- Design
- Microbiome analysis within a double-blind, placebo-controlled randomised trial (AZTEC)
- Population
- 693 infants born before 30 weeks at 28 UK centres
- Primary outcome
- Gut microbiome composition and antibiotic resistance genes
- Effect
- Lower diversity, more Staphylococcus and Enterobacter/Klebsiella, persistent erm(C) with azithromycin
AZTEC randomised infants born before 30 weeks at 28 UK units to ten days of intravenous azithromycin or placebo from birth, aiming to prevent chronic lung disease. This analysis of 693 infants sampled their stool for 21 days or until discharge.
Azithromycin reduced gut microbial diversity and Bifidobacterium, and increased Staphylococcus and Enterobacter/Klebsiella. Macrolide-resistance genes, including erm(C), rose and persisted to the end of sampling. Probiotics, given at unit discretion, raised diversity but did not offset the effect, and with azithromycin further enriched Enterobacter/Klebsiella and resistance genes.
The probiotic findings are observational, since probiotic use was not randomised. But the trial shows that a short prophylactic course in the first days of life reshapes the resistome of the most vulnerable infants.
- Count early neonatal macrolide exposure as a resistance pressure, not a neutral prophylaxis.
- Azithromycin enriched Enterobacter and Klebsiella, common causes of late-onset neonatal sepsis.
- Probiotics did not reverse the resistome changes in this trial.
- Weigh any neonatal prophylaxis against its effect on later infection and resistance.
Why it matters
Neonatal units drive resistant Klebsiella, and this shows how quickly a short course can shift the balance.
Don't overread it
Probiotic use was not randomised, so its apparent effects may reflect differences between units.
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