- Design
- Microbiome analysis within a double-blind randomised placebo-controlled trial (AZTEC)
- Population
- 693 infants born before 30 weeks at 28 centres
- Primary outcome
- Gut microbiome composition and antibiotic resistance genes over 21 days
- Effect
- Lower diversity and Bifidobacterium; more Staphylococcus, Enterobacter/Klebsiella and persistent erm(C)
This analysis comes from the AZTEC trial, which randomised 693 infants born before 30 weeks at 28 centres to ten days of intravenous azithromycin from birth or placebo, to prevent chronic lung disease. Stool samples were taken for up to 21 days or until discharge.
Azithromycin reduced gut microbial diversity and the share of Bifidobacterium, and increased Staphylococcus and Enterobacter/Klebsiella. Macrolide resistance genes, including erm(C), increased and persisted through the sampling period. Probiotics, given at unit discretion, raised diversity and Bifidobacterium but did not undo the azithromycin effect, and the combination was associated with more Enterobacter/Klebsiella and resistance genes.
The study measures the microbiome, not clinical outcomes, and the probiotic findings are not randomised. Its relevance is as the cost side of the ledger whenever a prophylactic antibiotic is considered in very preterm infants, where neonatal units in India already contend with high rates of resistant Klebsiella.
- Weigh microbiome disruption and resistance when considering any prophylactic antibiotic in very preterm infants.
- Avoid prolonged empirical antibiotics in preterm infants once cultures are negative and the infant is well.
- Do not assume probiotics offset the effects of an antibiotic course on the gut.
- Monitor local rates of resistant Klebsiella and Enterobacter in the neonatal unit.
Why it matters
Prophylactic antibiotics in the smallest infants leave a footprint that lasts beyond the course.
Don't overread it
The study measured the microbiome and resistance genes, not infection or long-term health.
The statistics, in plain English
This is a secondary analysis of a randomised trial, so the azithromycin effects are randomised comparisons. The probiotic effects are not, because units chose whether to give them, so differences may reflect the units rather than the probiotic.
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