For a study, researchers sought to determine the relationship between the timing of the administration of adjunctive azithromycin for prophylaxis during an unplanned cesarean birth and maternal infection and newborn morbidity. A secondary analysis of a randomized trial of supplementary azithromycin prophylaxis was performed in patients with singleton gestations experiencing unplanned cesarean birth. The time of the study drug’s introduction (after skin incision or 0–30 minutes, more than 30–60 minutes, or more than 60 minutes before skin incision) was the major exposure. Endometritis, wound infection, and other maternal infections occurring up to 6 weeks following cesarean birth were the major outcomes. Composite newborn morbidity, neonatal intensive care unit hospitalization for more than 72 hours, and neonatal sepsis were secondary outcomes. The relationship between azithromycin and outcomes was examined within each antibiotic timing group and provided as risk ratios (RRs) with 95% (CIs). To investigate changes in association by antibiotic timing, a Breslow-Day homogeneity test was used.

Antibiotics were started after skin incision (median 3 minutes, range 0–229 minutes) in 269 (13.4%), 0–30 minutes before skin incision in 1,378 (68.5%), and more than 30–60 minutes before skin incision in 270 (13.4%), and more than 60 minutes before skin incision (median 85 minutes, range 61–218 minutes) in 96 (of 2,013 participants) (4.8%). The RRs (95% CIs) of the infectious composite outcome for azithromycin were significantly lower in groups that started azithromycin after skin incision or within 1 hour before skin incision (after skin incision: RR 0.31, 95% CI 0.13–0.76; 0–30 minutes before: RR 0.62, 95% CI 0.44–0.89; more than 30–60 minutes before: 0.31, 95% CI 0.13–0.66). Patients who received azithromycin more than 60 minutes before skin incision had no increased risk (RR 0.59, 95% CI 0.10–3.36). When endometritis and wound infections were studied independently, the results were identical. Across all temporal groups, there was no significant difference in neonatal outcomes between azithromycin and placebo. Adjunctive azithromycin medication up to 60 minutes before or 3 minutes after skin incision was related to lower rates of maternal composite postoperative infection in unplanned cesarean births.