It's Time for a Change in Practice: Reducing Antibiotic Use Can Alter Antibiotic Resistance

Abstract

duction in otitis caused by resistant pneumococci among Jewish children <5 years of age that coincided with a period of reduced antibiotic use. A similar reduction was not seen among Bedouin children. Bedouin children had higher rates of antimicrobial use yearround compared with Jewish children, and although total use decreased in both groups during the summer months, use of cephalosporins and azithromycin did not decrease among Bedouin children during that time. 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 outpaReceived 9 January 2008; accepted 9 January 2008; electronically published 7 March 2008. Potential conflicts of interest: none reported. Reprints or correspondence: Dr. Cindy Friedman, Centers for Disease Control and Prevention. 1600 Clifton Rd., MS C-23, Atlanta, GA 30333 (crfriedman@cdc.gov). The Journal of Infectious Diseases 2008; 197:1082-3 This article is in the public domain, and no copyright is claimed. 0022-1899/2008/19708-0002 DOI: 10.1086/533450