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 MDA led to an overall reduction in all-cause childhood mortality in targeted communities. There is however concern about the potential of increased antimicrobial resistance in treated communities. This study evaluated the impact of azithromycin MDA on the prevalence of gastrointestinal carriage of macrolide-resistant bacteria in communities within the MORDOR Malawi study, 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. Diversity and global community structure of the gut was minimally impacted by treatment, however abundance of several species was altered by treatment. Notably, the putative human enteropathogen Escherichia albertii was more abundant after treatment. MDA with azithromycin increased carriage of macrolide-resistant bacteria, but had limited impact on clinically relevant bacteria. However, 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. Trial registration ClinicalTrial.gov, NCT02047981. Registered January 29th 2014, https://clinicaltrials.gov/ct2/show/NCT02047981

中文翻译：

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阿奇霉素大规模给药对儿童耐抗生素肠道微生物群的影响：一项随机对照试验

使用阿奇霉素进行大规模药物管理 (MDA) 是全球沙眼控制工作的主要策略。许多研究报告了 MDA 与阿奇霉素的次要作用，包括降低儿童死亡率、腹泻病和疟疾。最近，MORDOR 临床试验表明，MDA 导致目标社区全因儿童死亡率的总体降低。然而，人们担心接受治疗的社区可能会增加抗菌素耐药性。本研究评估了阿奇霉素 MDA 对 MORDOR 马拉维研究中社区中大环内酯类耐药细菌的胃肠道携带率的影响，此外还分析了治疗后肠道微生物组的变化。对于粪便宏基因组学，治疗前对 60 名儿童进行抽样，四轮 MDA 后对 122 名儿童进行抽样，一半接受阿奇霉素，一半接受安慰剂。阿奇霉素处理后携带大环内酯类耐药菌的比例增加。肠道的多样性和全球群落结构受到治疗的影响最小，但是治疗改变了几种物种的丰度。值得注意的是，推定的人类肠道病原体埃希氏菌在治疗后更加丰富。MDA 与阿奇霉素一起增加了大环内酯类耐药细菌的携带，但对临床相关细菌的影响有限。然而，治疗后肠道致病性埃希氏菌的丰度增加需要进一步、更高分辨率的研究。未来的研究应关注治疗次数和给药计划，以确保临床益处继续超过抗菌素耐药性携带的成本。试验注册 ClinicalTrial.gov，NCT02047981。2014 年 1 月 29 日注册，https://clinicaltrials.gov/ct2/show/NCT02047981