MRSA Response to Vancomycin Probed

SAN FRANCISCO—Vancomycin efficacy and its clinical outcomes in hemodialysis (HD) patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia may not be solely based on dose, treatment duration, and drug levels, according to a study presented at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy.

Recent evidence suggests that vancomycin has reduced activity against MRSA when minimal inhibitory concentrations (MICs) are high (1.5 mcg/mL or greater), and this may affect overall mortality. “The relationship between vancomycin MIC and outcomes in hemodialysis patients with MRSA bacteremia has not been explored in great detail,” said lead investigator Gargi Patel, PharmD, Clinical Teaching Hospital Pharmacist at the State University of New York Downstate Medical Center in Brooklyn, N.Y., who noted that HD patients are at high risk for MRSA bacteremia.

She and her colleagues conducted a single-center, retrospective study of 35 HD patients with MRSA bacteremia treated with vancomycin for at least 72 hours. To be included in the study, patients had to be aged 18 years or older and non-neutropenic. The investigators stratified subjects into three groups based on vancomycin MIC values. They collected demographic and microbiological data and information on past medical history and vancomycin treatment. In this study, vancomycin treatment outcomes were based on dose, duration, drug level, area under the curve/MIC ratio (AUC/MIC), and adverse effects. Overall outcomes were determined by MIC creep and clinical and microbiological failure.

Dr. Patel's team defined clinical failure death within seven or 30 days and microbiological failure as either MRSA bacteremia from 7-14 days during vancomycin therapy or recurrence within 60 days of vancomycin discontinuation.

The study revealed no differences in overall outcomes, but microbiological failure occurred more frequently in patients with MICs of 1.5 or greater compared with lower values. Patients with a low Charlson index score (low comorbidity burden) had high MICs.

Results showed that an AUC/MIC below 400 is an important predictor of vancomycin treatment failure in HD patients with MICs of 1.5 mcg/mL or higher, regardless of prior vancomycin exposure or comorbidites, Dr. Patel noted.

Moreover, the presence of an HD catheter and prior hospitalization within six months predicted which patients would be at risk of a high MIC.

“We were somewhat surprised that in this study, patients with low Charlson index score had high MICs for vancomycin,” Dr. Patel said. “Therefore, microbiological failure in these patients may be due to achievement of a low AUC/MIC.”

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