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Exploring the Past to Inform the Future to Optimize the Pharmacokinetics of Vancomycin in Children With Severe Burn

Catherine M Sherwin1,2,3,4, Nam K Tran5, Kevin Sullivan6

  • 1Dept of Pediatrics, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA.

Journal of Burn Care & Research : Official Publication of the American Burn Association
|October 4, 2022
PubMed

Insights

This study analyzed vancomycin pharmacokinetics in pediatric burn patients, finding that weight, age, and creatinine clearance significantly impact drug clearance and volume of distribution. These findings are crucial for optimizing vancomycin dosing in children with severe burns.

Area of Science:

  • Pediatric pharmacology
  • Burn injury management
  • Infectious disease pharmacokinetics

Background:

  • Sepsis is a major cause of mortality in pediatric burn patients.
  • Vancomycin is frequently used for severe burn injuries despite limited pharmacokinetic data in children.
  • Severe burns increase the risk of acute kidney injury (AKI), with over 50% incidence, complicating vancomycin therapy.

Purpose of the Study:

  • To characterize vancomycin population pharmacokinetics in pediatric patients with severe burns.
  • To identify key covariates influencing vancomycin clearance (CL) and volume of distribution (V).
  • To inform optimal vancomycin dosing strategies for this vulnerable population.

Main Methods:

  • Retrospective analysis of 115 pediatric patients (0.2 months to 18 years) with severe burns (>10% TBSA).
  • Intravenous vancomycin administration with blood sampling 6-12 hours post-infusion.
  • Population pharmacokinetic modeling using nonlinear mixed-effect modeling (Monolix).

Main Results:

  • A one-compartment model was developed, with V dependent on weight and CL influenced by age and estimated creatinine clearance (CrCL).
  • Median V was 1.25 L/kg and median CL was 0.15 L/h/kg for the study population (median age 4 years, weight 20 kg, %TBSA 40%).
  • Weight, age, and estimated CrCL were identified as significant covariates, explaining high variability in vancomycin CL and V.

Conclusions:

  • Vancomycin pharmacokinetics in pediatric burn patients are significantly influenced by weight, age, and estimated CrCL.
  • The developed population pharmacokinetic model provides insights into drug disposition in this population.
  • Accurate dosing based on these covariates is essential for achieving therapeutic efficacy and minimizing nephrotoxicity in pediatric burn patients.

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