Modeling Approach to Optimizing Dose Regimen of Vancomycin for Chinese Pediatric Patients with Gram-Positive Bacterial Infections

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.

Therapeutic Drug Monitoring of Vancomycin in Pediatric Patients: Defining a Therapeutic Drug Window

“…According to the latest international guidelines, monitoring the AUC 24 /MIC for vancomycin is recommended, with a target range of 400-600 [2] . Nevertheless, the practicality of monitoring AUC 24 /MIC in clinical settings is limited due to various factors, including the necessity for secondary sampling, the scarcity of specialized personnel, and the ambiguity surrounding PK/PD standards for pediatric patients [23] . Consequently, monitoring C min remains a widely adopted practice, even in most large tertiary medical institutions, emphasizing the crucial importance of further exploring the rational use of vancomycin through C min monitoring [24] .…”

Population pharmacokinetic analysis for dose regimen optimization of vancomycin in Southern Chinese children

“…The cutoff point (Figure S4) in predicting effectiveness showed that the median value of AUC/MIC was between 200 and 300 with an overall clinical effective rate of 92.6%, indicating that a relatively low exposure is effective for pediatric patients. 40 Another research in children with MRSA bacteremia showed that the relationship between vancomycin AUC 0-24 /MIC <400 and treatment failure could not be established. 41 Additionally, targeting the value above 400 in pediatrics would expose them to unnecessary adverse events.…”

Vancomycin population pharmacokinetics analysis in Chinese paediatric patients with varying degrees of renal function and ages: development of new practical dosing recommendations

“…We would like to mention that recent research indicates a possibly lower AUC target for Chinese paediatric patients. 40 Clinicians might consider this when interpreting our model’s simulation results, and adjust the dosing regimen according to their specific clinical requirements.…”