Duration of Intrapartum Prophylaxis and Concentration of Penicillin G in Fetal Serum at Delivery

Abstract

A minimum of 4 hours of intrapartum antibiotic prophylaxis before delivery is generally recommended to prevent early-onset group B Streptoccocus (GBS) because less than 4 hours may not achieve adequate levels of drug. The aim of this prospective cohort study was to compare fetal penicillin levels among fetuses exposed to less than 4 hours and those exposed for longer durations. Ninety-eight laboring GBS-positive women carrying singleton gestations 37 weeks’ or greater received 5 million units of intravenous penicillin G followed by a maintenance dose of 2.5 million units every 4 hours until delivery. Penicillin G levels in umbilical cord blood samples collected at delivery were measured by high-performance liquid chromatography. The investigators found that fetuses exposed to fewer than 4 hours of prophylaxis had significantly higher penicillin G levels than those exposed to greater than 4 hours (P = .003). Multivariable linear regression analysis showed that fetal penicillin G levels were associated with duration of exposure, time since last dose, dosage, and number of doses, but not maternal body mass index. Penicillin G levels increased linearly and peaked at approximately 1 hour (R2 = .40) and then decreased rapidly according to a power-decay model (R2 = .67). Cord blood levels did not accumulate after repeated maintenance dosing, and returned to baseline after each 4-hour interval. Fetal serum penicillin levels far exceeded the minimal inhibitory concentration less than 1 hour after the initial dose. Unlike previous findings, these data demonstrate that infants exposed to fewer than 4 hours of prophylaxis are not necessarily at increased risk for GBS sepsis. Given the rapid transfer of penicillin from mother to fetus, the authors suggest that antibiotic prophylaxis should be pursued even in the most precipitous of deliveries.