Editorial

Antimicrobial Prescribing in the United States: Good News, Bad News

ntimicrobial resistance is a global public health problem facing both the developed and developing world (1). It affects our ability to treat infections of major international importance, such as HIV infection, tuberculosis, and malaria, as well as common infections primary care physicians face daily, such as otitis media, sinusitis, and pneumonia. During the 1990s, pneumococcal drug resistance rose dramatically. By 1998, 24% of invasive isolates in the United States were resistant to penicillin and 14% were resistant to three or more drug classes (2). Antimicrobial resistance is promoted by antimicrobial use, whether that use is appropriate or inappropriate (3). The more antimicrobials are used, the greater the selective pressure for the emergence of resistant bacteria. Inappropriate use only compounds the problem. A paper by McCaig and Hughes (4), published in 1995, focused attention on the issue of inappropriate antimicrobial prescribing. On the basis of data from the National Ambulatory Medical Care Survey, a population-based analysis of physician practices in 1992, the U.S. Centers for Disease Control and Prevention (CDC) estimated that more than 40% of antimicrobial courses prescribed in physicians ofces were inappropriate (5). In 1995, the CDC launched a campaign to promote appropriate antimicrobial use, joining with other groups around the United States that had already begun to promote more appropriate prescribing. There are many denitions of appropriate use. For the CDCs Campaign for Appropriate Antibiotic Use in the Community (www.cdc.gov/drugresistance/community), appropriate prescribing is dened as prescribing antimicrobials only when they are likely to be benecial to the patient, selecting agents that will target the likely pathogens, and using these agents at the correct dose and for the proper duration. The primary focus of the campaign has been on developing principles for appropriate prescribing that would limit antimicrobial prescribing to conditions caused by bacteria (6, 7). While the CDC has worked with others to develop guidelines for selecting antimicrobials for treating respiratory infections in the community (8, 9), little effort has gone into promoting the use of targeted therapy. In 2002, McCaig and colleagues (10) reported good news: a dramatic decline in the prescribing of antimicrobial agents to children and adolescents in doctors ofces. Between 1989 1990 and 1999 2000, ofce-based prescribing to children decreased by 47%. Although the analysis did not allow a determination of the reasons for this decline, the ongoing efforts throughout the United States probably played some role. In this issue, Steinman and colleagues (11) take the analysis of prescribing one step further by looking at the changing patterns of antimicrobial selection during the 1990s. Their study turns the spotlight on the second component of appropriate antimicrobial use: targeted anti-

microbial therapy. Herein lies the bad news. Steinman and colleagues found that while overall prescribing declined during the 1990s, a shift occurred from using targeted therapy to using broader-spectrum agents. By 1998 1999, almost half of all antimicrobials prescribed to adults and 40% of those prescribed to children were broad spectrum. These agents were used extensively for bacterial infections, for which antimicrobial therapy may be benecial, and for colds and bronchitis, for which antimicrobial therapy is rarely useful. An interesting example is seen with prescribing for pharyngitis. Antimicrobials are recommended for patients with documented group A streptococcal pharyngitis (12 14). Fortunately, the etiologic agent, Streptococcus pyogenes, has not developed resistance to penicillin, and all treatment guidelines recommend the use of penicillin in patients who are not allergic. Streptococcus pyogenes has developed resistance to macrolides, and these agents are not recommended unless patients are allergic to penicillin (15). Despite these guidelines, however, use of broad-spectrum agents, including newer macrolides, is increasing for children and adults. One might ask, does it matter that broader-spectrum agents are being overused? What is the cost? Apart from the economic implications discussed by Steinman and colleagues, there are public health consequences. By their nature, broad-spectrum agents apply selective pressure to many groups of bacteria, affecting the microbial ora and encouraging the emergence of resistance outside the target organism. Using these agents when they are not indicated reduces their effectiveness when they are needed to treat other infections. For example, extended-spectrum macrolides and uoroquinolones are two important agents for the treatment of patients with community-acquired pneumonia but are also frequently used to treat infections where more targeted therapy is indicated (9, 16). Increasing use of these agents is associated with rising resistance among pneumococci around the world (17, 18). We must consider these drugs as precious, limited resources because for many agents, once resistance becomes prevalent in the community, there may be no going back (19). Steinman and colleagues present a number of explanations for the trends they observed, citing in particular the inuence of pharmaceutical marketing on both prescribers and the general public. In 2001, the 14 largest pharmaceutical companies spent $9 billion on marketing all of their products, including antimicrobials, to primary care physicians and consumers (20). No marketing is undertaken for targeted agents, such as penicillin, amoxicillin, and erythromycin, which are no longer under patent protection. Those of us in public health may be partly to blame. As we sound the alarm about the peril of rising antimicrobial resistance, we may be inadvertently promoting inap1 April 2003 Annals of Internal Medicine Volume 138 Number 7 605

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Editorial

Antimicrobial Prescribing in the United States: Good News, Bad News

propriate use of broad-spectrum agents. We should inform the public that drug resistance is a problem that has the potential to affect everyones health, but we must do this while making sure patients and prescribers understand when broad-spectrum agents are indicated and when they are not. We should be encouraged by the work being done to promote appropriate antimicrobial use in the United States by coalitions made up of representatives of public health, managed care, health care purchasers, professional societies and schools, and industry. This work has undoubtedly been responsible for some of the declines in antimicrobial use reported by Steinman and colleagues. Now is the time to roll up our sleeves and start improving antimicrobial selection.
Richard E. Besser, MD Centers for Disease Control and Prevention Atlanta, GA 30333
Requests for Single Reprints: Richard E. Besser, MD, Respiratory

Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road (MS C23), Atlanta, GA 30333; e-mail, rbesser@cdc.gov. Ann Intern Med. 2003;138:605-606.

References
1. Institute of Medicine. Emerging Infections: Microbial Threats to the Health of the United States. Washington, DC: National Academy Pr; 1994. 2. Whitney CG, Farley MM, Hadler J, Harrison LH, Lexau C, Reingold A, et al. Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States. N Engl J Med. 2000;343:1917-24. [PMID: 11136262] 3. Lipsitch M, Samore MH. Antimicrobial use and antimicrobial resistance: a population perspective. Emerg Infect Dis. 2002;8:347-54. [PMID: 11971765] 4. McCaig LF, Hughes JM. Trends in antimicrobial drug prescribing among ofce-based physicians in the United States. JAMA. 1995;273:214-9. [PMID: 7807660] 5. Emmer C, Besser R. Combating antimicrobial resistance: intervention programs to promote appropriate antibiotic use. Infections in Medicine. 2002;19: 160-73. 6. Dowell SF. Principles of judicious use of antimicrobial agents for pediatric

upper respiratory tract infections. Pediatrics. 1998;101:S163-84. 7. Gonzales R, Bartlett JG, Besser RE, Cooper RJ, Hickner JM, Hoffman JR, et al. Principles of appropriate antibiotic use for treatment of acute respiratory tract infections in adults: background, specic aims, and methods. Ann Intern Med. 2001;134:479-86. [PMID: 11255524] 8. Dowell SF, Butler JC, Giebink GS, Jacobs MR, Jernigan D, Musher DM, et al. Acute otitis media: management and surveillance in an era of pneumococcal resistancea report from the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group. Pediatr Infect Dis J. 1999;18:1-9. [PMID: 9951971] 9. Bartlett JG, Dowell SF, Mandell LA, File TM Jr, Musher DM, Fine MJ. Practice guidelines for the management of community-acquired pneumonia in adults. Infectious Diseases Society of America. Clin Infect Dis. 2000;31:347-82. [PMID: 10987697] 10. McCaig LF, Besser RE, Hughes JM. Trends in antimicrobial prescribing rates for children and adolescents. JAMA. 2002;287:3096-102. [PMID: 12069672] 11. Steinman MA, Gonzales R, Linder JA, Landefeld CS. Changing use of antibiotics in community-based outpatient practice, 19911999. Ann Intern Med. 2003;138:525-33. 12. Bisno AL, Gerber MA, Gwaltney JM Jr, Kaplan EL, Schwartz RH. Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. Infectious Diseases Society of America. Clin Infect Dis. 2002;35:113-25. [PMID: 12087516] 13. Schwartz B, Marcy SM, Phillips WR, Gerber MA, Dowell SF. Pharyngitisprinciples of judicious use of antimicrobial agents. Pediatrics. 1998;101: 171-4. 14. Cooper RJ, Hoffman JR, Bartlett JG, Besser RE, Gonzales R, Hickner JM, et al. Principles of appropriate antibiotic use for acute pharyngitis in adults: background. Ann Intern Med. 2001;134:509-17. [PMID: 11255530] 15. Martin JM, Green M, Barbadora KA, Wald ER. Erythromycin-resistant group A streptococci in schoolchildren in Pittsburgh. N Engl J Med. 2002;346: 1200-6. [PMID: 11961148] 16. Niederman MS, Mandell LA, Anzueto A, Bass JB, Broughton WA, Campbell GD, 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;163:1730-54. [PMID: 11401897] 17. Hyde TB, Gay K, Stephens DS, Vugia DJ, Pass M, Johnson S, et al. Macrolide resistance among invasive Streptococcus pneumoniae isolates. JAMA. 2001;286:1857-62. [PMID: 11597287] 18. Ho PL, Yung RW, Tsang DN, Que TL, Ho M, Seto WH, et al. Increasing resistance of Streptococcus pneumoniae to uoroquinolones: results of a Hong Kong multicentre study in 2000. J Antimicrob Chemother. 2001;48:659-65. [PMID: 11679555] 19. Levin BR. Minimizing potential resistance: a population dynamics view. Clin Infect Dis. 2001;33 Suppl 3:S161-9. [PMID: 11524714] 20. Petersen M. Less return in marketing of medicines, a study says. The New York Times. 2002;12 December:C5.

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