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Clin Infect Dis. 2011 Apr 15;52(8):969-74. doi: 10.1093/cid/cir078.

Vancomycin: we can't get there from here.

Author information

1
Albany College of Pharmacy and Health Sciences, Albany, New York 12208, USA.

Abstract

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
DOI:
10.1093/cid/cir078
[Indexed for MEDLINE]

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