Ampicillin-gentamicin versus ampicillin alone for prolonged prelabor rupture of membranes at term in group B streptococcus-negative patients: a randomized controlled trial.

Abstract

Prolonged prelabor rupture of membranes at term increases the risk of maternal and neonatal infections, yet the optimal prophylactic antibiotic regimen in patients with confirmed negative group B Streptococcus colonization remains unclear. We compared maternal and neonatal outcomes between 2 prophylactic antibiotic regimens, ampicillin plus gentamicin vs ampicillin alone, in patients with term prelabor rupture of membranes and confirmed negative group B Streptococcus colonization. This single-center, randomized controlled trial was conducted at a tertiary university-affiliated hospital between November 2022 and July 2025. Eligible participants were women with singleton term pregnancies, prelabor rupture of membranes ≥18 hours, and negative group B Streptococcus colonization. Patients were randomized 1:1 to receive intravenous ampicillin (2 g every 6 hours) plus gentamicin (5 mg/kg every 24 hours) or ampicillin alone, initiated 18 hours after prelabor rupture of membranes. The co-primary outcomes were the incidences of clinical chorioamnionitis and endometritis. Secondary outcomes included intrapartum fever, postpartum maternal infections, postpartum stay ≥5 days, and neonatal morbidity. Chorioamniotic cultures were obtained postpartum. Analyses were performed on an intention-to-treat basis. A total of 207 women were randomized (103 to ampicillin-gentamicin; 104 to ampicillin alone).Clinical chorioamnionitis occurred less frequently in the ampicillin-gentamicin group than in the ampicillin-alone group (1.9% vs 10.6%; P=.019; number needed to treat, 11.5; 95% confidence interval, 7-45). The endometritis rates were similar between the groups. Postpartum infectious morbidity was also lower in the combined-treatment group (1.9% vs 9.6%; P=.033), as was the rate of postpartum hospitalization ≥5 days (3.9% vs 13.5%; P=.024). In the ampicillin-gentamicin group, admission to the neonatal intensive care unit due to suspected early-onset sepsis was lower (2.9% vs 8.7%, P=.031) and positive chorioamniotic cultures were less frequent (20.9% vs 36.7%; P=.029). The prevalence of Enterobacteriaceae spp. was lower (12.1% vs 25.6%; P=.033). Among patients with confirmed negative group B Streptococcus colonization and with prolonged term prelabor rupture of membranes, clinical chorioamnionitis and postpartum maternal infectious morbidity were lower following prophylactic administration of ampicillin plus gentamicin compared to ampicillin monotherapy. Broader Gram-negative coverage may improve maternal outcomes and warrants further evaluation.