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

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Abstract
Recent guidelines recommend vancomycin trough concentrations between 15 and 20 mg/liter. In response, some clinicians increased vancomycin dosing to >= 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 >= 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 >= 18 years of age, (ii) were nonneutropenic, (iii) were on therapy for >48 h, (iv) had baseline serum creatinine levels of = 4 g/day and 220 patients taking = 4 g vancomycin/day, those receiving < 4 g vancomycin/day, and those receiving linezolid was noted (34.6%, 10.9%, and 6.7%, respectively; P = 0.001), and Kaplan-Meier analysis identified significant differences in time to nephrotoxicity for the high-vancomycin-dose cohort compared to those for groups taking the standard dose and linezolid. In the Cox model, patients taking >= 4 g vancomycin/day, a total body weight of >= 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.

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