Azithromycin Use Rose as Post-Cesarean Infections Fell

Use of adjunctive azithromycin increased, and postpartum infection rates declined among US patients undergoing unscheduled cesarean delivery after publication of trial evidence in 2016, according to an observational study published in JAMA. Investigators examined how the earlier trial’s findings were adopted in clinical practice and whether infection rates changed outside the trial setting.

Researchers used Epic Cosmos data covering 1,663,441 deliveries from 2013 through 2024, including 202,234 cesarean births and 1,461,207 vaginal births. Eligible patients received prenatal care, experienced labor, and delivered a liveborn singleton infant at 24–43 weeks’ gestation. Their mean age was 29.3 years, and the median body mass index at delivery was 31.8kg/m².

The difference-in-differences analysis compared births occurring from January 1, 2013, through September 28, 2016, with those occurring from January 1, 2017, through December 31, 2024. Vaginal births served as the control group for assessing changes among cesarean births. The primary outcomes were perioperative azithromycin administration and postpartum infection within 6 weeks of delivery.

Azithromycin use during cesarean delivery increased from 2.2% before publication to 39.6% afterward, while use during vaginal delivery changed from 0.01% to 0.04%. After adjustment, the increase for cesarean births relative to vaginal births was 37.6 percentage points (95% CI, 33.1–42.2). Investigators used patient-level linear regression to estimate these differences.

Postpartum infection rates decreased from 9.2% to 8.0% after cesarean delivery, while increasing from 2.0% to 2.7% after vaginal delivery. The adjusted difference-in-differences estimate was −2.0 percentage points (95% CI, −2.6 to −1.4). The authors concluded that azithromycin use increased and postpartum infections decreased after the trial evidence was published.

Source: Freret TS, Litman E, Wen T, Guise JM, Little SE, Clapp MA. Adoption of adjunctive azithromycin for unscheduled cesarean delivery and postpartum infections. JAMA. Published online September 14, 2026. doi:10.1001/jama.2026.15010