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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§

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

Author Information

From the *Division of Clinical Pharmacology, Department of Medicine, †Divisions of Infectious Diseases and General Pediatrics, Department of Pediatrics, ‡Department of Biopharmaceutical Sciences, and §Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA.

Accepted for publication October 7, 2008.

Supported by grant T32 GM07546 from the National Institute of General Medical Sciences and Grant T32 HD044331 from the National Institute of Child Health and Human Development.

Address for correspondence: Adam Frymoyer, MD, Division of Clinical Pharmacology, University of California, San Francisco, 513 Parnassus Ave., Box 0912, San Francisco, CA 94143-0912. E-mail: frymoyera@peds.ucf.edu.

© 2009 Lippincott Williams & Wilkins, Inc.