Larger Vancomycin Doses (at Least Four Grams per Day) Are Associated with an Increased Incidence of Nephrotoxicity

Recent guidelines recommend vancomycin trough concentrations between 15 and 20 mg/liter. In response, some clinicians increased vancomycin dosing to >or=4 g/day. Scant data are available regarding toxicities associated with higher vancomycin doses. The purpose of this study was to examine vancomycin-associated nephrotoxicity at >or=4 g/day. To accomplish the study objective, a cohort study among a random selection of patients receiving vancomycin or linezolid between 2005 and 2006 was performed. Patients were included if they (i) were >or=18 years of age, (ii) were nonneutropenic, (iii) were on therapy for >48 h, (iv) had baseline serum creatinine levels of <2.0 mg/dl, (v) did not suffer from cystic fibrosis, and (vi) had no intravenous contrast dye within the previous 7 days. For drug exposure, three treatment strata were created: standard vancomycin dose (or=4 g/day), and linezolid. Nephrotoxicity was defined as a serum creatinine increase of 0.5 mg/dl or 50%, whichever was greater, after therapy initiation. Stratified Kaplan-Meier analysis and Cox modeling were used to compare times to nephrotoxicity across groups. During the study, 246 patients on vancomycin (26 patients taking >or=4 g/day and 220 patients taking or=4 g vancomycin/day, those receiving or=4 g vancomycin/day, a total body weight of >or=101.4 kg, estimated creatinine clearance of </=86.6 ml/min, and intensive care unit residence were independently associated with time to nephrotoxicity. The data suggest that higher-dose vancomycin regimens are associated with a higher likelihood of vancomycin-related nephrotoxicity.