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Terri B. Hyde, MD; Kathryn Gay, VMD,MS; David S. Stephens, MD; Duc J. Vugia, MD,MPH; Margaret Pass, MS; Susan Johnson; Nancy L. Barrett, MS,MPH; William Schaffner, MD; Paul R. Cieslak, MD; Peggy S. Maupin; Elizabeth R. Zell, MStat; James H. Jorgensen, PhD; Richard R. Facklam, PhD; Cynthia G. Whitney, MD,MPH; for the Active Bacterial Core Surveillance/Emerging Infections Program Network

JAMA. 2001;286:1857-1862.

Context  Macrolide antibiotics, including erythromycin, clarithromycin, and azithromycin, are the mainstays of empirical pneumonia therapy. Macrolide resistance among Streptococcus pneumoniae, the most common cause of community-acquired pneumonia, is increasing in the United States. Whether resistance is a significant problem or whether macrolides remain useful for treatment of most resistant strains is unknown.

Objective  To examine the epidemiology of macrolide-resistant pneumococci in the United States.

Design and Setting  Analysis of 15 481 invasive isolates from 1995 to 1999 collected by the Centers for Disease Control and Prevention's Active Bacterial Core surveillance system in 8 states.

Main Outcome Measures  Trends in macrolide use (1993-1999) and resistance and factors associated with resistance, including examination of 2 subtypes, the M phenotype, associated with moderate minimum inhibitory concentrations (MICs), and the MLS_B phenotype, associated with high MICs and clindamycin resistance.

Results  From 1993 to 1999, macrolide use increased 13%; macrolide use increased 320% among children younger than 5 years. Macrolide resistance increased from 10.6% in 1995 to 20.4% in 1999. M phenotype isolates increased from 7.4% to 16.5% (P<.001), while the proportion with the MLS_B phenotype was stable (3%-4%). The median erythromycin MIC (MIC₅₀) of M phenotype isolates increased from 4 µg/mL to 8 µg/mL. In 1999, M phenotype strains were more often from children than persons 5 years or older (25.2% vs 12.6%; P<.001) and from whites than blacks (19.3% vs 11.2%; P<.001).

Conclusions  In the setting of increasing macrolide use, pneumococcal resistance has become common. Most resistant strains have MICs in the range in which treatment failures have been reported. Further study and surveillance are critical to understanding the clinical implications of our findings.

Author Affiliations: Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases (Drs Hyde, Facklam, and Whitney and Ms Zell), Epidemic Intelligence Service, Epidemiology Program Office, Centers for Disease Control and Prevention (Dr Hyde), and Emory University School of Medicine, Department of Veterans Affairs Medical Center (Drs Stephens and Gay), Atlanta, Ga; California Department of Health and Human Services, Berkeley (Dr Vugia); Johns Hopkins University School of Hygiene and Public Health, Baltimore, Md (Ms Pass); Minnesota Department of Health, School of Public Health, Minneapolis (Ms Johnson); Connecticut Department of Public Health, Hartford (Ms Barrett); Department of Preventive Medicine, Vanderbilt Medical Center, Nashville, Tenn (Dr Schaffner); Oregon Department of Human Service, Health Division, Portland (Dr Cieslak); Monroe County Health Department of Human Service, Rochester, NY (Ms Maupin); and University of Texas Health Science Center, San Antonio (Dr Jorgensen).
   Listings of members of the Active Bacterial Core Surveillance/Emerging Infections Program Network were published previously (N Engl J Med. 2000;343:1917 and JAMA. 2001;285:1729).

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