Thomas P. Lodise
Results from a multi-center study of hospitalized adults with MRSA bloodstream infections suggest that vancomycin dosing should be guided by the area under the curve, or AUC, not the AUC/MIC ratio, and that day-2 AUCs should be maintained below 515 to maximize efficacy and minimize acute kidney injury, or AKI, researchers reported.
In the study, higher day-2 vancomycin exposures in patients with bacteremia were not associated with a lower incidence of treatment failure, but were associated with higher rates of AKI, Thomas P. Lodise, PharmD, PhD, a professor at the Albany College of Pharmacy and Health Sciences, explained to Infectious Disease News.
Writing in Clinical Infectious Diseases, Lodise and colleagues noted that despite vancomycin being the most commonly administered antibiotic in hospitals, “optimal exposure targets remain controversial.”
“For serious MRSA infections, current guidelines recommend targeting trough concentrations between 15 and 20 mg/L for patients with serious infections due to [Staphylococcus] aureus,” Lodise told Infectious Disease News. “Despite widespread clinical adoption of these recommendations, supportive data are limited and largely derived from single-center retrospective studies.”
In their study, Lodise and colleagues evaluated the association between day-2 vancomycin exposures and the outcomes of patients with MRSA bacteremia. The primary outcome was treatment failure, defined as 30-day mortality or persistent bacteremia for 7 days or longer. AKI was the secondary outcome.
The prospective, multicenter, observational study included 14 facilities and 265 hospitalized patients and was conducted between November 2014 and December 2015. The researchers compared rates of treatment failure between patients who did or did not achieve day-2 area AUC/MIC thresholds of 650 or greater by broth microdilution, or 320 or greater by Etest.
According to the findings, treatment failure occurred in 18% of patients and AKI in 26%. Lodise and colleagues reported that achievement of the two prespecified day-2 AUC/MIC thresholds was not associated with less treatment failure, and they did not identify any alternative day-2 AUC/MIC thresholds associated with lower treatment failure.
“This multicenter prospective study that utilized individualized estimates of exposure based on measured concentrations was performed to evaluate the relationship between day-2 vancomycin exposure profiles and outcomes in patients with MRSA bacteremia,” Lodise said. “Despite the recommendation to monitor troughs in clinical practice, the collective findings suggest that vancomycin dosing should be guided by the AUC and day-2 AUCs should be maintained between 400 and 515.”
According to the study, patients who demonstrated a day-2 AUC of 515 or less experienced the best global outcomes, such as no treatment failure or AKI.
“To optimally dose an antibiotic, you need a firm understanding of its therapeutic range,” Lodise said. “This understanding has been lacking for vancomycin and this study suggests the therapeutic range is between [approximately] 400 and 515 to minimize AKI and maintain outcomes for patients with MRSA bloodstream infections.”
Keith A. Rodvold , PharmD, professor of pharmacy practice at the University of Illinois at Chicago College of Pharmacy, responded to the findings in a related editorial.
“Just as in the 1980s and 1990s, the controversies and debates about the value of serum vancomycin concentrations for dosing of vancomycin will continue mainly because of the wide dose-response relationship of vancomycin observed in various types of infections and patient populations, as well as the difficulties to clearly establishing dose-toxicity relationship in seriously ill patients with MRSA infections,” Rodvold wrote. “In view of the limitations of existing reports, sound clinical judgement must always rule the kingdom of vancomycin use.”
Disclosures: Lodise and Rodvold report numerous ties with industry. Please see the study for all other authors’ relevant financial disclosures.