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Pediatric Infectious Disease Journal:
doi: 10.1097/INF.0b013e3181906e40
Original Studies

Current Recommended Dosing of Vancomycin for Children With Invasive Methicillin-Resistant Staphylococcus aureus Infections Is Inadequate

Frymoyer, Adam MD*; Hersh, Adam L. MD, PhD†; Benet, Leslie Z. PhD‡; Guglielmo, B Joseph PharmD§

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Abstract

Background: Vancomycin area-under-the-concentration-time-curve (AUC) for 24 hours divided by the minimum inhibitory concentration (MIC) (AUC24/MIC) >400 optimally treats invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in adults. It is unknown whether recommended vancomycin dosing regimens for children achieve this value.

Methods: AUC24/MIC was calculated in children using vancomycin doses of 40 and 60 mg/kg/d. AUC24 was calculated as daily dose/vancomycin clearance. Vancomycin clearance in children was estimated by 2 approaches: (1) previously literature-reported vancomycin clearance, and (2) calculated vancomycin clearance using previously derived predictor models and a hypothetical population of healthy children. Representative MIC of hospital MRSA isolates was used (0.5, 1.0, and 2.0 μg/mL).

Results: The MIC50/90 for pediatric MRSA isolates in the previous year was 1.0 μg/mL. With a dose of 40 mg/kg/d, both approaches consistently predicted AUC24/MIC <400 when MIC was 1.0 μg/mL. At 60 mg/kg/d, AUC24/MIC >400 was more readily achieved when MIC was 1.0 μg/mL, however, an MIC of 2.0 μg/mL resulted in AUC24/MIC <400 for both dosing regimens.

Conclusions: A vancomycin dose of 40 mg/kg/d in children is unlikely to achieve the recommended pharmacodynamic target of AUC24/MIC >400 for invasive MRSA infections even when MIC is 1.0 μg/mL. A starting dose of 60 mg/kg/d should be used in settings where isolates with MIC of 1.0 are common. Alternatives to vancomycin should strongly be considered for patients with MIC ≥2.0 μg/mL.

© 2009 Lippincott Williams & Wilkins, Inc.

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