Current recommended dosing of vancomycin for children with invasive methicillin-resistant Staphylococcus aureus

Adam Frymoyer1, Adam L Hersh, Leslie Z Benet

  • 1Department of Medicine, University of California, San Francisco, CA 94143-0912, USA. frymoyera@peds.ucf.edu

Abstract

Insights

Pediatric vancomycin dosing of 40 mg/kg/d is insufficient for invasive MRSA infections. A 60 mg/kg/d dose is recommended when MRSA MIC is 1.0, with alternatives needed for higher MICs.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Pediatrics

Background:

  • Optimal treatment for invasive MRSA infections in adults requires a vancomycin area-under-the-concentration-time-curve (AUC24/MIC) >400.
  • Current vancomycin dosing regimens in children have not been evaluated against this target.

Purpose of the Study:

  • To determine if standard vancomycin doses (40 and 60 mg/kg/d) achieve the target AUC24/MIC >400 in children with invasive MRSA infections.

Main Methods:

  • AUC24/MIC was calculated in children using 40 and 60 mg/kg/d vancomycin doses.
  • Vancomycin clearance was estimated using literature values and predictive models.
  • Calculations were performed using representative MRSA minimum inhibitory concentrations (MICs) of 0.5, 1.0, and 2.0 µg/mL.

Main Results:

  • A vancomycin dose of 40 mg/kg/d consistently resulted in AUC24/MIC <400 when MRSA MIC was 1.0 µg/mL.
  • A dose of 60 mg/kg/d more readily achieved AUC24/MIC >400 for MIC = 1.0 µg/mL.
  • However, an MIC of 2.0 µg/mL led to AUC24/MIC <400 for both dosing regimens.

Conclusions:

  • A 40 mg/kg/d vancomycin dose is unlikely to achieve the therapeutic target for invasive MRSA in children, even with MIC = 1.0 µg/mL.
  • A starting dose of 60 mg/kg/d is recommended when MRSA isolates with MIC = 1.0 µg/mL are prevalent.
  • Vancomycin alternatives should be considered for infections with MIC ≥ 2.0 µg/mL.

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