Prophylactic azithromycin left resistance genes in preterm guts

Design

Microbiome analysis within a double-blind, placebo-controlled randomised trial (AZTEC)

Population

693 infants born before 30 weeks' gestation at 28 neonatal units

Primary outcome

Gut microbiome composition and antibiotic resistance genes

Effect

Azithromycin lowered diversity and Bifidobacterium and raised persistent erm(C) carriage

AZTEC was a double-blind, placebo-controlled trial of ten days of intravenous azithromycin from birth in babies born before 30 weeks, aimed at preventing chronic lung disease. This analysis studied stool samples from 693 infants at 28 units for three weeks or until discharge.

Azithromycin reduced gut microbial diversity and the share of Bifidobacterium, and increased Staphylococcus and Enterobacter or Klebsiella. Macrolide resistance genes, including erm(C), rose and persisted throughout sampling. Probiotics, given at unit discretion, restored some diversity but did not undo the effect, and the combination further raised Enterobacter or Klebsiella and total resistance genes.

Every prophylactic antibiotic in a neonatal unit carries an ecological cost. This study measures it for azithromycin.

• Weigh microbiome and resistance effects when considering prophylactic azithromycin in preterm infants.
• Do not assume probiotics offset antibiotic-driven microbiome damage.
• Expect more macrolide-resistant organisms in units that use azithromycin prophylaxis widely.
• Include resistance surveillance in any neonatal antibiotic stewardship programme.

Why it matters

Prophylaxis judged on lung outcomes alone misses a resistance cost that persists.

Don't overread it

This measured gut organisms and resistance genes, not infections or long-term outcomes.

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