PURPOSE: The aim of this study was to evaluate the effect of the 4 times per year mass azithromycin distributions on the ocular surface microbiome of children in a trachoma endemic area.

METHODS: In this cluster-randomized controlled trial, children aged 1 to 10 years in rural communities in the Goncha Seso Enesie district of Ethiopia were randomized to either no treatment or treatment with a single dose of oral azithromycin (height-based dosing to approximate 20 mg/kg) every 3 months for 1 year. Post hoc analysis of ocular surface Chlamydia trachomatis load, microbial community diversity, and macrolide resistance determinants was performed to evaluate differences between treatment arms.

RESULTS: One thousand two hundred fifty-five children from 24 communities were included in the study. The mean azithromycin coverage in the treated communities was 80% (95% CI: 73%-86%). The average age was 5 years (95% CI: 4-5). Ocular surface C. trachomatis load was reduced in children treated with the 4 times per year azithromycin (P = 0.0003). Neisseria gonorrhoeae, Neisseria lactamica, and Neisseria meningitidis were more abundant in the no-treatment arm compared with the treated arm. The macrolide resistance gene ermB was not different between arms (P = 0.63), but mefA/E was increased (P = 0.04) in the azithromycin-treated arm.

CONCLUSIONS: We found a reduction in the load of C. trachomatis and 3 Neisseria species in communities treated with azithromycin. These benefits came at the cost of selection for macrolide resistance.