(1278) Azithromycin for labored cesarean complicated by IAI is associated with reduced postpartum infection and readmission

The C/SOAP trial (late 2016) showed that perioperative azithromycin for cesarean birth after labor reduces postpartum infection; patients with IAI were excluded. We sought to analyze if azithromycin use in this excluded population is associated with reductions in infectious outcomes.

Study Design:

This was a retrospective cohort study (2013-2025) using the Epic Cosmos platform, a nationwide database of patients receiving care at Epic EHR sites. Laboring persons with a delivery encounter billing diagnosis of IAI who gave birth to a liveborn singleton by cesarean delivery at 24-43 weeks were included. The primary exposure was perioperative azithromycin. The primary outcomes were identified from ICD codes and occurred within 6 weeks. They included: 1) a composite of post-discharge infection (endometritis, wound infection, or other infection), and 2) hospital readmission for infection. We used Poisson regression with fixed effects for delivery department and year to estimate relative risks, adjusting for maternal age, delivery BMI, diabetes, parity, prior cesarean delivery, reaching the second stage, rupture of membranes ≥ 18 hours, and gestational age.

Results:

The cohort comprised 31,909 persons with IAI; azithromycin was administered to 10,733 (33.6%). There was a rapid increase in use among cesarean births after 2016, from 2.0% in 2013 to 58.7% in 2024 (Figure). The rate of post-discharge infection was 8.9% without and 7.3% with azithromycin (p < 0.001); readmission rates were 2.7 vs 2.1% (p < 0.001). In both the unadjusted and adjusted models, azithromycin was associated with lower rates of post-discharge infection (RR 0.77, 95% CI: 0.69 – 0.85; aRR: 0.76, 95% CI: 0.69 – 0.84) and hospital readmission for infection (RR 0.73, 95% CI: 0.60 – 0.88; aRR: 0.72, 95% CI: 0.59 – 0.87).

Conclusion:

Azithromycin administration in laboring persons with IAI undergoing cesarean birth increased >20-fold after publication of the C/SOAP trial, despite being an exclusion criteria. However, its use was associated with 20-30% reductions in post-discharge infection and readmission for infection.