Adjunctive azithromycin at unscheduled caesarean is being adopted, and infections are falling

Design

Difference-in-differences analysis of a large EHR database (Epic Cosmos)

Population

1,663,441 deliveries, including 202,234 caesarean births, 2013-2024

Primary outcome

Perioperative azithromycin use and postpartum infection within 6 weeks

Effect

Use +37.6 points (95% CI 33.1-42.2); infection -2.0 points (95% CI -2.6 to -1.4)

Using an EHR database of 1,663,441 deliveries (202,234 caesarean), a difference-in-differences analysis compared antibiotic use and postpartum infection before and after 2016 trial evidence that adjunctive azithromycin reduces infection at unscheduled caesarean, with vaginal births as a control.

Azithromycin use at caesarean rose from 2.2% (2013-2016) to 39.6% (2017-2024), an adjusted difference-in-differences of 37.6 percentage points. Over the same period, post-caesarean infection fell from 9.2% to 8.0%, an adjusted difference-in-differences of -2.0 percentage points against the vaginal-birth trend.

The actionable point is confirmatory rather than new: adjunctive azithromycin alongside standard prophylaxis for an unscheduled (intrapartum) caesarean is trial-supported and its uptake tracks lower infection at population scale. Where local protocols have not yet adopted it, this is a prompt to review them. The design is observational, so the infection fall is consistent with, not proof of, the drug's effect.

• Azithromycin use at unscheduled caesarean rose from 2.2% to 39.6% after 2016 trial evidence.
• Post-caesarean infection fell by about 2 percentage points over the same period.
• Add azithromycin to standard prophylaxis specifically for unscheduled (intrapartum) caesarean.
• Review local caesarean prophylaxis protocols if they have not adopted it.
• The adoption-infection link is observational, consistent with the original trial.

Why it matters

It shows a proven prophylaxis step has been widely adopted and is associated with fewer infections, and flags where it has not.

Don't overread it

This is an adoption analysis, not the randomised trial; it supports, rather than independently proves, azithromycin's benefit.

The statistics, in plain English

A difference-in-differences compares the change in caesarean births against the change in vaginal births, which helps separate the drug's effect from background trends; it remains observational and cannot fully exclude other changes over time.

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