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Published in: Gut Pathogens 1/2022

01-12-2022 | Enteropathogenic Escherichia Coli | Research

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

Authors: Harry Pickering, John D. Hart, Sarah Burr, Richard Stabler, Ken Maleta, Khumbo Kalua, Robin L. Bailey, Martin J. Holland

Published in: Gut Pathogens | Issue 1/2022

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Abstract

Background

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.

Results

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.

Conclusions

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
Appendix
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Metadata
Title
Impact of azithromycin mass drug administration on the antibiotic-resistant gut microbiome in children: a randomized, controlled trial
Authors
Harry Pickering
John D. Hart
Sarah Burr
Richard Stabler
Ken Maleta
Khumbo Kalua
Robin L. Bailey
Martin J. Holland
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Gut Pathogens / Issue 1/2022
Electronic ISSN: 1757-4749
DOI
https://doi.org/10.1186/s13099-021-00478-6

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