Comment on “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”

About 8% of term pregnancies experience prelabor rupture of membranes (PROM). To reduce the risk of maternal and neonatal morbidity, current guidelines recommend induction of labor within 24 hours of PROM. For patients with known and unknown group B Streptococcus (GBS) colonization, intrapartum antibiotic prophylaxis is recommended to prevent early-onset neonatal sepsis. In women with suspected chorioamnionitis (which affects up to 12% of term pregnancies), Ureaplasma urealyticum and Mycoplasma hominis are the most common pathogens isolated from amniotic fluid cultures. However, the proportion of cultures positive for Escherichia coli has increased from 12.5% up to 43% from the 1980s to the past decade. Findings from a meta-analysis of 5 randomized controlled trials (RCTs) showed that antibiotic prophylaxis given to patients with term or near-term prolonged PROM reduced the rates of chorioamnionitis and endometritis versus placebo or no treatment. However, there was variation in the antibiotic regimens and GBS colonization status. The aim of this study was to compare the use of ampicillin with gentamicin and ampicillin alone in pregnancies affected by PROM on maternal and neonatal outcomes. This was an open-label RCT conducted in a university-affiliated hospital from November 2022 to March 2024. Included were patients 18 years or older with singleton, term pregnancies in vertex position, with unknown GBS colonization status, and PROM 12 to 18 hours. Excluded were those with allergy to penicillin or gentamicin, contraindications to vaginal delivery, antibiotic treatment within the last 7 days, chorioamnionitis before 19 hours of PROM, and unknown timing of PROM. Participants were randomized 1:1 to receive 1 of 2 antibiotic regimens: ampicillin with gentamicin or ampicillin alone. The primary outcome was clinical chorioamnionitis. Secondary maternal outcomes included puerperal endometritis, peripartum infections (chorioamnionitis or endometritis), intrapartum fever, and a composite outcome of postpartum maternal morbidity. Secondary neonatal outcomes included a composite of neonatal sepsis, admission to the neonatal intensive care unit (NICU), empiric antibiotic treatment in the NICU, sepsis workup, and infection-related hospitalization ≥5 days. Results from the cultures were classified into 5 groups: Enterobacteriaceae, GBS, anaerobes, Enterococcus faecalis, and negative. A total of 204 patients were included in the analysis, with 102 randomized to each antibiotic regimen. There was a lower rate of clinical chorioamnionitis in the ampicillin with gentamicin group versus ampicillin-alone group 1.0% vs 7.8%, respectively; risk ratio (RR), 0.12; 95% CI, 0.02-0.98; P = 0.035. To prevent one case of clinical chorioamnionitis, the number needed to treat was 14.7 (95% CI, 10.2-27.0). For the maternal outcomes, the ampicillin with gentamicin group had lower rates of intrapartum fever (7.8% vs 17.6%; P = 0.36), total peripartum infections (1.0% vs 9.8%; P = 0.005), and infection-related hospitalization (0% vs 5.9%; P = 0.029). The composite for neonatal outcomes occurred less frequently in the ampicillin with gentamicin group (10.8% vs 21.6%; RR, 0.50; 95% CI, 0.15-0.85; P = 0.036). The ampicillin with gentamicin group had fewer positive Enterobacteriaceae than the ampicillin-alone group (20% vs 51%; P < 0.001). For both groups, there was an 80% rate of ampicillin resistance among Enterobacteriaceae cultures. In conclusion, intrapartum antibiotic prophylaxis of ampicillin with gentamicin was associated with lower rates of clinical chorioamnionitis as well as fewer maternal and neonatal adverse composite outcomes in term pregnancies with PROM. (Summarized from Abu Shqara R, Glikman D, Goldinfeld G, et al. 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. Am J Obstet Gynecol. 2025;233:321.e1-10. doi: 10.1016/j.ajog.2025.03.011)