Antibiotic selection pressure and macrolide resistance in nasopharyngeal XXXX : a cluster-randomized clinical trial.

@entity1 @entity7706 @entity11738 @entity114 @entity4580 @entity7187 @entity328
BACKGROUND: It is widely thought that widespread antibiotic use selects for community antibiotic resistance, though this has been difficult to prove in the setting of a community-randomized clinical trial. In this study, we used a randomized clinical trial design to assess whether macrolide resistance was higher in communities treated with mass @entity4580 for @entity11738 , compared to untreated control communities. METHODS AND FINDINGS: In a cluster-randomized trial for @entity11738 control in Ethiopia, 12 communities were randomized to receive mass @entity4580 treatment of @entity1 aged 1-10 years at months 0, 3, 6, and 9. Twelve control communities were randomized to receive no antibiotic treatments until the conclusion of the study. Nasopharyngeal swabs were collected from randomly selected @entity1 in the treated group at baseline and month 12, and in the control group at month 12. Antibiotic susceptibility testing was performed on @entity328 isolated from the swabs using Etest strips. In the treated group, the mean prevalence of @entity4580 resistance among all monitored @entity1 increased from 3.6% (95% confidence interval [CI] 0.8%-8.9%) at baseline, to 46.9% (37.5%-57.5%) at month 12 (p = 0.003). In control communities, @entity4580 resistance was 9.2% (95% CI 6.7%-13.3%) at month 12, significantly lower than the treated group (p < 0.0001). @entity114 resistance was identified in 0.8% (95% CI 0%-4.2%) of isolates in the control group at 1 year, and in no isolates in the @entity1 -treated group at baseline or 1 year. CONCLUSIONS: This cluster-randomized clinical trial demonstrated that compared to untreated control communities, nasopharyngeal pneumococcal resistance to @entity7187 was significantly higher in communities randomized to intensive @entity4580 treatment. Mass @entity4580 distributions were given more frequently than currently recommended by the World Health Organization's @entity11738 program. @entity4580 use in this setting did not select for resistance to penicillins, which remain the drug of choice for @entity7706 . TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00322972. Please see later in the article for the Editors' Summary.
