Ampicillin and gentamicin prophylaxis is superior to ampicillin alone in patients with prelabor rupture of membranes at term: the results of a randomized clinical trial.

Abstract

Background: Prelabor rupture of membranes (PROM) is a risk factor for maternal and neonatal infectious morbidity. Ampicillin is indicated for patients with unknown group B Streptococcus (GBS) status and PROM>18h. Although ampicillin-resistant Enterobacteriaceae contribute to maternal and neonatal infectious morbidity, current guidelines on intrapartum antibiotic prophylaxis primarily target GBS and do not adequately cover Enterobacteriaceae.

Objective: To compare maternal and neonatal infectious morbidity between two antibiotic regimens: ampicillin and gentamicin vs. ampicillin alone.

Study design: This randomized-controlled trial was conducted between November 2022 and March 2024 in a tertiary university-affiliated hospital. Inclusion criteria were a term singleton pregnancy >37 0/7, vertex presentation, unknown GBS status, and PROM without active labor. Exclusion criteria included penicillin/gentamicin allergy, contraindications for vaginal delivery, and current antibiotic treatment. The participants were randomized at 12-18h post-PROM, to receive ampicillin and gentamicin (n=102), or ampicillin alone (n=102). They were blinded from the allocation until antibiotics initiation at 18h post-PROM. The antibiotics were administered until delivery. The primary outcome was clinical chorioamnionitis. Secondary maternal outcomes were puerperal endometritis, peripartum infections, intrapartum fever, and a composite of postpartum maternal morbidity, defined as the presence of puerperal endometritis, postpartum antibiotic treatment exceeding 24 hours, wound infection, or infection-related hospitalization >5 days. A neonatal composite adverse outcome included culture-proven neonatal sepsis, admission to the neonatal intensive care unit (NICU), empiric antibiotic treatment in the NICU, performance of a sepsis workup, and infection-related hospitalization >5 days. Microbiologic findings were assessed from chorioamniotic swab cultures. An intention-to-treat analysis was performed. The number needed-to-treat was calculated for the primary outcome. Multivariate logistic regression was conducted to predict clinical chorioamnionitis, after controlling for antibiotic regimen, PROM duration, delivery number, body mass index, delivery week, maternal age, meconium staining, and diabetes mellitus.

Results: Ampicillin and gentamicin treatment was associated with lower rates of clinical chorioamnionitis (1/102 (1.0%) vs. 8/102 (7.8%), p=0.035), intrapartum fever (8/102 (8.0%) vs. 18/102 (18.0%), p=0.036), and overall peripartum infections (1/102 (1.0%) vs. 10/102 (9.8%), p=0.005). The number needed-to-treat to prevent one case of clinical chorioamnionitis was 14.7 (95% confidence interval: 10.2-27.0). The rate of the composite postpartum maternal complications was also lower in the ampicillin and gentamicin group (0/102 (0%) vs. 6/102 (5.9%), p=0.029). Ampicillin and gentamicin treatment was associated with lower rates of the composite neonatal adverse outcome (11/102 (10.8%) vs. 22/102 (21.6%), p=0.036) and sepsis workups (8/102 (7.8%) vs. 18/102 (17.6%), p=0.036), and a shorter median NICU stay (3.0 vs. 3.5 days, p=0.047). The frequency of positive Enterobacteriaceae cultures in chorioamniotic swab samples was lower following ampicillin and gentamicin (17/85 (20%) vs. ampicillin alone 45/89 (51%), p<0.001).

Conclusions: In term PROM, ampicillin and gentamicin prophylaxis, compared to ampicillin alone, resulted in lower rates of clinical chorioamnionitis, maternal postpartum complications, and neonatal adverse outcomes. It is time to reconsider the antimicrobial prophylactic regimen in term PROM.