Prevencion de Exacervaciones Antib Leida

T h e n e w e ngl a nd j o u r na l o f m e dic i n e

n engl j med 367;19 nejm.org november 8, 20121866

To the Editor: Wenzel et al. review the use of macrolide therapy for the prevention of COPD ex-acerbations. However, we have some concerns about the extrapolation of their conclusions worldwide. Different epidemiologic characteris-tics, rates of antibiotic resistance, and mecha-nisms of resistance among respiratory pathogens could be encountered in different countries.

The prevalence of macrolide-resistant Strepto-coccus pneumoniae, a major type of bacteria iso-lated in patients admitted for COPD exacerba-tion, is close to 96% in some Asian countries.1 Moreover, there are two common mechanisms of macrolide resistance in S. pneumoniae. The first mechanism involves the site where macrolides bind to the ribosome; this mechanism accounts for more than 90% of the macrolide-resistant isolate strains in Europe and confers high resis-tance (minimum inhibitory concentration, 64 g per milliliter).2 The second mechanism is caused by an efflux pump; this mechanism ac-counts for more than 65% of the macrolide-re-sistant isolate strains in the United States3 and confers a low level of macrolide resistance (minimum inhibitory concentration, 4 g per milliliter). The study conducted by Albert et al.4 was performed in the United States.

Before the use of azithromycin can be recom-mended worldwide, further studies should be performed in different geographic areas.

Carolina Garcia-Vidal, M.D., Ph.D. Diego Viasus, M.D., Ph.D. Jordi Carratal, M.D., Ph.D.Hospital Universitari de Bellvitge Barcelona, Spain [email protected]

No potential conflict of interest relevant to this letter was re-ported.

1. Hsueh PR, Teng LJ, Lee LN, Yang PC, Ho SW, Luh KT. Ex-tremely high incidence of macrolide and trimethoprim-sulfa-methoxazole resistance among clinical isolates of Streptococcus pneumoniae in Taiwan. J Clin Microbiol 1999;37:897-901.2. Reinert RR, Reinert S, van der Linden MY, Cil MY, Al-Lah-ham A, Appelbaum P. Antimicrobial susceptibility of Strepto-coccus pneumoniae in eight European countries from 2001 to 2003. Antimicrob Agents Chemother 2005;49:2903-13.3. Brown SD, Farrell DJ, Morrissey I. Prevalence and molecular analysis of macrolide and fluoroquinolone resistance among isolates of Streptococcus pneumoniae collected during the 2000-2001 PROTEKT US Study. J Clin Microbiol 2004;42:4980-7.4. Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med 2011;365:689-98. [Erratum, N Engl J Med 2012;366:1356.]

DOI: 10.1056/NEJMc1210335

To the Editor: In their review of long-term azith-romycin use for prevention of COPD exacerba-tions, Wenzel and coauthors acknowledge the risk of the development of infection with macro-lide-resistant nontuberculous mycobacteria, and they recommend screening for mycobacteria be-fore the initiation of azithromycin therapy and not administering this prophylaxis to patients with positive sputum cultures. The relationship between macrolides and nontuberculous myco-bacteria may be more complex than described, however. In addition to the specific risk of mac-rolide resistance,1 retrospective studies involving patients with cystic fibrosis suggest that azithro-mycin may increase the risk of the development of infections with nontuberculous mycobacte-ria,2,3 and widespread use of long-term azithro-mycin may in part explain the alarming increase in the incidence of infections with nontubercu-lous mycobacteria observed in patients with cystic fibrosis. Experimental evidence suggests a paradoxical effect of azithromycin on nontuber-culous mycobacteria, with bactericidal effects offset by reduced mycobacterial killing through inhibition of macrophage autophagy3 a more complex picture than that depicted in Figure 1 of the article by Wenzel et al. As the authors note, the long-term adverse effects of macrolide use in patients with COPD remain unknown, but clini-cians should remain alert to the possibility of the development of nontuberculous mycobacterial disease in patients during prolonged use of azith-romycin prophylaxis.

Stephen J. Chapman, D.M.Oxford Radcliffe Hospitals Oxford, United Kingdom [email protected]

No potential conflict of interest relevant to this letter was re-ported.

1. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007;175:367-416. [Erratum, Am J Respir Crit Care Med 2007;175:744-5.]2. Levy I, Grisaru-Soen G, Lerner-Geva L, et al. Multicenter cross-sectional study of nontuberculous mycobacterial infec-tions among cystic fibrosis patients, Israel. Emerg Infect Dis 2008;14:378-84.3. Renna M, Schaffner C, Brown K, et al. Azithromycin blocks autophagy and may predispose cystic fibrosis patients to myco-bacterial infection. J Clin Invest 2011;121:3554-63.

DOI: 10.1056/NEJMc1210335

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Prevencion de Exacervaciones Antib Leida

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