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

Antimicrobial resistance is a global public health prob-lem facing both the developed and developing world(1). It affects our ability to treat infections of major inter-national importance, such as HIV infection, tuberculosis,

and malaria, as well as common infections primary carephysicians face daily, such as otitis media, sinusitis, andpneumonia. During the 1990s, pneumococcal drug resis-tance rose dramatically. By 1998, 24% of invasive isolatesin 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 selectivepressure for the emergence of resistant bacteria. Inappro-priate use only compounds the problem. A paper by Mc-Caig and Hughes (4), published in 1995, focused attention

on the issue of inappropriate antimicrobial prescribing. Onthe basis of data from the National Ambulatory MedicalCare Survey, a population-based analysis of physician prac-tices in 1992, the U.S. Centers for Disease Control andPrevention (CDC) estimated that more than 40% of anti-microbial courses prescribed in physicians offices were in-appropriate (5). In 1995, the CDC launched a campaignto promote appropriate antimicrobial use, joining withother groups around the United States that had alreadybegun to promote more appropriate prescribing.

There are many definitions of appropriate use. Forthe CDCs Campaign for Appropriate Antibiotic Use in

the Community (www.cdc.gov/drugresistance/community),appropriate prescribing is defined as prescribing antimicro-bials only when they are likely to be beneficial to the pa-tient, selecting agents that will target the likely pathogens,and using these agents at the correct dose and for theproper duration. The primary focus of the campaign hasbeen on developing principles for appropriate prescribingthat would limit antimicrobial prescribing to conditionscaused by bacteria (6, 7). While the CDC has worked withothers to develop guidelines for selecting antimicrobials fortreating respiratory infections in the community (8, 9), littleeffort has gone into promoting the use of targeted therapy.

In 2002, McCaig and colleagues (10) reported goodnews: a dramatic decline in the prescribing of antimicrobialagents to children and adolescents in doctors offices. Be-tween 19891990 and 19992000, office-based prescrib-ing to children decreased by 47%. Although the analysisdid not allow a determination of the reasons for this de-cline, the ongoing efforts throughout the United Statesprobably played some role.

In this issue, Steinman and colleagues (11) take theanalysis of prescribing one step further by looking at thechanging patterns of antimicrobial selection during the1990s. Their study turns the spotlight on the second com-ponent of appropriate antimicrobial use: targeted anti-

microbial therapy. Herein lies the bad news. Steinman andcolleagues found that while overall prescribing declinedduring the 1990s, a shift occurred from using targetedtherapy to using broader-spectrum agents. By 19981999,

almost half of all antimicrobials prescribed to adults and40% of those prescribed to children were broad spectrum.These agents were used extensively for bacterial infections,for which antimicrobial therapy may be beneficial, and forcolds and bronchitis, for which antimicrobial therapy israrely useful.

An interesting example is seen with prescribing forpharyngitis. Antimicrobials are recommended for patients

with documented group A streptococcal pharyngitis (1214). Fortunately, the etiologic agent, Streptococcus pyogenes,has not developed resistance to penicillin, and all treatmentguidelines recommend the use of penicillin in patients who

are not allergic. Streptococcus pyogenes has developed resis-tance to macrolides, and these agents are not recom-mended unless patients are allergic to penicillin (15). De-spite these guidelines, however, use of broad-spectrumagents, including newer macrolides, is increasing for chil-dren and adults.

One might ask, does it matter that broader-spectrumagents are being overused? What is the cost? Apart fromthe economic implications discussed by Steinman and col-leagues, there are public health consequences. By their na-ture, broad-spectrum agents apply selective pressure tomany groups of bacteria, affecting the microbial flora and

encouraging the emergence of resistance outside the targetorganism. Using these agents when they are not indicatedreduces their effectiveness when they are needed to treatother infections. For example, extended-spectrum macro-lides and fluoroquinolones are two important agents forthe treatment of patients with community-acquired pneu-monia but are also frequently used to treat infections wheremore targeted therapy is indicated (9, 16). Increasing useof these agents is associated with rising resistance amongpneumococci around the world (17, 18). We must con-sider these drugs as precious, limited resources because formany agents, once resistance becomes prevalent in thecommunity, there may be no going back (19).

Steinman and colleagues present a number of explana-tions for the trends they observed, citing in particular theinfluence of pharmaceutical marketing on both prescribersand the general public. In 2001, the 14 largest pharmaceu-tical companies spent $9 billion on marketing all of theirproducts, including antimicrobials, to primary care physi-cians and consumers (20). No marketing is undertaken fortargeted agents, such as penicillin, amoxicillin, and eryth-romycin, 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 antimicro-bial resistance, we may be inadvertently promoting inap-

Editorial

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propriate use of broad-spectrum agents. We should informthe public that drug resistance is a problem that has thepotential to affect everyones health, but we must do this

while making sure patients and prescribers understandwhen broad-spectrum agents are indicated and when theyare not.

We should be encouraged by the work being done topromote appropriate antimicrobial use in the United Statesby coalitions made up of representatives of public health,managed care, health care purchasers, professional societiesand schools, and industry. This work has undoubtedlybeen responsible for some of the declines in antimicrobialuse reported by Steinman and colleagues. Now is the timeto roll up our sleeves and start improving antimicrobialselection.

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 Preven-tion, 1600 Clifton Road (MS C23), Atlanta, GA 30333; e-mail,

rbesser@cdc.gov.

Ann Intern Med. 2003;138:605-606.

References1. Institute of Medicine. Emerging Infections: Microbial Threats to the Healthof 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 theUnited States. N Engl J Med. 2000;343:1917-24. [PMID: 11136262]

3. Lipsitch M, Samore MH. Antimicrobial use and antimicrobial resistance: apopulation perspective. Emerg Infect Dis. 2002;8:347-54. [PMID: 11971765]

4. McCaig LF, Hughes JM. Trends in antimicrobial drug prescribing amongoffice-based physicians in the United States. JAMA. 1995;273:214-9. [PMID:7807660]

5. Emmer C, Besser R. Combating antimicrobial resistance: intervention pro-grams 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 respiratorytract infections in adults: background, specific aims, and methods. Ann InternMed. 2001;134:479-86. [PMID: 11255524]

8. Dowell SF, Butler JC, Giebink GS, Jacobs MR, Jernigan D, Musher DM, etal. Acute otitis media: management and surveillance in an era of pneumococcalresistancea report from the Drug-resistant Streptococcus pneumoniaeTherapeu-

tic 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 inadults. Infectious Diseases Society of America. Clin Infect Dis. 2000;31:347-82.[PMID: 10987697]

10. McCaig LF, Besser RE, Hughes JM. Trends in antimicrobial prescribingrates for children and adolescents. JAMA. 2002;287:3096-102. [PMID: 12069672]

11. Steinman MA, Gonzales R, Linder JA, Landefeld CS. Changing use ofantibiotics in community-based outpatient practice, 19911999. Ann InternMed. 2003;138:525-33.

12. Bisno AL, Gerber MA, Gwaltney JM Jr, Kaplan EL, Schwartz RH. Practiceguidelines for the diagnosis and management of group A streptococcal pharyngi-tis. 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. Pharyngi-tisprinciples 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-resistantgroup 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, Camp-bell GD, et al. Guidelines for the management of adults with community-ac-quired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, andprevention. 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. Increasingresistance of Streptococcus pneumoniae to fluoroquinolones: results of a HongKong multicentre study in 2000. J Antimicrob Chemother. 2001;48:659-65.[PMID: 11679555]

19. Levin BR. Minimizing potential resistance: a population dynamics view. ClinInfect Dis. 2001;33 Suppl 3:S161-9. [PMID: 11524714]

20. Petersen M. Less return in marketing of medicines, a study says. The NewYork Times. 2002;12 December:C5.

2003 American College of Physicians

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

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