Population Pharmacokinetics and Dosing Optimization of Vancomycin in Infants, Children, and Adolescents with Augmented Renal Clearance.

Augmented renal clearance (ARC) can cause underexposure to vancomycin, thereby increasing the risk of treatment failure. Our objective was to evaluate population pharmacokinetics and optimize the dosing regimen of vancomycin in a pediatric population with ARC. Sparse pharmacokinetic sampling and therapeutic drug monitoring (TDM) data were collected from pediatric patients with ARC treated with vancomycin. A pharmacokinetic model was developed using NONMEM 7.2. The dosing regimen was optimized using Monte Carlo dose simulations. A total of 242 vancomycin serum concentrations from 113 patients (age range, 0.4 to 14.9 years; 49 females and 64 males) were available. The mean vancomycin dose was 58.8 mg/kg body weight/day (13.6 mg/kg/dose), and the mean vancomycin serum trough concentration was 6.5 mg/liter. A one-compartment pharmacokinetic model with first-order elimination was developed. Body weight and age were the most significant and positive covariates for clearance and volume of distribution. For the pediatric population with ARC, the current recommended vancomycin dose of 60 mg/kg/day was associated with a high risk of underdosing. To reach the target area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC) ratio of 400 to 700 in these pediatric patients, the vancomycin dose should be increased to 75 mg/kg/day for infants and children between 1 month and 12 years of age and 70 mg/kg/day for adolescents between 12 and 18 years of age. In conclusion, a one-compartment pharmacokinetic model with first-order elimination was established with body weight and age as significant covariates. An optimal dosing regimen was developed in pediatric patients with ARC aged 1 month to 18 years.

[Effect of augmented renal clearance on plasma concentration of vancomycin and treatment outcome in children with methicillin-resistant Staphylococcus aureus infection].

OBJECTIVE: To investigate the effect of augmented renal clearance (ARC) on plasma concentration of vancomycin, bacteriological outcome, and clinical outcome in children with methicillin-resistant Staphylococcus aureus (MRSA) infection treated by vancomycin. METHODS: A retrospective analysis was performed for the clinical data of 60 critically ill children who were treated with vancomycin due to MRSA infection from January 2013 to July 2017 and underwent plasma concentration monitoring. According to estimated glomerular filtration rate, these children were divided into an ARC group with 19 children and a normal renal function group with 41 children. The two groups were compared in terms of the use of vancomycin, plasma concentration of vancomycin, and treatment outcome. RESULTS: The children in the ARC group had an age of 1-12 years, and the ARC group had significantly higher body weight and body surface area than the normal renal function group (P<0.05). Compared with the normal renal function group, the ARC group had a significantly lower initial trough concentration of vancomycin and a significantly lower proportion of children who achieved the effective trough concentration of vancomycin (10-20 mg/L) (P<0.05). There were no significant differences in bacteriological outcome and clinical outcome between the two groups (P>0.05), but the ARC group had significantly longer length of stay in the pediatric intensive care unit (PICU) and length of hospital stay than the normal renal function group (P<0.05). CONCLUSIONS: ARC can significantly reduce the trough concentration of vancomycin and prolong the length of PICU stay and the length of hospital stay in children with MRSA infection. Idividualized medication should be administered to children with ARC.

A population pharmacokinetic model for individualised dosage regimens of vancomycin in Chinese neonates and young infants.

Population pharmacokinetic (PPK) modelling is an easy and impartment method for estimating drug concentration for use inindividualized therapy, especially for young patients and to help protect drug-induced diseases. The purpose of this study was to develop a PPK model for effective dosing of vancomycin in Chinese neonates and young infants. The PPK modelling tool Phoenix® NLME™ was use to assess demographic and routine clinical pharmacokinetic (PK) data retrospectively collected for patients admitted to Children's Hospital of Chongqing Medical University between 2011 and 2016. Data of patients admitted to the hospital between January and June of 2017 were used in validation study, and the final model was also preliminary validated in 2 cases in another hospital. A total of 421 serum samples from 316 patients were included in the initial PPK analysis. A two-compartment PPK model was developed, and exponential-error model was used to describe inter-individual variability of clearance. Residual variability was described by an additive model. The final PPK model was demonstrated as valid by internal and external model evaluation. Of note, the clearance and volume of vancomycin in Chinese neonates and young infants may be greater than in Caucasians. Herein, we describe the establishment of an accurate PPK model of vancomycin for Chinese neonates and young infants, which may be useful as a dosing algorithm for this particular paediatric population.