Population pharmacokinetics of cefazolin administered as prophylaxis in paediatric patients undergoing cardiac surgery

Abstract

INTRODUCTION: This study describes cefazolin pharmacokinetics in paediatric patients undergoing cardiac surgery using cardiopulmonary bypass to optimise antimicrobial prophylaxis. METHODS: A prospective, single-centre, observational study was conducted to describe cefazolin pharmacokinetics in paediatric patients undergoing cardiac surgery. Cefazolin was administered intravenously before skin incision, every three hours intraoperatively, and every eight hours postoperatively. Blood samples were collected on 6-8 occasions intraoperatively and six postoperatively, depending on re-dosing. Unbound cefazolin concentrations were measured using a chromatographic assay and analysed using a population pharmacokinetic approach in Monolix®. Dosing simulations were performed to determine the optimal regimen to maintain unbound cefazolin concentrations above the minimum inhibitory concentration for 100% of the dosing interval (fT(>MIC)) in both intraoperative and postoperative phases. RESULTS: Sixty-eight patients were recruited and included in the pharmacokinetic model. Conventional cefazolin dosing regimens (preoperative 50 mg/kg, intraoperative 25 mg/kg 3 -hly and postoperative 25 mg/kg 8 -hly) resulted in subtherapeutic concentrations in up to 16.8% of paediatric patients postoperatively in cardiac surgery requiring cardiopulmonary bypass. Target attainment decreased with increasing eGFR. Dosing simulations indicated that increasing the postoperative dose to 25 mg/kg 3 -hly or using extended and continuous infusions achieves target attainment for all groups. DISCUSSION: Postoperative cefazolin concentrations in paediatric patients undergoing cardiopulmonary bypass are often inadequate to maintain optimal antimicrobial prophylaxis. More frequent postoperative dosing or the use of extended and continuous infusion strategies can ensure effective target attainment, potentially reducing the risk of surgical site infections in this vulnerable population.