New method and lower dosing of vancomycin could treat MRSA with reduced AKI

Achieving typical area under the curve to minimum inhibitory concentrations of vancomycin was not associated with a lower rate of treatment failure but was associated with increased risk of acute kidney injury (AKI), a study found.

Lower doses of vancomycin may successfully treat methicillin-resistant Staphylococcus aureus (MRSA) bacteremia while reducing risk of acute kidney injury (AKI), a recent study found.

The prospective observational study included 265 adults with MRSA bacteremia from 14 hospitals. The patients were divided by whether they achieved area under the curve to minimum inhibitory concentration (AUC/MIC) thresholds of vancomycin of at least 650 by broth microdilution or 320 by Etest. These thresholds have been previously associated with lower incidence of treatment failure, which the study defined as mortality within 30 days or persistent bacteremia at seven days. Results were published by Clinical Infectious Diseases on June 3.

Treatment failure occurred in 18% of patients; 26% developed AKI. Patients who achieved the vancomycin thresholds did not have lower rates of treatment failure, and the study was not able to identify a threshold associated with lower risk of treatment failure. Higher AUC on day 2 was associated with AKI risk. Patients with an AUC of 515 or less had the greatest likelihood of avoiding both treatment failure and AKI, leading the authors to conclude that this value should be a target for vancomycin dosing in such patients. They noted that few patients in the study had AUCs below 400, so they weren't able to find a lower bound on the therapeutic range.

“These results have important implications for clinical practice. Clinicians and guideline authors should reassess the balance of benefits and risks of targeting higher AUC/MIC for patients with MRSA bacteremia,” the authors said. “The findings also suggest that vancomycin dosing should be guided by the AUC instead of the AUC/MIC ratio.” They noted that issues with MIC include the narrow range of MIC values among contemporary MRSA isolates, the imprecision of MIC measurement, the variability of testing methods, and the delay until values are available.

The study was limited by the factors inherent in observational research, the authors noted. It also only included adult, non-neutropenic, nondialysis patients, and nearly all MRSA isolates in the study had vancomycin MICs under 2 mg/L.

An accompanying editorial noted that most medical centers report not being ready yet to change from trough-based dosing of vancomycin to AUC-based dosing, but more literature and guidelines on the topic might lead them to consider adding it to practice. “This study, along with several other recent publications, suggest that an AUC range between 400 to 600 μg×h/mL was most commonly linked to clinical success, whereas an increased risk for vancomycin-associated acute kidney injury or nephrotoxicity occurs when an AUC threshold exceeds a range of 600 to 800 μg×h/mL,” the editorialist said.