Clinical Application Value of Pharmacokinetic Parameters of Vancomycin in Children Treated in the Pediatric Intensive Care Unit

Abstract

Objective: To explore the efficacy and safety of vancomycin as measured by pharmacokinetic/pharmacodynamic parameters in children with severe infection in the Pediatric Intensive Care Unit (PICU) and to determine the appropriate threshold for avoiding nephrotoxicity.

Methods: The medical records of hospitalized children with severe infection treated with vancomycin in the PICU of a tertiary pediatric hospital from September 2018 to January 2021 were retrospectively collected. Univariate analysis was used to assess the correlation between vancomycin pharmacokinetic/pharmacodynamic parameters and therapeutic efficacy or vancomycin-related nephrotoxicity. Binary logistic regression was used to analyze the risk factors for vancomycin-related nephrotoxicity. The vancomycin area under the concentration-time curve over 24 h (AUC_0-24) threshold was determined by receiver operating characteristic (ROC) curve analysis.

Results: One hundred and 10 patients were included in this study. Seventy-six patients (69.1%) exhibited clinically effective response, while the rest exhibited clinically ineffective response. There were no significant differences in APACHE II score, steady-state trough concentration, peak concentration or AUC_0-24 of vancomycin between the effective and ineffective groups. Among the 110 patients, vancomycin-related nephrotoxicity occurred in 15 patients (13.6%). Multivariate analysis showed that vancomycin treatment duration, trough concentration, and AUC_0-24 were risk factors for vancomycin-related nephrotoxicity. The ROC curve indicated that AUC_0-24 < 537.18 mg.h/L was a suitable cutoff point for predicting vancomycin-related nephrotoxicity.

Conclusion: No significant correlations were found between the trough concentration or AUC_0-24 of vancomycin and therapeutic efficacy when the daily dose of vancomycin was approximately 40 mg/kg d, while the trough concentration and AUC_0-24 were both closely related to vancomycin-related nephrotoxicity. The combination of AUC_0-24 and trough concentration for therapeutic drug monitoring may reduce the risk of nephrotoxicity.

Keywords: children; nephrotoxicity; pharmacokinetics/pharmacodynamics; therapeutic drug monitoring; vancomycin.

FIGURE 1

Time curve of vancomycin concentration.

FIGURE 2

ROC curves of prediction probability and vancomycin nephrotoxicity of two models (the area under the ROC curve of the AUC_0–24 model was 0.935, 95% CI: 0.878–0.992, P < 0.001; the area under the ROC curve of the trough concentration model was 0.928, 95% CI: 0.868–0.989, P < 0.001).

FIGURE 3

ROC curve of the AUC_0–24 prediction level of vancomycin-related nephrotoxicity (the area under ROC curve = 0.774, 95% CI: 0.648–0.900, P = 0.001).