Benzylpenicillin Concentrations in Intrapartum Group B Streptococcus Prevention Guidelines; A Systematic Review of the Evidence

INTRODUCTION: Intrapartum antibiotics are often used to reduce neonatal risk of early-onset Group B Streptococcus (GBS) disease. Protocols aim to achieve a fetal serum and amniotic fluid concentration above the minimum inhibitory concentration (MIC) of GBS at the time of birth. AIMS: We aimed to summarise the evidence for currently recommended doses of benzylpenicillin by comparing intrapartum fetal serum and amniotic fluid concentrations of benzylpenicillin with the associated MIC of GBS at the time of birth. METHODS: We systematically reviewed PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, and Embase databases. We sought studies in which umbilical cord blood and/or amniotic fluid were examined for Benzylpenicillin concentrations after intrapartum intravenous administration. RESULTS: Seven studies were included, using a variety of doses, applying different assay techniques, and reporting a wide range of concentrations reported in the umbilical cord serum and amniotic fluid. Concentrations were often significantly higher than the target MIC of 0.125 mcg/mL. Significant methodological limitations included reporting of total concentrations of antibiotic only and substantial protocol violations. DISCUSSION: There is a lack of high-quality evidence to support the current dosing of intrapartum antibiotics, with regards to whether appropriate MICs are achieved in the fetus. Studies applying rigorous methodology and accounting for drug protein binding are required to determine the dosing regimens required to achieve these concentrations in the umbilical cord serum and amniotic fluid.