A Randomized Controlled Trial
ABSTRACT
OBJECTIVE:
To compare prophylactic oral cephalexin and metronidazole with placebo for 48 hours after cesarean delivery following membrane rupture on the frequency of composite infection morbidity postpartum among pregnant individuals with obesity.
METHODS:
This randomized, double-blind clinical trial was conducted at two medical centers from August 2017 to August 2023. We enrolled women with obesity (pregnancy body mass index [BMI] 30 or higher) and ruptured membranes (for 4 hours or more) undergoing cesarean delivery who were also receiving standard intravenous preoperative prophylaxis with cefazolin and azithromycin. Participants were assigned randomly to receive either oral cephalexin (500 mg) and metronidazole (500 mg) or an identical placebo every 8 hours for 48 hours after their cesarean delivery. The primary outcome was a composite of infection complications, defined as a composite of endometritis, surgical site infection, or other postcesarean infections (pelvic septic thrombosis, abdominal or pelvic abscess based on radiologic diagnosis) within 30 days after cesarean delivery. With an anticipated relative risk reduction of 50% and a two-sided α=.05 with 80% power and a 1:1 ratio of exposed to unexposed, a total sample size of 302 participants was planned to detect a reduction in the primary outcome from 25% in the placebo group to 12.5% in the antibiotic group.
RESULTS:
Of the 321 women who were randomized (mean±SD age 27.5±6.1 years, mean±SD BMI 38.4±6.8), 160 received cephalexin–metronidazole and 161 received placebo with a total of 284 (88.5%) who completed the study per protocol. The overall rate of the composite infection outcome was 6.2% (95% CI, 3.8–9.5%). In the cephalexin–metronidazole group, 9 women (5.6%) developed the composite compared with 11 women (6.8%) in the placebo group (difference 1.2%, 95% CI, −2.5% to 5.0%; odds ratio 0.81, 95% CI, 0.33–2.02; P=.64). No serious adverse events, including allergic reactions, were reported in either group.
CONCLUSION:
In women with obesity undergoing cesarean delivery with an extended-spectrum preoperative antibiotic regimen that included azithromycin, the addition of a postoperative 48-hour course of oral cephalexin and metronidazole did not significantly lower the rate of infection complications within 30 days after delivery.