Cefuroxime is an antibiotic recommended for surgical site infection prevention in cardiac surgery. However, the dosing regimens commonly used do not sustain therapeutic concentrations throughout surgery. The aim of this study was to conduct a population analysis of CXM pharmacokinetics (PK), and to propose an optimized dosing regimen.
Adult patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) received a 1500 mg CXM intravenous bolus, followed by a 750 mg bolus at CPB priming then every 2 h. Model-based PK simulations were used to develop an optimized dosing regimen and evaluate its efficacy in attaining various concentration thresholds, including those recommended in US and European guidelines.
In total, 447 CXM measurements were acquired in 50 patients. A two-compartment model best fitted the data, total body weight and creatinine clearance determining interpatient variability in the central and peripheral volumes of distribution, and in elimination clearance, respectively. Using our optimized dosing regimen, different dosing schemes adapted to bodyweight and renal function were calculated to attain total concentration thresholds ranging from 12 to 96 mg/L. Our simulations showed that the dosing regimens recommended in US and European guidelines failed to maintain concentrations above 48 mg/L. Our individualized dosing strategy was capable of assuring therapeutic CXM concentrations conforming to each target threshold.
Our model yielded an optimized CXM dosing regimen adapted to bodyweight and renal function, and sustaining therapeutic concentrations consistent with each desired threshold. The optimal target concentration and necessary duration of its maintenance in cardiac surgery still remain unclear.