Vancomycin AUC/MIC Ratio and 30-Day Mortality in Patients with Staphylococcus aureus Bacteremia

Abstract

A ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of >400 has been associated with clinical success when treating Staphylococcus aureus pneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all serious S. aureus infections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a "real-world" context by following a cohort of 182 patients with S. aureus bacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively; P < 0.001). Obtaining the recommended vancomycin target AUC/MIC of >400 using BMD was not associated with lower 30-day all-cause or attributable mortality from SAB (P ‫؍‬ 0.132 and P ‫؍‬ 0.273, respectively). However, an alternative vancomycin AUC/MIC of >373, derived using classification and regression tree analysis, was associated with reduced mortality (P ‫؍‬ 0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, >373) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of >400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods.

Establishment of an AUC 0–24 Threshold for Nephrotoxicity Is a Step towards Individualized Vancomycin Dosing for Methicillin-Resistant Staphylococcus aureus Bacteremia

“…It is well known that the AUC 0 -24 /MIC ratio is a PD parameter associated with treatment success (13,17). This PD parameter is dependent on MIC value, which is higher with Etest MIC-based results than with broth microdilution MIC results (18)(19)(20). Overall, our data indicate that individualized dosing is feasible, with clinicians able to optimize vancomycin doses to attain appropriate PD targets when MIC data become available from the microbiological laboratory.…”

Genetic and Molecular Predictors of High Vancomycin MIC in Staphylococcus aureus Bacteremia Isolates

“…The primary outcome was vancomycin Etest MIC, categorized into low (Յ1.5 mg/liter) or elevated (Ͼ1.5 mg/liter) groups, as defined by our previous findings (6). Secondary outcomes included persistent bacteremia (defined as blood cultures positive for S. aureus taken Ն7 days after the index positive blood culture), and recurrent bacteremia (defined as a new episode of SAB after having documented negative blood cultures occurring within 30 days of the index positive blood culture) (18).…”

Optimizing the Clinical Use of Vancomycin

“…However, it must be noted that the vancomycin MIC for S. aureus varies depending on the testing method used. Etest yields MICs of 0.5-to 1.5-log 2 dilutions higher than those determined by broth microdilution (BMD) (10,(14)(15)(16)(17)(18)(19). In this review, unless otherwise noted, all of the AUC/MIC ratios are Etest measures; Etest is the recommended method for measuring the MIC for MRSA bloodstream infection isolates (18).…”