Cefazolin administration prior to caesarean delivery and breastmilk microbiome: a nested cohort within a randomised clinical trial.

OBJECTIVES: Consistent with guidelines, anaesthetists administer pre-incision cefazolin to patients having caesarean delivery in Australia. These antibiotics may impact the breastmilk microbiome. We hypothesised that the breastmilk microbiome of mothers administered cefazolin would differ from those administered placebo. METHODS: In this nested cohort within a randomised clinical trial, samples were collected from adult females having caesarean delivery. Patients received cefazolin 2 g in 100 mL normal saline (cefazolin group) or 100 mL normal saline (placebo group) prior to skin incision. Breastmilk samples were collected by participants on post-operative day 14 and 30 and immediately frozen. Microbial composition of samples was assessed via long-read 16S rRNA sequencing. RESULTS: From the cefazolin group, there were 12 samples (day 14) and 13 (day 30). From the placebo group, there were 11 (day 14) and 9 (day 30). Full-length 16S rRNA sequencing yielded sufficient reads to characterise the breastmilk microbiota at both time points. Cefazolin exposure was associated with alterations in the composition, including increased abundances of the aerobic species Roseateles spp. and Cutibacterium acnes and a predominance of Gram-negative taxa. These shifts suggest suppression of Gram-positive commensals. The resulting microbial communities appeared relatively static and enriched with less-characterised, environmentally associated genera, indicating that cefazolin may potentially disrupt normal breastmilk microbial maturation by creating niches preferentially occupied by antibiotic-tolerant taxa. CONCLUSIONS: In this small, restricted sample, cefazolin exposure prior to delivery exerted modest effects on the breastmilk microbiome. The clinical implications require further evaluation in a larger, diverse population.