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American Journal of Epidemiology Advance Access originally published online on November 30, 2005
American Journal of Epidemiology 2006 163(2):160-170; doi:10.1093/aje/kwj021
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American Journal of Epidemiology Copyright © 2005 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.

Original Contribution

Mechanisms by Which Antibiotics Promote Dissemination of Resistant Pneumococci in Human Populations

Matthew H. Samore1, Marc Lipsitch2,3, Stephen C. Alder1, Bassam Haddadin1, Greg Stoddard1, Jacquelyn Williamson1, Katherine Sebastian1, Karen Carroll4, Onder Ergonul2,3, Yehuda Carmeli1 and Merle A. Sande5

1 Division of Clinical Epidemiology, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT
2 Department of Epidemiology, Harvard School of Public Health, Boston, MA
3 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA
4 Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD
5 Department of Medicine, University of Washington School of Medicine, Seattle, WA

Correspondence to Dr. Matthew Samore, Department of Clinical Epidemiology, School of Medicine, University of Utah, 50 North Medical Drive, Room AC230A, Salt Lake City, UT 84132 (e-mail: matthew.samore{at}hsc.utah.edu).

Mechanisms by which antimicrobials contribute to dissemination of pneumococcal resistance are incompletely characterized. A serial cross-sectional study of nasopharyngeal pneumococcal carriage in healthy, home-living children ≤6 years of age was conducted in four rural communities—two in Utah (1998–2003) and two in Idaho (2002–2003). Prevalence odds ratios for carriage of resistant pneumococci (ORres) and of susceptible pneumococci (ORsus) were estimated. Dynamic transmission models were developed to facilitate a mechanistic interpretation of ORres and ORsus and to compare the population impact of distinct antimicrobial classes. A total of 5,667 cultures were obtained; 25% of the cultures were positive, and 29% of isolates exhibited reduced susceptibility to penicillin. The adjusted ORres for recent individual and sibling cephalosporin use was 2.2 (95% confidence interval: 1.4, 3.4) and 1.8 (95% confidence interval: 1.0, 3.3), respectively. Neither individual nor sibling penicillin use was associated with increased ORres. Rather, recent use of penicillins was associated with decreased carriage of susceptible pneumococci (ORsus = 0.2, 95% confidence interval: 0.1, 0.3). In simulations, both types of effects promoted dissemination of resistant pneumococci at the population level. Findings show that oral cephalosporins enhance the risk of acquiring resistant pneumococci. Penicillins accelerate clearance of susceptible strains. The effect of penicillins in increasing resistance is shared equally by treated and untreated members of the population.

cephalosporins; drug resistance, microbial; nasopharyngeal diseases; penicillins; Streptococcus pneumoniae

Abbreviations: CI, confidence interval; ORC, odds ratio for carriage of resistant pneumococci using carriers of susceptible pneumococci as the comparison group; ORres, odds ratio for carriage of resistant pneumococci; ORsus, odds ratio for carriage of susceptible pneumococci


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