Indirect effect of oral azithromycin on the gut resistome of untreated children: a randomized controlled trial

Catherine E Oldenburg, Armin Hinterwirth, Lee Worden, Ali Sié, Clarisse Dah, Lucienne Ouermi, Boubacar Coulibaly, Lina Zhong, Cindi Chen, Kevin Ruder, Thomas M Lietman, Jeremy D Keenan, Thuy Doan, Catherine E Oldenburg, Armin Hinterwirth, Lee Worden, Ali Sié, Clarisse Dah, Lucienne Ouermi, Boubacar Coulibaly, Lina Zhong, Cindi Chen, Kevin Ruder, Thomas M Lietman, Jeremy D Keenan, Thuy Doan

Abstract

Background: Antibiotic use by one individual may affect selection for antimicrobial resistance in close contacts. Here we evaluated whether oral antibiotic treatment of one child within a household affected the gut resistome of an untreated cohabiting child.

Methods: Households with at least two children <5 y of age were randomized in a 1:1 fashion to a 5d course of azithromycin or placebo. To evaluate indirect effects of azithromycin treatment on the gut resistome, we randomly assigned one child in the house to azithromycin and one to placebo. In placebo households, each child received placebo. We performed DNA sequencing of rectal swabs collected 5 d after the last antibiotic dose. We estimated risk ratios for the presence of genetic resistance determinants at the class level using modified Poisson models for children in azithromycin households compared with placebo households and assessed the composition of the resistome using permutational analysis of variance (PERMANOVA).

Results: Of 58 children (n = 30 azithromycin households, n = 28 placebo households) with post-treatment rectal swabs, genetic resistance determinants were common but there was no significant difference at the class (p = 0.54 for macrolides) or gene (p = 0.94 for structure by PERMANOVA, p = 0.94 for diversity) level between untreated children in azithromycin households compared with placebo households.

Conclusions: The results are encouraging that one child's antibiotic use may not influence the resistome of another child. Trial registration: ClinicalTrials.gov NCT03187834.

Keywords: antimicrobial resistance; azithromycin; randomized controlled trial.

© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Figures

Figure 1.
Figure 1.
Consolidated Standards of Reporting Trials diagram for participants included in the study and analysis.
Figure 2.
Figure 2.
Abundance (normalized reads) of macrolide resistance genes in children treated with placebo living in households with another child treated with placebo or azithromycin.

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Source: PubMed

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