Abstract
The aim of this study was to establish the population pharmacokinetics (PK) model of Vancomycin for Chinese pediatric patients which can extrapolate to whole age periods by bridging the published adult population PK model and the established pediatric population PK model. The final consolidated population PK model was used to explore the correlation of pharmacokinetics/pharmacodynamics (PK/PD) indices and efficacy of vancomycin and to provide evidence for the optimized regimen of vancomycin in Chinese pediatric patients with Gram-positive bacterial infection. 108 pediatric patients with Gram-positive infections from 2 pediatric hospitals in China in the first period of the prospective multi-center vancomycin clinical observational study were enrolled to establish the population PK model. A one-compartment population PK model was established and validated. The correlation between vancomycin PK/PD indices [trough concentration (Cmin), peak concentration (Cmax), 0–24 h area under the curve (AUC0–24) and the area under the curve to minimum inhibitory concentration ratio (AUC0–24/MIC)] and the overall clinical outcomes (clinical efficacy and microbiological efficacy) in Chinese pediatric patients were evaluated. There is no significant correlation between PK/PD indices and clinical efficacy or microbiological efficacy. Considering the high clinical effective rate (>90%) and median AUC0–24/MIC values of 200–300, Chinese pediatric patients with Gram-positive bacterial infection may be suitable for lower AUC0–24/MIC target value compared to the target value of 400–600 recommended by IDSA guideline. Different optimal dose regimen of vancomycin for Chinese pediatric patients should be considered. Further evaluation in more prospective studies will be needed.
Highlights
Since the 1980s, vancomycin has been the first-line treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection
Gram-positive infections who received vancomycin therapy ≥5 days and who were under therapeutic drug monitoring (TDM) were enrolled in this study
Among the previous reported the pediatric vancomycin population PK models (Liu et al, 2017; Zane et al, 2017), only a small part of the models believe that creatinine clearance is a factor affecting vancomycin CL
Summary
Since the 1980s, vancomycin has been the first-line treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. In March 2020, the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP) published the revised consensus guideline for therapeutic monitoring of vancomycin for MRSA infection (Rybak et al, 2020). In this consensus guideline, predictive target value of the area under the curve to minimum inhibitory concentration ratio (AUC0–24/MIC) based on population pharmacokinetic analysis combined with Bayesian approaches was recommended for therapeutic drug monitoring, and trough concentration monitoring alone is no longer recommended. The target value of AUC0–24/MIC recommended by the consensus guideline is 400–600, for both adults and pediatric patients
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