Impact of azithromycin mass drug administration on the antibiotic resistant gut microbiome: a randomized, controlled trial

Mass drug administration (MDA) with azithromycin is the primary strategy for global trachoma control efforts. Numerous studies have reported secondary effects of MDA with azithromycin, including reductions in childhood mortality, diarrhoeal disease and malaria. Most recently, the MORDOR clinical trial demonstrated that treatment led to an overall reduction in all-cause childhood mortality in targeted communities. There is however considerable concern about the potential of increased antimicrobial resistance in treated communities.This study evaluated the impact of azithromycin MDA on prevalence of gastrointestinal carriage of macrolide-resistant bacteria in communities within the MORDOR Malawi study site, while additionally profiling changes in the gut microbiome after treatment. For faecal metagenomics, 60 children were sampled prior to treatment and 122 children after four rounds of MDA, half receiving azithromycin and half placebo.The proportion of bacteria carrying macrolide resistance increased after azithromycin treatment; the effect was enhanced in children treated within six months of sampling. Diversity and global community structure of the gut was minimally impacted by treatment, however abundance of several individual species was altered by treatment. Notably, the putative human enteropathogen Escherichia albertii was more abundant after treatment.The impacts of MDA with azithromycin, including increased carriage of macrolide resistant bacteria, were enhanced in children treated more recently, suggesting effects may be transient. Increased abundance of enteropathogenic Escherichia species after treatment requires further, higher resolution investigation. Future studies should focus on the number of treatments and administration schedule to ensure clinical benefits continue to outweigh costs in antimicrobial resistance carriage.