Vancomycin-associated nephrotoxicity was reported in 0-5% of patients in the 1980s. This has been confirmed by numerous clinical trials comparing novel anti-methicillin-resistant Staphylococcus aureus (MRSA) agents to vancomycin at the Food and Drug Administration (FDA) approved dose of 1 g q12h. Treatment failures of vancomycin in patients with MRSA infections have been reported despite in vitro susceptibility. These failures have led to the utilization of vancomycin doses higher than those approved by the FDA. Higher doses are being administered to achieve goal vancomycin trough concentrations of 10-20 μg/mL recommended by several Infectious Diseases Society of America (IDSA) endorsed clinical practice guidelines. Recent studies suggest that increased rates of nephrotoxicity are associated with aggressive vancomycin dosing. These increased rates are confounded by concomitant nephrotoxins, renal insufficiency, and/or changing hemodynamics. These studies have also demonstrated that vancomycin's nephrotoxicity risk is minimal in patients without risk factors for nephrotoxicity. Clinicians unwilling to dose vancomycin in accordance with clinical practice guidelines should use an alternative agent since inadequate dosing increases the likelihood of selecting heteroresistant MRSA isolates.

BackgroundPrevious studies have established a correlation between vancomycin troughs and nephrotoxicity. However, data are currently lacking regarding the effect of guideline-recommended weight-based dosing on nephrotoxicity in methicillin-resistant Staphylococcus aureus bacteremia (MRSAB).MethodsAdults who were at least 18 years of age with methicillin-resistant Staphylococcus aureus bacteremia and received of empiric vancomycin therapy for at least 48 hours (01/07/2002 and 30/06/2008) were included in this multicenter, retrospective cohort study. The association between guideline-recommended, weight-based vancomycin dosing (at least 15 mg/kg/dose) and nephrotoxicity (increase in serum creatinine (SCr) by more than 0.5 mg/dl or at least a 50% increase from baseline on at least two consecutive laboratory tests) was evaluated. Potential independent associations were evaluated using a multivariable general linear mixed-effect model.ResultsOverall, 23% of patients developed nephrotoxicity. Thirty-four percent of the 337 patients who met study criteria received weight-based dosing. The cohort was composed of 69% males with a median age of 55 years. The most common sources of MRSAB included skin/soft tissue (32%), catheter-related bloodstream bacteremia (20%), pulmonary (18%). Eighty-six percent of patients received twice daily dosing. Similar rates of nephrotoxicity were observed regardless of the receipt of guideline-recommended dosing (22% vs. 24%, OR 0.91 [95% CI 0.53-1.56]). This finding was confirmed in the multivariable analysis (OR 1.52 [95% CI 0.75-3.08]). Independent predictors of nephrotoxicity were (OR, 95% CI) vancomycin duration of greater than 15 days (3.36, 1.79-6.34), weight over 100 kg (2.74, 1.27-5.91), Pitt bacteremia score of 4 or greater (2.73, 1.29-5.79), vancomycin trough higher than 20 mcg/ml (2.36, 1.07-5.20), and age over 52 years (2.10, 1.08-4.08).ConclusionsOver one out of five patients in this study developed nephrotoxicity while receiving vancomycin for MRSAB. The receipt of guideline-recommended, weight-based vancomycin was not an independent risk factor for the development of nephrotoxicity.