):286-292.

226. Toshihiko S, MD, Yoshinori N, Jackson J, et al. Systematic review and meta-analysis: urinary antigen tests for legionellosis. Chest. 2009;136:1576-1585.

227. Centers for Disease Control and Prevention. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged >/= 65 years: recommendations of the advisory committee on immunization practices (ACIP). MMWR. 2014;63(37):822-825.

228. World Health Organization. Fact Sheet: Pneumonia. Available at http://www.who.int/mediacentre/factsheets/fs331/en. Last accessed August 14, 2018.

229. Centers for Disease Control and Prevention. Legionella (Legionaires' disease and Pontiac fever). Available at https://www.cdc.gov/pneumonia/atypical/index.html. Last accessed August 14, 2018.

230. Hicks LA, Garrison LE, Nelson GE, Hampton LM. Legionellosis—United States, 2000–2009. MMWR. 2011;60(32):1083-1086.

231. Centers for Disease Control and Prevention. Chlamydophila pneumoniae Infection. Available at http://www.cdc.gov/pneumonia/atypical/chlamydophila.html. Last accessed August 14, 2018.

232. Ramirez JA, Wiemken TL Peyrani P, et al. Adults hospitalized with pneumonia in the United States: incidence, epidemiology, and mortality. Clin Infect Dis. 2017;65:1806-1812.

233. American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171(4):388-416.

Evidence-Based Practice Recommendations Citations

1. Kirsch J, Mohammed TH, Kanne JP, et al. ACR Appropriateness Criteria: Acute Respiratory Illness in Immunocompetent Patients. Reston, VA: American College of Radiology; 2013. Available at https://acsearch.acr.org/docs/69446/Narrative. Last accessed August 22, 2018.

2. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38. Available at https://academic.oup.com/cid/article/52/3/e18/306145. Last accessed August 22, 2018.

3. Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25-e76. Available at https://academic.oup.com/cid/article/53/7/e25/424286. Last accessed August 22, 2018.

4. Institute for Clinical Systems Improvement. Prevention of Ventilator-Associated Pneumonia: Health Care Protocol. Bloomington, MN: Institute for Clinical Systems Improvement; 2011. Available at https://www.icsi.org/_asset/y24ruh/VAP-Interactive1111.pdf. Last accessed August 22, 2018.

39100 • Caring for the Geriatric Patient

Alice Yick Flanagan, PhD, MSW

Allan G. Hedberg, PhD

www.netce.com

Copyright © 2019 NetCE, All rights reserved.

The aging process can become a very challenging time in a person's life. Geriatric patients may have psychologic, sociologic, and physical changes resulting from aging, and it is often difficult for the aging person to understand and accept the changes that are taking place, to maintain a positive level of functioning for as long as possible, and to compensate for ongoing losses. Age-sensitive practice is crucial and will continue to grow more important as the nation's demographic shifts and life expectancy increases. The older segment of the population is extremely diverse in terms of the span of developmental, social, and psychologic needs. Resilience and potentiality rather than decline and deficits should be emphasized throughout all assessments and interventions.

Table of Contents

39100 • Caring for the Geriatric Patient

Course Overview

Audience

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planner

Division Planner Disclosure

About the Sponsor

Disclosure Statement

1. INTRODUCTION

2. AGE-RELATED DISEASE

OSTEOPOROSIS

OSTEOARTHRITIS

ANEMIA

GERIATRIC FAILURE TO THRIVE

FALLS

SEXUAL DYSFUNCTION

DEPRESSION AND SUICIDE

3. THE AGING BRAIN

THE PROGRESSIVE DEMENTIA PROCESS

4. ELDER ABUSE

5. END-OF-LIFE CONSIDERATIONS

Works Cited

Evidence-Based Practice Recommendations Citations

39100 • Caring for the Geriatric Patient

Education Category. Geriatrics

Release Date. 02/01/2019

Expiration Date. 01/31/2022

Course Overview

The aging process can become a very challenging time in a person's life. Geriatric patients may have psychologic, sociologic, and physical changes resulting from aging, and it is often difficult for the aging person to understand and accept the changes that are taking place, to maintain a positive level of functioning for as long as possible, and to compensate for ongoing losses. Age-sensitive practice is crucial and will continue to grow more important as the nation's demographic shifts and life expectancy increases. The older segment of the population is extremely diverse in terms of the span of developmental, social, and psychologic needs. Resilience and potentiality rather than decline and deficits should be emphasized throughout all assessments and interventions.

Audience

This course is designed for nurses in a variety of practice settings who work with older patients.

Course Objective

The purpose of this course is to provide nurses with an overview of the physical and psychosocial considerations necessary when providing care to geriatric patients.

Learning Objectives

Upon completion of this course, you should be able to:

1. Outline the clinical presentation and approach to treatment for age-related diseases such as osteoporosis, osteoarthritis, anemia, and geriatric failure to thrive.

2. Identify signs of mild cognitive impairment and dementia, and differentiate between dementia and conditions that mimic dementia in the elderly patient.

3. Define elder abuse and the different forms of elder abuse.

4. Describe the approach to care near the end of life.

Faculty

Alice Yick Flanagan, PhD, MSW, received her Master’s in Social Work from Columbia University, School of Social Work. She has clinical experience in mental health in correctional settings, psychiatric hospitals, and community health centers. In 1997, she received her PhD from UCLA, School of Public Policy and Social Research. Dr. Yick Flanagan completed a year-long post-doctoral fellowship at Hunter College, School of Social Work in 1999. In that year she taught the course Research Methods and Violence Against Women to Masters degree students, as well as conducting qualitative research studies on death and dying in Chinese American families.

Previously acting as a faculty member at Capella University and Northcentral University, Dr. Yick Flanagan is currently a contributing faculty member at Walden University, School of Social Work, and a dissertation chair at Grand Canyon University, College of Doctoral Studies, working with Industrial Organizational Psychology doctoral students. She also serves as a consultant/subject matter expert for the New York City Board of Education and publishing companies for online curriculum development, developing practice MCAT questions in the area of psychology and sociology. Her research focus is on the area of culture and mental health in ethnic minority communities.

Allan G. Hedberg, PhD, received his Master's in psychology from Northern Illinois University and his PhD in clinical psychology from Queen's University in Ontario, Canada. He has practiced clinical psychology in mental health centers, hospitals, and rehabilitation units as well as in private practice since 1969. More recently, he has maintained an active consultation service to patients and staff of nursing homes and assisted living facilities in the Central Valley of California. Over this time, Dr. Hedberg has consulted with staff, trained staff, and assisted in the establishment of appropriate programs for elderly patients with special needs, such as Alzheimer's disease.

Faculty Disclosure

Contributing faculty, Alice Yick Flanagan, PhD, MSW, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Contributing faculty, Allan G. Hedberg, PhD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planner

Jane C. Norman, RN, MSN, CNE, PhD

Division Planner Disclosure

The division planner has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

1. INTRODUCTION

The aging process can become a very challenging time in a person's life. Geriatric patients may have psychologic, sociologic, and physical changes resulting from aging, and it is often difficult for the aging person to understand and accept the changes that are taking place, to maintain a positive level of functioning for as long as possible, and to compensate for ongoing losses. Age-sensitive practice is crucial and will continue to grow more important as the nation's demographic shifts and life expectancy increases. The older segment of the population is extremely diverse in terms of the span of developmental, social, and psychologic needs. Resilience and potentiality rather than decline and deficits should be emphasized throughout all assessments and interventions.

2. AGE-RELATED DISEASE

Biologic and physiologic changes are part of aging. The losses in the physical arena for the elderly can be numerous, which may then compound and/or have implications in social and psychologic arenas. Studies have shown that brain tissues atrophy due to natural cell degeneration, with the volume of the brain decreasing by 15% or more between adolescence and old age [1]. The health status of older persons with vision and hearing loss is poorer compared with those without vision or hearing loss [2]. In a study of more than 1,000 elders, 53.7% of those with impaired vision also had hypertension, compared with 43.1% of those without impaired vision. Of those with impaired hearing, 27.6% experienced heart disease, compared with 18.6% of those without a hearing loss [2]. Interestingly, the rates double when persons have both hearing and vision impairment. Almost one-fifth (19.9%) of persons with both impairments had experienced a stroke, while only 8% with no sensory loss had experienced a stroke [2].

With the increase in life expectancy, there is also an increase in the incidence of acute and chronic illnesses, such as cardiovascular diseases and hypertension. As a part of the aging process, the composition of vascular structures changes, affecting how peripheral arteries dilate and constrict [3]. The result is often hypertension, which affects 1 billion individuals worldwide [4]. Epidemiologic studies have noted that 12% to 14% of adults 65 years of age and older have hypertension [3].

A variety of diseases occur primarily in geriatric patients. However, it is important not to use age as the only criterion to determine the type of treatment for chronic disease among the elderly. Frail elders should be assessed and treatment tailored for their specific needs [5].

OSTEOPOROSIS

Osteoporosis is the most common type of metabolic bone disease. It results either from the body's inability to form new bone or from an increased resorption of formed bone. Essentially, when there is an imbalance between osteoblastic and osteoclastic activity, skeletal problems arise. Risk factors, such as advanced age, family history, race, estrogen deficiency, tobacco use, steroid use, low calcium intake, physical inactivity, and low body weight, contribute to this condition [6].

Primary, age-related, or low-turnover osteoporosis results from decreasing bone mineral density and bone quality with age. Normal aging processes decrease gonadal function, and physical activity is usually less strenuous. Everyone reaches a peak bone mass around the third decade of life, usually between 25 to 30 years of age. The maximum bone mineral density achieved by any individual depends upon genetic factors, nutrition, endocrine status, and physical activity. Bone density then gradually decreases as the individual ages. This primary type of osteoporosis is due to decreased bone formation without declining osteoclastic action. The molecular changes that lead to this type of osteoporosis are not clear at this time; however, micrographs of bone show loss of trabecular plates in cancellous bone [7].

Postmenopausal osteoporosis causes most of the skeletal difficulties in the adult female population. Again, these molecular processes are not well understood. It is known that declining estrogen levels cause an increase in osteoclastic activity with a resulting imbalance between skeletal formation and resorption [8]. Estrogens act on nuclear receptors of both osteoblasts and osteoclasts. Deficiency of estrogen leads to, among other effects, the upregulation of osteoprotegerin ligand gene transcription and increased production of macrophage colony stimulating factor, both of which result in increased osteoclastic activity [9].

Osteoporosis is often a silent disease without obvious indications that it is present. However, there are some signs and symptoms that may accompany the development of the condition, including [8,10]:

- Decreasing height (patients may lose 10–15 cm in height due to collapsing vertebrae)

- Back pain (typically in the lower thoracic and lumbar areas [T5–L5])

- Development of a kyphosis or curvature of the upper back (Dowager's hump)

- Fracture occurring with minimal trauma

- Low body weight and weight loss of more than 1% per year in the elderly

- Suspicion of vitamin D deficiency (e.g., due to low intake or little exposure to sunshine)

Any of these findings in a patient should lead to an evaluation for osteoporosis.

Routine bone mineral density screening has been recommended for women 65 years of age and older, regardless of risk, and for women 50 to 69 years of age with clinical risk factors for fracture [7,11,12,13,14]. The International Society for Clinical Densitometry and the National Osteoporosis Foundation also have recommended routine screening for men 70 years of age and older, regardless of risk factors, and for men 50 to 69 years of age when concerns exist about the patient's risk factor profile [7,11]. The U.S. Preventive Services Task Force has determined that the evidence is insufficient to recommend routine screening for osteoporosis in men [13].

According to National Osteoporosis Foundation guidelines, postmenopausal women and men 50 years of age and older who present with any of the following should be considered for treatment [7]:

- Hip or vertebral (clinical or morphometric) fracture

- T-score at the femoral neck or spine of <-2.5 (after evaluation has excluded secondary causes)

- Low bone mass (T-score between -1.0 and -2.5 at femoral neck or spine) and 10-year probability of hip fracture >3% or 10-year probability of major osteoporosis-related fracture >20%

These recommendations are also supported by the American Association of Clinical Endocrinologists [15]. Although the guidelines are helpful, it is important to remember that treatment should be considered on an individual basis, because T- and Z-scores are only part of a patient's workup [7,16].

Numerous treatment options exist, including [7]:

- Diet/supplementation

- Exercise

- Medications

OSTEOARTHRITIS

Osteoarthritis is a leading cause of activity limitation and absenteeism among working-age adults and is associated with a significant decline in function among older individuals. Osteoarthritis is by far the most common type of arthritis and is one of the leading chronic diseases in the United States, affecting an estimated 27 million individuals 25 years of age and older and nearly 50% of people by 65 years of age [17,18]. It is the leading cause of chronic disability in individuals older than 70 years [19].

Historically, osteoarthritis has been considered a disease of articular cartilage, but research has indicated that the condition involves the entire joint organ [19,20,21]. The loss of articular cartilage has been thought to be the primary change, but a combination of cellular changes and biomechanical stresses causes several secondary changes, including subchondral bone remodeling; the formation of osteophytes; the development of bone marrow lesions; changes in the synovium, joint capsule, ligaments, and periarticular muscles; and meniscal tears and extrusion [22,23,24,25,26]. These changes lead to structural and functional changes in the joint, causing pain, disability, and psychologic distress [21].

The diagnosis of osteoarthritis at most joints is made primarily on the basis of clinical findings, with imaging studies and laboratory tests more useful for ruling out other diagnoses rather than for confirming the diagnosis of osteoarthritis [27,28,29].

There is currently no curative therapy for osteoarthritis, and treatments to alter or arrest the disease process are few and mostly ineffective [22]. Thus, management is focused on decreasing pain and increasing function [30,31]. The optimal management of osteoarthritis encompasses both nonpharmacologic and pharmacologic measures, beginning with basic modalities and following a so-called pyramid approach as the disease progresses or symptoms do not respond [32]. Several factors should be considered when selecting treatment modalities, including risk factors (e.g., age, comorbidity, overweight/obesity), the level of pain and functional limitations, signs of inflammation, and degree of structural damage [33]. Operative treatment for osteoarthritis should be delayed until all possible nonoperative options have been exhausted [22]. In general, the indications for operative treatment are debilitating pain and major limitations in function and activities of daily living [22,34].

ANEMIA

The incidence of anemia increases with age, and anemia can be common in the elderly patient. However, it should not be accepted as a part of normal aging. Growing scientific evidence suggests that the consequences of untreated geriatric anemia are significant, with poor outcomes associated with geriatric patients with anemia and increased morbidity and mortality over five years [35,36].

Conceptually, the causes of anemia can be divided into four main categories: blood loss, hemolysis, bone marrow factor deficiency or suppression, and splenic sequestration, each of which may occur alone or concomitantly. A complete patient history will provide information regarding chronic illness, history of anemia, specialty consults, and history of blood transfusions. Elderly patients with dementia may be unable to provide an accurate medical history. In these cases, caregivers and family may be good sources of information. If certain tests and diagnostics have already been completed, they may not need to be repeated.

Elderly patients with anemia may have vague, non-specific symptoms, and because the symptoms are non-specific, they are often overlooked or of limited help in differentiating between the types of anemia. Older patients are at greater risk for falls, cognitive decline, fatigue, and weakness as a result of advanced age, making the identification of anemia even more difficult [37]. Patients with mild anemia may remain asymptomatic. New-onset, easy fatigue, increased weakness, and shortness of breath are useful clues. Other symptoms may include tachycardia, bradycardia, dyspnea, chest pain, dizziness, headache, cold hands and feet, restless legs syndrome, and tarry stools. On occasion, patients may complain of visible changes in or discomfort of the tongue or lips, indicative of atrophic glottis and cheilitis. The severity of symptoms is dependent on the rapidity of onset, degree of anemia, physical status, and age of the patient [38]. Because anemia may be multifactorial, complete evaluation is necessary.

Treatment of anemia in elderly patients is largely dependent upon the etiology and the clinical signs and symptoms of the disease. For the most part, treatment of the underlying cause should result in improvements in hemoglobin levels. However, for the many patients for whom the cause is unknown, treatment is controversial. Decisions regarding the treatment plan should be individualized and based on a variety of factors, including patient goals, functional status, and presence of comorbidities [39]. Although treatment with erythropoietin-stimulating agents may result in significant improvements in hemoglobin levels, this approach has not been fully studied in patients with unexplained anemia and there is no evidence of pharmacologic treatment improving elderly patients' quality of life, physical function, or disability [40]. Due to the low risk of adverse effects, lifestyle interventions are often a first approach, including improvements in diet and vitamin supplementation. In most patients with mild disease, this may be sufficient.

GERIATRIC FAILURE TO THRIVE

Undesired weight loss in the elderly causes a reduced quality of life and contributes to serious illness. Elderly residents of nursing facilities who lose 5% of their body weight in one month are 4.6 times more likely to die within one year [41]. Poor prognosis is also associated with low prealbumin and cholesterol levels. Malnutrition in the elderly can result in pressure sores, functional decline, longer rehabilitation, and multiple medical complications.

Evidence Based Practice Recommendation

According to the Hartford Institute for Geriatric Nursing, a loss of 10 pounds over a six-month period, whether intentional or unintentional, in a geriatric patient is a critical indicator for further assessment.

https://consultgeri.org/geriatric-topics/nutrition-elderly

Last Accessed: January 11, 2019

Level of Evidence: VI (opinions of respected authorities/consensus panels) and V (care report/program evaluation/narrative literature reviews)

Failure to thrive is defined by the Institute of Medicine as "weight loss of more than 5%, decreased appetite, poor nutrition, and physical inactivity, often associated with dehydration, depression, immune dysfunction, and low cholesterol" [42]. It is not a single disease or medical condition. Rather, it is a multidimensional problem that requires a multidisciplinary approach for its treatment. The four chief characteristics of geriatric failure to thrive are impaired physical function, malnutrition, depression, and cognitive impairment [43]. Failure to thrive is commonly used as a nonspecific diagnosis when a patient loses weight due to an unknown cause. After the diagnosis is made, it stimulates further assessment and interventions. Each of the domains of geriatric failure to thrive should be evaluated to determine areas in which the elder is having difficulty.

Geriatric practitioners often order extensive diagnostic work-ups for these patients, which do not always reveal a reversible cause. It is a challenge to differentiate disease states common for older patients versus "normal aging." Furthermore, large amounts of Medicare dollars are paid to hospitals at the very end of the patient's life [44]. This raises the ethical dilemma of providing "futile care" that is cost intensive and yields few benefits.

Despite costly, time-intensive medical evaluations, 25% to 35% of patients with geriatric failure to thrive have no obvious medical cause for this weight loss [41,45]. If weight loss is attributed to the normal aging process, this can prevent early interventions from being employed.

When developing a treatment plan, it is important to take a holistic and interdisciplinary approach in order to address all of the domains of geriatric failure to thrive [43]. Input from medical specialists, nursing staff, social workers, and physical, speech, and occupational therapists should be considered. Treatment efforts addressing only the physical effects of geriatric failure to thrive will most likely not achieve the desired results. For patients with both acute and chronic illnesses, acute infections and conditions should be resolved before a longer term plan is implemented.

During periods of acute illness, an elderly patient can experience a decline in function, and resolution of the acute condition may return the patient to his or her baseline. Common acute illnesses that cause physical and cognitive function deficits in older adults include urinary tract infection, pneumonia, dehydration, and exacerbation of congestive heart failure or chronic obstructive pulmonary disease. Extended periods of bed rest also prove detrimental and can cause severe debility. Delirium can develop, requiring the use of physical or chemical restraints. Acute medical conditions also increase nutritional requirements at a time when nutritional intake is often reduced secondary to poor eating. After the acute issue is resolved, medical treatment may be provided for any other conditions present. Optimization of treatment of chronic illnesses is crucial in the care of patients with failure to thrive.

FALLS

Mobility is affected by muscle atrophy associated with advanced age. Muscle strength, for example, can decline 30% to 40% between 30 and 80 years of age [46]. This can lead to falls, which are common among the elderly. Thirty percent of those 65 years of age and older have fallen within the last 12 months, and 50% of persons older than 80 years of age have experienced a fall in the last 12 months [46]. The causes of these falls vary and include environmental factors, sensory losses, medical factors, and psychiatric conditions, such as depression or cognitive impairments [46,47]. Most falls among the elderly occur in the morning. This is not surprising given that the majority of activity and movement occur during this time [48]. Loss of ambulatory mobility is also common after hospitalization among older adults. This phenomenon, known as hospital-associated disability, is present in previously independent and ambulatory adults who have impaired mobility upon hospital discharge. It occurs among 16% to 65% of adults 65 years and older [49]. Infrequent ambulation and bed rest are the most commonly cited causes [49].

Falls often precipitate fractures in individuals with low bone mineral density. They occur for a variety of reasons and may involve multiple factors (e.g., problems with balance, mobility, vision, lower extremity weakness, and/or blood pressure circulation). Falls are a major contributor to hip fractures and have also been associated with an increased risk of spine, wrist, pelvis, and upper arm fractures. Preventive measures should include regular vision checks, elimination of medications that may cause dizziness, low blood pressure, or confusion, and elimination of environmental obstacles (e.g., removing throw rugs, installing night lights). Another important fall prevention measure is physical activity, which may help to improve muscle strength and balance. Physical activity, performed an average of three times each week for a duration of 30 to 45 minutes, should be encouraged in the elderly [8].

SEXUAL DYSFUNCTION

Sexual dysfunction is a highly prevalent condition. Among U.S. adults 18 to 59 years of age, an estimated 31% of men and 43% of women have sexual function concerns. Sexual problems are most prevalent in older men and young women [50,51,52]. However, postmenopausal women may experience sexual pain related to physiologic changes resulting from diminished estrogen.

Female Sexual Dysfunction

Older women may be anxious and have diminished sexual response from believing myths related to "normal" sexual behavior with aging. Women with erroneous beliefs may place unrealistic expectations on self (e.g., "Normal woman always orgasm from vaginal penetration") or partners (e.g., "Not getting instantly erect means you are no longer attracted to me") [53].

Genitourinary syndrome of menopause affects up to 45% of postmenopausal women [54]. Independent of dyspareunia, female sexual dysfunction can develop in women with genitourinary syndrome of menopause from recurrent urinary tract infections (and resultant interruptions of daily functioning), reduced libido, and impaired mood and social interactions from nocturia-induced sleep loss. Urinary urgency and concerns over possible incontinence can render sex unpleasant due to fear of odor, embarrassment, shame, or loss of self-esteem. Women may develop anxiety or depression over symptoms they associate with aging and age-related bodily changes [55]. The loss of vulvovaginal tissue elasticity, vaginal wall thinning, and decreased vaginal lubrication with vaginal atrophy increase the risks of micro-tears, genital lesions, and sexually transmitted infections during intercourse [55].

Male Sexual Dysfunction

Male sexual dysfunction broadly includes sexual pain and/or diminished or loss of sexual desire/interest, arousal, function, or orgasm, and diagnosis requires patient distress in addition to impairment [56]. The conditions most associated with elderly men include erectile dysfunction and hypoactive sexual desire disorder.

Age is strongly linked to erectile dysfunction, due to increased oxidative stress, penile endothelial dysfunction, vascular changes, and decline of circulating steroids [57,58]. The prevalence of erectile dysfunction is 1% to 10% in men younger than 40 years of age, 2% to 9% in men 40 to 49 years of age, 20% to 40% in men 60 to 69 years of age, and 50% to 100% in men 70 years of age or older [59,60,61]. In male hypoactive sexual desire disorder, problems with sexual desire are reported by 6% of younger men (18 to 24 years of age) and 41% of older men (66 to 74 years of age). It is a persistent problem in 1.8% of men [56].

Following assessment and diagnosis, management options should be discussed with the patient to seek the best solution. Options are now available such that, regardless of etiology, every man who wishes to be sexually active can do so. Patients benefit when education, sexual counseling, and/or psychologic therapy is combined with pharmacotherapy.

DEPRESSION AND SUICIDE

Major depression or persistent depressive disorder (dysthymia) with an age of onset after 60 years is referred to as late-onset depression. It is characterized by a greater presence of apathy and less lifetime presence of personality pathology than depression of earlier onset. Older patients tend to exhibit more vegetative signs and cognitive disturbance and complain less of dysphoria. In this population, major depression may be misattributed to physical illness, dementia, or the aging process itself [62].

Depression in the elderly is widespread, often undiagnosed, and usually untreated. Several factors contribute to missed diagnoses of depression in the elderly, including differences in presenting symptoms, stereotyping, provider and organizational barriers, and polypharmacy [63]. Older adults are less likely than younger adults to report feelings of dysphoria such as sadness, unhappiness, or irritability, suggesting that the standard diagnostic criteria for depression may be more difficult to apply to older adults or that older adults are disinclined to disclose such feelings [62,64].

Similar to other subgroups, depressed elderly often present with nonspecific somatic complaints such as insomnia, appetite disturbances, lack of energy, fatigue, chronic pain, constipation, and musculoskeletal disorders [63]. Stigma also contributes to the denial among elderly patients of the psychologic symptoms of depression and refusal to accept the diagnosis. This appears to be particularly the case with older men, who also have the highest rates of suicide in later life [62,65].

Healthcare professionals are not immune from harboring the stereotypes of the elderly often found among society in general. These can include attitudes that a depressive response to interpersonal loss, physical limitation, or changing societal role is an inevitable and even normal aspect of aging [66,67,68,69]. The elderly may view their suicidal thoughts as age-appropriate [70]. When held by patients and family members, these erroneous beliefs can lead to under-reporting of symptoms and lack of effort on the part of family members to seek care for patients [68,69]. When held by clinicians, these beliefs can result in delayed or missed diagnoses, less effective treatment, or suicide in the elderly patient. Studies have shown that a great majority of geriatric suicide cases have visited a physician within one month of their suicide [66,70].

The elderly account for roughly 16.37% of suicides but only 13.75% of the population [71]. Suicide rates rise with age for men, especially after 65 years of age, and the suicide rate in elderly men is 5.25 times that of same-aged women; nearly 84% of elderly suicides are among men [71]. The overall rate of elderly suicide is 15.4 per 100,000. However, the rate is 32.24 per 100,000 among elderly white men and 50.67 per 100,000 among white men older than 85 years of age, a rate that is almost 2.5 times the rate for men of all ages. In contrast, the suicide rate of women declines after 60 years of age [71].

Although undiagnosed and/or untreated depression is the primary cause of suicide in the elderly, suicide completion is rarely preceded by only one factor. Risk factors for suicide in this population include a previous suicide attempt; mental illness; physical illness or uncontrollable pain; fear of a prolonged illness; major changes in social roles, such as retirement; loneliness and social isolation (especially in older men who have recently lost a loved one); and access to means, such as firearms in the home [71].

3. THE AGING BRAIN

In America, more than 8,000 people turn 60 years of age every day. By 2050, it is projected that there will be more people older than 60 years of age than young people [72]. The number of people 65 years of age or older will increase more than two-fold to almost 98.2 million by 2060, representing more than 20% of the American population [72]. Indeed, a population shift is occurring in the United States.

Research indicates that neural mismatches begin to appear in individuals as young as 40 years of age, resulting in increased vulnerability to distraction [73]. By 65 years of age, one-fourth of the population struggles with a failing memory and a range of mild cognitive problems. Most notable is the "senior moment" of forgetting a person's name; this is known as paraphasia. As cognitive and biologic changes take place, aging persons are forced to learn compensatory skills to continue functioning as best they can for as long as possible.

Further, by 85 years of age, 32% of men and women will experience symptoms of dementia or Alzheimer disease [74]. After 65 years of age, the number of cases doubles every five years. There are additional factors, aside from age, that increase the risk of developing Alzheimer disease. For example, a family history of dementia is a contributing factor to the rate and degree of decline. It also appears that individuals whose mothers had Alzheimer disease are more at risk for the disease than those whose fathers had Alzheimer disease [75]. Patients with a maternal history of Alzheimer disease have an altered level of amyloid and free radicals, the proteins involved with oxidative stress [75].

Normal signs of aging can be distinguished from the more advanced signs of mild cognitive impairment (MCI), dementia, and Alzheimer disease. Normal aging may include the following behavioral changes or losses:

- Forgetting names of people one rarely sees, such as a former neighbor

- Forgetting parts of an experience, such as parts of a vacation trip with a friend

- Occasionally misplacing an item, such as car keys or a cell phone

- Extreme mood changes related to a relevant or appropriate cause, such as recalling the death of a spouse

- Temporarily being unable to recall a specific fact while telling a story or a past event or experience

- Change and loss of interest in various age-related activities

Nonetheless, the normal brain is an aging brain, and steps should be taken to maintain or improve everyday functioning. The following steps can be taken to improve the brain's functioning throughout one's life [76,77]:

- Stay physically active.

- Stop smoking or never start.

- Avoid excess alcohol.

- Engage in cognitive training.

- Maintain social networks.

- Protect the brain from toxic exposure and closed head injury.

- Eat a nutritious and balanced diet.

- Ingest the daily required minimum of vitamins, minerals, omega fatty acids, water, fruits, and vegetables.

- Sleep six to eight hours each night.

- Engage in an array of social, intellectual, spiritual, and physical activities.

- Maintain a positive attitude about life events and circumstances.

- Engage in an active life of service to others.

- Control stress and learn to cope well with daily stressful events.

- Keep personal belongings and things well organized.

- Focus on the goals of what one desires to pursue and achieve.

- Treat any psychologic problem early, such as attention deficit hyperactivity disorder, depression, and substance abuse.

THE PROGRESSIVE DEMENTIA PROCESS

Mild Cognitive Impairment

Through the process of aging and traumatic events, mild signs of neurologic dysfunction may begin to show. MCI is a spectrum of mild but persistent memory loss that lies between normal age-related memory loss and diagnosed dementia and Alzheimer disease. The memory deficits are beyond those expected for the person's age, and the individual persistently forgets meaningful information that he or she wants to remember. However, other cognitive functions may be normal, there is little loss of ability to work or function in typical daily activities, and there are no other clinical signs of dementia. MCI affects 15% to 20% of the aging population [74]. The presence of MCI may be the factor that influences the course of dementia toward Alzheimer disease. The signs of MCI go beyond those described as normal signs of aging. This level of impairment may last for a short time or for years.

In one study of older individuals without dementia, 16% had signs of MCI [78]. Of these, 69% had amnestic MCI and 31% had nonamnestic MCI. The prevalence of MCI increased with age and was greater in men, those who were never married, and those with an ApoE3/4 or ApoE4/4 genotype. Another study found that MCI was less prevalent among those with higher educational and income levels [79]. Further, there is some evidence that brain atrophy may be slowed in those with MCI with high doses of homocysteine-lowering B vitamins [80]. The fact that women are less likely than men to have MCI suggests that they may transition from normal cognition to dementia at a later age and more abruptly.

While progressive, the first step on the pathway to dementia is not always memory loss. Impairments of other cognitive skills, such as map reading, working jigsaw puzzles, and other visuospatial skills mediated in the right hemisphere of the brain, may be early signs of cognitive impairment [81]. Researchers have found that financial decision making and arithmetic functions decline one to three years earlier than memory functions [82]. Other signs were related to executive and attentional skill decline. Such research findings are important to the process of early detection of MCI, which can lead to earlier initiation of treatment and preventative measures for more advanced cognitive impairment. Early intervention among high-risk populations is an urgent area of research and experimental studies.

Dementia

Dementia is a progressive and profound disruption in brain function and intellectual capacity. The primary signs include problems with memory, language, spatial-temporal reasoning, judgment, emotionality, thought disorder, and personality. Dementia is a subtle progressive loss of cognitive functioning, with memory loss as its hallmark impairment, particularly loss of short-term memory. The ability to concentrate, make judgments, problem solve, and engage in abstract thought processes is also impaired. Personality and mood changes distinct from previous experiences are likely to develop, such as depression, apathy, elation, and anger. Impulse control becomes a major impairment with associated difficulties in social and physical relationships. Finally, grandiose and persecutory delusions are fairly common, especially in the more advanced stages of dementia [83]. It is possible for a young person to have dementia, but this is usually a result of a neurologic traumatic event or major illness with neurologic corollaries.

Dementia is a physical illness as well. It progressively shuts down the body as the brain is attacked. The first signs of dementia are generally related to reduced physical agility and strength, not just cognitive skills. Dementia can continue for years, but in the advanced stages, life expectancy is similar to that seen with advanced terminal cancer [84].

While 60% to 80% of cases of advancing dementia are categorized as the Alzheimer type, other disorders may fall within the broader classification of dementia [74]. These include but are not limited to [74,85]:

- Vascular dementia: Rapid onset secondary to multi-infarct events

- Huntington disease with dementia: Progressive inherited breakdown of the central nervous system in early adulthood affecting movement, cognition, and emotions

- Human immunodeficiency virus (HIV) with dementia: Slow-onset dementia related to the progressive HIV infectious process affecting speed of motion, memory coordination, socialization, affect, and thought processes

- Parkinson disease with dementia: Dementia beginning about one year after the diagnosis of Parkinson disease has been affirmed

- Dementia with Lewy bodies: Characterized by visual hallucinations, an impairment of visuospatial/constructional functioning with a rapid onset and rapid decline, and often Parkinsonian motor dyscontrol and cognitive loss

- Frontotemporal degeneration: Generally related to a traumatic impact to the frontal lobe, as in a motor vehicle accident, fall, or a career in boxing or similar sports with a repetitive cranial impact

- Mixed dementia: Characterized by the hallmark abnormalities of more than one type of dementia—most commonly Alzheimer disease combined with vascular dementia

- Creutzfeldt-Jakob disease: Degenerative neurologic disorder associated with early development of dementia and the presence of prions, a type of infectious protein

There are also many reversible conditions that can mimic dementia [74]. For this reason, dementias should be fully assessed and diagnostically clarified [86]. Specific disorders known to cause pseudodementias include but are not limited to:

- Reactions to medications

- Metabolic disturbances

- Vision and hearing deficits

- Nutritional deficiencies

- Endocrine abnormalities

- Infections

- Subdural hematoma

- Brain tumors and hydrocephalus

- Atherosclerosis

Likewise, there are irreversible conditions known to play a significant and contributing role in dementia onset. These fall into three primary nosologic categories: systemic changes, neuropathologic changes, and underlying basic diseases. It is essential that a competent diagnostic evaluation is conducted to sort out these conditions and determine if dementia is diagnostically present or if dementia is a symptomatic trait of another medical or physical condition. The following sample of physical conditions may or may not present with dementia:

- Closed head trauma

- Brain tumors

- Hydrocephalus

- Developmental disability

- Infections

- Chronic depression

- Deficiency diseases (e.g., vitamin B12 deficiency)

- Exposure to toxins, drugs, and metals

- Metabolic disorders

- Vascular disorders (e.g., cerebrovascular accident and transient ischemic attacks)

- Degenerative diseases of the central nervous system

- Huntington disease

- Anoxia

- Acquired immunodeficiency syndrome (AIDS)

- Multiple sclerosis

- Drug-induced psychotic state

- Congestive heart failure

- Diseases of unknown origin

- Thyroid dysfunction

- Creutzfeldt-Jakob disease

- Korsakoff syndrome

An annual screening system is under development for the early detection of dementia [87,88,89]. It is proposed that this type of screening might be incorporated into an annual physical examination or incorporated into wellness screening programs. The results of a screening assessment would indicate if a referral for neuropsychologic assessment or further evaluation is needed. A baseline would need to be established at 65 or 70 years of age to ensure that a reasonably accurate profile could be established and false positives minimized.

Alzheimer Disease

Alzheimer disease is an advanced type of dementia named for German physician Alois Alzheimer, who first identified the neuritic plaques and neurofibrillary tangles now recognized as the classic signs of Alzheimer disease. It is thought that these brain changes and conditions result from the destruction of neurons that produce acetylcholine in the cerebral cortex. With Alzheimer disease, the brain is believed to have a loss of nerve cells in certain areas and a corresponding reduction in the levels of neurotransmitters. Alzheimer disease is rapidly progressive, and its pattern and progression is individualistic [90].

As noted, the primary symptoms of dementia are mild-to-moderate impairments in memory, reasoning ability, and judgment, and the same symptoms are present in Alzheimer disease but to a greater degree. Alzheimer disease also often includes personality changes, bouts of agitation and combativeness, falling, wandering, and depression. The risk of self-harm from accidents and falls becomes progressively more likely. According to the Alzheimer's Association, the warning signs of Alzheimer disease are [91]:

- Life is disrupted by memory loss.

- Planning and problem solving are a challenge.

- Familiar tasks are more difficult to complete.

- Time and place are common issues of confusion.

- Visual images and spatial relationships are problematic.

- Speaking and writing become difficult.

- Items are easily misplaced, and steps are hard to retrace.

- Judgment is poorly misguided.

- Work and social events are generally avoided.

- Mood and personality show signs of change.

- Behavioral agitation and becoming out of control at times

- Linguistic fixity (i.e., repeating words or phrases for lengthy periods)

However, it is important to remember that the signs and progression of the disease varies greatly among patients. Eventually, all patients with Alzheimer disease will require constant care with activities of daily living. Wandering and sundowning are frequent problems. It is vital that lost patients are found within 24 hours, as after this period the odds are strong that they will develop a serious illness, be injured, or die, as patients with Alzheimer disease are essentially unable to ask for help.

Many people with dementia will not progress to Alzheimer disease. However, of all those with dementia, 60% to 80% develop the pattern of Alzheimer disease [74]. AD is more prevalent in women than men. Of the 5.3 million people 65 years of age and older with Alzheimer disease in the United States, 3.3 million are women and 2 million are men. Among people 71 years of age and older, 16% of women have Alzheimer disease and other dementias, compared with 11% of men [74]. The number of new cases of Alzheimer disease increases dramatically with age. In 2018, approximately 66,000 new cases of Alzheimer disease are expected to occur among individuals 65 to 74 years of age. This number increases to 173,000 among those 75 to 84 years of age, and to 245,000 among those 85 years of age and older, with the annual number of new cases projected to double by 2050 [74].

Among individuals 70 years of age, 61% of those with Alzheimer disease are expected to die before age 80, compared with 30% of those without the disease [74]. Alzheimer disease is also a condition with catastrophic impact and complex care needs. In 2017, more than 16 million Americans provided 18.4 billion hours of unpaid care to individuals with Alzheimer disease and other dementias [74]. It is anticipated that deaths due to dementia will gradually increase from about 400,000 in 2010 to 1 million worldwide in 2030 [92].

Total home care with hired caretakers or placement in a nursing home is necessary as Alzheimer disease progresses to higher levels of impairment. While family members may wish to be the sole caretakers, the level of care needed very often reaches a point that is beyond their level of ability, stamina, and time. If the family is unable to provide the needed care themselves, they may make arrangements for care provided in a loving and compassionate manner by a third party, such as a friend, a home health care provider, or a nursing home. Who provides the day-to-day care is less important than the quality of care provided relative to the patient's needs and level of functioning.

As the progression of Alzheimer disease is rapid, it is important to consider if any family member has any "unfinished business" that should be constructively addressed early in the disease process. Devoting time to being a care provider is reasonable when there is a clear sign that long overdue forgiveness, past hurts, or neurotic attachments have been resolved. If there are issues that are unaddressed, this may result in further injury in addition to historical hurts and dysfunctional relationships. While the care level may look reasonable, it may really be subtly destructive. Neurotic attachments are all too common and create a host of care problems.

Dementia with Lewy Bodies

An estimated 1.3 million people in the United States have dementia with Lewy bodies, a total of 10% to 20% of all dementia cases [93]. Dementia with Lewy bodies is not readily diagnosed, as it presents with symptoms closely aligned to Alzheimer disease and/or Parkinson disease. If inaccurately diagnosed, a proper care plan will not be formulated and the patient and his or her family will be unable to prepare for the disease's progression.

Lewy bodies, named for F.H. Lewy, who first described the condition in 1914, result from a buildup of alpha-synuclein protein in neurons in the brain [94]. This is distinct from the beta-amyloid protein fragments (plaques) and twisted strands of tau proteins (tangles) found in Alzheimer disease [94]. Dementia with Lewy bodies is associated with dysfunction of the lower brain, brainstem, and subcortical, paralimbic, limbic, and cortical structures vital to movement and cognition. The severity of symptoms fluctuates over time, with improvements and regressions [90]. However, this dementia will eventually progress to catastrophic disability and death, as with Alzheimer disease.

The most common signs and symptoms of dementia with Lewy bodies are visual hallucinations, spontaneous parkinsonism, narcoleptic sensitivity, a tendency to act out vivid and frightening dreams, and fluctuations in cognition, alertness, clarity of thought, and attention [95].

Patients with dementia with Lewy bodies have more difficulty with visual perception and memory, processing speed, and attention/concentration [93]. Visual tasks are more likely to be distorted than in most patients with Alzheimer disease. Visual distortions tend to show up early in the dementia process, including distortions in writing, drawing, and misjudging distances. Brighter light may reduce visual hallucinations, as will removing reflective or patterned surfaces (e.g., mirrors, wallpaper with designs) and having the patient stare directly at the hallucination [95]. Hallucinations are often not acknowledged by the family; healthcare providers must ask about them directly, especially early in the dementia process.

To assess dementia with Lewy bodies, a standardized and validated screening tool, such as the Mayo Fluctuations Composite Scale, should be used. Neuroimaging may be useful to distinguish dementia with Lewy bodies from vascular dementia [94]. Treatment to reduce symptoms may be indicated. Acetylcholinesterase inhibitors are the medications of choice, including donepezil, rivastigmine, and galantamine. This class of medication has been shown to improve attention, sleep, ambulation, motor coordination, and visual hallucinations for patients with dementia with Lewy bodies [93]. The medication regimen should be re-evaluated every six months and altered or maintained as the relative benefits indicate [96]. Due to neuroleptic sensitivity and reduced dopamine, typical neuroleptic or antipsychotic medications, such as haloperidol, ziprasidone, and olanzapine, should be avoided as much as possible for the treatment of psychotic symptoms. If such medication is used, patients will experience increased or worsened symptoms and become more rigid.

4. ELDER ABUSE

Abused and neglected elders, who may be mistreated by their spouses, partners, children, or other relatives, are among the most isolated of all victims of family violence. In a national study conducted by the National Institute of Justice in 2010, 4.6% of participants (community dwelling adults 60 years of age or older) were victims of emotional abuse in the past year, 1.6% physical abuse, 0.6% sexual abuse, 5.1% potential neglect, and 5.2% current financial abuse by a family member [97]. The estimated annual incidence of all elder abuse types is 2% to 10%, but it is believed to be severely under-measured. According to one study, only 1 in 14 cases of elder abuse are reported to the authorities [98].

The prevalence rate of elder abuse in institutional settings is not clear. However, in one nonprobability study, 36% of nursing and aide staff disclosed to having witnessed at least one incident of physical abuse by other staff members in the preceding year. When asked whether they themselves perpetrated physical abuse against an elderly resident, 10% admitted they had [99]. In a random sample survey, 24.3% of respondents reported at least one incident of elder physical abuse perpetrated by a nursing home staff member [100].

It is important to understand that the needs of older patients will increase, as will the numbers of elder victims of violence. Because elder abuse can occur in family homes, nursing homes, board and care facilities, and even medical facilities, healthcare professionals should remain keenly aware of the potential for abuse. When abuse occurs between elder partners, it is primarily manifested in one of two ways, either as a long-standing pattern of marital violence or as abuse originating in old age. In the latter case, abuse may be precipitated by issues related to advanced age, including the stress that accompanies disability and changing family relationships [101].

Evidence Based Practice Recommendation

The U.S. Preventive Services Task Force concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for abuse and neglect in all older or vulnerable adults.

https://jamanetwork.com/journals/jama/fullarticle/2708121

Last Accessed: January 11, 2019

Strength of Recommendation: I (Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.)

It is important to understand that the domestic violence dynamic involves not only a victim but a perpetrator as well. For example, an adult son or daughter who lives in the parents' home and depends on the parents for financial support may be in a position to inflict abuse. This abuse may not always manifest itself as violence, but can lead to an environment in which the elder parent is controlled and isolated. The elder may be hesitant to seek help because the abuser's absence from the home may leave the elder without a caregiver [101]. Because these elderly victims are often isolated, dependent, infirm, or mentally impaired, it is easy for the abuse to remain undetected. Healthcare professionals in all settings should remain aware of the potential for abuse and keep a watchful eye on this particularly vulnerable group.

5. END-OF-LIFE CONSIDERATIONS

As a result of ongoing advances in medicine, the trajectory of illness for many diseases has shifted, yielding an increasing number of patients needing palliative care throughout the continuum of care and, especially, at the end of life. High-quality palliative care focuses on the physical, psychosocial, and spiritual well-being of the patient as well as the family. Palliative care at the end of life is delivered most effectively through hospice.

Because palliative care focuses on the physical and psychosocial needs of the patient and his or her family, the patient's and family's perspectives are vital considerations in developing high-quality palliative care programs. An early survey of patients with life-limiting diseases identified five priorities for palliative care: receiving adequate treatment for pain and other symptoms, avoiding inappropriate prolongation of life, obtaining a sense of control, relieving burden, and strengthening relationships with loved ones [102]. In another study, a spectrum of individuals involved with end-of-life care (physicians, nurses, social workers, chaplains, hospice volunteers, patients, and recently bereaved family members) echoed these findings, with the following factors being noted as integral to a "good death:" pain and symptom management, clear decision making, preparation for death, completion, contributing to others, and affirmation of the whole person [103].

The priorities set by patients and healthcare professionals were considered carefully in the structuring of clinical practice guidelines for high-quality palliative care developed by the National Consensus Project for Quality Palliative Care. These guidelines are organized according to eight domains [104]:

- Structure and process of care

- Physical aspects

- Psychologic and psychiatric aspects

- Social aspects

- Spiritual, religious, and existential aspects

- Cultural aspects

- Care of the patient nearing the end of life

- Ethical and legal aspects

In the last days, the goals of the healthcare team are to ensure a peaceful death for the patient and to support the family during the dying process and throughout grief and mourning. The focus for the patient is management of symptoms and emotional and spiritual ease, and the focus for the family is education to prepare them for the dying process.

Works Cited

1. Epstein R. Brutal truths: about the aging brain. Discover. 2012;33(8):48-76.

2. Crews JE. The role of public health in addressing aging and sensory loss. Generations. 2003;27(10):83-90.

3. Wong J, Wong S. Evidence-based care for the elderly with isolated systolic hypertension. Nurs Health Sci. 2005;7(1):67-75.

4. Klymko KW. Assessment: cognitive assessment in elderly African American adults with hypertension. J Gerontol Nurs. 2005;31(11):15-20.

5. Materson BJ, Garcia-Estrada M, Preston RA. Hypertension in the frail elderly. J Am Soc Hypertens. 2016;10(6):536-541.

6. National Osteoporosis Foundation. Are You at Risk? Available at https://www.nof.org/preventing-fractures/general-facts/bone-basics/are-you-at-risk. Last accessed January 10, 2019.

7. National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2014.

8. Office of the Surgeon General. Bone Health and Osteoporosis: A Report of the Surgeon General. Available at https://www.ncbi.nlm.nih.gov/books/NBK45513. Last accessed January 10, 2019.

9. Shevde NK, Bendixen AC, Dienger KM, Pike JW. Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism involving c-Jun repression. Proc Natl Acad Sci U S A. 2000;97(14):7829-7834.

10. Moayyeri A, Luben RN, Bingham SA, Welch AA, Wareham NJ, Khaw KT. Measured height loss predicts fractures in middle-aged and older men and women: the EPIC-Norfolk prospective population study. J Bone Miner Res. 2008;23(3):425-432.

11. International Society for Clinical Densitometry. ISCD Official Positions. Available at http://www.iscd.org/official-positions/official-positions. Last accessed January 10, 2019.

12. The North American Menopause Society. Management of osteoporosis in postmenopausal women: 2010 position statement of The North American Menopause Society. Menopause. 2010;17(1):25-54.

13. U.S. Preventive Services Task Force. Osteoporosis: Screening. Available at https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/osteoporosis-screening1. Last accessed January 10, 2019.

14. Cheung AM, Feig DS, Kapral M, et al. Prevention of osteoporosis and osteoporotic fractures in postmenopausal women: recommendation statement from the Canadian Task Force on Preventive Health Care. CMAJ. 2004;170(11):1665-1667.

15. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists and American College of Endocrinology for clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract. 2016;22(Suppl 4):1-42.

16. Licata AA. Diagnosing primary osteoporosis: it's more than a T-score. Cleve Clin J Med. 2006;73(5):473-476.

17. Lawrence R, Felson DT, Helmick CG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008;58:26-35.

18. Centers for Disease Control and Prevention. Arthritis-Related Statistics. Available at https://www.cdc.gov/arthritis/data_statistics/arthritis-related-stats.htm. Last accessed January 10, 2019.

19. Lozada CJ. Osteoarthritis. Available at https://emedicine.medscape.com/article/330487-overview. Last accessed January 10, 2019.

20. Aspden RM. Osteoarthritis: a problem of growth not decay? Rheumatology. 2008;47(10):1452-1460.

21. Hunter DJ. Imaging insights on the epidemiology and pathophysiology of osteoarthritis. Rheum Dis Clin N Am. 2009;35(4):447-463.

22. Hunter DJ, Felson DT. Osteoarthritis. BMJ. 2006;332(7542):639-642.

23. American College of Rheumatology. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum. 2000;43(9):1905-1915.

24. Pollard TCB, Gwilym SE, Carr AJ. The assessment of early osteoarthritis. J Bone Joint Surg Br. 2008;90-B(4):411-421.

25. Dequeker J, Luyten FP. The history of osteoarthritis-osteoarthrosis. Ann Rheum Dis. 2008;67(1):5-10.

26. Ding C, Jones G, Wluka AE, Cicuttini F. What can we learn about osteoarthritis by studying a healthy person against a person with early onset of disease? Curr Opin Rheumatol. 2010;22(5):520-527.

27. Altman R, Kuritzky L, Ruoff G. Improving long-term management of osteoarthritis: strategies for primary care physicians. J Fam Pract. 2009;58(2 Suppl):S17-S24.

28. Hinton R, Moody RL, Davis AW, Thomas SF. Osteoarthritis: diagnosis and therapeutic considerations. Am Fam Physician. 2002;65(5):841-848.

29. Cibere J. Do we need radiographs to diagnose osteoarthritis? Best Pract Res Clin. 2006;20:27-38.

30. Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis. Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008;16(2):137-162.

31. Zhang W, Nuki G, Moskowitz RW, et al. OARSI recommendations for the management of hip and knee osteoarthritis. Part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage. 2010;18(4):476-499.

32. Langworthy M, Saad A, Langworthy NM. Conservative treatment modalities and outcomes for osteoarthritis: the concomitant pyramid of treatment. Phys Sports Med. 2010;38(2):133-145.

33. Jordan K, Arden NK, Doherty M, et al. EULAR recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2003;62(12):1145-1155.

34. Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012;64(4):465-474.

35. Riva E, Tettamanti M, Mosconi P, et al. Association of mild anemia with hospitalization and mortality in the elderly: the Health and Anemia population-based study. Haematologica. 2009;94(1):22-28.

36. Lefebvre P, Duh MS, Buteau S, Bookhart B, Mody SH. Medical costs of untreated anemia in elderly patients with pre-dialysis chronic kidney disease. J Am Soc Nerphrol. 2006;17(12):3497-3502.

37. Smith DL. Anemia in the elderly. Am Fam Physician. 2000;62(7):1565-1572.

38. Lipschitz D. Medical and functional consequences of anemia in the elderly. J Am Geriatr Soc. 2003;51(3 Suppl):S10-S13.

39. Price EA, Schrier SL. Anemia in the Older Adult. Available at https://www.uptodate.com/contents/anemia-in-the-older-adult. Last accessed January 10, 2019.

40. Makipour S, Kanapuru B, Ershler WB. Unexplained anemia in the elderly. Semin Hematol. 2008;45(4):250-254.

41. Ryan C, Bryant E, Eleazer P, Rhodes A, Guest K. Unintentional weight loss in long-term care: predictor of mortality in the elderly. South Med J. 1995;88(7):721-724.

42. Ali N. Failure to Thrive in Elderly Adults. Available at https://emedicine.medscape.com/article/2096163-overview. Last accessed January 10, 2019.

43. Robertson RG, Montagnini M. Geriatric failure to thrive. Am Fam Physician. 2004;70(2):343-350.

44. The Henry J. Kaiser Family Foundation. End-of-Life Hospital Spending for Medicare Beneficiaries with Chronic Health Conditions Varies Widely, Study Finds. Available at https://khn.org/morning-breakout/dr00051385. Last accessed January 15, 2019.

45. Smith KL, Greenwood C, Payette H, Alibhai SMH. An approach to the nonpharmacologic and pharmacologic management of unintentional weight loss among older adults. Geriatr Aging. 2007;10(2):91-98.

46. Oliver D. Older people who fall: why they matter and what you can do. Br J Community Nurs. 2007;12(11):500-507.

47. Delaune MF, Ciolek C. Falls in community dwelling older adults: examination and evaluation. Magazine of Physical Therapy. 2007;15(11):34-41.

48. Dhargave P, Sendhilkumar R. Prevalence of risk factors for falls among elderly people living in long-term care homes. J Clin Gerontology Geriatrics. 2016;7(3):99-103.

49. Doherty-King B, Yoon JY, Pecanac K, et al. Frequency and duration of nursing care related to older patient mobility. J Nurs Scholarsh. 2014;46(1):20-27.

50. Shifren JL, Monz BU, Russo PA, Segreti A, Johannes CB. Sexual problems and distress in United States women: prevalence and correlates. Obstet Gynecol. 2008;112(5):970-978.

51. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA. 1999;281(6):537-544.

52. Laumann EO, Nicolosi A, Glasser DB, et al. Sexual problems among women and men aged 40–80 y: prevalence and correlates identified in the Global Study of Sexual Attitudes and Behaviors. Int J Impot Res. 2005;17(1):39-57.

53. Lamont J, Society of Obstetricians and Gynaecologists of Canada. Female sexual health consensus clinical guidelines. J Obstet Gynaecol Can. 2012;34(8):769-783.

54. Nappi RE, Kokot-Kierepa M. Vaginal health: insights, views & attitudes (VIVA)—results from an international survey. Climacteric. 2012;15(1):36-44.

55. Goldstein I, Dicks B, Kim NN, Hartzell R. Multidisciplinary overview of vaginal atrophy and associated genitourinary symptoms in post-menopausal women. Sex Med. 2013;1(2):44-53.

56. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.

57. Andersson KE. Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction. Pharmacol Rev. 2011;63(4):811-859.

58. Buvat J, Maggi M, Gooren L, et al. Endocrine aspects of male sexual dysfunctions. J Sex Med. 2010;7(4 Pt 2):1627-1656.

59. Lewis RW, Fugl-Meyer KS, Corona G, et al. Definitions/epidemiology/risk factors for sexual dysfunction. J Sex Med. 2010;7(4 Pt 2):1598-1607.

60. Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP, McKinlay JB. Incidence of erectile dysfunction in men 40 to 69 years old: longitudinal results from the Massachusetts Male Aging Study. J Urol. 2000;163(2):460-463.

61. Tsertsvadze A, Yazdi F, Fink HA, et al. Diagnosis and Treatment of Erectile Dysfunction. Evidence Report/Technology Assessment No.171. Rockville, MD: Agency for Healthcare Research and Quality; 2009.

62. Robinson L, Smith M, Segal J. Depression in Older Adults: Recognizing the Signs and Getting the Right Treatment. Available at https://www.helpguide.org/articles/depression/depression-in-older-adults.htm. Last accessed January 10, 2019.

63. Mitchell J, Trangle M, Degnan B, et al., for the Institute for Clinical Systems Improvement. Depression, Adult in Primary Care. 17th ed. Available at https://www.icsi.org/guidelines__more/catalog_guidelines_and_more/catalog_guidelines/catalog_behavioral_health_guidelines/depression. Last accessed January 10, 2019.

64. Kessler RC, Birnbaum H, Bromet E, Hwang I, Sampson N, Shahly V. Age differences in major depression: results from the National Comorbidity Survey Replication (NCS-R). Psychol Med. 2010;40(2):225-237.

65. Xu J, Murphy SL, Kochanek KD, Bastian B, Arias E. Deaths: final data for 2016. Natl Vital Stat Rep. 2018;67(5):1-75.

66. Substance Abuse and Mental Health Services Administration. The Treatment of Depression in Older Adults: Depression and Older Adults: Key Issues. Rockville, MD: Center for Mental Health Services, Substance Abuse and Mental Health Services Administration, US Department of Health and Human Services; 2011.

67. Mitchell AJ, Rao S, Vaze A. Do primary care physicians have particular difficulty identifying late-life depression? A meta-analysis stratified by age. Psychother Psychosom. 2010;79(5):285-94.

68. Law J, Laidlaw K, Peck D. Is depression viewed as an inevitable consequence of age? The "understandability phenomenon" in older people. Clinical Gerontologist. 2010;33(3):194-209.

69. Uncapher H, Arean PA. Physicians are less willing to treat suicidal ideation in older patients. J Am Geriatr Soc. 2000;48:188-192.

70. Fischer LR, Wei F, Solberg LI, Rush WA, Heinrich RL. Treatment of elderly and other adult patients for depression in primary care. J Am Geriatr Soc. 2003;51(11):1554-1562.

71. American Association of Suicidology. Facts and Statistics. Available at http://www.suicidology.org/resources/facts-statistics. Last accessed January 10, 2019.

72. Administration on Aging. A Profile of Older Americans: 2016. Available at https://acl.gov/sites/default/files/Aging%20and%20Disability%20in%20America/2016-Profile.pdf. Last accessed January 10, 2019.

73. Fernandes MA, Pacurar A, Moscovitch M, Grady C. Neural correlates of auditory recognition under full and divided attention in younger and older adults. Neuropsychologia. 2006;44(12):2452-2464.

74. Alzheimer's Association. 2018 Alzheimer's Disease Facts and Figures. Available at https://www.alz.org/alzheimers-dementia/facts-figures. Last accessed January 10, 2019.

75. Mosconi LG, Glodzik L, Mistur R, et al. Oxidative stress and amyloid-beta pathology in normal and individuals with a maternal history of Alzheimer's. Biol Psychiatry. 2010;68(10):913-921.

76. Bergland C. What Is the Best Way to Improve Your Brain Power For Life? Available at https://www.psychologytoday.com/blog/the-athletes-way/201401/what-is-the-best-way-improve-your-brain-power-life. Last accessed January 10, 2019.

77. Alzheimer's Association. Brain Health. Available at https://www.alz.org/brain-health/brain_health_overview.asp. Last accessed January 10, 2019.

78. Petersen RC, Roberts RO, Knopman DS, et al. Prevalence of mild cognitive impairment is higher in men: the Mayo Clinic study on aging. Neurology. 2010;75(10):889-897.

79. Stagnitti MN. Person Characteristics of the Elderly Reporting One or More Cognitive Disorders, 2007. Available at https://meps.ahrq.gov/data_files/publications/st310/stat310.shtml. Last accessed January 10, 2019.

80. Smith JC, Nielson KA, Woodard JL, et al. Interactive effects of physical activity and APOE-ε4 on BOLD semantic memory activation in healthy elders. Neuroimage. 2011;54(1):635-644.

81. Willis SL, Tennstedt SL, Marsiske M et al. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA. 2006;296(23):2805-2814.

82. Martin RC, Annis SM, Darling LZ, Wadley V, Harrell L, Marson DC. Loss of calculation abilities in patients with mild and moderate Alzheimer disease. Arch Neurol. 2003;60(11):1585-1589.

83. Mayo Clinic. Dementia. Available at https://www.mayoclinic.org/diseases-conditions/dementia/symptoms-causes/syc-20352013. Last accessed January 10, 2019.

84. Mitchell SL, Teno JM, Kiely DK, et al. The clinical course of advanced dementia. N Engl J Med. 2009;361(16):1529-1538.

85. Alzheimer's Association. Types of Dementia. Available at https://www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia. Last accessed January 10, 2019.

86. Green R. Diagnosis and Management of Alzheimer's Disease and Other Dementias. 2nd ed. West Islip, NY: Professional Communications; 2005.

87. American Academy of Developmental Medicine and Dentistry. NTG-EDSD Screening Instrument. Available at https://aadmd.org/index.php?q=ntg/screening. Last accessed January 10, 2019.

88. National Task Group on Intellectual Disabilities and Dementia Practices. NTG-EDSD. Available at https://aadmd.org/sites/default/files/Draft%20NTG-EDSD-Final.pdf. Last accessed January 10, 2019.

89. Cordell CB, Borson S, Boustani M, et al. Alzheimer's Association recommendations for operationalizing the detection of cognitive impairment during the Medicare Annual Wellness Visit in a primary care setting. Alzheimers Dementia. 2013;9(2):141-150.

90. Shankle W, Amen D. Preventing Alzheimer's: Ways to Help Prevent, Delay, Detect, and Even Halt Alzheimer's Disease and Other Forms of Memory Loss. New York, NY: Penguin Group; 2004.

91. Alzheimer's Association. 10 Early Signs and Symptoms of Alzheimer's. Available at https://www.alz.org/alzheimers-dementia/10_signs. Last accessed January 10, 2019.

92. Fodale V, Ritchie K, Rasmussen LS, Mandal PK. Anesthetics and Alzheimer's disease: research and background. J Alzheimers Dis. 2010;22(S3):1-3.

93. McKeith IG, Burn D, O'Brien J, Perry R, Perry E. Dementia with Lewy bodies. In: Davis KL, Charney D, Coyle JT, Nemeroff C (eds). Neuropsychopharmacology: The Fifth Generation of Progress. Philadelphia, PA: Lippincott Williams & Wilkins; 2002: 1301-1315.

94. Crystal HA. Dementia with Lewy Bodies. Available at https://emedicine.medscape.com/article/1135041-overview. Last accessed January 10, 2019.

95. Hamilton J. Considering alternative causes of dementia: is it Alzheimer's disease or dementia with Lewy bodies? California Psychol. 2010;43(6):12-14.

96. Suda S, Sugihara G, Suyama R, Mori N, Takei N. Donepezil and concurrent sertraline treatment is associated with increased hippocampal volume in a patient with depression. J Clin Psychiatry. 2010;71(6):806-808.

97. National Center for Injury Prevention and Control. NISVS 2010 Findings on Victimization by Sexual Orientation. Available at https://www.cdc.gov/violenceprevention/pdf/nisvs_sofindings.pdf. Last accessed January 10, 2019.

98. Erez E, Bach S. Immigration, domestic violence, and the military: the case of "military brides." Violence Against Women. 2003;9(9):1093-1117.

99. U.S. Government Accountability Office. Military Personnel: Sustained Leadership and Oversight Needed to Improve DOD's Prevention and Treatment of Domestic Abuse. Available at https://www.gao.gov/new.items/d10923.pdf. Last accessed January 10, 2019.

100. Krimm J, Heinzer MM. Domestic violence screening in the emergency department of an urban hospital. J Natl Med Assoc. 2002;94(6):484-491.

101. Military One Source. Preventing Abuse and Neglect. Available at https://www.militaryonesource.mil/family-relationships/family-life/preventing-abuse-neglect. Last accessed January 10, 2019.

102. Singer PA, Martin DK, Kelner M. Quality end-of-life care: patients' perspectives. JAMA. 1999;281:163-168.

103. Steinhauser K, Clipp EC, McNeilly M, et al. In search of a good death: observations of patients, families, and providers. Ann Intern Med. 2000;132:825-832.

104. National Consensus Project for Quality Palliative Care Consortium Organizations. Clinical Practice Guidelines for Quality Palliative Care. 4th ed. Pittsburgh, PA: National Consensus Project; 2018.

Evidence-Based Practice Recommendations Citations

1. DiMaria-Ghalili RA. Nutrition in the elderly. In: Boltz M, Capezuti E, Fulmer T, Zwicker D (eds). Evidence-Based Geriatric Nursing Protocols for Best Practice. 4th ed. New York, NY: Springer Publishing Company; 2012. Available at https://consultgeri.org/geriatric-topics/nutrition-elderly. Last accessed January 11, 2019.

2. U.S. Preventive Services Task Force. Screening for intimate partner violence, elder abuse, and abuse of vulnerable adults: U.S. Preventive Services Task Force final recommendation statement. JAMA. 2018;320(16):1678-1687. Available at https://jamanetwork.com/journals/jama/fullarticle/2708121. Last accessed January 11, 2019.

96101 • Frontotemporal Degeneration

Ellen Steinbart, RN, MA

www.netce.com

Copyright © 2018 NetCE, All rights reserved.

Frontotemporal degeneration (FTD) is a group of brain disorders causing progressive deterioration in behavior, language, and/or movement. There are presently approximately 60,000 people with FTD in the United States. Onset generally occurs between 50 and 70 years of age, making FTD one of the most common presenile dementias. FTD affects the frontal and temporal lobes of the brain, which control emotions, judgment, personality, memory and language. The clinical diagnosis of FTD can be challenging, as some symptoms overlap with Alzheimer disease and other forms of dementia. FTD can be categorized based on its primary symptoms into three basic types: behavioral variant FTD, primary progressive aphasia, and progressive motor decline. Although most FTD does not appear to be inherited, genetics does play a role in a significant minority of cases. There is no effective treatment or cure for FTD, but there are strategies for management of symptoms. This course will discuss the possible causes and pathophysiology, diagnosis, and management strategies for FTD.

Table of Contents

96101 • Frontotemporal Degeneration

Course Overview

Audience

Course Objective

Learning Objectives

Faculty

Faculty Disclosure

Division Planners

Division Planners Disclosure

About the Sponsor

Disclosure Statement

1. INTRODUCTION

2. EPIDEMIOLOGY OF FTD

3. PATHOGENESIS AND PATHOPHYSIOLOGY OF FTD

4. CLINICAL PRESENTATION

BEHAVIORAL PRESENTATION

LANGUAGE PRESENTATION

FTD OVERLAP WITH MOVEMENT DISORDERS

5. CLINICAL DIAGNOSIS OF FTD

6. GENETICS AND FTD

7. MANAGEMENT OF FTD

CAREGIVER SUPPORT

8. PROGRESSION OF FTD

9. RESEARCH RELATED TO FTD

10. CASE STUDY

11. CONCLUSION

12. RESOURCES

Works Cited

Evidence-Based Practice Recommendations Citations

96101 • Frontotemporal Degeneration

Education Category. Psychiatric / Mental Health

Release Date. 11/01/2018

Expiration Date. 10/31/2021

Course Overview

Frontotemporal degeneration (FTD) is a group of brain disorders causing progressive deterioration in behavior, language, and/or movement. There are presently approximately 60,000 people with FTD in the United States. Onset generally occurs between 50 and 70 years of age, making FTD one of the most common presenile dementias. FTD affects the frontal and temporal lobes of the brain, which control emotions, judgment, personality, memory and language. The clinical diagnosis of FTD can be challenging, as some symptoms overlap with Alzheimer disease and other forms of dementia. FTD can be categorized based on its primary symptoms into three basic types: behavioral variant FTD, primary progressive aphasia, and progressive motor decline. Although most FTD does not appear to be inherited, genetics does play a role in a significant minority of cases. There is no effective treatment or cure for FTD, but there are strategies for management of symptoms. This course will discuss the possible causes and pathophysiology, diagnosis, and management strategies for FTD.

Audience

This course is designed for physicians, nurses, and allied health and mental health professionals who may intervene to support patients with frontotemporal degeneration and their families.

Course Objective

The purpose of this course is to provide healthcare professionals with current information on frontotemporal degeneration (FTD). Understanding the epidemiology, pathology, clinical features, diagnostic process, genetics, symptom treatment/management, role of brain autopsy, and current research provides a foundation for the care of patients with FTD and support for their families.

Learning Objectives

Upon completion of this course, you should be able to:

1. Describe the epidemiology of frontotemporal degeneration (FTD) in the United States.

2. Explain the brain changes of FTD and their general clinical manifestations.

3. Identify the three general presentations of FTD.

4. Review how a clinical diagnosis of FTD is made, including differentiation from Alzheimer disease.

5. Summarize the role of genetics in FTD.

6. Discuss strategies for managing symptoms of FTD and providing support to family caregivers.

7. Identify goals of current research on FTD.

Faculty

Ellen Steinbart, RN, MA, received a Bachelor of Arts from Macalester College in 1972, a Bachelor of Science in Nursing from Cornell University-New York Hospital School of Nursing in 1974, and a Master of Arts from the University of Washington School of Nursing in 1979. She worked as a hospital medical-surgical nurse and an intensive-care burn unit nurse, and she taught medical-surgical nursing at the University of Washington School of Nursing. For 25 years, she was a research nurse at the University of Washington, coordinating research projects on the role of genetics in dementia, including frontotemporal degeneration. She is now retired.

Faculty Disclosure

Contributing faculty, Ellen Steinbart, RN, MA, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planners

John M. Leonard, MD

Jane C. Norman, RN, MSN, CNE, PhD

Division Planners Disclosure

The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

1. INTRODUCTION

Frontotemporal degeneration (FTD) is a group of brain disorders characterized by behavior and language problems and also overlapping with some motor/movement diseases. FTD causes progressive deterioration in a person's ability to function as the result of damage to the frontal and temporal lobes of the brain. FTD is also referred to as frontotemporal dementia, frontotemporal lobar degeneration, and Pick disease.

Dr. Arnold Pick, a Czech neurologist, psychiatrist, and neuropathologist, first described frontal and temporal lobe atrophy causing dementia and progressive aphasia in 1892 [1]. The clinical syndrome subsequently became known as "Pick disease." FTD is the third leading cause of dementia across all age groups, after Alzheimer disease (AD) and Lewy body dementia [2]. It is one of the most common causes of early-onset dementia, with onset typically between 45 and 64 years of age [2,3].

The clinical presentation of FTD can be complex, and obtaining an accurate diagnosis can be challenging. The unique clinical symptoms of FTD, neuropsychologic assessment, and brain imaging can help distinguish it from AD and other dementias. There is presently no effective treatment for FTD, and symptom management can be challenging for healthcare providers and family caregivers. Research is in progress to better understand FTD, hopefully leading to effective treatment, cure, and prevention of this devastating disease.

2. EPIDEMIOLOGY OF FTD

It is estimated that FTD affects approximately 60,000 people in the United States [3]. As noted, the age of onset for FTD is typically 45 to 64 years, with a mean of 58.5 years and a reported range between 21 and 80 years of age [2,3,4,5]. In the United States, the prevalence in people 45 to 64 years of age is estimated at 15 to 22 per 100,000 population; the incidence in this group is 2.7 to 4.1 per 100,000 [5]. It is estimated that 60% of those with FTD have onset between 45 and 64 years of age; 10% have onset before 45 years of age, and 30% have onset after 64 years of age [5]. FTD is now considered by some to be the most common form of pre-senile dementia in patients younger than age 60, even more common than AD in this group [6,7,8].

FTD affects both men and women. However, it is unclear if men and women are affected equally, or if some subtypes of FTD may be more common in one gender or the other [9]. Significant time (average: 3.6 years) often passes between symptom onset and actual clinical diagnosis [5].

The disease duration for FTD can range from 2 to 20 years from symptom onset to death, with a mean duration of 6 to 13 years [3,5]. Pneumonia is the most common cause of death [3].

3. PATHOGENESIS AND PATHOPHYSIOLOGY OF FTD

Patients with FTD experience a progressive loss of neurons in the frontal and anterior temporal lobes, resulting in atrophy in these areas of the brain. They may also develop gliosis in the frontal and temporal lobes where neurons have been lost or damaged.

In FTD, affected neurons have an abnormal accumulation of protein within the cell, called inclusions. Three types of intra-neuronal inclusions have been identified, based on the protein involved. In some cases, the inclusions are composed of an abnormal form of the protein tau. In other patients, the inclusions are composed of the transactive response DNA-binding protein 43 (TDP-43). In a smaller number of FTD cases, the inclusions are composed of fused in sarcoma (FUS) protein [10].

The frontal and anterior temporal lobes of the brain control executive functions (e.g., planning, organizing, abstract thinking, judgment, decision making), personality, social behavior, and language. The changes associated with FTD causes impairments in executive function, personality, behavior, and/or language. The location of the neurodegeneration correlates fairly well with the clinical presentation [10]. Changes in other areas of the brain may cause overlapping movement problems. While the cause of most cases of FTD is not known, some cases are now known to be caused by genetic mutations.

4. CLINICAL PRESENTATION

FTD causes a gradual, progressive decline in behavior and/or language; movement disorders may also be involved. Behavior or language problems are typically the first and most prominent symptoms of FTD, whereas memory problems are the first symptoms of AD [5]. Subtypes of FTD have been identified based on clinical presentation (Table 1). Behavioral variant FTD (bvFTD) is the most common form and involves changes in behavior, personality, and emotions. Language presentations are referred to as primary progressive aphasia (PPA) and can take one of three forms: nonfluent/agrammatic variant PPA (nfvPPA), semantic variant PPA (svPPA), or logopenic variant PPA (lvPPA) [11]. Nonfluent/agrammatic PPA begins with problems in speech production, while svPPA involves impaired word comprehension and object recognition and lvPPA involves word-finding problems. A movement presentation may appear as progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), or motor neuron disease (MND). Some patients may present with symptoms that overlap the different subtypes of FTD or may develop symptoms of other subtypes of FTD as the disease evolves. As more is learned about FTD, the terminology and classification of the subtypes may be revised.

Table 1: FORMS OF FRONTOTEMPORAL DEGENERATION

Behavioral presentation

- Behavioral variant FTD (bvFTD)

Language presentation, variants of primary progressive aphasia (PPA)

- Nonfluent agrammatic PPA (nfvPPA), also called progressive non-fluent aphasia (PNFA)

- Semantic variant PPA (svPPA), also called semantic dementia (SD)

- Logopenic variant PPA (lvPPA) (often found to have Alzheimer disease pathology at autopsy)

Associated movement disorders (not classified as FTD, but have shared symptoms)

- Corticobasal syndrome (CBS)

- Progressive supranuclear palsy (PSP)

- Motor neuron disease, also called amyotrophic lateral sclerosis (FTD/MND or FTD/ALS)

Source: Complied by Author

BEHAVIORAL PRESENTATION

Behavioral Variant FTD

As noted, bvFTD is the most common type of FTD, estimated to account for more than half of all cases [12]. The prominent features include disinhibition, apathy/inertia, loss of empathy, compulsive behaviors, hyper-orality, and impaired executive function (Table 2) [13]. People with FTD may become socially withdrawn, inflexible, and impulsive. They may have a shortened attention span and a tendency to be easily distracted. Behavior may become socially inappropriate. People with bvFTD are usually unaware of the changes in their personality and behavior and the impact these changes have on others. Memory and visual-spatial functioning are initially relatively spared in bvFTD. Some individuals with bvFTD may develop symptoms similar to Parkinson disease, such as bradykinesia, rigidity, postural instability, and masked face.

Table 2: BEHAVIORAL VARIANT FTD

Major Clinical Features

Examples

Disinhibition

Making inappropriate comments, taking food off someone else's table at a restaurant, telling sexual jokes, shoplifting, hitting

Apathy

Less involved in old hobbies or activities, deterioration in personal hygiene

Loss of empathy

Indifferent when a family member is hurt

Compulsive behaviors

Repeating the same phrase, clapping hands in the same pattern repeatedly, checking the time repeatedly

Hyper-oral behaviors

Overeating, eating one certain type of food, eating excessive sweets

Impaired executive function

Poor performance at work, poor financial decisions, difficulty planning and preparing a meal

Source: Complied by Author

LANGUAGE PRESENTATION

Nonfluent/Agrammatic Variant PPA

Nonfluent/agrammatic variant PPA, also referred to as progressive non-fluent aphasia (PNFA), accounts for about 25% of all FTD cases and involves problems with language expression [12]. People with nfvPPA have difficulty producing speech but retain the meaning of words and know what they want to say. As a result, speech may become hesitant, slow, and labored. Speech patterns may be "agrammatic" or "telegraphic," meaning that only the most important content words are used, without connecting words. For example, a patient might say "Tuesday…hospital…sister." Patients with nfvPPA have difficulty talking on the telephone and tend to talk progressively less. Eventually, some may become mute. While in the early stages, these patients continue to understand the speech of others, but this comprehension is eventually lost also. Reading and writing skills are better preserved than speech, although these abilities are also eventually lost. As the disease progresses, patients may develop behavioral symptoms. Some individuals with nfvPPA may develop extrapyramidal symptoms of rigidity and tremors, as seen in corticobasal syndrome (CBS) and PSP.

Semantic Variant PPA

Semantic variant PPA, also referred to as semantic dementia, represents about 20% of FTD cases [12]. Semantic variant PPA involves the loss of understanding of the meaning of words and objects. Speech is still fluent and grammatically correct, but people with svPPA have a declining ability to comprehend the meaning of words (especially nouns) or to recognize familiar objects or faces. For example, a person with svPPA who is very familiar with vegetables might read a menu and ask: "What is broccoli?" If shown a picture of a carrot, the patient may not be able to name it and may not recognize the word when told. There are progressive word-finding problems, reading and spelling skills decline, and retrieving names becomes difficult. Later in the disease, people with svPPA may develop behavioral changes similar to those seen in patients with bvFTD.

Logopenic Variant PPA

Logopenic variant PPA is characterized by difficulty retrieving words, resulting in slow speech with frequent pauses. These patients may also have trouble repeating long phrases and understanding complex sentences. Eventually, people with lvPPA may become mute. Reading and writing skills are initially preserved, but these decline as the disease progresses. People with lvPPA have word-finding problems similar to people with AD and are often found to have AD pathology at autopsy [8].

For all patients with suspected language presentations of FTD, it is important to consider the role of culture and preferred language.

FTD OVERLAP WITH MOVEMENT DISORDERS

Progressive Supranuclear Palsy

PSP is a neurodegenerative condition characterized by problems with gait and balance, causing postural instability, falls, and difficulty with eye movement coordination. The pathophysiology of PSP shows a loss of cells in the basal ganglia, substantia nigra, subthalamus, and brainstem, and affected neurons have inclusions composed of abnormal tau protein. There are similarities between PSP and Parkinson disease, including bradykinesia, rigidity, masked face, dysarthria, dysphagia, apathy, and depression. Some people with PSP develop behavioral problems, but these are often milder than those seen in other types of FTD. Some people with PSP may develop progressive memory and language problems, and there may be a decline in executive function.

Corticobasal Syndrome

CBS is a neurodegenerative condition that may initially present with movement problems, dementia, or both. In CBS, there is atrophy in multiple areas of the brain, including the frontoparietal regions, basal ganglia, and cerebral peduncles. Neuronal inclusions are usually composed of abnormal tau protein. Signs of CBS typically begin with decreased movement on one side of the body, muscle rigidity, and tremor. A hand, arm, or leg on the affected side may demonstrate apraxia (i.e., inability to make the limb follow commands). Patients may describe the affected limb as not feeling like a part of their body, a sensation referred to as "alien limb syndrome." Symptoms may become bilateral as the disease progresses. People with CBS may also experience personality changes, executive dysfunction, and language problems as the disease progresses.

FTD with Motor Neuron Disease

Approximately 15% of people with FTD also develop problems with motor neurons that control voluntary movement [10]. This is referred to as FTD with motor neuron disease (FTD/MND) or FTD with amyotrophic lateral sclerosis (FTD/ALS). Pathologically, in addition to frontal and temporal lobe atrophy, there is also atrophy in the motor regions of the cortex and loss of motor neurons in the brain stem and spinal cord. In FTD/MND, damaged neurons usually have abnormal inclusions composed of the protein TDP-43. Patients may present with behavior or language problems, but then additionally develop muscle problems, including weakness, stiffness, twitches, cramps, and/or atrophy. Muscle problems can affect arms, legs, face, mouth, and tongue, causing patients to experience clumsiness, dysphagia, dysarthria, and hyper-reflexia. An estimated 15% of patients with MND or ALS go on to develop behavioral and executive dysfunction symptoms of FTD as their disease progresses [10].

5. CLINICAL DIAGNOSIS OF FTD

The diagnosis of FTD can be challenging because of the wide range of symptoms, the relatively early age of onset, and the slow progression. There is no single test to diagnose FTD, and it may be initially misdiagnosed as a psychiatric disorder (e.g., depression, schizophrenia), AD, Parkinson disease, or vascular dementia. Accurate diagnosis of FTD is important because some of the medications used to treat these other diseases may be detrimental to patients with FTD. Patients with suspected FTD are often referred to neurologists or neuropsychologists with special expertise in FTD and related neurodegenerative disorders for a comprehensive evaluation.

The clinical diagnosis of FTD is based on the clinical history, family history, neurologic examination, neuropsychologic evaluation, and neuroimaging. Other tests may also be performed for differential diagnosis. The diagnostic process may take time, and the diagnosis may change as more tests are done or as new symptoms appear.

The clinical history is obtained from the patient and his/her family or friends. It is important that family or friends provide information regarding symptoms, as patients are often unaware of their behavior changes.

The family history should focus on whether any other relatives have had a neurodegenerative disease. Any cases of dementia, language problems, or movement disorders should be noted, along with specific information about symptoms, diagnosis, age of onset, course of disease, age at death, and autopsy findings. Such background information may be valuable for both diagnosis and understanding genetic risk.

The neurologic examination typically includes assessment of the patient's general appearance and speech, mental status, cranial nerves, motor system, sensation, reflexes, and cerebellar function (coordination and balance). Consulting a neurologist who has knowledge and experience in FTD can be valuable when reaching a definitive diagnosis.

The neuropsychologic examination assesses brain function and may identify areas of the brain that have been damaged. It typically involves an interview and the administration of written tests. These tests may focus on attention and concentration, memory, orientation, language, visual-spatial abilities, and/or executive functions (e.g., reasoning, planning, organizing, problem solving). Patients with FTD may show deterioration in the areas of attention and concentration, language, and executive function, but may do relatively well on memory and visual-spatial tests.

The Neuropsychiatric Inventory (NPI) may be administered to caregivers of patients with suspected FTD. This survey helps assess behavior and psychopathology by inquiring about the patient's delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability, unusual motor activity, nighttime behavioral problems, and eating abnormalities.

Brain scans are important tools in the diagnosis of FTD. Computed tomography (CT) may be done to determine if there is a tumor, hemorrhage, or other brain injury that could account for the symptoms. Magnetic resonance imaging (MRI) provides better visualization of the brain than CT and is often done to evaluate brain atrophy when FTD is suspected. Patients with FTD have progressive frontal and anterior temporal atrophy apparent on MRI. Typically, in bvFTD, there is atrophy of the frontal lobe (involved in personality, judgment, and executive function) and the anterior temporal lobe. In nfvPPA, there is left frontal lobe atrophy (involved in speech production). In svPPA, the atrophy is focused in the anterior temporal lobe (involved in language and face recognition). In specialty or research centers, positron emission tomography (PET), single photon emission computed tomography (SPECT), or functional MRI (fMRI) brain scans may to done to further evaluate brain functioning.

While there is no laboratory test that can diagnose FTD, some tests may be ordered to rule out other diseases with symptoms similar to those of FTD. Blood work may be ordered to identify dehydration, thyroid disease, vitamin B12 deficiency, or infections affecting the brain. An electroencephalogram (EEG) may be done if there is concern that seizures might be causing the patient's symptoms. In the early stages of FTD, EEG findings are usually normal or have non-specific findings. Lumbar puncture may be done to evaluate cerebral spinal fluid and rule out rare brain infections or cancer. Electromyography may be used to identify muscle weakness or myoclonus if MND (or ALS) is being considered as a possible diagnosis. In addition, language evaluation by a speech pathologist can be an important tool in diagnosing patients with nonfluent/agrammatic, semantic, or logopenic variant PPA.

It may be challenging to clinically differentiate FTD from early AD (Table 3). The only way to establish an unquestionable diagnosis of FTD is through a brain autopsy after a patient has died. Examination of the brain tissue will show the precise location and severity of the brain atrophy, and microscopic studies can determine the protein composition of the inclusions in affected neurons.

Table 3: EARLY SIGNS AND SYMPTOMS OF FTD VERSUS ALZHEIMER DISEASE

Clinical Features

FTD

Alzheimer Disease

Hallmark

Decline in behavior, language, and/or movement; memory is retained initially

Decline in memory; socially appropriate behavior is retained initially

Initial language problems

May involve speech production, understanding words and recognizing familiar objects, or retrieving words

Word-finding or name recall

Age at onset

Usually 45 to 64 years of age

Usually 65 years of age or older

Movement problems

May have early movement disorder, with gait and balance problems, rigidity, apraxia, or muscle weakness

Usually no movement problems early in disease

Source: [3,8,14]

For families, brain autopsy can confirm the diagnosis (or identify a different cause of the dementia) and bring a measure of closure. Accurate diagnosis may be especially important if there is concern about genetic risk to other family members.

Discussion about brain autopsy should be handled delicately and with compassion at a time that is appropriate for the family; the subject may be emotionally difficult for some families. Introducing the topic ahead of time allows families to consider their feelings about brain autopsy aside from the emotional crisis of the death of a loved one and the immediate time pressure of funeral arrangements. Families may then discuss the topic among themselves and come to consensus.

Should a family wish to have a brain autopsy done when the patient dies, the physician can help identify a pathology service experienced in neurologic disorders and preliminary logistical planning can be done ahead of time. Arrangements may be coordinated with a research center that specializes in brain autopsy for FDT. The autopsy is done as soon as possible after death, often within 6 to 24 hours. The procedure is not disfiguring, so open-casket funerals may be planned if the family so chooses.

In addition to answering families' questions regarding diagnosis, brain autopsy can also aid researchers in better understanding the correlation between the clinical signs of FTD and the pathologic changes in the brain. This may benefit future generations by improving diagnosis and advancing research on therapies for FTD.

6. GENETICS AND FTD

Understanding of the role of genetics in FTD is still evolving. Presently, it appears that most cases of FTD (approximately 60%) are sporadic, meaning one person in a family has the disease, there is no family history of any relative with the disease, and the disease does not appear to be inherited.

However, approximately 40% of those with FTD report a family history of one or more relatives with a neurodegenerative disease [6,9,10]. This is referred to as familial FTD. In some cases of familial FTD, no specific genetic mutation can be identified as the cause. The risk to family members of a person with familial FTD without an identified genetic mutation is increased over the general population, but the specific increased risk is unclear.

An estimated 10% to 20% of all FTD cases are caused by an inherited genetic mutation [6,8]. Patients with a strong family history of multiple relatives with FTD and/or MND are more likely to have an inherited form of FTD caused by a genetic mutation. Genetic mutations causing FTD are inherited in an autosomal dominant inheritance pattern, meaning each child of an affected parent is born with a 50% chance of inheriting the genetic mutation.

Several specific genetic mutations have been identified as being implicated in inherited FTD. In 1998, the first gene associated with hereditary FTD—the microtubule-associated protein tau (MAPT) gene on chromosome 17—was discovered [15,16]. Mutations in this gene cause an abnormal accumulation of tau protein in affected neurons. MAPT mutations are thought to account for 2% to 11% of familial FTD cases [17]. These mutations most commonly cause bvFTD but may also cause svPPA, PSP, and/or CBS. FTD symptoms may vary widely, even within families.

In 2006, mutations in the progranulin (GRN) gene on chromosome 17 were discovered to cause FTD [18,19]. Mutations in the GRN gene cause abnormal accumulations of TDP-43 protein in affected neurons. GRN mutations are thought to represent about 5% to 10% of all inherited FTD cases [17]. They most commonly cause bvFTD, but are also associated with nfvPPA and CBS. GRN mutations appear to have decreased penetrance, meaning that, for unknown reasons, some people with the mutation may not develop symptoms of the disease.

In 2011, the genetic mutation C9orf72 was discovered on chromosome 9 [20,21]. Mutations in C9orf72 cause an abnormal accumulation of TDP-43 in affected neurons. To date, C9orf72 mutations are the most common genetic cause of FTD, found in about 25% of familial FTD and 6% of sporadic cases [22]. C9orf72 mutations appear to cause FTD (usually bvFTD or language presentation), MND, and a combination of FTD and MND.

Evidence Based Practice Recommendation

According to the European Federation of Neurological Societies, genetic testing for mutations in PGRN and MAPT is clearly indicated and useful for genetic counseling in patients with autosomal dominant frontotemporal degeneration, regardless of the presence or severity of extrapyramidal features.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1468-1331.2010.02985.x

Last Accessed: October 25, 2018

Strength of Recommendation/Level of Evidence: B (Established as probably useful based on at least one convincing prospective study or overwhelming retrospective study evidence)

Other very rare genetic mutations have also been associated with FTD. Mutations in the gene valosin-containing protein (VCP) on chromosome 9, charged multivesicular body protein 2B (CHMP2B) on chromosome 3, TAR DNA-binding protein (TARDBP), FUS, TBK1, EXT2, and SQSTM1 have been associated with FTD [29].

Clinical genetic testing is available for the MAPT, GRN, and C9orf72 genetic mutations causing hereditary FTD, as well as some of the other very rare genetic mutations. Genetic testing may be ordered after informed consent and clear discussion of the implications with the patient and his/her family. For patients with FTD, identification of a genetic mutation confirms the diagnosis of FTD and provides information about risk to other family members. Each of the patient's siblings and each of the patient's children would be at 50/50 risk for having inherited the genetic mutation causing FTD. If a genetic mutation causing FTD is identified, other at-risk family members may be tested.

If a genetic mutation causing FTD is identified in a patient with FTD, unaffected at-risk family members could choose to have pre-symptomatic (predictive) genetic testing done to determine if they have inherited the genetic mutation that would someday cause FTD. Individuals considering pre-symptomatic genetic testing are referred for formal professional genetic counseling to help them make the best decision regarding whether or not to learn their FTD genetic status.

7. MANAGEMENT OF FTD

There is presently no treatment to slow the progression of or cure FTD. No medication has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of FTD; however, medications used to treat other disorders may be prescribed off-label for the management of FTD symptoms. Their use may be limited by the potential adverse effects. Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), may be prescribed for behavioral symptoms of FTD, and low-dose trazodone has been used for agitation and aggression [9]. While the anticholinesterase inhibitors donepezil, galantamine, and rivastigmine are beneficial for some patients with AD, they generally have not been helpful for patients with FTD [9]. The glutamate NMDA receptor antagonist memantine, used for moderate-to-severe AD, has been used for patients with FTD as well, but a 2013 study showed that it provided no benefit to patients with FTD and that it may be harmful to cognition [23]. Antipsychotics are occasionally used to treat significant agitation and behavioral symptoms, but only with caution, as antipsychotics can have serious adverse effects such as extrapyramidal adverse effects (parkinsonism), depression, sedation, falls, incontinence, and disinhibition, and patients with FTD may have an increased susceptibility to the these effects [9]. Elderly patients with dementia who take antipsychotics have a 1.6- to 1.7-fold increase in mortality secondary to cardiac problems or infection, prompting the FDA to issue a warning about their use in older patients with behavioral disturbances [9]. L-DOPA has shown a minimal response for parkinsonism in patients with PSP and CBD [28]. Research is being done to further evaluate the use of available medications for the management of FTD and to find new, more effective treatments.

Management of FTD includes providing care to patients with FTD and support to their families. Caring for a person with FTD involves managing the symptoms, keeping the patient safe, and providing help in activities of daily living.

Apathy is a common symptom in patients with bvFTD, often resulting in neglect of their personal hygiene and grooming. Supervision, encouragement, and help with bathing, dressing, and grooming may be needed. For behavioral problems, simple interventions like distraction (e.g., introducing a new activity) may help interrupt the troublesome behavior. For some patients, modification of the environment or behavior may help minimize the potential for harm. For example, if the patient is pacing, creating a safe route for him or her to walk can be helpful. Physical therapists may be able to help develop an exercise program to maintain mobility. Exercise has also been shown to improve mood and cognition and may improve behavior management in patients with dementia [24]. If behaviors such as agitation or aggression become severe, a medication may be prescribed off-label to control difficult or dangerous behaviors. Supervision may be necessary to ensure patients take medications as prescribed.

Some individuals with FTD have eating problems, such as overeating, eating just one type of food, or craving sweets. For these patients, it may be necessary to monitor weight and provide help with meal preparation to provide a balanced, nutritious diet. Access to additional foods, drinks, or sweets should be limited.

Speech pathologists or therapists may be helpful in diagnosing the specific language problems exhibited by patients with FTD, including nonfluent/agrammatic, semantic, or logopenic variant PPA. Speech therapy may also help patients to find new communication strategies, such as sign language, carrying cards with specific messages, or using a computer with pre-programmed words or phrases [25]. Such techniques may help those with language problems communicate with family and friends. Speech therapists may also be able to evaluate and address swallowing problems, if these arise.

Caring for a patient with FTD includes maintaining a safe environment for the patient and for those around him/her. A structured environment and keeping the daily routine the same is often helpful. In addition, persons with FTD should no longer drive, and safety measures should be taken at home, especially in the kitchen and bathroom. If a patient with FTD shows aggression, disinhibition, or poor judgment, close supervision is necessary when he/she is around others, especially children or the frail elderly, to prevent them from being inadvertently harmed.

It also may be necessary to monitor the patient's behavior in public places. If an individual displays inappropriate behavior, tense situations may be diffused by explaining that he or she has FTD and cannot control his/her behavior. Simple cards with this brief explanation can be made, carried, and shared with people who might be disturbed by a patient's inappropriate behavior.

If a patient with FTD has gait and balance problems, measures should be taken to prevent falls. This may include keeping the home environment free of obstacles and loose rugs and installing shower bars and a raised toilet seat. Mobility aids may be helpful. Occupational therapists should provide intervention to help patients with FTD complete activities of daily living as the disease progresses.

CAREGIVER SUPPORT

FTD places enormous burdens on the family. Most dementia care is provided at home by family caregivers, often spouses. Caregivers for those with FTD face physical, emotional, and financial challenges. FTD caregiver burden, stress, and depression are greater even than that seen with AD [26,27].

The first challenge that families of those with FTD may face is obtaining an accurate diagnosis. The process can involve years of uncertainty and stress before the correct clinical diagnosis of FTD is made. Even during the diagnosis process, support for families begins with information and education about FTD. Accurate information can lead to understanding and a greater sense of control over the stressful situation. It is important for families and caregivers to understand that the behavior changes they observe are the result of the disease. Their loved one may display behaviors that are embarrassing, offensive, self-centered, uncaring, and aggressive, with complete lack of insight about how the behavior affects others. The caregiver may feel like he/she is suddenly living with a stranger.

The aggression, disinhibition, and poor judgment associated with FTD can put family members at risk of harm. Because FTD affects people at a relatively young age, there may still be children in the home. Families should recognize the risk to others in the home and seek help creating strategies to keep themselves and other family members safe.

Language may be impaired in people with FTD, making communication difficult. This can interfere not only with communication between the patient and the caregiver, but it can also limit participation in larger social activities. Speech therapy can provide new approaches to communication, helping not only the patient but also the caregiver.

Because FTD usually begins at a relatively young age, it can cause a significant financial burden for families. There may be loss of income, and retirement benefits may be affected because the patient is unable to continue working. Financial and legal issues that should be addressed include insurance, social security disability, financial planning for the future (when additional care will be needed), power-of-attorney arrangements, and a living will. Social workers, financial advisors, and attorneys are resources available to families to help address these issues.

The demands on caregivers increase as FTD progresses. Caregivers will be required to provide more supervision and increasing assistance for activities of daily living. While providing care for an individual with FTD, the caregiver may also be grieving the loss of his or her previously healthy loved one. Family caregivers can become physically and emotionally exhausted, and they may feel isolated in their role as caregiver. Interventions to help reduce caregiver stress include an individualized patient management plan, environmental changes to promote safety and facilitate care, and strengthening caregiver coping strategies and skills. Family caregivers should be encouraged to ask for and accept help in caring for their loved one with FTD, allowing them to take time for themselves and address their own health needs. Connection with community resources may also be helpful. Community resources for FTD caregivers include national organizations such as the Association for Frontotemporal Degeneration, attorneys and financial planners, social service programs, adult day care programs, respite care, support groups, and individual or family counseling.

Family caregivers should look ahead and consider how they wish care to be provided to their loved one as FTD progresses. Patients with FTD will become more dependent and more difficult to safely manage at home by a family caregiver as the disease progresses. Social workers can be a good resource to caregivers as they consider options such as extra in-home nursing care, care communities, and long-term care facilities. Locating an appropriate care facility that accepts patients with FTD can be challenging. These patients are often younger, stronger, and more active than the typical residents of care facilities. Facility staff may need education and support to understand the unique features of FTD and to learn how to provide care to these patients while maintaining a safe environment for all residents in the facility.

Nurses play an important role in caring for those with FTD and providing support to their families. Nurses interact with patients with FTD and their families in the outpatient clinic setting, in-home care setting, and long-term care facility and may be involved in monitoring symptoms, developing and implementing individualized patient care plans, and providing direct patient care. It is important for all healthcare providers to coordinate care for the patient with FTD. All members of the interdisciplinary healthcare team can support families by listening to them, providing ongoing information and education about FTD, offering guidance to improve caregiving skills, and helping families connect to appropriate resources.

8. PROGRESSION OF FTD

The prognosis for people with FTD is poor. FTD worsens progressively, usually over several years, and patients require increasing behavioral supervision and personal care. Eventually, people with advanced FTD become mute and bedbound and require full care at home or in a care facility. As patients with FTD become more debilitated, they are vulnerable to complications such as infections and falls. The most common cause of death in people with FTD is infection (e.g., pneumonia) [3,8]. The average duration of the disease is 6 to 13 years, but it can range from 2 to 20 years [3,5].

9. RESEARCH RELATED TO FTD

The goals for research on FTD include gaining a better understanding of the pathology; identifying causes and risk factors (genetic and environmental); improving the diagnosis of FTD through enhanced neuroimaging, biomarkers, and characterization of clinical features; developing therapies to treat, cure, or prevent FTD; and exploring new ways to support family caregivers. However, research on FTD is challenging. It is an uncommon disease, so awareness is low, there are fewer potential subjects available for research studies, and there is a relatively small market for medications. FTD is a complicated disease with a wide variety of presentations (behavior, language, and movement problems) and underlying causes (sporadic and genetic). Pathologically, microscopic brain inclusions may consist of different abnormal proteins (e.g., tau, TDP-43, FUS), but there are no good biomarkers to diagnose FTD or to monitor the progression of the disease. Drug development faces the challenge of creating a medication to treat FTD that can cross the blood/brain barrier.

Despite these challenges, the pace of research on FTD has accelerated rapidly. There are an increasing number of studies and a better awareness of the varied symptoms of FTD. In the past few decades, there have been discoveries of the genetic mutations underlying some causes of FTD and a growing understanding of the changes that occur in the brain of those with FTD. Presently, there are clinical trials underway for potential medications to treat FTD. Information on clinical research studies, including participation in studies, can be found at the National Institutes of Health website https://clinicaltrials.gov.

10. CASE STUDY

Patient A was a high school homecoming queen who completed two years of college, worked in an office, then married and had three children. She was an energetic homemaker and an active community volunteer, serving as school parent-teacher association president for several years, and was fastidious about her appearance.

Patient A's mother, three maternal uncles, a maternal grandfather, and great-grandmother died with dementia; her brother and maternal aunt are living with the disease. The mean age of onset of dementia in the family is 51 years, and the mean age at death is 67 years.

When Patient A is 52 years of age, her husband notices changes in her behavior. She often appears distracted, and her impeccable grooming declines. She is less affectionate toward him and she stops participating in community activities. She has difficulty making arrangements for a planned vacation. Her previously gourmet meals become simple, functional meals. She becomes obsessed with repeatedly raking the lawn, eventually killing all the grass in the yard. When her grandchildren visit, Patient A alternates between ignoring them and playing too rough. Patient A begins to impulsively leave the house for fast-paced walks, but she always returns home and never gets lost. She frequently visits a local shopping mall, getting down on her hands and knees looking for dropped change near the cash registers. She is once stopped by mall security for shoplifting. When shopping with her husband, she approaches strangers, stands inappropriately close to them, and announces "We don't know you."

Patient A's husband brings her to a dementia clinic for evaluation. A neurologic examination and neuropsychologic testing are completed. Memory and visual-spatial performance are in the normal range, but personality, judgment, and executive function show significant decline. A brain MRI shows frontal and anterior temporal lobe atrophy, and the diagnosis of familial bvFTD is made. Clinical genetic testing identifies a mutation in the MAPT gene on chromosome 17, the believed cause of the dementia.

Patient A's husband stops working in order to care for her at home. As her disease progresses, Patient A requires increasing care and supervision. She spends much of her day watching television, writing numbers in a notebook, and pacing. She develops a craving for sweets and often rummages through kitchen cabinets looking for candy. At mealtime, Patient A stuffs her mouth with food before chewing and swallowing properly, precipitating episodes of choking. She also develops a pattern of hand-clapping that she repeats every few minutes, along with the phrase "We haven't had any phone calls lately."

Patient A's husband is encouraged to accept help from others (such as their adult children), consider local adult day care programs, and utilize respite care at a nearby nursing home. He is in monthly phone contact with nursing staff to review symptoms and develop strategies for managing symptoms. At different times during her illness, Patient A is prescribed an antidepressant and an antipsychotic medication (off label) to treat difficult behavioral symptoms, but both were eventually discontinued. The family faces financial difficulties as a result of the husband's loss of income, diminished retirement benefits, and the later cost of nursing home care. Social work support helps the family address issues such as insurance, social security benefits, adult day care programs, and selecting a nursing facility for eventual long-term care.

When Patient A is 60 years of age, her husband is no longer able to care for her at home and she is admitted to a skilled nursing facility. She is incontinent and requires full care for all activities of daily living. Her husband visits twice daily, and she always appears to recognize him. That same year, Patient A dies unexpectedly of a myocardial infarction. A brain autopsy is done and confirms the diagnosis of FTD.

Patient A's husband shares the results of her genetic testing and autopsy with their three adult children. Each of Patient A's three children is at a 50% risk for having inherited the MAPT genetic mutation. Two of the children request pre-symptomatic genetic testing. The two children who request pre-symptomatic genetic testing are referred to professional genetic counselors. After genetic counseling, they both choose to have pre-symptomatic genetic testing done. One defers getting the results for two years, underscoring the very difficult personal decision it can be to choose pre-symptomatic genetic testing.

Patient A demonstrated the typical symptoms of bvFTD and her evaluation was done at a dementia center by specialists with expertise in FTD, so her initial diagnosis was strong. The neurologic evaluation, blood tests, neuropsychologic testing, and neuroimaging together led to the clinical diagnosis of bvFTD. Patient A's family history showed a pattern of autosomal dominant inheritance. The genetic cause of her FTD was confirmed by clinical genetic testing, which documented a mutation in the MAPT gene.

11. CONCLUSION

FTD is now recognized as one of the most common causes of dementia in persons younger than 65 years of age. This course has provided an overview of FTD epidemiology, pathophysiology, clinical presentation, diagnosis, management, prognosis, and current research. Understanding FTD can help healthcare professionals provide better care to patients with FTD and support to their families.

12. RESOURCES

Association for Frontotemporal Degeneration

Radnor Station Building 2, Suite 320

290 King of Prussia Road

Radnor, PA 19087

(866) 507-7222

https://www.theaftd.org

National Institute on Aging

Building 31, Room 5C27

31 Center Drive, MSC 2292

Bethesda, MD 20892-2292

(800) 222-2225

https://www.nia.nih.gov

National Institute of Neurological Disorders and Stroke

P.O. Box 5801

Bethesda, MD 20824

(800) 352-9424

https://www.ninds.nih.gov

Works Cited

1. Pick A. Ueber die Beziehungen der senile Hirnatrophie zur Aphasie. Prager Medicinische Wochenschrift. 1892;17(16):165-167.

2. Arvanitakis Z. Update on frontotemporal dementia. Neurologist. 2010;16(1):16-22.

3. Association for Frontotemporal Degeneration. Disease Overview. Available at https://www.theaftd.org/what-is-ftd/disease-overview. Last accessed September 30, 2018.

4. Hodges JR, Davies R, Xuereb J, Kril J, Halliday G. Survival in frontotemporal dementia. Neurology. 2003;61(3): 349-354.

5. Knopman DS, Roberts RO. Estimating the number of persons with frontotemporal lobar degeneration in the U.S. populationJ Mol Neurosci. 2011;45(3):330-335.

6. Ghosh S, Lippa CF. Clinical subtypes of frontotemporal dementia. Am J Alzhiemers Dis Other Demen. 2015;30(7):653-661.

7. Wang X, Shen Y, Chen W. Progress in frontotemporal dementia research. Am J Alzheimers Dis Other Demen. 2013;28(1):15-23.

8. UCSF Memory and Aging Center. Frontotemporal Dementia. Available at https://memory.ucsf.edu/frontotemporal-dementia. Last accessed September 30, 2018.

9. Seltman RE, Matthews BR. Frontotemporal lobar degeneration. CNS Drugs. 2012;26(10):841-870.

10. Sieben A, VanLangenhove T, Engelborghs S, et al. The genetics and neuropathology of frontotemporal lobar degeneration.Acta Neuropathol. 2012;124:353-372.

11. Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76:1006-1014.

12. Johnson JK, Diehl J, Mendez MF, et al. Frontotemporal lobar degeneration: demographic characteristics of 353 patients.Arch Neurol. 2005;62(6):925-930.

13. Rascovsky k, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioral variant of frontotemporal dementia. Brain. 2011;134(Pt 9):2456-2477.

14. Alzheimer's Association. Frontotemporal Dementia (FTD). Available at https://www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/frontotemporal-dementia. Last accessed September 30, 2018.

15. Hutton M, Lendon CL, Rizzu P, et al. Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17. Nature. 1998;393(6686):702-705.

16. Poorkaj P, Bird TD, Wijsman E, et al. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol. 1998;43(6):815-825.

17. Rohrer JD, Warren JD. Phenotypic signatures of genetic frontotemporal dementia. Curr Opin Neurol. 2011;24:542-549.

18. Baker M, Mackenzie IR, Pickering-Brown SM, et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006;442(7105):916-919.

19. Cruts M, Gijselinck I, van der Zee J, et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature. 2006;442(7105):920-924.

20. DeJesus-Hernandez M, Mackinzie IR, Boeve BF, et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron. 2011;72:245-256.

21. Renton AE, Majounie E, Waite A, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. 2011;72:257-268.

22. Majounie E, Renton AE, Mok K, et al. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol. 2012;11:323-330.

23. Boxer AL, Knopman DS, Kaufer DI, et al. Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomized, double-blind, placebo-controlled trial. Lancet Neurol. 2013;12(2):149-156.

24. Ahlskog JE, Geda YE, Graff-Radford NR, et al. Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clin Proc. 2011;86(9):876-884.

25. Mesulam M. Primary progressive aphasia: a dementia of the language network. Dement Neuropsychol. 2013;7(1):2-9.

26. Wong C, Merrilees J, Ketelle R. The experience of caregiving: differences between behavioral variant of frontotemporal dementia and Alzheimer disease. Am J Geriatr Psychiatry. 2012;20(8):724-728.

27. Mioshi E, Bristow M, Cook R, Hodges JR. Factors underlying caregiver stress in frontotemporal dementia and Alzheimer's disease. Dement Geriatr Cogn Disord. 2009;27(1):76-81.

28. Association for Frontotemporal Degeneration. Treating FTD. Available at https://www.theaftd.org/for-health-professionals/treating-ftd. Last accessed September 30, 2018.

29. Olney NT, Spina S, Miller BL. Frontotemporal dementia. Neuro Clin. 2017;35(2):339-374.

Evidence-Based Practice Recommendations Citations

1. Burgunder JM, Finsterer J, Szolnoki Z, et al. EFNS guidelines on the molecular diagnosis of channelopathies, epilepsies, migraine, stroke, and dementias. Eur J Neurol. 2010;17(5):641-648. Available at https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1468-1331.2010.02985.x. Last accessed October 25, 2018.