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The impact of prophylactic azithromycin on the developing preterm gut microbiome and resistome

In brief

Ten days of azithromycin increased resistance genes in preterm infants

In a randomized trial of 693 infants born before 30 weeks, 10 days of azithromycin reduced gut microbial diversity and health-associated Bifidobacterium while increasing potentially harmful bacteria and macrolide-resistance genes. The resistance gene erm(C) remained detectable through follow-up, and probiotics did not fully offset the changes; longer-term effects on infant health and resistance remain unknown.

Journal
Gut microbes (Q1)
Published
15 October 2026
Study design
Randomized controlled trial
Evidence level
Level 1, High (CEBM 1b)
Authors
Sinead Ahearn-Ford, Ali Aboklaish, Gregory R Young, John Lowe, Andrea C Masi, David Gallacher, et al.
PMID
42879303
DOI
10.1080/19490976.2026.2748147

Why clinicians should know about it

  • Picked for Neonatology (top studies of the week, 18 October 2026): Azithromycin reduced diversity, increased pathobionts and macrolide‑resistance genes

Abstract

Early-life antibiotic exposure can profoundly impact the developing preterm gut microbiome and resistome, with short- and long-term consequences for health. In a large multi-center (n = 28) study of 693 preterm infants, we investigated the effects of 10 d of prophylactic intravenous azithromycin on the gut microbiome and antibiotic resistance genes (ARGs). The AZithromycin ThErapy for Chronic Lung Disease of Prematurity (AZTEC) study was a double blind, randomized, placebo-controlled trial of preterm infants (born < 30 weeks of gestation), treated from birth for 10 d with either intravenous azithromycin or placebo, and sampled longitudinally for 21 d or discharge. Using 16S rRNA gene sequencing, antibiotic susceptibility testing, and quantitative PCR, we show azithromycin reduced microbial diversity and the relative abundance of health-associated Bifidobacterium and increased relative abundances of pathobionts Staphylococcus and Enterobacter/Klebsiella. This early azithromycin treatment increased the number of macrolide-resistant genes, including the presence of erm (C), which persisted for the duration of the study. Probiotic use (at individual unit discretion) increased alpha diversity and Bifidobacterium relative abundance, but did not fully mitigate the effects of azithromycin receipt. Combined azithromycin and probiotics further increased the enrichment of Enterobacter/Klebsiella and total ARGs, including erm(C). These findings highlight the impacts of antibiotic and probiotic use, both important in balancing infection control issues and microbiome disruption and antimicrobial resistance.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.