Effect of Biannual Azithromycin Distribution to Infants on Community Gut Resistome and Microbiome: A Cluster-Randomized, Controlled Trial

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Résumé

ABSTRACT. Biannual azithromycin administration to preschool children in sub-Saharan Africa improved childhood mortality but selected for antibiotic resistance (AMR). WHO guidelines recommended focusing treatment on infants ages 1–11 months old to reduce mortality while minimizing selection of AMR. The Infant Mortality Reduction by the Mass Administration of Azithromycin study was a double-masked, placebo-controlled, cluster-randomized trial that investigated these WHO guidelines. Health centers from three regions of Burkina Faso were randomized in a 2:1 ratio to receive either biannual azithromycin (67%) or placebo (33%) distribution to children 1–11 months old. A total of 3,524 rectal samples from children ages 1–59 months old from 60 randomly selected communities were included in the analysis. The prespecified primary outcome was the community-level fold change in macrolide resistance determinants between arms at the 24-month time point. Macrolide resistance determinants in the gut of children in communities whose infants received azithromycin did not increase compared with those in communities treated with placebo (1.05-fold change). Similarly, the fold changes for resistance determinants for beta-lactams, metronidazole, sulfonamides, tetracycline, and trimethoprim were 0.99-fold, 1.00-fold, 1.22-fold, 0.96-fold, and 0.96-fold, respectively. At 6 months after the fourth treatment, there were no detectable differences in the microbiome structure (Euclidean permutational multivariate analysis of variance) and Shannon diversity index between treatment arms. These results suggest that biannual azithromycin administration to children 1–11 months old did not lead to a significant long-lasting increase in gut AMR or alterations of the gut microbiomes of children 1–59 months old in the community.

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