title: Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity.
abstract: 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 (<4 g/day), high 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 <4 g/day) and 45 patients on linezolid met the criteria. A significant difference in nephrotoxicity between patients receiving >or=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 >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.
authors.affiliation: Department of Pharmacy Practice, Albany College of Pharmacy, Albany, NY 12208, USA. Lodiset@acp.edu
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Lodise
authors.forename: Ben
authors.initials: B
authors.lastname: Lomaestro
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Graves
authors.forename: G L
authors.initials: GL
authors.lastname: Drusano
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015994:Incidence; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage / Q000009:adverse effects; D014640:Vancomycin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D014640:Vancomycin; D003404:Creatinine; D000069349:Linezolid