Macrolide and non-macrolide 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 is known to select for antimicrobial resistance (AMR). The World Health Organization (WHO) recommends ongoing surveillance of AMR in the context of azithromycin distribution. Here, we evaluated the impact of twice-yearly distribution of azithromycin compared to placebo on AMR in the gut of children participating in a trial 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 2019-2023. 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 DNA-seq. We assessed the fold-change in macrolide and non-macrolide resistance determinants between treatment groups after 36 months. Results 483 samples from 41 communities were analyzed at 36 months. Macrolide resistance determinants were not statistically significantly higher in the azithromycin group compared to the placebo group (fold-change 1.21, 95% confidence interval, CI, 0.96 to 1.52, P =0.62). There was no evidence of a difference in non-macrolide resistance genes, for example, beta-lactam resistance was similar between treatment groups (fold-change 1.05, 95% CI 0.79 to 1.40, P =0.81). 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 non-macrolide genetic resistance determinants at 36 months. Trial Registration ClinicalTrials.gov NCT03676764 KEY POINTS Twice-yearly mass distribution of azithromycin to children aged 1-59 months did not lead to a statistically significant difference in genetic macrolide or nonmacrolide resistance determinants in the gut after 36 months of distributions.