Maternal and Perinatal Outcomes Associated with Intrapartum Antibiotic Regimens in Women with Prolonged Membrane Rupture and Unknown Group B Streptococcus Status: A Retrospective Comparative Study

Objectives: The aim of the study was to compare maternal, neonatal, and microbiological outcomes among patients with unknown group B Streptococcus (GBS) status and prolonged rupture of membranes (ROM ≥18 h) who received intrapartum prophylaxis with either ampicillin or clindamycin. Design: A retrospective comparative cohort. Materials: A total of 1,507 term singleton pregnancies with ROM ≥18 h and unknown GBS colonization status were included in the study: 1,418 received ampicillin, and 89 received clindamycin due to reported penicillin allergy. Setting: The study was conducted in a tertiary university-affiliated hospital in northern Israel, from March 2020 to May 2024. Methods: Patients were stratified by antibiotic regimen. The co-primary outcomes were clinical chorioamnionitis and neonatal intensive care unit (NICU) admission. Secondary outcomes included maternal complications (intrapartum fever, endometritis, cesarean delivery) and neonatal morbidities (Apgar <7, cord pH <7.1, respiratory distress, and ventilation support). Post-delivery chorioamniotic membrane swabs were cultured. Multivariate logistic regression was used to identify independent predictors of outcomes. Results: Compared to ampicillin, clindamycin treatment was associated with higher rates of clinical chorioamnionitis (14.6% vs. 2.3%, p < 0.001), intrapartum fever (28.1% vs. 4.1%, p < 0.001), maternal sepsis (2.2% vs. 0.3%, p = 0.011), puerperal endometritis (13.5% vs. 2.6%, p < 0.001), cesarean delivery (36.0% vs. 18.1%, p < 0.001), and postpartum antibiotic use (14.6% vs. 5.4%, p < 0.001). Among neonates of patients treated with clindamycin compared to ampicillin, the rates were higher for NICU admission (19.1% vs. 4.4%, p < 0.001), Apgar <7 at 5 min (4.5% vs. 0.8%, p = 0.001), cord pH <7.1 (7.9% vs. 2.0%, p < 0.001), respiratory distress (13.5% vs. 5.4%, p < 0.001), and ventilation support (invasive 2.2% vs. 0.2%, p = 0.019; non-invasive 7.9% vs. 1.1%, p < 0.001). Hypoxic brain injury occurred more frequently in the clindamycin group (2.2% vs. 0.1%, p = 0.016). GBS was isolated more often in chorioamniotic cultures of patients treated with clindamycin (19.1% vs. 1.1%, p < 0.001). In multivariable analysis, clindamycin treatment (adjusted odds ratio [aOR] 7.7, 95% CI: 3.8–15.5, p < 0.001) and artificial ROM (aOR 2.6, 95% CI: 1.1–6.3, p = 0.031) were independently associated with clinical chorioamnionitis. Clindamycin treatment was also independently associated with NICU admission (aOR 3.71, 95% CI: 1.9–7.1, p < 0.001). Other factors associated with NICU admission were the presence of meconium-stained amniotic fluid (aOR 3.28, 95% CI: 1.7–6.2, p < 0.001), clinical chorioamnionitis (aOR 3.11, 95% CI: 1.3–7.2, p = 0.009), and umbilical cord pH <7.1 (aOR 4.76, 95% CI: 1.9–11.4, p < 0.001). Limitations: Limitations include the retrospective, single-center design; the small size of the clindamycin group; and the absence of penicillin allergy verification via skin testing. Conclusions: Among women with unknown GBS status and prolonged ROM, the prophylactic use of clindamycin compared to ampicillin was associated with higher rates of maternal infectious morbidity and adverse neonatal outcomes. These findings underscore the importance of minimizing clindamycin use when possible, particularly given concerns about GBS resistance.