Macrolide and Nonmacrolide Resistance After 36 Months of Mass Azithromycin Distribution in Burkina Faso: A Cluster Randomized Trial

BACKGROUND: Biannual mass azithromycin distribution to children aged 1-59 months reduces all-cause child mortality but selects for antimicrobial resistance (AMR). The World Health Organization (WHO) recommends ongoing surveillance of AMR in the context of azithromycin distribution. We evaluated the impact of twice-yearly distribution of azithromycin compared to placebo on AMR in the gut of children in Burkina Faso. METHODS: The Community Health with Azithromycin Trial (CHAT) was a 1:1 cluster randomized placebo-controlled trial in Nouna District, Burkina Faso, from 2019 to 2023. Communities were randomized in a 1:1 fashion to twice-yearly azithromycin (20 mg/kg) or matching placebo. At 36 months, rectal swabs were collected from a random sample of 15 children per community in 48 communities participating in the trial and assessed for AMR genetic resistance determinants using next-generation DNA sequencing (DNA-seq). We assessed the fold-change in macrolide and nonmacrolide resistance determinants between treatment groups after 36 months. RESULTS: A total of 483 samples from 41 communities were analyzed at 36 months. There was no evidence of a difference in macrolide resistance determinants in the azithromycin group compared to the placebo group (fold-change, 1.21; 95% confidence interval [CI], .96-1.52; P = .62). There was no evidence of a difference in nonmacrolide resistance genes; for example, beta-lactam resistance was similar between treatment groups (fold-change, 1.05; 95% CI, .79-1.40; P = .81). CONCLUSIONS: In this setting in Burkina Faso, twice-yearly azithromycin distributions to children aged 1-59 months did not lead to statistically significant differences in macrolide or nonmacrolide genetic resistance determinants at 36 months. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03676764.