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]

Predicting High Vancomycin Minimum Inhibitory Concentration in Methicillin-Resistant Staphylococcus aureus Bloodstream Infections.

Clin Infect Dis. 2011 Apr;52(8):997-1002

Authors: Lubin AS, Snydman DR, Ruthazer R, Bide P, Golan Y

Background.?Increased mortality, treatment failure, and hospital length of stay have been reported in patients treated with vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia when their isolates have a vancomycin minimum inhibitory concentration (MIC) >?1 ?g/mL. Automated testing often fails to identify these isolates. We developed a simple clinical rule to predict vancomycin MIC of 2 ?g/mL in patients with MRSA bacteremia. Methods.?This cohort study was conducted at a tertiary care hospital and an affiliated acute rehabilitation facility. Consecutive patients with MRSA bacteremia from 2001 through 2007 were prospectively identified. Patient characteristics were examined for their association with high vancomycin MIC and a predictive model was created. Results.?A total of 296 MRSA bacteremic episodes among 272 patients were identified; 19% of the episodes had isolates with a vancomycin MIC of 2 ?g/mL. Variables associated with a vancomycin MIC of 2 ?g/mL included older age (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.5-10.4); prior vancomycin (OR, 3.8; 95% CI, 1.9-7.6) or daptomycin (OR, 7.9; 95% CI, 1.8-34.0) exposure; the presence of a nontunneled central venous catheter (OR, 1.9; 95% CI, 1.1-3.4) or prosthetic heart valve (OR, 3.6; 95% CI, 1.3-10.0); a history of MRSA bacteremia (OR, 3.0; 95% CI, 1.6-5.6); and the presence of sepsis (OR, 2.7; 95% CI, 1.4-5.1) or shock (OR, 2.2; 95% CI, 1.1-4.2) at the time of culture. The final predictive rule included age >?50 years (3 points), prior vancomycin exposure (2 points), history of MRSA bacteremia (2 points), history of chronic liver disease (2 points), and presence of a nontunneled central venous catheter (1 point). A score cutoff of ??4 resulted in a sensitivity of 75% and specificity of 59% (negative predictive value, 91%; positive predictive value, 30%). Conclusions.?Several factors that predict high vancomycin MIC were identified, and a simple predictive tool was created to help clinicians determine which patients are likely to have MRSA isolates with high vancomycin MIC.

PMID: 21460313 [PubMed - in process]