Desired vancomycin trough concentration to achieve an AUC0-24/MIC ≥400 in Chinese children with complicated infectious diseases

Abstract

A vancomycin steady-state trough concentration (Cmin) of 15-20 mg/L is recommended for achieving a ratio of the 24-hour area under the curve to the minimum inhibitory concentration (AUC0-24/MIC) of ≥400 in adults. Since few paediatric data are available, our objectives were to (a) measure the pharmacokinetic indices of vancomycin and (b) determine the correlation between Cmin and AUC0-24/MIC in paediatric patients. Population-based pharmacokinetic modelling was performed for paediatric patients to estimate the individual parameters. The relationship between Cmin and the calculated AUC0-24/MIC was explored using linear regression and a probabilistic framework. A sensitivity analysis was also conducted using Monte Carlo simulations. Body-weight significantly influenced the pharmacokinetics of vancomycin. Based on real data and simulations, Cmin ranges of 5.0-5.9 and 9.0-12.9 mg/L were associated with AUC0-24/MIC ≥400 for MIC values of ≤0.5 and ≤1 mg/L, respectively. Vancomycin regimens of 10 and 15 mg/kg every 6 hours achieved a Cmin of 5.0-5.9 mg/L and AUC0-24/MIC ≥400 in >90% of the children when MIC was ≤0.5 mg/L. At a MIC of ≤1 mg/L, vancomycin at 15 mg/kg every 6 hours achieved Cmin of 9.0-12.9 mg/L and AUC0-24/MIC ≥400 in 2.0- and 1.6-fold as many children compared to a dose of 10 mg/kg every 6 hours, respectively. Vancomycin Cmin values of 5.0-12.9 mg/L were strongly predictive of achieving AUC0-24/MIC ≥400, and rational dosing regimens of 10-15 mg/kg q6h were required in paediatric patients, depending on the pathogen.