title: High-dose intravenous vancomycin therapy and the risk of nephrotoxicity.
abstract: OBJECTIVE
  National 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.
  
  
  METHODS
  This 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Administration 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.
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: srostas@partners.org.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Rostas
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: David W
authors.initials: DW
authors.lastname: Kubiak
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Calderwood
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000453:epidemiology; D061605:Administration, Intravenous; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D014640:Vancomycin / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: acute kidney injury; dose-response relationship; drug; vancomycin