Optimizing Vancomycin Therapy in Critically Ill Children: A Population Pharmacokinetics Study to Inform Vancomycin...

Area of Science:

• Pharmacology
• Pediatric Critical Care
• Biomarkers

Background:

• Area under the curve (AUC)-guided vancomycin therapy is recommended for efficacy.
• Estimating kidney function in critically ill children for vancomycin dosing is challenging.
• Current methods for estimating kidney function may be inadequate for optimizing vancomycin therapy.

Purpose of the Study:

• To develop and validate population pharmacokinetic (PK) models for vancomycin AUC estimation in critically ill children.
• To evaluate novel kidney biomarkers as covariates for vancomycin clearance.
• To determine optimal sampling times for accurate Bayesian AUC estimation.

Main Methods:

• Prospective enrollment of 50 critically ill children receiving vancomycin.
• Nonparametric population PK modeling using Pmetrics with kidney biomarkers (cystatin C-based eGFR, urinary NGAL) as covariates.
• Multiple-model optimization for defining optimal sampling times.
• Comparison of Bayesian posterior AUC with noncompartmental analysis AUC.

Main Results:

• A two-compartment model best described vancomycin PK.
• Cystatin C-based eGFR and urinary NGAL improved vancomycin clearance model likelihood.
• Models using cystatin C-based eGFR or creatinine-based eGFR facilitated accurate and precise vancomycin AUC estimation.
• Bias and imprecision were low for AUC predictions across tested models.

Conclusions:

• Population PK models incorporating kidney biomarkers enable accurate vancomycin AUC estimation in critically ill children.
• Cystatin C-based eGFR is a valuable covariate for vancomycin clearance modeling.
• These findings support improved therapeutic drug monitoring for vancomycin in pediatric critical care.