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

In 30 seconds

This multicentre, double-blind, randomised, placebo-controlled trial examined the effects of 10 days of prophylactic intravenous azithromycin on the gut microbiome and resistome of 693 preterm infants born before 30 weeks’ gestation. Infants were sampled longitudinally for 21 days or until discharge. Azithromycin reduced microbial diversity and the relative abundance of Bifidobacterium, while increasing Staphylococcus and Enterobacter/Klebsiella. It also increased macrolide-resistance genes, including erm(C), which remained detectable throughout the study. Probiotic use did not fully offset azithromycin-associated changes.

Key findings

• Azithromycin reduced gut microbial diversity and relative Bifidobacterium abundance, while increasing relative abundances of Staphylococcus and Enterobacter/Klebsiella.
• Azithromycin increased macrolide-resistance genes, including erm(C), which persisted for the duration of the study.
• Probiotic use increased alpha diversity and Bifidobacterium relative abundance but did not fully mitigate azithromycin’s effects.
• Combined azithromycin and probiotic use further enriched Enterobacter/Klebsiella and total antibiotic resistance genes, including erm(C).

Why it matters

The findings show that prophylactic antibiotic exposure in very preterm infants can alter early gut microbial composition and increase resistance-gene burden during the observed period. Probiotics were associated with some microbiome differences but did not eliminate these effects. These results underscore the need to weigh infection-control considerations against potential microbiome disruption and antimicrobial resistance when evaluating early antibiotic use.

What to keep in mind

Follow-up was limited to 21 days or discharge, so the study does not establish whether the observed microbiome and resistance-gene changes persist beyond this period.