Increased Use of Adjunctive Azithromycin After Unscheduled Cesarean Delivery Associated With Lower Postpartum Infection Rates Background
A US analysis of 1.66 million deliveries found that adjunctive azithromycin use during cesarean delivery increased from 2.2% before 2016 to 39.6% during 2017–2024. Over the same period, postpartum infection after cesarean delivery declined from 9.2% to 8.0%. The findings suggest that evidence from the 2016 clinical trial was followed by substantial adoption in routine practice and lower postpartum infection rates.
KEY FINDINGS: In this large US observational analysis, publication of randomized trial evidence in 2016 was followed by a substantial increase in adjunctive azithromycin use during unscheduled cesarean delivery and a relative reduction in postpartum infections. The study provides evidence that clinical trial findings were subsequently incorporated into routine practice beyond the original trial setting. Because this was an observational difference-in-differences analysis rather than a new randomized trial, the findings demonstrate an association between adoption of the intervention and changes in infection rates rather than establishing causality.
BACKGROUND: Unscheduled cesarean delivery is associated with a higher risk of postpartum infection. A 2016 clinical trial showed that adding azithromycin to standard antibiotic prophylaxis could reduce postoperative infections in patients undergoing unscheduled cesarean delivery. This study evaluated whether use of adjunctive azithromycin increased after publication of that trial and whether postpartum infection rates subsequently changed in routine US practice.
DETAILS: Investigators conducted a difference-in-differences analysis using Epic Cosmos data from 2013 through 2024. The analysis included pregnant individuals who received prenatal care, experienced labor, and delivered a live singleton infant at 24 to 43 weeks' gestation. Cesarean deliveries served as the treatment group and vaginal deliveries as the comparison group, allowing changes occurring after publication of the 2016 trial to be assessed relative to trends in vaginal births.
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The study included 1,663,441 deliveries, comprising 202,234 cesarean births and 1,461,207 vaginal births. The primary outcomes were perioperative azithromycin administration and postpartum infection occurring within 6 weeks of delivery. The investigators compared births from January 1, 2013, through September 28, 2016, with those occurring from January 1, 2017, through December 31, 2024.
Before publication of the 2016 trial, azithromycin was administered during 2.2% of cesarean births compared with 0.01% of vaginal births. During 2017-2024, use increased to 39.6% of cesarean births and 0.04% of vaginal births. The adjusted difference-in-differences estimate for cesarean births was 37.6 percentage points (95% CI, 33.1 to 42.2). Postpartum infection after cesarean delivery declined from 9.2% during the pre-2016 period to 8.0% during 2017-2024. Among vaginal births, infection rates changed from 2.0% to 2.7%, producing an adjusted difference-in-differences estimate of -2.0 percentage points (95% CI, -2.6 to -1.4) for cesarean births. The findings therefore showed that, following publication of the randomized trial, adjunctive azithromycin use increased substantially among patients undergoing unscheduled cesarean delivery while postpartum infection rates decreased relative to the comparison group.
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Source: Freret, T. S., Litman, E., Wen, T., et al. Adoption of Adjunctive Azithromycin for Unscheduled Cesarean Delivery and Postpartum Infections. JAMA. 2026; Published: September 14, 2026. DOI: 10.1001/jama.2026.15010.
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