title: Identification of risk factors for nephrotoxicity in patients receiving extended-duration, high-trough vancomycin therapy.
abstract: BACKGROUND
  In the past, impurities in vancomycin formulations were thought to contribute to nephrotoxicity. In contrast, when current, purer formulations are dosed at conventional trough levels (i.e., 5-15 mg/L), the incidence of nephrotoxicity is relatively low. Recent guidelines have recommended targeting higher vancomycin trough levels in treatment of complicated methicillin-resistant Staphylococcus aureus infections. Dosing based on these higher trough levels may be associated with nephrotoxicity, so the potential risk factors for vancomycin-associated nephrotoxicity require clearer definition.
  
  
  OBJECTIVE
  To determine the occurrence of nephrotoxicity in patients receiving more than 7 days of vancomycin therapy with high trough levels (15-20 mg/L) and to identify and evaluate specific risk factors related to development of vancomycin-associated nephrotoxicity (i.e., serum creatinine ≥ 44.2 μmol/L or increase ≥ 50% [i.e., ≥ 26.2 μmol/L] from baseline on 2 consecutive days).
  
  
  METHODS
  Health care records were reviewed for patients seen at 2 major teaching hospitals between January 2008 and March 2011. Patients who had attained high trough levels of vancomycin were screened for eligibility. Patients with unstable renal function, those undergoing hemodialysis, and those for whom dosage and/or sampling times were unclear were excluded. Univariate and multivariate analyses were performed to identify risk factors associated with nephrotoxicity. Univariate variables with p < 0.1 were included in the logistic regression model.
  
  
  RESULTS
  Of the 176 patients with high trough levels included in the analysis, 24 (14%) experienced nephrotoxicity. In univariate analysis, admission to a general medicine unit (the setting of care for 16 [67%] of the 24 patients with nephrotoxicity) and extended duration of vancomycin treatment were identified as risk factors for nephrotoxicity (p < 0.1). Other risk factors included gastrointestinal comorbidity (p = 0.056), malignancy (p = 0.044), and febrile neutropenia (p = 0.032). Multivariate analysis identified treatment on general medicine units and treatment courses longer than 7 days as independent predictors of vancomycin-associated nephrotoxicity.
  
  
  CONCLUSIONS
  Patients being treated on general medicine units and those receiving vancomycin for more than 7 days had an increased likelihood of experiencing nephrotoxicity. The increased risk for patients on general medicine units is likely multifactorial. The relationship between treatment duration and risk of nephrotoxicity appeared to be linear. When using extended-duration, high-trough vancomycin therapy, clinicians should be vigilant in monitoring for nephrotoxicity.
authors.affiliation: , BSc(Pharm), ACPR, is a Clinical Pharmacist with Providence Healthcare, Vancouver, British Columbia.
authors.forename: Claire
authors.initials: C
authors.lastname: Contreiras
authors.affiliation: , BSc(Pharm), ACPR, PharmD, is a Clinical Specialist, Internal Medicine, St Paul's Hospital, and Clinical Associate Professor, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia.
authors.forename: Michael
authors.initials: M
authors.lastname: Legal
authors.affiliation: , BSc(Pharm), ACPR, PharmD, FCSHP, is a Pharmacotherapeutic Specialist, Antimicrobial Stewardship and Infectious Diseases, Vancouver General Hospital; Clinical Professor, Faculty of Pharmaceutical Sciences, The University of British Columbia; and Associate Member, Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia.
authors.forename: Tim T Y
authors.initials: TT
authors.lastname: Lau
authors.affiliation: , BSc, BSc(Pharm), ACPR, PharmD, is a Pharmacy Consultant for the British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia.
authors.forename: Rosanne
authors.initials: R
authors.lastname: Thalakada
authors.affiliation: , BSc(Pharm), ACPR, PharmD, FCSHP, is Clinical Coordinator, Providence Healthcare, Lower Mainland Pharmacy Services, and Clinical Professor, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Shalansky
authors.affiliation: , BS(Pharm), PharmD, FASHP, FCCP, FCSHP, FCAHS, is Professor, Faculty of Pharmaceutical Sciences, and Distinguished University Scholar, The University of British Columbia; and Clinical Pharmacy Specialist, Children's and Women's Health Centre of British Columbia, Vancouver, British Columbia. She is also the Editor of CJHP .
authors.forename: Mary H H
authors.initials: MH
authors.lastname: Ensom
keywords: high-trough therapy; nephrotoxicity; vancomycin