Objectives: Augmented renal clearance (
ARC) of primarily renally eliminated
antibacterial agents may result in subtherapeutic
antibiotic concentrations and, as a consequence, worse clinical outcomes.
Cefathiamidine is frequently used as empirical antimicrobial
therapy in children with
ARC, but pharmacokinetic studies in infants are lacking. This population pharmacokinetic study in infants with
ARC was conducted to determine optimal dosing regimens of
cefathiamidine. Methods: The population pharmacokinetics was conducted in 20 infants treated with
cefathiamidine. Plasma samples of
cefathiamidine were collected using opportunistic sampling, and the concentrations were detected by UPLC-MS/MS. Data analysis was performed to determine pharmacokinetic parameters and to characterize pharmacokinetic variability of
cefathiamidine using nonlinear mixed effects modelling (NONMEM) software program. Results: The data (n = 36) from 20 infants (age range, 0.35-1.86 years) with
ARC were fitted best with a 1-compartment model. Allometrically scaled weight and age as significant covariates influenced
cefathiamidine pharmacokinetics. The median (range) values of estimated clearance and the volume of distribution were 0.22 (0.09-0.29) L/h/kg and 0.34 (0.24-0.41) L/kg, respectively. Monte Carlo simulations showed that the
cefathiamidine doses of 100 mg/kg/day q12 h, 50 mg/kg/day q8 h and 75 mg/kg/day q6 h were chosen for bacteria with MIC 0.25, 0.5 and 2 mg/L, respectively. Conclusion: The population pharmacokinetic model of
cefathiamidine for infants with
ARC was developed. The PTA - based dosing regimens were recommended based on the final model.