Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity

Antimicrob Agents Chemother. 2008 Apr;52(4):1330-6. doi: 10.1128/AAC.01602-07. Epub 2008 Jan 28.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / administration & dosage
  • Acetamides / adverse effects
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / adverse effects
  • Cohort Studies
  • Creatinine / blood
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Incidence
  • Kidney / drug effects*
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / epidemiology*
  • Linezolid
  • Male
  • Middle Aged
  • Oxazolidinones / administration & dosage
  • Oxazolidinones / adverse effects
  • Vancomycin* / administration & dosage
  • Vancomycin* / adverse effects


  • Acetamides
  • Anti-Bacterial Agents
  • Oxazolidinones
  • Vancomycin
  • Creatinine
  • Linezolid