Bacterial Resistance: Are We Running Out of Antibiotics?

Course #94212 - $20 • 5 Hours/Credits


Study Points

  1. Describe the effects of antimicrobials and the mechanisms of bacterial resistance.
  2. Review the etiology of emerging resistant organisms in the healthcare setting.
  3. Discuss the impact of and possible control measures for methicillin-resistant Staphylococcus aureus (MRSA).
  4. List and compare additional resistant organisms that may be encountered in the healthcare setting.
  5. Outline ways to control and prevent the development of microbial resistance in healthcare facilities, including patient education and outreach to non-English-proficient patients.

    1 . Antimicrobials that inhibit the growth of microbes are referred to as
    A) microbicidal.
    B) beta-lactams.
    C) microbiostatic.
    D) aminoglycosides.

    EFFECTS OF ANTIMICROBIALS

    By its mechanism of action, an antimicrobial can either kill susceptible microbes (i.e., microbicidal) or inhibit their growth (i.e., microbiostatic). Antimicrobial drugs have been developed against the whole range of microbial pathogens, including viruses, bacteria, fungi, and many parasites. With respect to bacterial pathogens, examples of bacteriostatic antibiotics are the tetracyclines, macrolides, sulfonamides, and chloramphenicol. Bactericidal drugs include the beta-lactams, carbapenems, vancomycin, and aminoglycosides [13].

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    2 . Sulfonamides act on micro-organisms by
    A) inhibiting cell wall synthesis.
    B) altering membrane permeability.
    C) inhibiting essential folate metabolites.
    D) inhibiting protein or nucleic acid synthesis.

    EFFECTS OF ANTIMICROBIALS

    Mechanisms by which antimicrobials act on susceptible organisms include [13,14]:

    • Inhibition of cell wall synthesis (penicillins, cephalosporins, vancomycin)

    • Alteration of membrane permeability (polymyxins, amphotericin B, imidazoles)

    • Inhibition of protein or nucleic acid synthesis (aminoglycosides, tetracycline, chloramphenicol, erythromycin, rifampin, clindamycin)

    • Inhibition of essential folate metabolites (trimethoprim, sulfonamides)

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    3 . Use of a broad-spectrum antimicrobial often produces a greater disruption of the patient's normal flora, resulting in
    A) super infection.
    B) pseudomembranous colitis.
    C) colonization by resistant strains.
    D) All of the above

    EFFECTS OF ANTIMICROBIALS

    When the infecting organism and its susceptibility are known, it is unnecessary to use a broad-spectrum antimicrobial. Broad-spectrum antimicrobials may disrupt the patient's normal flora and cause colonization by resistant strains, super infection, or pseudomembranous colitis. For specific therapy, the safest narrow-spectrum antibiotic should be selected, or, in some situations, a combination of drugs should be used.

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    4 . Chromosomal resistance
    A) occurs frequently.
    B) is a result of spontaneous mutation.
    C) is expressed as a change in the cell membrane permeability.
    D) is a mutation in the gene locus that controls cellular replication.

    MECHANISMS OF BACTERIAL RESISTANCE

    Chromosomal and extrachromosomal changes can lead either to drug destruction (e.g., beta-lactamases destroy penicillin and cephalosporin derivatives) or to an alteration of drug-receptor/target sites (e.g., methicillin resistance in S. aureus). Although it occurs infrequently, chromosomal resistance results from spontaneous mutation in the gene locus that controls susceptibility to a drug and is usually expressed as a change in the drug-receptor/target site.

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    5 . Extrachromosomal drug resistance
    A) usually mediates resistance to a single antimicrobial.
    B) is spread mainly to daughter cells from generation to generation.
    C) enables micro-organisms to distribute genetic material more slowly.
    D) is potentially more serious than chromosomal resistance when achieved by plasmid exchange.

    MECHANISMS OF BACTERIAL RESISTANCE

    Extrachromosomal drug resistance achieved by plasmid exchange is potentially more serious and enables micro-organisms to distribute genetic material more rapidly. Chromosomal change is spread mainly to daughter cells from generation to generation. Extrachromosomal resistance involving plasmids can spread between organisms to different strains and even to different species of bacteria. Chromosomal changes usually mediate resistance to a single antimicrobial, while plasmids usually code for resistance to several antimicrobials [20].

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    6 . Which of the following organisms has shown a resistance to oxacillin?
    A) Pneumococci
    B) Meningococci
    C) Staphylococcus aureus
    D) Haemophilus influenzae

    EMERGING RESISTANCE

    According to 2011–2014 data, 15 pathogen groups accounted for about 87% of reported healthcare-associated infections, the most common being Escherichia coli (15%), S. aureus (12%), Klebsiella spp. (8%), and coagulase-negative staphylococci (8%) [167]. Nearly 20% of cases were associated with drug-resistant phenotypes. This is important to note because, in the last several decades, there has been an increase in the ability of these common bacteria to resist standard antibiotics. Examples of this antibiotic resistance include [13]:

    • Ampicillin resistance: Haemophilus influenzae, E. coli, Salmonella

    • Penicillin resistance: Pneumococci, meningococci

    • Methicillin/oxacillin resistance: S. aureus

    • Vancomycin resistance: Enterococci

    • Imipenem-cephalosporin resistance:Pseudomonas

    • Carbapenem resistance: Enterobacteriaceae

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    7 . Of the following documented resistances, which occurred first in the United States?
    A) Linezolid resistance
    B) Methicillin-resistant S. aureus
    C) Penicillinase-producing S. aureus
    D) Vancomycin resistance among enterococci

    EMERGING RESISTANCE

    Although some organisms remain sensitive to antibiotics for many years, this is not usually the case. From a historical perspective, the major antibiotic resistance events include [22,54,136,166]:

    • Penicillinase-producing S. aureus, which first appeared in the late 1950s

    • Methicillin-resistant S. aureus (MRSA), which appeared in the 1960s

    • Aminoglycoside (e.g., gentamicin, tobramycin) resistance among gram-negative bacilli (1970s)

    • MRSA resistance to fluoroquinolones (1980s)

    • Vancomycin resistance among enterococci (1987–1990s)

    • The necessity of combination therapy (usually isoniazid, rifampin, pyrazinamide, and ethambutol) in the treatment of tuberculosis (TB) (1990s)

    • Linezolid resistance (first reported in 1999, before the drug had received U.S. Food and Drug Administration [FDA] approval)

    • Metallo-beta-lactamase-producing bacteria (1990s)

    • Fluoroquinolone-resistant Clostridium difficile (2000s)

    • Carbapenem-resistant Enterobacteriaceae (2000s)

    • Colistin-resistant E. coli (2016)

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    8 . The rate at which resistant organisms develop is not solely a function of the use of antimicrobials in humans. It is also influenced by the use of these agents in
    A) agriculture.
    B) aquaculture.
    C) animal husbandry.
    D) All of the above

    FACTORS THAT ENCOURAGE THE DEVELOPMENT OF RESISTANCE

    As discussed, resistance to antibiotics is an emerging problem in medicine, and its effects are being noted on an ever-increasing scale. Multidrug-resistant organisms are diminishing the ability to control the spread of infectious diseases. The rate at which resistant organisms develop is not solely a function of the use of antimicrobials in humans. It is also influenced by the use of these agents in veterinary medicine, animal husbandry, agriculture, and aquaculture, as has been emphasized in a report on bacterial resistance issued by the U.S. Office of Technology Assessment [24].

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    9 . Resistant organisms are estimated to be responsible for how much in excess direct healthcare spending each year?
    A) $20 billion
    B) $30 billion
    C) $40 billion
    D) $55 billion

    IMPACT OF RESISTANT PATHOGENS ON HEALTHCARE COSTS

    The growth of resistant organisms in healthcare settings has had a significant effect on healthcare costs. Although it is difficult to calculate, researchers estimate that resistant organisms are responsible for up to $20 billion in direct healthcare costs each year, with an additional $35 billion in indirect costs (e.g., lost productivity) [54].

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    10 . Approximately what percentage of community- and hospital-acquired S. aureus isolates are penicillin-resistant?
    A) 9%
    B) 25%
    C) 60%
    D) 90%

    SPECIFIC ORGANISMS AND DISEASES

    In the early 1940s, when penicillin first became available, S. aureus isolates were highly susceptible. By the early 1950s, 65% to 80% of nosocomial isolates were reported to be resistant to penicillin. Now, more than 90% of community- and hospital-acquired S. aureus isolates are penicillin-resistant [13].

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    11 . The MRSA epidemic in the United States is predominantly caused by the
    A) ST1 strain.
    B) USA100 strain.
    C) USA300 strain.
    D) USA400 strain.

    SPECIFIC ORGANISMS AND DISEASES

    The prevalent community-acquired strain in the United States appears to have evolved from the methicillin-susceptible S. aureus (MSSA) strain known as ST8. The resistant strains have been designated by the CDC as USA300 and USA400, with USA300 being more common [36,37]. Both strains are characterized by the Panton-Valentine leukocidin (PVL) gene and the SCCmec IV element, which are responsible for the resistance to beta-lactam antibiotics and rarely identified in healthcare-associated MRSA isolates [38]. The USA400 strains (designated ST1) were first seen in the Midwest in 1966 and appear to have more S. aureus toxins than the USA300 strains. The epidemic is predominately caused by the USA300 strain, which is a clone of the ST8 and now found throughout the United States.

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    12 . MRSA infections most commonly present as
    A) urinary tract infections.
    B) cerebrovascular infections.
    C) skin and soft tissue lesions.
    D) lung and respiratory system infections.

    SPECIFIC ORGANISMS AND DISEASES

    Healthy children and adults commonly carry S. aureus in the anterior nares. In most individuals, this carriage state is transient, lasting a matter of weeks. At any given time, an estimated 30% of the U.S. population has S. aureus nasal carriage [38,40]. Healthcare workers have a 50% to 90% higher S. aureus nasal carriage rate than the general population. S. aureus can be easily transferred from the anterior nares to the skin and other body areas (e.g., pharynx, axilla, rectum, perineum); consequently, when given a portal of entry, it can cause a significant infection [13,38]. MRSA infections most commonly present as skin and soft tissue inflammatory lesions (e.g., cellulitis, furuncles) and have been reported as an emerging cause of recurrent skin and soft tissue disease among otherwise healthy persons outside the healthcare setting [38,41]. In 2005, an estimated 14 million outpatient healthcare visits were related to infections of the skin and soft tissue [42].

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    13 . One important risk factor for acquiring MRSA during hospitalization is
    A) a short hospital stay.
    B) no prior antibiotic therapy.
    C) stay in a labor and delivery unit.
    D) exposure to a colonized or infected person.

    SPECIFIC ORGANISMS AND DISEASES

    As noted, MRSA is thought to be transmitted within institutions from patient to patient primarily via hand carriage of healthcare workers who have been contaminated by contact with colonized or infected patients or with devices, items, or environmental surfaces that have been contaminated with body fluids containing MRSA. Colonized or infected healthcare workers may also be reservoirs [43]. The role of the environment seems to be less important, except in burn units, ICUs, and other special facilities where prevention and control measures should be tailored to the area's unique needs and population [53]. Other risk factors for acquiring MRSA during hospitalization vary and depend on the population studied and specific circumstances. Important risk factors include prolonged hospitalization, the length of the period preceding antimicrobial therapy, stay in an ICU or burn unit, or exposure to a colonized or infected patient [13,43].

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    14 . The preferred treatment for both community-acquired and healthcare-associated MRSA has been
    A) tetracycline.
    B) vancomycin.
    C) clindamycin.
    D) quinupristin/dalfopristin.

    SPECIFIC ORGANISMS AND DISEASES

    Vancomycin has been the preferred treatment for both community-acquired and healthcare-associated MRSA. However, concerns have been raised about its efficacy, particularly over its slow bactericidal activity, emergence of resistant strains, and possible "MIC creep" among susceptible strains [82]. Strains of MRSA with reduced susceptibility to vancomycin were first discovered in Japan in 1996. Resistant strains are called VISA and VRSA. Several documented cases of VRSA infection have occurred worldwide, with most occurring in the United States, but as of 2014, these instances are exceedingly rare and are able to be treated with other FDA-approved antimicrobials [83,124]. In January 2011, the American Society of Health-System Pharmacists, the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists published consensus-based recommendations for vancomycin dosing and monitoring [82].

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    15 . Which of the following is NOT a risk factor for the development of vancomycin-resistant enterococci (VRE)?
    A) Prior hospitalization
    B) Immunosuppression
    C) Age younger than 60 years
    D) Exposure to invasive devices

    SPECIFIC ORGANISMS AND DISEASES

    Several risk factors have been identified for VRE, including age older than 60 years, prior hospitalization, placement in the ICU, major underlying disease, surgery, immunosuppression, exposure to invasive devices, and long-term antibiotic therapy [125]. The reservoirs most often identified in outbreaks of VRE include infected or colonized patients, healthcare workers' hands, and contaminated inanimate objects. Risk of transmission is greatly increased in patients receiving care at multiple facilities and in patients who are transported between acute care, ambulatory and/or chronic care, and long-term care environments [9,53,72].

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    16 . Penicillin-resistant Streptococcus pneumoniae occurs in a number of different pneumococcal serotypes, but it appears to be much more prevalent among those types that most frequently cause
    A) death.
    B) disease in children.
    C) more virulent forms of the disease.
    D) disease resistant to all other types of treatment.

    SPECIFIC ORGANISMS AND DISEASES

    Penicillin resistance occurs in a number of different pneumococcal serotypes, but it appears to be much more prevalent among those types that most frequently cause disease in children. This is consistent with the hypothesis that many of these organisms originate in children and spread to adults. This concept is supported by the occurrence of outbreaks of resistant pneumococci in childcare facilities.

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    17 . Of the following conditions caused by penicillin-resistant S. pneumoniae, the most difficult to treat is
    A) influenza.
    B) bacteremia.
    C) pneumonia.
    D) acute otitis media.

    SPECIFIC ORGANISMS AND DISEASES

    Crowded conditions, such as those found in day care centers, and prior beta-lactam antibiotic therapy are the principal predisposing factors to colonization and disease. Populations at greatest risk include the elderly, children younger than 2 years of age, African Americans, American Indians, Alaska Natives, and persons with underlying medical conditions, including human immunodeficiency virus (HIV) infection and sickle-cell disease [99]. Acute otitis media and meningitis are the two conditions caused by resistant pneumococci that are the most difficult to treat [102]. Treating meningitis is especially challenging when caused by a strain of S. pneumoniae that is highly resistant to penicillin and third-generation cephalosporins [101]. The concentration of beta-lactams in cerebrospinal fluid and middle ear fluid are frequently inadequate to allow prompt elimination of some intermediate and highly resistant pneumococcal strains.

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    18 . Multidrug-resistant tuberculosis (MDR-TB) is defined by the CDC as M. tuberculosis bacilli that are resistant to at least
    A) isoniazid.
    B) isoniazid and rifampicin.
    C) isoniazid, rifampicin, and any fluoroquinolone.
    D) isoniazid, rifampicin, any fluoroquinolone, and at least one second-line drug.

    SPECIFIC ORGANISMS AND DISEASES

    In the 1950s, streptomycin was found to effectively treat TB; however, resistance soon developed, not only to streptomycin but also to several other antibiotics, including rifampin, isoniazid, pyrazinamide, and ethambutol, all of which had previously shown reasonable effectiveness against TB. MDR-TB was subsequently defined by the CDC as M. tuberculosis bacilli that are resistant to at least the two most effective antituberculosis drugs, isoniazid and rifampicin. The emergence of MDR-TB has become a serious threat to elimination of the disease [114]. XDR-TB has been defined as M. tuberculosis bacilli that are resistant to isoniazid and rifampin, plus resistant to any fluoroquinolone, and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin) [119,120]. Because of its resistance to both first- and second-line drugs, treatment of patients with XDR-TB often is ineffective. XDR-TB is of particular concern in patients with HIV or other immunodeficiency [119].

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    19 . Proper vaccination of medical staff and patients to prevent infection is an effective method to prevent the spread of all of the following, EXCEPT:
    A) S. aureus
    B) H. influenzae
    C) S. pneumoniae
    D) N. meningitides

    METHODS OF PREVENTING RESISTANCE

    Many infections in hospitalized or institutionalized patients are the direct result of indwelling urinary catheters, central venous catheters, and intubation. These invasive medical devices should be avoided unless they are clearly indicated. In addition, proper vaccination of medical staff and patients to prevent infection is an effective method to prevent the spread of S. pneumoniae, Haemophilus influenzae, and Neisseria meningitides [10].

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    20 . Which of the following is considered an aspect of prevention of transmission of resistant micro-organisms?
    A) Cohorting patients
    B) Vaccination of patients
    C) Judicious use of new antimicrobials
    D) Restricted use of broad-spectrum antibiotics

    METHODS OF PREVENTING RESISTANCE

    Another step is to prevent transmission of resistant bacteria between patients. A simple, effective method of infection containment is hand washing [10]. Participation in hospital infection control programs also is necessary [20]. A coordinated effort to contain pathogens according to hospital infection control guidelines makes it easier to prevent the spread of multidrug-resistant bacteria.

    Education in basic infection control practices, such as Contact Precautions, should not be confined only to direct clinical caregivers. Any person entering a patient's room, from physicians to maintenance personnel, increases the possibility of the organism progressing from that room to another patient's room or other hospital areas. All persons in contact with a patient infected with a resistant organism should be diligent about necessary precautions.

    Cohorting patients who have resistant organisms is an accepted practice to control transmission and involves placing patients with similar infections together in rooms. This is effective unless an immunocompromised patient who has been treated successfully is placed in the same room with a patient who is still infectious. In these cases, transmission is possible. Cross-contamination also is a constant danger in the hospital setting. Resistant infections can be particularly dangerous in acute-care facilities that involve treatment of immunocompromised patients, such as oncology wards. All long-term care facilities, including acute or subacute facilities or skilled nursing facilities, face the same length of stay, cohorting, and discharge difficulties, as do short-term acute-care facilities.

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