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

Background: Vancomycin area-under-the-concentratoin-time-curve (AUC) for 24 hours divided by the minimum inhibitory concentration (MIC) (AUC(24)/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: AUC(24)/MIC was calculated in children using vancomycin doses of 40 and 60 mg/kg/d. AUC(24) 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 mu g/mL). Results: The MIC50/90 for pediatric MRSA isolates in the previous year was 1.0 mu g/mL. With a dose of 40 mg/kg/d, both approaches consistently predicted AUC(24)/MIC <400 when MIC was 1.0 mu g/mL. At 60 mg/kg/d, AUC(24)/MIC >400 was more readily achieved when MIC was 1.0 mu g/mL, however, an MIC of 2.0 mu g/mL resulted in AUC(24)/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 AUC(24)/MIC >400 for invasive MRSA infections even when MIC is 1.0 mu g/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 mu g/mL.