Adjunctive azithromycin at unscheduled cesarean spread widely and postpartum infection fell

Design

Difference-in-differences analysis of electronic health record data (Epic Cosmos), 2013 to 2024

Population

1,663,441 deliveries; 202,234 cesarean and 1,461,207 vaginal births

Primary outcome

Perioperative azithromycin use and postpartum infection within 6 weeks

Effect

Azithromycin use +37.6 percentage points (95% CI 33.1 to 42.2); postpartum infection -2.0 percentage points (-2.6 to -1.4)

This US study used Epic Cosmos electronic records on 1.66 million deliveries between 2013 and 2024, with cesarean births as the treatment group and vaginal births as the comparison, and looked at what changed after a 2016 randomised trial showed azithromycin reduced postpartum infection after unscheduled cesarean delivery.

Azithromycin use at cesarean rose from 2.2% (721 of 32,970) before the trial to 39.6% (67,094 of 169,264) after, an adjusted difference-in-differences of 37.6 percentage points (95% CI 33.1 to 42.2). Postpartum infection after cesarean fell from 9.2% to 8.0%, while it rose from 2.0% to 2.7% after vaginal birth; the adjusted difference-in-differences was -2.0 percentage points (95% CI -2.6 to -1.4).

The design is observational and the infection decline cannot be assigned to azithromycin alone, since other practice changes occurred. Still, uptake was only about 40% eight years after the trial, which leaves many patients without it. In India, where cesarean rates are high in many settings, local obstetric guidance and antibiotic stewardship should decide the approach.

• Check whether your unit's protocol includes adjunctive azithromycin at unscheduled cesarean delivery
• Agree dosing and timing with the obstetric team and your local protocol rather than from this study
• Audit postpartum infection rates after cesarean to see whether practice has changed
• Weigh stewardship and local resistance patterns when adding macrolide cover

Why it matters

It shows how slowly a proven intervention reaches practice, and that uptake can be measured.

Don't overread it

The fall in infection is associated with wider use, but the design cannot attribute it to azithromycin alone.

The statistics, in plain English

Difference-in-differences compares the change over time in cesarean births with the change in vaginal births, to remove trends affecting both. It assumes that without the intervention the two groups would have moved in parallel, which cannot be proven.

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