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.
This course is designed for all physicians, osteopaths, and physician assistants, especially those working in the emergency department, outpatient settings, pediatrics, nursing homes, and intensive care units.
NetCE is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. NetCE is accredited by the International Association for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.
NetCE designates this enduring material for a maximum of 10 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 10 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. NetCE is authorized by IACET to offer 1 CEU(s) for this program.
This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency.
The purpose of this course is to provide physicians with the information necessary to recognize, appropriately treat, and prevent pneumonia and its complications, thereby helping to alleviate a major clinical illness and important public health burden.
Upon completion of this course, you should be able to:
- Analyze the development and classification of pneumonia infection.
- Evaluate the epidemiology and risk factors of community-acquired pneumonia.
- Identify etiological factors of community-acquired pneumonia, including pathogens most commonly associated with infection in adults and children.
- Use established diagnostic criteria to appropriately identify and categorize community-acquired pneumonia.
- Develop a management plan for a given case of community-acquired pneumonia in an adult or child, including the selection of empiric antibiotic therapy appropriate to clinical context and site of care.
- Devise prevention strategies, including vaccination, for community-acquired pneumonia.
- Identify the epidemiology and risk factors of hospital-acquired, ventilator-associated, and nursing home-acquired pneumonia.
- Describe etiological factors of healthcare-associated pneumonia.
- Analyze and select treatment options for the various types of healthcare-associated pneumonia.
- Identify and implement measures to reduce the risk for pneumonia associated with healthcare facilities.
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.
Contributing faculty, Lori L. Alexander, MTPW, ELS, MWC, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.
John M. Leonard, MD
Ronald Runciman, MD
The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.
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.
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.
Supported browsers for Windows include Microsoft Internet Explorer 9.0 and up, Mozilla Firefox 3.0 and up, Opera 9.0 and up, and Google Chrome. Supported browsers for Macintosh include Safari, Mozilla Firefox 3.0 and up, Opera 9.0 and up, and Google Chrome. Other operating systems and browsers that include complete implementations of ECMAScript edition 3 and CSS 2.0 may work, but are not supported.
Pneumonia is a lower respiratory tract, parenchymal infection of the lung usually marked by fever, productive cough, pleuritic chest pain, 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. This is an important distinction as HCAP carries a greater risk for less common, multidrug-resistant bacterial pathogens.
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 [1,2,3,4,5]. 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. Following a modest increase among adults older than 45 years of age during the decade of the 1990s, the rate of hospitalization for pneumonia has been relatively stable since 2000 (Table 1) . 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 .
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 15.9 per 100,000 in 2013 (Table 2) . 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].
Adherence to guideline-directed treatment of pneumonia has been low, despite studies demonstrating higher rates of adverse outcomes and inappropriate use of antimicrobials in association with lack of adherence [14,15,16,17,18,19,20,21]. Adherence has been shown to vary across hospitals and settings; among specialties, with lower rates associated with non-pulmonologists; and according to patient variables (e.g., presence or absence of comorbidities or recent use of antibiotics) [19,20,22,23]. Several barriers to guideline adherence have been reported, including lack of familiarity, concerns about the practicality of recommended antibiotics, increased cost, lack of documented improved outcomes, and potential conflict with other guidelines . Time spent on educational activities has been found to be a significant factor associated with positive attitudes toward 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 HCAP 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 and treatment of CAP and HCAP.
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 . 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, chronic disease, or old age, are more susceptible to infection .
Pneumonia is often classified according to its causative pathogens (i.e., viral, bacterial, fungal, or parasitic), but specific causative pathogens 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 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: hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and HCAP (Table 3) [2,28]. 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 .
TYPES OF PNEUMONIA
|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|
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 . Bacteria isolated from cases of early-onset HAP (within 4 days after admission) are usually sensitive to available drugs . In contrast, late-onset HAP (i.e., more than 5 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 .
Determining accurate incidence rates for CAP is challenging because case definition varies across studies and case reporting often links pneumonia with influenza. Approximately 5 to 6 million cases are diagnosed annually, with about 1 million occurring in older adults . 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 . The average overall mortality rate for hospitalized adults is 12%, but the rate is higher—about 30% to 40%—for adults who require admission to an intensive care unit (ICU) . The estimated direct and indirect financial costs are $3.7 billion and $1.8 billion, respectively .
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 .
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% .
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 . 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) . 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 .
The primary risk factors for CAP are age, comorbidities, and smoking history. 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 . 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. Diseases or medications that suppress the immune system increase the risk among all ages [39,42].
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 .
Overall, the most common cause of CAP among adults and children is Streptococcus 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 likely causative pathogens—bacterial and viral—vary in relation to the patient's age, illness severity, and clinical context (Table 4) [29,30,47].
MOST LIKELY ETIOLOGIES OF COMMUNITY-ACQUIRED PNEUMONIA ACCORDING TO PATIENT AGE AND SETTING
|Age and/or Setting||Most Likely Pathogens|
|Inpatient, not intensive care unit||
|Intensive care unit||
|Birth to 3 weeks||
|3 weeks to 3 months||
|4 months to 4 years||
|5 to 15 years||
Bacterial causes of CAP predominate, accounting for at least half of all adult cases, including older individuals [9,42]. Common bacterial pathogens other than S. pneumoniae include Haemophilus spp., S. aureus, and gram-negative bacilli [25,26,29,48]. Atypical bacterial pathogens account for nearly one-quarter of bacterial pneumonia cases; the most common atypical pathogens are Mycoplasma pneumoniae and Chlamydophila pneumoniae, followed by Legionella spp. .
The distribution of pneumonia microbial etiology 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 . Of the 419 patients who had blood cultures, 7 (1.4%) were positive, all for S. pneumonia. 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 .
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 . 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 . 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 .
Studies have indicated that 5% to 20% of adult CAP may be caused by a viral pathogen . 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 .
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 . On rare occasions fungal and parasitic pathogens are isolated in association with CAP syndrome.
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 . 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]. 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. Two or more viral pathogens are common .
Bacteria are the cause of CAP in seriously ill, hospitalized children more often than in children treated on an outpatient basis . 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 M. pneumoniae in older children and C. pneumoniae in infants . As with adults, severe CAP caused by S. aureus is encountered during outbreaks of influenza . 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].
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)
Pleuritic chest pain
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 . Pulse oximetry should also be done. The most clinically significant individual findings are (in descending order) egophony, bronchial breath sounds, and dullness on percussion .
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 . 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 :
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 . 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 . Radiographic findings are generally not useful in identifying a specific pathogen, although multilobar infiltrates suggest infection with S. pneumoniae, S. aureus, or Legionella pneumophila, and patchy, interstitial infiltrates suggest a viral or mycoplasmal etiology (47, 49].
The challenge of diagnosis is complicated by the lack of cost-effective, reliable, and rapidly available tests to discriminate between viral and bacterial pneumonia . 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 . 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 . 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 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 :
Active alcohol abuse
Chronic severe liver disease
Positive test result for pneumococcal urinary antigen
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 .
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 . 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 .
Sputum stain and culture are also considered optional, but are recommended when specific conditions are present :
Active alcohol abuse
Severe obstructive/structural lung disease
Positive result for urinary Legionella antigen test
Positive result for urinary pneumococcal antigen test
Sputum culture and Gram stain should also be submitted from all hospitalized patients who are moderately ill or who warrant admission to an ICU . 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 6 hours after initiation of antibiotic therapy, pneumococci were identified by Gram stain in 63% and by culture in 89% of cases .
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 .
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%) . 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 chronic obstructive pulmonary disease (COPD), human immunodeficiency virus (HIV), immunosuppressive therapy, or organ transplantation.
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% . 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 .
Molecular diagnostic testing holds promise for providing more accurate and complete information on pathogens than conventional techniques have provided. Studies show that real-time PCR is significantly more sensitive and specific for the detection of the main respiratory viruses that cause CAP, in addition to M. pneumoniae and C. pneumoniae [24,33]. However, molecular assays are expensive and not currently widely available .
Over the past several years, researchers have been evaluating biomarkers for their usefulness in diagnosis. 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 .
The clinical presentation of CAP in children is somewhat similar to that in adults, but specific signs and symptoms can differ in their presentation according to age and offer varying value as predictive factors. For example, a cough is usually productive in older children but dry in infants and young children [30,60]. Nonspecific irritability and restlessness may be the primary symptoms in infants.
During the physical examination, the clinician should look for signs of hypoxia and dehydration, as well as retractions, tachypnea, and use of accessory muscles . The clinician should also evaluate the upper respiratory tract for evidence of rhinorrhea, otitis media, and pharyngitis . 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 .
As with pneumonia in adults, the accuracy of any one sign or symptom in predicting the likelihood of pneumonia is limited . Several clinical rules have been developed for predicting the likelihood of pneumonia in children on the basis of signs and symptoms. These rules have shown that the presence of at least two of the following signs—fever, tachypnea, and reduced oxygen saturation—is associated with a high likelihood of the disease; the absence of all three indicates a low likelihood . 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 .
Unlike diagnosis in adults, a chest radiograph is not the diagnostic standard for community-acquired pneumonia in children. The PIDS/IDSA guideline notes that routine chest radiographs are not necessary for children who can be treated as outpatients . Posteroanterior and lateral chest radiographs should be made for children with suspected or documented hypoxemia or significant respiratory distress . Radiographs should also be made for children who are hospitalized for management of the disease .
Unlike the situation in adults, titers of shed virus in children are high . Thus, rapid antigen testing of nasal or throat swabs for influenza and other respiratory viruses should be done for infants and young children . 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 . Urinary antigen detection tests often have false-positive results in children and are therefore not recommended for the diagnosis of pneumococcal pneumonia.
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 [36,63,64,65,66]. The recommendations in each guideline differed somewhat, but the principles were the same . To eliminate the confusion associated with separate guidelines, the IDSA and ATS jointly developed a guideline for CAP that was published in 2007 . 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 . 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 .
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 . Many physicians admit patients to the hospital when they could be managed effectively on an outpatient basis . This decision requires a careful evaluation of the severity of illness. 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 . However, each scale has advantages and disadvantages, and none factor in all clinical considerations (such as comorbidities or social factors) . 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) . 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 .
PNEUMONIA SEVERITY INDEX: POINT SCORING SYSTEM FOR STEP 2 OF THE PREDICTION RULE FOR ASSIGNMENT TO RISK CLASSES II, III, IV, AND V
|Nursing home resident||+10|
|Demographic factor (age)|
|Congestive heart failure||+10|
|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|
|Partial pressure of arterial oxygen <60 mm Hgd||+10|
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 . 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 (PaO2), and age (older than 80 years) . 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 .
It is estimated that admission to an ICU is needed for 10% to 20% of patients hospitalized with CAP . The IDSA/ATS guideline establishes major and minor criteria for direct admission to an ICU . 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 :
Increased respiratory rate (≥30 breaths per minute)
Low PaO2/fraction of inspired oxygen ratio (≤250)
Uremia (blood urea nitrogen level ≥20 mg/dL)
Leukopenia (white blood cell [WBC] count <4,000 cells/mm3)
Thrombocytopenia (platelet count <100,000 cells/mm3)
Hypothermia (core temperature <36°C [96.8°F])
Hypotension requiring aggressive fluid resuscitation
The goal of antibiotic treatment of pneumonia is to eradicate the bacterial load (or maximally reduce it) while minimizing the potential for the development of resistance . The initial treatment is empirical and is selected according to patient variables and setting (Table 6) . Macrolides have frequently been used to treat pneumonia because of their effectiveness against S. pneumoniae and atypical pathogens, and these drugs are recommended for the outpatient treatment of mild pneumonia in previously healthy adults who have not been exposed to antimicrobials within the past 3 months . Macrolide resistance is four times more likely in adult patients who have received this class of drug within the past 3 months, in which case a fluoroquinolone is recommended for treatment of CAP . Also, selection of a fluoroquinolone is recommended for adults who have comorbidities or a compromised immune system . 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. A respiratory fluoroquinolone or a ß-lactam plus a macrolide may also be used for patients with CAP who are hospitalized on a general floor . Adults admitted to an ICU need empirical 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 beta-lactams . The IDSA/ATS guideline also recommends antibiotic therapy for specific pathogens (Table 7) .
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 3 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 3 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|
|Cefotaxime, ceftriaxone, or ampicillin-sulbactam||Strong recommendation, level I and II evidence|
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|
For adults with obvious viral CAP, it is unclear whether antibiotic treatment is beneficial and there has been no consensus about specific antivirals except for neuraminidase inhibitors for pneumonia caused by influenza viruses .
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 4 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 . 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 4 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 .
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 . 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 7 days. It is recommended that the oral antibiotic be either the same drug or within the same drug class as the intravenous antibiotic . 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 :
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 5 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 . A 5- to 7-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 (2 to 3 weeks) should be considered, depending on severity of illness and response to therapy.
The clinical response to initial antibiotic therapy is unsatisfactory in approximately 15% of adults with CAP . 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 . 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 .
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 7 days in 71% of patients treated with guideline-recommended antibiotics and in 57% of those treated with nonadherent regimens . The use of guideline-adherent 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%) . In a Canadian study of adults (mean age: 51 years) who had primarily mild pneumonia, significantly lower mortality rates were associated with guideline-adherent antibiotics than with nonadherent antibiotics (1% vs 6%) . Lower mortality was also significantly associated with the use of macrolides compared with fluoroquinolones (0.2% vs. 3%) . 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 . 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 . 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 .
Despite the benefits of guideline-adherent treatment and the wide dissemination of the guideline for management of pneumonia in adults, adherence has been low, especially with regard to antibiotic selection, with rates ranging from 9% to 82% [14,15,16,17,18,20]. In a study of more than 34,000 patients in a managed care organization, adherence to the 2003 IDSA guideline in ambulatory settings was 52% for patients who were previously healthy and had not had recent exposure to antibiotics . The rate of adherence was better (82%) for patients who had comorbidities and no recent exposure to antibiotics . One study found that most cases of guideline-discordant use of antibiotics for older adults represent undertreatment . 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 .
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 . 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 . 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 . 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 . The use of a standardized evidence-based order set was associated with a decrease in mortality and was also cost-effective .
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 6 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.
The PIDS/IDSA guideline 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 . The guideline was 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 guideline 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.
To aid in making site-of-care decisions, the PIDS/IDSA guideline recommends that a child or infant with CAP be hospitalized if any of the following factors are present :
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 :
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
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 . 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) . 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 . 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 . 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 . 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.
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|
|Inpatient (all ages)|
|Fully immunizedband minimal local penicillin resistance in invasive strains of pneumococcus||
|Not fully immunized and/or significant local penicillin resistance in invasive strains of pneumococcus||
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 . 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 . 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 .
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 .
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 . It is assumed that more data will become available over time.
Evidence suggests that severe pneumonia is one 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% and 72% for all causes .
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% . A time to clinical stability of more than 72 hours has been associated with a significantly higher rate of adverse outcomes than shorter times . 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 1 year as high as 28% .
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 can serve as a guide for a follow-up plan, with closer follow-up for people in whom clinical stability is not achieved until more than 72 hours after admission [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].
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 . 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 . Sequelae occurred in approximately 54% of children who had pneumonia caused by adenovirus.
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) . Other strategies include improved hand hygiene compliance and adherence to healthy lifestyle behaviors.
HIGH-PRIORITY AND HIGH-RISK GROUPS FOR VACCINATION
|Annual influenza 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, the 23-valent pneumococcal polysaccharide vaccine (PPSV23), has been recommended for use in selected adults with conditions of impaired immunity, and for all adults older than 65 years of age . This vaccine provides some protection against 85% to 90% of the pneumococcal serotypes that cause invasive disease in these populations . 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 .
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 . 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 .
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) . 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 http://www.cdc.gov/vaccines/schedules.
IMMUNIZATION SCHEDULE RECOMMENDED BY THE ACIP
|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|
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 . 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 . 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) . 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 :
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 . 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 .
The PIDS and the IDSA also echo the ACIP recommendations in their guideline :
Children should be immunized with vaccines for bacterial pathogens, includingS. 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, 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).
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 . 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 community-acquired pneumonia, the rate of mortality or ICU admission was 40% lower among those who had received prior PPSV23 vaccination .
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 community-acquired pneumonia 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 . 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 . The rate of outpatient CAP visits has not changed significantly for this population [5,10].
Despite the wide distribution of the ACIP immunization schedule and public campaigns about the importance of vaccination, rates of both pneumococcal and influenza vaccination are low and vary across racial/ethnic populations. According to national surveys, the overall rate of pneumococcal vaccination is approximately 65% for adults 65 years and older, and the rate is substantially lower (approximately 19%) for younger adults in high-risk groups . For both groups, the rate is highest for the white population and lowest for Hispanic persons 65 years of age and older and younger Asian adults categorized as high risk (Table 11) . The national rate of influenza vaccination among adults 65 years and older is 72%, with lower rates for younger adults, especially those at high risk (Table 12) . Several 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].
RATE OF PNEUMOCOCCAL VACCINATION AMONG ADULTS 19 YEARS OF AGE AND OLDERa
|Race/Ethnicity||High-Risk Adults 19 to 64 Years||Adults 65 Years and Older|
|Hispanic or Latino||14.8%||39.0%|
|aBased on data from the National Health Interview Survey, United States, 2010.|
RATE OF INFLUENZA VACCINATION AMONG ADULTS ACCORDING TO AGE AND RACE/ETHNICITY
|Adults 65 Years and Older|
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 .
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 PCV doses . The rate varies according to race/ethnicity, with the lowest rates among Asian and black children (Table 13) . The rate of influenza vaccination is lower, with rates ranging from 48.5% to 59.4% for children 6 months to 17 years of age. In contrast to racial/ethnic variations for other rates, the lowest rate is found for white children, and the highest, for Asian children (Table 14) . The vaccination rate for white children is lowest across all age groups, except for children 6 to 23 months of age. Across all races/ethnicities, the lowest rates occur in the 13- to 17-years age group .
RATE OF INFLUENZA VACCINATION AMONG ADULTS ACCORDING TO AGE AND RACE/ETHNICITY
|Total (6 Months to 17 Years)||6 to 23 Months||2 to 4 Years||5 to 12 Years||13 to 17 Years|
|American Indian/Alaska Native||55.7%||71.7%||56.3%||62.4%||33.7%|
|aIncludes Native Hawaiian, other Pacific Islander, multiracial, and other races.|
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 15) . 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 . 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].
HEALTHY PEOPLE 2020 TARGETS FOR PNEUMOCOCCAL AND INFLUENZA VACCINATION RATES
|Target Population||Target Rate||Baseline Rate for Improvement (Year)|
|4 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|
|3 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)|
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%) . In contrast, concern about side effects was more common among white individuals (15%) than among black and Hispanic individuals (10% and 6%, respectively) . 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 . 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 . 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 .
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 . 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" . 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 . 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 . The NVS takes fewer than 3 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?" . 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 . 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 16). 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 . Clinicians should give their patients a list of online resources that provide balanced information on vaccines (Table 17). Differences in beliefs about vaccines across racial/ethnic groups indicate that targeted messages developed for specific demographic subgroups may be useful . 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.
BARRIERS TO OPTIMAL VACCINATION AND POSSIBLE 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.|
RESOURCES ABOUT VACCINATIONS FOR PATIENTS AND PARENTS
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 18) . Clinicians should identify high-risk patients in their practice and take special steps to ensure that these patients receive appropriate vaccinations.
HEALTHCARE PROVIDER RECOMMENDATIONS FOR INFLUENZA AND PNEUMOCOCCAL VACCINATIONS BY PATIENT TYPE
|Patient Type||Influenza Vaccine||Pneumococcal Vaccine|
|Aged ≥50 years||28%a||15%||4%||18%a|
|Aged ≥65 years||37%||28%||65%||55%|
|Chronic lung disease||45%||40%||68%||55%|
|Chronic liver disease||22%||16%||27%||20%|
|Chronic kidney disease||22%||12%||25%||17%|
|Weak immune system||17%||20%||24%||29%|
|Complications or risk from other illness||25%||17%||28%||23%|
|Close contact with someone at high risk||24%||22%||11%||10%|
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 .
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 . 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 . 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 3-week intervention program at one inner city emergency department, participants were provided appropriate immunizations when they were at high risk for specific diseases . 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.
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.
In 2005, the ATS/IDSA published guidelines for the management of adults with HAP, VAP, and HCAP, defining these categories 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 type of HAP that develops more than 48 to 72 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 pathogen infection. Within the category of HCAP, nursing home-acquired pneumonia is the type with the most published data and will be discussed in this course.
Approximately 3 to 10 cases of HAP occur per 1,000 hospital admissions . Pneumonia as a complication of hospitalization increases length of stay (by more than 1 week), increases mortality risk, and adds an additional cost of care that can reach $40,000 per case .
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]. The financial cost is high, with a report of $30,000 per adult stay in one study . Pediatric VAP has not been as well studied as in adults. It occurs most commonly in children 2 to 12 months of age .
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 bacteria 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].
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 . 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 . Use of a PPI or histamine2 receptor antagonist is also thought to be a risk factor . Surgery-related factors included prolonged duration of surgery (i.e., more than 3 to 4 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 .
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 5-day period following intubation, decreasing to 2% per day for days 5 through 10, and to 1% per day for longer durations . In a population of children who had cardiothoracic surgery, pneumonia risk correlated with mechanical ventilation for longer than 3 days . Nearly half of all cases of VAP develop within the first 4 days of mechanical ventilation .
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 . In one study, VAP was most frequently associated with ICU admission diagnoses of postoperative care, neurologic conditions, sepsis, and cardiac complications .
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 . Older age, male gender, and antipsychotic and anticholinergic medications have also been reported to increase risk [23,42].
Most cases of pneumonia associated with a healthcare facility are caused by aspiration of bacteria originating in the nasopharynx or the stomach [26,28]. The most common bacterial causes vary among institutions, but some trends have been found.
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 . Candida spp. and Aspergillus fumigatus may cause pneumonia in patients who have had organ transplantation or who have a compromised immune system and neutropenia.
Among adults with no previous antibiotic exposure, the most common bacterial causes of HAP are S. pneumoniae, H. influenzae, Escherichia coli, Klebsiella 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 . 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% . 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 .
The causes of HAP in children have not been well studied. However, outbreaks of pneumonia caused by RSV have been common in pediatric wards .
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 . Although bacteria are the primary causative agents, viruses and saprophytic fungi have also been implicated as well .
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 .
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 . 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].
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 . 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 .
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 :
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/mm3
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, noting that the specimens can be obtained by bronchoscopy or another means and that cultures can be quantitative or semiquantitative . 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 . In addition, mortality did not differ between invasive or noninvasive methods of obtaining samples.
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) .
It has been emphasized that this approach, and empiric treatment of HCAP in general, requires knowledge of the infection history (hospital flora) of the healthcare facility and of individual patient units [35,148,164]. Microbiology laboratory reports can provide such details, and physicians should prescribe initial antibiotics that are likely to be active against these pathogens.
The ATS/IDSA guideline provides several general recommendations for the management of both HAP and VAP :
Obtain a specimen 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 specimen.
Prescribe early, appropriate, broad-spectrum antibiotic therapy with adequate doses.
Choose an empiric therapy regimen that includes agents from a different antibiotic class than any the patient has recently received.
Consider de-escalation of antibiotics after data are available on the results of cultures of specimens from lower respiratory tract cultures and the clinical response.
Use a shorter duration of antibiotic therapy (i.e., 7 or 8 days) for patients with uncomplicated VAP who have received appropriate therapy initially, have had a good clinical response, and have no evidence of infection with nonfermenting gram-negative bacilli.
Selection of specific antimicrobial therapy depends on the timing of onset and 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 19). For late-onset pneumonia and/or patients at increased risk for multidrug-resistant organisms, a broad-spectrum antibiotic therapy is recommended.
RECOMMENDED ANTIBIOTIC THERAPY FOR HEALTHCARE-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|
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 . However, the ATS/IDSA guideline notes that linezolid may have advantages over vancomycin for pneumonia caused by MRSA . 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 . The findings led the authors to suggest that the benefit of linezolid may be related to factors other than bacterial clearance. The use of inhalational (aerosolized) antibiotics, alone or in combination with systemic antibiotic therapy, has proven useful for the management of highly resistant gram-negative bacillary pneumonia .
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 . 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.
The ATS/IDSA guideline provides some direction for choice of antibiotic therapy but does not specify a distinct management protocol for nursing home-acquired pneumonia. There is little evidence of clinical superiority of one approach over another [26,28,143].
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 . 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 . 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 . 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.
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 . 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.
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 . 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 8 weeks before surgery, when possible, is recommended for current smokers . 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) .
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 . 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 .
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, prevention of VAP is addressed in the CDC's guideline on preventing HCAP and the ATS/IDSA guideline on the management of HCAP [28,93]. All of these guidelines 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 .
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 . The bundle includes the following interventions :
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 20) .
PRACTICAL STEPS IN FOLLOWING GUIDELINES TO PREVENT VENTILATOR-ASSOCIATED PNEUMONIA
|Assessment of Readiness to Extubate and Sedative Interruptions|
|Elevation of the Head of the Bed|
|Oral Care with Chlorhexidine|
|Prophylaxis of Peptic Ulcer Disease|
|Prophylaxis of Deep Venous Thrombosis|
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 . There are risks to this approach, including the potential for increased pain, anxiety, and desaturation . However, sedation interruption has been further demonstrated to reduce the complications of prolonged mechanical ventilation . The SHEA/IDSA guideline recommends daily assessment of the readiness to wean and the use of weaning protocols . 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 .
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 . 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 . 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 .
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 . 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 . 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 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 World Health Organization (WHO) recommends avoiding the use of these agents . 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 . The ATS/IDSA guideline states that the risks and benefits of prophylaxis should be weighed carefully . 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 . However, peptic ulcer prophylaxis is recommended for children, as appropriate for age and health status .
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 . This recommendation also applies to children, as appropriate for age and health status .
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 . 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 . 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 .
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 . 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 . Although the cost of the tube is higher than traditional tubes, the overall cost savings in preventing VAP more than compensates . 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 . 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 . Again, the CDC, the ATS/IDSA, and the SHEA/IDSA guidelines recommend the use of noninvasive ventilation when possible [28,93,171].
Quality improvement and infection control initiatives and strategies have led to a substantial decrease in the rates of VAP since the early 2000s . 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 .
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 :
Pneumococcal vaccination of patients at admission, if indicated
Annual influenza vaccination for residents
Annual influenza vaccination for nursing facility staff
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 . The ACIP notes that the TIV is preferred over LAIV for workers who are in close contact with severely immunosuppressed people requiring protective isolation . In addition, the Joint Commission began including vaccination programs in its accreditation standards in 2007 .
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 .
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 :
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 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 . The CDC guideline states the specific indications for washing hands, the recommended hand hygiene techniques, and recommendations about fingernails and the use of gloves . 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 :
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 8-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 . 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 . Single interventions are unlikely to be effective.
A man, 73 years of age, with a history of coronary disease, COPD, benign prostatic hyperplasia, and type 2 diabetes is admitted from an assisted-living facility because of weakness, loss of appetite, and low-grade fever. He had been admitted elsewhere for similar symptoms 3 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 central cavitation.
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 is available, conforms to the ATS/IDSA guideline. 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 community-acquired pneumonia; 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.
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. Guidelines for diagnosis and treatment are available for both community-acquired pneumonia and HCAP (which includes HAP, VAP, and nursing home-acquired pneumonia). 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 community-acquired and nursing home-acquired pneumonia, determining the site of care is an important initial decision point. Guidelines from IDSA/ATS, PIDS/IDSA, and ATS outline criteria for the need for hospitalization or ICU admission. 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.
Treatment according to guidelines 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 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 must develop strategies that target these barriers as well as 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 identify high-risk patients in their practice and take special steps to ensure that these patients receive appropriate vaccinations. 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.
1. Centers for Disease Control and Prevention. Pneumonia. Available at http://www.cdc.gov/nchs/fastats/pneumonia.htm. Last accessed August 20, 2015.
2. 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.
3. Haessler S, Schimmel JS. Managing community-acquired pneumonia during flu season. Cleve Clin J Med. 2012;79(1):67-78.
4. 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.
5. Kronman M, Hersh AL, Feng R, Huang Y-S, Lee GE, Shah SS. Ambulatory visit rates and antibiotic prescribing for children with pneumonia, 1994–2007. Pediatrics. 2011;127(3):411-418.
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. Newman R, Hedican EB, Herigon JC, Williams DD, Williams AR, Newland JG. Impact of a guideline on management of children hospitalized with community-acquired pneumonia. Pediatrics. 2012;129(3):e597-e604.
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. Switzer G, Halm E, Chang C-CH, Mittman BS, Walsh MB, Fine MJ. Physician awareness and self-reported use of local and national guidelines for community-acquired pneumonia. J Gen Intern Med. 2003;18(10):816-823.
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. 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.
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.
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.
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. Sarkar M, Hennessy S, Yang YX. Proton-pump inhibitor use and the risk for community-acquired pneumonia. Ann Intern Med. 2008;149(6):391-398.
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.
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. Niederman MS, Bass JB Jr, Campbell GD. Guidelines for the initial management of adults with community-acquired pneumonia: diagnosis, assessment of severity, and initial antimicrobial therapy. Am Rev Respir Dis. 1993;148(5):1418-1426.
64. Bartlett JG, Breiman RF, Mandell LA, File TM Jr. Community-acquired pneumonia in adults: guidelines for management. Clin Infect Dis. 1998;26(4):811-838.
65. Bartlett JG, Dowell SF, Mandell LA, File Jr TM, Musher DM, Fine MJ. Practice guidelines for the management of community-acquired pneumonia in adults. Clin Infect Dis. 2000;31(2):347-382.
66. 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.
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 http://www.jointcommission.org/immunization. Last accessed August 20, 2015.
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. National Network for Immunization Information. Pneumococcal Disease. Available at http://www.immunizationinfo.org. Last accessed August 20, 2015.
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 W, Lu P-J, Singleton JA, et al. Adult vaccination coverage—United States, 2010. MMWR. 2012;61(4):66-72.
103. Setse R, Euler GL, Gonzalez-Feliciano AG, et al. Influenza vaccination coverage—United States, 2000–2010. MMWR. 2011;60(1):38-41.
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. Centers for Disease Control and Prevention. Vaccines and Immunization. Available at http://www.cdc.gov/vaccines. Last accessed August 20, 2015.
113. Centers for Disease Control and Prevention. Final State-Level Influenza Vaccination Coverage Estimates for the 2010–2011 Season—United States, National Immunization Survey and Behavioral Risk Factor Surveillance System, August 2010 through May 2011. Available at http://www.cdc.gov/flu/fluvaxview/coverage_1011estimates.htm. Last accessed August 20, 2015.
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.
116. Johnson D, Nichol KL, Lipczynski K. Barriers to adult immunization. Am J Med. 2008;121(7 Suppl 2):S28-S35.
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 http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=1&lvlid=6. Last accessed August 20, 2015.
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 http://factfinder.census.gov/faces/tableservices/jsf/pages/productview.xhtml?pid=ACS_13_5YR_DP02&src=pt. Last accessed August 20, 2015.
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.
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 20, 2015.
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 20, 2015.
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; [Epub ahead of print].
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. FDA Public Health Notification: Reprocessing of Reusable Ultrasound Transducer Assemblies Used for Biopsy Procedures. Available at http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/ucm062086.htm. Last accessed August 20, 2015.
207. Boyce JM, Pittet D. Guideline for hand hygiene in health-care settings. MMWR. 2002;51(RR16):1-44.
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: 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.
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. Summary retrieved from National Guideline Clearinghouse at http://www.guideline.gov/content.aspx?id=47676. Last accessed August 27, 2015.
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. Summary retrieved from National Guideline Clearinghouse at http://www.guideline.gov/content.aspx?id=25412. Last accessed August 27, 2015.
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. Summary retrieved from National Guideline Clearinghouse at http://www.guideline.gov/content.aspx?id=34433. Last accessed August 27, 2015.
4. Institute for Clinical Systems Improvement. Prevention of Ventilator-Associated Pneumonia: Health Care Protocol. Bloomington, MN: Institute for Clinical Systems Improvement; 2011. Summary retrieved from National Guideline Clearinghouse at http://www.guideline.gov/content.aspx?id=36063. Last accessed August 27, 2015.
Mention of commercial products does not indicate endorsement.