High-Dose Intravenous Vancomycin Therapy and the Risk of Nephrotoxicity

PurposeNational guidelines recommend higher serum trough concentrations when using vancomycin to treat certain clinical conditions, but there is concern that higher-dose vancomycin therapy causes nephrotoxicity. We evaluated risk factors associated with nephrotoxicity in patients receiving high-dose intravenous vancomycin.MethodsThis retrospective cohort study evaluated the clinical outcome of 80 hospitalized adult patients with normal baseline renal function who received ≥4 g/d of intravenous vancomycin for ≥48 hours between January 1, 2011, and December 31, 2011. After abstracting clinical risk factors, we used an analysis by methods of best clinical subsets to develop a multivariable model predicting nephrotoxicity in patients receiving high-dose vancomycin.FindingsThe overall rate of nephrotoxicity in the study population was 6%. Trough concentrations >20 mg/L were identified in a similar proportion of patients who did and did not develop nephrotoxicity. Patients who developed nephrotoxicity trended toward having a lower body mass index, higher daily dose, longer duration of therapy, and greater exposure to intravenous contrast and nephrotoxic medications. In a multivariable model, the combination of intravenous contrast and nephrotoxic medications was a significant predictor of nephrotoxicity, and duration of high-dose vancomycin was a significant confounder.ImplicationsAdministration of high-dose intravenous vancomycin may have less associated nephrotoxicity than previously reported, although duration of vancomycin therapy may play a role. Concomitant exposure to intravenous contrast and other nephrotoxic medications is a more significant predictor of developing nephrotoxicity than vancomycin dose or trough.