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

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Abstract
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.