Background
Group B Streptococcus (GBS) is a leading cause of severe early onset neonatal sepsis and accounts for significant global morbidity and mortality.1 Intrapartum antibiotic prophylaxis (IAP) using intravenous benzylpenicillin is advised.2 Alteration in pharmacokinetics can occur due to pregnancy-related physiological changes. We aimed to describe the intrapartum pharmacokinetics of benzylpenicillin and determine dosing regimens that might improve clinical use—reduce total drug requirement while maintaining microbiological and clinical activity.
Methods
We conducted aprospective cohort study at Liverpool Women’s Hospital. Pregnant women eligible for benzylpenicillin IAP were enrolled and received the standard-of-care — intermittent IV benzylpenicillin: 3 g loading dose at onset of labor, and 1.5g every 4 h until delivery. Blood samples (3 mL) were collected at pre-dose, 0.25, 0.5, 1, 2 and 4 h post dose. A single cord blood sample (umbilical vein) was obtained at delivery. Benzylpenicillin concentrations were quantified using a validated LC-MS/MS assay. A population pharmacokinetic model was fitted to the data using a non-parametric methodology. Monte Carlo simulations were performed to determine optimal dosing regimens (target exposure: 100%fT > MIC).
Results
A two-compartment model linked to an umbilical cord compartment adequately described maternal disposition of intrapartum benzylpenicillin. The volume of the central compartment and clearance were 16.55 L and 41.24 L/h, respectively. Simulations show that a lower regimen of benzylpenicillin: 2.4 g loading dose, followed by 1.2 g every 4 h result in adequate drug exposure — with plasma fCmin > 0.125 mg/L for 100% of the dosing interval in > 90% of the simulated population. Continuous infusion regimens resulted in higher target attainment rates when compared to intermittent infusions.
Conclusion
There is potential to reduce penicillin drug burden and consider advantages of portable continuous infusions during labor.
References
- Panneflek TJR, Hasperhoven GF, Chimwaza Y, et al. Intrapartum antibiotic prophylaxis to prevent Group B streptococcal infections in newborn infants: a systematic review and meta-analysis comparing various strategies. eClinicalMedicine. 2024;74.
- Hughes R, Brocklehurst P, Steer P, Heath P, Stenson B, on behalf of the Royal College of Obstetricians and Gynaecologists. Prevention of Early-onset Neonatal Group B Streptococcal Disease. BJOG: An International Journal of Obstetrics & Gynaecology. 2017;124(12):e280-e305.
