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-hourly and postoperative 25 mg/kg 8-hourly) 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-hourly 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.
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BibTeX
@article{cheng2026population,
title = {{Population pharmacokinetics of cefazolin administered as prophylaxis in paediatric patients undergoing cardiac surgery}},
author = {Vesa Cheng and Jessica Suna and Xin Liu and Gregory Moloney and Supreet Marathe and Suzanne Parker and Jacobus Ungerer and Brett Mcwhinney and Prem Venugopal and Nelson Alphonso and Jason A. Roberts},
journal = {Anaesthesia Critical Care \& Pain Medicine},
year = {2026},
month = oct,
doi = {10.1016/j.accpm.2025.101653},
url = {https://hal.science/hal-05825555v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Population pharmacokinetics of cefazolin administered as prophylaxis in paediatric patients undergoing cardiac surgery
AU - Vesa Cheng
AU - Jessica Suna
AU - Xin Liu
AU - Gregory Moloney
AU - Supreet Marathe
AU - Suzanne Parker
AU - Jacobus Ungerer
AU - Brett Mcwhinney
AU - Prem Venugopal
AU - Nelson Alphonso
AU - Jason A. Roberts
PY - 2026
DA - 2026/10/20
JO - Anaesthesia Critical Care & Pain Medicine
DO - 10.1016/j.accpm.2025.101653
UR - https://hal.science/hal-05825555v1
AB - 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-hourly and postoperative 25 mg/kg 8-hourly) 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-hourly 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.
SN - 2352-5568
ER -