Reducing Antibiotic Use Can Alter Antibiotic Resistance.

Friedman CR, Whitney CG. It's Time for a Change in Practice: Reducing Antibiotic Use Can Alter Antibiotic Resistance. J Infect Dis 2008 Apr 15;197:1082.(Editorial)
This article is in the public domain, and no copyright is claimed.
0022-1899/2008/19708-0002
DOI: 10.1086/533450

http://www.journals.uchicago.edu/doi/full/10.1086/533450
http://www.journals.uchicago.edu/doi/pdf/10.1086/533450

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The Journal of Infectious Diseases 2008;197:1082–1083
This article is in the public domain, and no copyright is claimed.
0022-1899/2008/19708-0002
DOI: 10.1086/533450

EDITORIAL COMMENTARY
It's Time for a Change in Practice: Reducing Antibiotic Use Can Alter Antibiotic Resistance
Cindy R. Friedman and Cynthia G. Whitney
Centers for Disease Control and Prevention, Atlanta, Georgia
Received 9 January 2008; accepted 9 January 2008; electronically published 7 March 2008.
Potential conflicts of interest: none reported.
(See the article by Dagan et al., on pages 1094–102; the article by Peters et al., on pages 1087–93; and the editorial commentary by Rice, on pages 1079–81.)
Reprints or correspondence: Dr. Cindy Friedman, Centers for Disease Control and Prevention, 1600 Clifton Rd., MS C-23, Atlanta, GA 30333 (crfriedman@cdc.gov).

In this issue of the Journal, Dagan et al. [1] present important findings demonstrating a link between reduced antibiotic use during the summer months and a rapid seasonal decrease in antibiotic-resistant pneumococci that cause otitis media. The investigation in southern Israel showed a summertime reduction in otitis caused by resistant pneumococci among Jewish children

As the authors point out, the relationship between antibiotic use and resistance is complex. Models suggest that resistance imposes a cost on bacterial fitness and that reducing antibiotic use will favor the selection of sensitive strains over resistant ones by decreasing selective pressure [2, 3]. In addition, the total amount of antimicrobial use may not be the only driver of resistance; the specific types of antibiotics used are probably important, the fitness cost derived from resistance mutations may vary among different bacterial strains, and bacteria may develop mechanisms over time that overcome some or all of the fitness cost. Although antibiotic use has been linked to resistance in several studies [4–6], few have shown a decline in antibiotic resistance after a reduction in antibiotic use [7]. In Israel, the drop in resistance was seen in one segment of the population (Jews) but not among another distinct group (Bedouins). Is it possible that, among Jewish children, overall antimicrobial use fell below a threshold at which the fitness cost of resistance was stronger than the selective pressure driving antimicrobial resistance? The low use of azithromycin and cephalosporins among the Jewish population, especially during the summer months, may have also helped decrease the prevalence of resistant pneumococci that caused otitis media.

Over the last 2 decades, the Institute of Medicine has declared antimicrobial resistance to be a global health threat [8, 9]. Factors that may affect the development of antimicrobial resistance are numerous and include dose, duration of treatment and class of antibiotic (selective pressure), disease transmission and exposure rates, host susceptibility (e.g., vaccination status), and transmissibility (fitness cost) of the pathogen. Three areas have been the main foci for the prevention and control of antimicrobial resistance: (1) vaccines, (2) development of new antibiotics, and (3) reducing inappropriate antimicrobial use. Over the past few years, pneumococcal conjugate vaccine use has been shown to decrease antibiotic resistance by reducing the burden of disease caused by resistant pneumococci and targeting pneumococcal strains that most often tend to be resistant [10]. New classes or more potent versions of existing antibiotics can be useful for the treatment of resistant infections. However, there are barriers to both vaccine and new drug development. New product development is often time consuming and expensive, and manufacturers may have few incentives to develop new antibiotics or vaccines. Therefore, preserving existing antibiotics for as long as possible by reducing inappropriate antimicrobial use is of paramount importance.

In the United States, 55% (26 million) of all antibiotics prescribed for acute respiratory tract infections (e.g., upper respiratory tract infections, otitis media, sinusitis, pharyngitis, and bronchitis) in the outpatient setting are probably not needed, based on estimates of the proportion of these infections that are caused by bacteria. In 1999, the estimated cost of these inappropriate antibiotic prescriptions was $732 million of the $1.32 billion spent on outpatient antibiotics [11]. Why do physicians continue to prescribe antibiotics inappropriately for acute respiratory infections in the outpatient setting? Research has shown that physicians are concerned that patients expect an antibiotic when they come to the office for an acute respiratory tract infection, that distinguishing bacterial from viral respiratory tract infections is difficult, and that time constraints preclude explaining to a patient why an antibiotic is not necessary; in many situations, writing a prescription may be faster than not writing one [12]. The same study showed that patients believe that antibiotics are needed if there is green nasal discharge and that antibiotics help them to feel better and return to work, school, or day care quickly. Patients state that, if they do not need an antibiotic, they want a clear explanation of why not [12].

The article by Dagan et al. provides evidence that reducing antimicrobial use may indeed reduce resistant infections; the challenge now is for clinicians to reduce unnecessary use. Multifaceted appropriate-antimicrobial-use campaigns that target both physicians and patients have been shown to decrease inappropriate prescribing significantly [13, 14]. National and local campaigns to reduce inappropriate antibiotic use have been developed in both the United States and Europe [15, 16] and may be needed in other regions. In the United States, the Get Smart: Know When Antibiotics Work campaign (http://www.cdc.gov/drugresistance/community/), sponsored by the Centers for Disease Control and Prevention, is a public health program aimed at decreasing unnecessary antimicrobial use in the community and ultimately reducing antimicrobial resistance by promoting appropriate prescribing among providers, decreasing the demand for antibiotics by the public, and promoting adherence to dose and duration once an antibiotic has been prescribed.

The focus of the program has been on the 5 conditions that account for most inappropriate prescribing in the community: upper respiratory tract infections, otitis media, sinusitis, pharyngitis, and acute bronchitis. The campaign has developed public service announcements, media tool kits, patient information brochures and Web sites, appropriate-use guidelines for providers (endorsed by professional societies), physician detailing sheets, pharmacy education programs, viral prescription pads, medical school and residency educational curricula, and continuing medical education programs. Although educational programs such as Get Smart have begun in many places, the paradigm shift needed among clinicians to reduce antimicrobial use below a level that drives resistance has not yet been achieved. This shift may require additional measures. Dagan et al. refer prominently to the use of antibiotic-restriction policies; such policies may be practical in certain settings. However, additional methods—such as validated treatment algorithms, decision support systems, and rapid diagnostic tests that can help clinicians identify patients for whom antibiotics are not needed—may help reduce inappropriate antibiotic use to a level at which a change in the prevalence of antibiotic resistance can occur.
National data have shown a general decline in outpatient antibiotic use for acute respiratory tract infections over the past decade in the United States [17], likely because of appropriate-use campaigns and vaccines (such as pneumococcal conjugate vaccine). Skeptics argue that although interventions can reduce inappropriate use of antibiotics, this drop in prescriptions may not be enough to reduce or reverse the development of antibiotic resistance. The lack of data suggesting how much of a decline in use is necessary to achieve a decline in resistance, or whether a reduction could result in such a change, has fueled some of this skepticism. The analysis presented by Dagan et al. provides solid evidence that reducing antibiotic use can lead to a reduction in resistant pneumococcal infections. In addition, their findings provide a start toward estimating how much of a drop in use is necessary to reverse the spread of antibiotic-resistant strains.

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