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Am Fam Physician. 2014;89(12):938-941

Author disclosure: No relevant financial affiliations.

In a recently issued report, the Centers for Disease Control and Prevention (CDC) estimated the national burden of illnesses and deaths caused by the most common and most worrisome antibiotic-resistant pathogens.1 The report focused on 16 antimicrobial-resistant bacterial pathogens, as well as Candida infections, which together account for more than 2 million illnesses and at least 23,000 deaths every year in the United States.1 The report also included information on Clostridium difficile infections, which, like antibiotic resistance, are driven by antibiotic use. C. difficile causes more than 250,000 clinical infections annually and is associated with more than 14,000 deaths every year in the United States.1

In this report, the CDC categorized 18 pathogens (eTable A) into three groups (urgent, serious, and concerning) based on seven criteria: clinical impact, economic impact, incidence, 10-year projection of incidence, transmissibility, availability of effective antibiotics, and barriers to prevention.1 Three types of bacteria were included in the urgent category: carbapenem-resistant Enterobacteriaceae, drug-resistant Neisseria gonorrhoeae, and C. difficile. In the past, drug-resistant strains of Enterobacteriaceae and N. gonorrhoeae have shown a propensity to spread rapidly in the United States and around the world. Some strains of carbapenem-resistant Enterobacteriaceae are currently untreatable with available antibiotics, and the cephalosporin agents to which some gonococci are now showing emerging resistance are the last available drugs to effectively treat this infection. Thus, further spread of these strains constitutes a public health crisis. C. difficile infections already cause significant morbidity and mortality, and a recently emerging epidemic strain, BI/NAP1/027, appears to be more virulent.

MicroorganismNotable information
Urgent
Clostridium difficileA1 ,A2 Deaths related to C. difficile increased 400% between 2000 and 2007, in part because of a stronger strain
Most infections are connected to receiving medical care
Hand sanitizer does not kill C. difficile, and hand washing may not be sufficient
Carbapenem-resistant Enterobacteriaceae A3 Difficult to treat and, in some cases, untreatable
Kills up to one-half of patients who get bloodstream infections
Easily spreads antibiotic resistance to other bacteria
Drug-resistant Neisseria gonorrhoeaeA4 Cases in the United States are more prevalent in the West and among men who have sex with men
All patients treated for gonorrhea should routinely be offered condoms, referred for risk-reduction counseling, and retested for gonorrhea three months later
Serious
Multidrug-resistant AcinetobacterA5 Increasingly common in U.S. health care facilities; hard to treat
Noted in U.S. service members wounded in Iraq and Afghanistan
Drug-resistant CampylobacterA6 Most cases are sporadic and not part of outbreaks
Ciprofloxacin (Cipro) resistance to Campylobacter increased from 12% in 1997 to 24% in 2011
Fluconazole- (Diflucan-) resistant Candida (fungus)A7 A9 Antifungal resistance in mucosal candidiasis varies by species
Extended spectrum β-lactamase–producing Enterobacteriaceae A10 ,A11 Infections have become more common in recent years
Once confined largely to hospitals, these bacteria, especially Escherichia coli, are increasingly common in community-acquired infections, particularly urinary tract infections
Vancomycin-resistant EnterococcusA12 A14 Enterococci are the fifth most common cause of health care–associated infections
Most likely to be found in urine and in wounds; may pose a risk for spreading in the outpatient setting
Multidrug-resistant Pseudomonas aeruginosaA15 ,A16 About 8% of all health care–associated infections are caused by P. aeruginosa; about 13% of severe P. aeruginosa health care–associated infections are multidrug resistant
P. aeruginosa may be isolated from outpatients with otitis, skin rash, and urinary tract infections
Drug-resistant non-typhoidal SalmonellaA17 ,A18 Estimated 1.2 million cases occur each year in the United States; most go unreported
About 100,000 cases (8%) are caused by drug-resistant Salmonella
Outbreaks occur each year; some involve multiple states and/or national distribution
Drug-resistant Salmonella serotype Typhi A19 Estimated 5,700 cases annually in the United States
Most (up to 75%) are acquired during international travel
Increasing resistance to antibiotics, especially fluoroquinolones
Drug-resistant ShigellaA20 High-risk groups include children in day care centers (younger than five years) and their caregivers, men who have sex with men, international travelers, and persons in custodial institutions
Increasing resistance to ciprofloxacin and azithromycin (Zithromax) is of particular concern
Methicillin-resistant Staphylococcus aureusA21 A23 Although overall cases of invasive methicillin-resistant S. aureus are declining, the proportion of community-associated infections has increased
Should be considered in the differential diagnosis of skin and soft tissue infections
Serious
Drug-resistant Streptococcus pneumoniaeA24 Increasing threat of antibiotic resistance makes vaccination according to the Advisory
Committee on Immunization Practices recommendations for children and adults more important
Drug-resistant tuberculosis A25 ,A26 Number of tuberculosis cases is declining in the United States 63% of tuberculosis cases in the United States occur among foreign-born persons
Proportion of primary multidrug-resistant tuberculosis cases occurring among foreign-born persons has been increasing
Concerning
Vancomycin-resistant S. aureusA27 Rare; 13 cases have been identified in the United States since 2002
Severity of the consequences of S. aureus resistance to vancomycin require continued vigilance for this pathogen
Erythromycin-resistant group A StreptococcusA28 Penicillin remains the drug of choice, but the resistance to other drugs needed for patients allergic to penicillin is worrisome
Of samples tested by the Centers for Disease Control and Prevention, 10% were erythromycin resistant and 3.4% were clindamycin resistant
Clindamycin-resistant group B StreptococcusA29 Neonates, pregnant women, and persons older than 65 years with underlying conditions are at highest risk
Penicillin remains the drug of choice, but the resistance to other drugs needed for patients allergic to penicillin is worrisome

Prevention strategies can be effective, but the major goals of the CDC report are to (1) increase awareness of the magnitude and looming risk of untreatable infections, and (2) spur concerted action, both to prevent further spread of resistant pathogens and to preserve the effectiveness of existing antibiotics. Thinking of antibiotics as a precious and diminishing resource has engendered the concept of antimicrobial stewardship, a defined set of practices designed to improve the appropriate use of antimicrobial agents.2 Table 1 lists steps to help implement resistance prevention strategies. Family physicians have an important role in combating antibiotic resistance through carefully prescribing antibiotics, educating patients, and identifying and reporting unexpected treatment failures and suspected resistance.

StepsSuggestions for implementation
Improve antibiotic prescribing
Use current clinical guidelines to support rational and appropriate antibiotic prescribing
  • Share unremarkable findings during the examination (e.g., “no inflammation” or “normal breathing”), while acknowledging the patient is sick

  • Determine the likelihood of a bacterial infection, especially for upper respiratory tract infections

  • Provide a specific diagnosis (e.g., “viral bronchitis” vs. “virus”)

  • Weigh benefits vs. harms of antibiotics

  • Implement judicious prescribing strategies

Communicate with patients about when and why antibiotics may not be necessary
  • Explain that unnecessary antibiotic use can be harmful (e.g., adverse effects associated with antibiotic use, potential resistance development)

  • Explain that treating viral infections with antibiotics does not work

  • Explicitly plan treatment of symptoms by describing the expected normal course of the illness, and instruct patients to call or come back if symptoms persist or worsen; consider providing care packages with nonantibiotic therapies

Educate patients if an antibiotic is needed
  • Encourage adherence

  • Discuss potential adverse effects

Create an office environment that promotes a reduction in antibiotic use
  • Start the process in the waiting room with videos, posters, and other materials

  • Hang posters in examination rooms to display a commitment to not prescribe antibiotics for viral infections

  • Involve office personnel in the reinforcement of the physician's messages

Prevent infections and the spread of resistant bacteria
Ensure that all patients get recommended vaccinations
  • Provide pneumococcal and influenza vaccines (to help avoid secondary bacterial infections), which are particularly important

Prevent cross-transmission
Monitor antibiotic-resistant infections
Report notifiable diseases
  • When appropriate, report to the health department any diseases caused by bacteria on the Centers for Disease Control and Prevention's list of urgent and serious pathogens (reporting requirements differ by U.S. state and Canadian province); antibiotic-resistant strains of some bacteria (e.g., methicillin-resistant S. aureus) are reportable in some states

Be alert for treatment failures
  • Consider the possibility of antibiotic resistance in cases of treatment failure; obtain laboratory confirmation and notify local public health authorities in cases of unusual or unexpected treatment failure

There are three main elements of preventing and controlling antibiotic resistance that are most applicable to outpatient practice. First, physicians must improve their antibiotic prescribing. Antibiotic use is the principal driver of antibacterial resistance. A considerable proportion of antibiotics in inpatient and outpatient settings are prescribed in cases when they are not needed or in which the choice of antibiotic, the dose, or the duration of therapy is inappropriate.3,4 Rates of outpatient antibiotic prescribing vary widely by region and state—a much greater variation than is likely explained by differences in patient populations or rates of bacterial diseases.5 It has been documented that inappropriate antibiotic prescribing, especially for viral upper respiratory tract infections, is common in ambulatory care.6 These illnesses are the most common reason for seeking medical attention in the United States and are associated with up to 75% of total antibiotic prescriptions each year.7 The causes of the overuse of antibiotics, which is a problem throughout the world, are complex and well described.8,9

The second main element is preventing infections and the spread of resistance. Preventing an infection eliminates the possibility that the infection could be drug resistant. Immunization and rigorous infection control, including hand washing, clearly reduce the likelihood of infection. On its website, the CDC provides information for patients on how to protect themselves from many types of infections, such as by ensuring safe food handling to prevent Salmonella and Campylobacter infections10 and by avoiding gonorrhea and other sexually transmitted infections.11 Counseling patients on how to avoid spreading or becoming infected with resistant pathogens in the community is an important role for physicians. For example, if an athlete is diagnosed with a methicillin-resistant Staphylococcus aureus infection, he or she should keep the wound properly covered, avoid whirlpools or therapy pools, shower after participation, clean uniforms and equipment after each use, and report infection to coaches and trainers.

The third main element is public health reporting. Gathering, analyzing, and disseminating information on resistant infections and the prevalence of resistant microorganisms is a critical strategy that informs clinical and public health decision making. A key component of detecting emerging and spreading resistance is identifying the cause of unexpected treatment failures. Patients who return with persistent or recurrent symptoms shortly after treatment should be retested by culture, and isolates should be submitted for antimicrobial susceptibility testing. Any case of unexplained treatment failure or a positive culture result after appropriate empiric treatment should be reported promptly to local or state health departments.12 Ultimately, public health surveillance is dependent on reporting by physicians and laboratories.

The nightmare scenario of the spread of pan-resistant bacteria is a real and frightening possibility. Cases of untreatable infections are already occurring. Preventing and controlling resistance requires the engagement of many different sectors of society. However, the physician's role in this effort is singularly important.12 As the threat becomes more urgent, the leadership of the medical community is the most critical factor to ensure a successful response.

The findings and conclusions of this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. Mention of trade names or commercial products does not constitute endorsement or recommendation for use by the U.S. government.

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