Research Article: Antibiotic Selection Pressure and Macrolide Resistance in Nasopharyngeal Streptococcus pneumoniae: A Cluster-Randomized Clinical Trial

Date Published: December 14, 2010

Publisher: Public Library of Science

Author(s): Alison H. Skalet, Vicky Cevallos, Berhan Ayele, Teshome Gebre, Zhaoxia Zhou, James H. Jorgensen, Mulat Zerihun, Dereje Habte, Yared Assefa, Paul M. Emerson, Bruce D. Gaynor, Travis C. Porco, Thomas M. Lietman, Jeremy D. Keenan, Steven M. Opal

Abstract: Jeremy Keenan and colleagues report that during a cluster-randomized clinical trial in Ethiopia, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to receive azithromycin compared with untreated control communities.

Partial Text: Antibiotic selection pressure is thought to be an important mechanism of selecting for antibiotic resistance in populations [1]. High antibiotic use is correlated with antibiotic resistance in ecological studies [2]–[10], and cross-sectional, cohort, and case-control studies have confirmed these findings [11]–[13]. Although these studies suggest that population-level antibiotic pressure is associated with resistance, these study designs are subject to bias [14],[15]. A randomized controlled trial would provide the strongest evidence for a causal relationship between community antibiotic consumption and resistance.

The study had approval from the Committee for Human Research of the University of California, San Francisco, Emory University, and the Ethiopian Science and Technology Commission. The study was carried out in accordance with the Declaration of Helsinki and overseen by a Data Safety and Monitoring Committee appointed by the National Institutes of Health-National Eye Institute.

This cluster-randomized clinical trial demonstrates that frequent antibiotic use selects for community-level antibiotic resistance. In communities randomized to four azithromycin treatments within 1 y, azithromycin resistance was observed in 47% of all swabbed children and 62% of children colonized with pneumococcus; this was significantly higher than untreated control communities, in which resistance was found in 9% of swabbed children and 12% of children colonized with pneumococcus. Genotype analyses were consistent with the widely accepted theory that antibiotic selection pressure increases community antibiotic resistance by reducing susceptible bacterial strains and allowing clonal expansion of existing resistant strains.



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