title: Relationship between vancomycin trough concentrations and nephrotoxicity: a prospective multicenter trial.
abstract: Several single-center studies have suggested that higher doses of vancomycin, aimed at producing trough concentrations of >15 mg/liter, are associated with increased risk of nephrotoxicity. We prospectively assessed the relative incidence of nephrotoxicity in relation to trough concentration in patients with documented methicillin-resistant Staphylococcus aureus (MRSA) infections at seven hospitals throughout South Carolina. Adult patients receiving vancomycin for at least 72 h with at least one vancomycin trough concentration determined under steady-state conditions were prospectively studied. The relationship between vancomycin trough concentrations of >15 mg/ml and the occurrence of nephrotoxicity was assessed using univariate and multivariate analyses, controlling for age, gender, race, dose, length of therapy, use of other nephrotoxins (including contrast media), intensive care unit (ICU) residence, episodes of hypotension, and comorbidities. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or a ≥ 50% increase from the baseline for two consecutive measurements. MICs of vancomycin for the MRSA isolates were also determined. A total of 288 patients were studied between February 2008 and June 2010, with approximately one-half having initial trough concentrations of ≥ 15 mg/ml. Nephrotoxicity was observed for 42 patients (29.6%) with trough concentrations >15 mg/ml and for 13 (8.9%) with trough concentrations of ≤ 15 mg/ml. Multivariate analysis revealed vancomycin trough concentrations of >15 mg/ml and race (black) as risk factors for nephrotoxicity in this population. Vancomycin trough concentrations of >15 mg/ml appear to be associated with a 3-fold increased risk of nephrotoxicity.
authors.affiliation: Department of Clinical Pharmacy and Outcome Sciences, South Carolina College of Pharmacy, Charleston and Columbia, South Carolina 29425, USA. bossoja@musc.edu
authors.forename: John A
authors.initials: JA
authors.lastname: Bosso
authors.forename: Jean
authors.initials: J
authors.lastname: Nappi
authors.forename: Celeste
authors.initials: C
authors.lastname: Rudisill
authors.forename: Marlea
authors.initials: M
authors.lastname: Wellein
authors.forename: P Brandon
authors.initials: PB
authors.lastname: Bookstaver
authors.forename: Jenna
authors.initials: J
authors.lastname: Swindler
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Mauldin
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000097:blood; D003404:Creatinine / Q000097:blood; D003428:Cross Infection / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D005260:Female; D006761:Hospitals / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D007674:Kidney Diseases / Q000139:chemically induced / Q000453:epidemiology*; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D013022:South Carolina / Q000453:epidemiology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D016896:Treatment Outcome; D014640:Vancomycin / Q000009:adverse effects / Q000097:blood
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D003404:Creatinine