Desired vancomycin trough concentration to achieve an AUC_0‐24/MIC ≥400 in Chinese children with complicated infectious diseases

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Abstract

A vancomycin steady-state trough concentration (C_min ) of 15-20 mg/L is recommended for achieving a ratio of the 24-hour area under the curve to the minimum inhibitory concentration (AUC_0-24 /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 C_min and AUC_0-24 /MIC in paediatric patients. Population-based pharmacokinetic modelling was performed for paediatric patients to estimate the individual parameters. The relationship between C_min and the calculated AUC_0-24 /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, C_min ranges of 5.0-5.9 and 9.0-12.9 mg/L were associated with AUC_0-24 /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 C_min of 5.0-5.9 mg/L and AUC_0-24 /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 C_min of 9.0-12.9 mg/L and AUC_0-24 /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 C_min values of 5.0-12.9 mg/L were strongly predictive of achieving AUC_0-24 /MIC ≥400, and rational dosing regimens of 10-15 mg/kg q6h were required in paediatric patients, depending on the pathogen.

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