(679) Timing of adjunctive azithromycin administration and postpartum infection

The C/SOAP trial (2016) showed that perioperative azithromycin for labored cesarean birth reduces postpartum infection. Optimal administration timing, such as the interval before delivery or relation to umbilical cord clamping, is unknown. Our objective was to analyze whether infectious complication rates vary by timing of administration.

Study Design:

This was a retrospective cross-sectional study (2019-2025) using the nationwide Epic Cosmos platform. Laboring persons who gave birth to a liveborn singleton by cesarean delivery at 24-43 weeks were included. Exclusion criteria included no documented antibiotic administration. Initiation time of azithromycin was categorized as: no administration (reference), before birth ( > 60 min, 41-60 min, 21-40 min, 0-20 min) or after birth (1-20 min, > 20 min). The primary outcome, adapted from the C/SOAP trial, was a composite of endometritis, wound infection, or other infection within 6 weeks, identified by ICD codes. Poisson regression with fixed effects for delivery department and calendar year was used to estimate relative risks, adjusting for maternal age, delivery BMI, parity, diabetes, prior cesarean birth, reaching the second stage, rupture of membranes ≥ 18 hours, and gestational age at delivery.

Results:

The cohort included 141,528 individuals; azithromycin was administered to 66,951 (47.3%). Timing of azithromycin administration varied widely (Figure 1). The median administration time was 18 min before birth [IQR: 9 – 33 min before birth]. In the adjusted model, compared to no administration, azithromycin initiated from 0 to 60 minutes before birth was associated with decreased infection (Figure 2). Administration after delivery (and thus cord clamping) was not associated with reduced infection, although this may be confounded by urgency of delivery.

Conclusion:

The timing of azithromycin administration for labored cesarean birth varies widely nationwide. Our findings suggest the rate of infectious complications also varies by timing and is lower when given in the hour before delivery.