Vancomycin: We Can't Get There from Here.
Clin Infect Dis. 2011 Apr;52(8):969-74
Authors: Patel N, Pai MP, Rodvold KA, Lomaestro B, Drusano GL, Lodise TP
(See the article by Kullar et al, on pages 975-981.) Background.?We sought to characterize the pharmacodynamic profile of the more intensive vancomycin dosing regimens currently used in response to the recent vancomycin guidelines. Methods.?A series of Monte Carlo simulations was performed for vancomycin regimens ranging from .5 g intravenous (IV) Q12H to 2 g IV Q12H. The probability of achieving an AUC/MIC ratio ? 400 for each dosing regimen was calculated for minimum inhibitory concentrations (MICs) from .5 to 2 mg/L. The risk of nephrotoxicity for each regimen was derived from a previously published vancomycin trough-nephrotoxicity logistic regression function. Restricted analyses were performed that only included subjects with troughs between 15 and 20 mg/L. Results.?At a MIC of 2 mg/L, even the most aggressive dosing regimen considered (2 g every 12 h) only yielded a probability of target attainment (PTA) of 57% while generating a nephrotoxicity probability upward of 35%(.) At a MIC of 1 mg/L, ?3 g per day provided PTA in excess of 80% but were associated with unacceptable risks of nephrotoxicity. In the restricted analyses of subjects with troughs between 15 and 20 mg/L, all regimens produced a PTA of 100% at MICs ?1 mg/L. The PTA was variable among the regimens at a MIC of 2 mg/L and was highly dependent on the total daily dose administered. Conclusions.?This study indicates that vancomycin may not be useful for treating serious methicillin-resistant Staphylococcus aureus (MRSA) infections with MIC values > 1 mg/L where PTA is questionable. Since an AUC/MIC ratio ? 400 is target associated with efficacy, one should consider incorporating computation of AUC when monitoring vancomycin.
PMID: 21460308 [PubMed - in process]