title: Incidence of nephrotoxicity and association with vancomycin use in intensive care unit patients with pneumonia: retrospective analysis of the IMPACT-HAP Database.
abstract: BACKGROUND
  The 2005 guidelines from the American Thoracic Society and the Infectious Diseases Society of America recommend vancomycin trough levels of 15 to 20 mg/L for the therapy of hospital-acquired (HAP), ventilator-associated (VAP), and health care-associated (HCAP) pneumonia.
  
  
  OBJECTIVE
  The goal of this article was to report the incidence of nephrotoxicity and associated risk factors in intensive care unit patients who received vancomycin for the treatment of HAP, VAP, and HCAP.
  
  
  METHODS
  This was a retrospective analysis of data from a multicenter, observational study of pneumonia patients. Antibiotic-associated nephrotoxicity was defined as either an increase in serum creatinine ≥0.5 mg/dL or 50% above baseline, from initiation of vancomycin to 72 hours after completion of therapy. Univariate and multivariate logistic regression analyses were performed to identify risk factors for development of renal dysfunction.
  
  
  RESULTS
  Of the 449 patients in the database, 240 received at least one dose of vancomycin and 188 had sufficient data for analysis. In these 188 patients, 63% were male. Mean (SD) age was 58.5 (17.2) years, and the mean Acute Physiology and Chronic Health Evaluation II score was 19.4 (6.4). Nephrotoxicity occurred in 29 of 188 (15.4%) vancomycin-treated patients. In multivariate analysis, initial vancomycin trough levels ≥15 mg/L (odds ratio [OR], 5.2 [95% CI, 1.9-13.9]; P = 0.001), concomitant aminoglycoside use (OR, 2.67 [95% CI, 1.09-6.54]; P = 0.03), and duration of vancomycin therapy (OR for each additional treatment day, 1.12 [95% CI, 1.02-1.23]; P = 0.02) were independently associated with nephrotoxicity. The incidence of nephrotoxicity increased as a function of the initial vancomycin trough level, rising from 7% at a trough <10 mg/L to 34% at >20 mg/L (P = 0.001). The mean time to nephrotoxicity decreased from 8.8 days at vancomycin trough levels <15 mg/L to 7.4 days at >20 mg/L (Kaplan-Meier analysis, P = 0.0003).
  
  
  CONCLUSIONS
  Nephrotoxicity may be common among intensive care unit patients with pneumonia treated with broad-spectrum antibiotic therapy that includes vancomycin. The finding that an initial vancomycin trough level ≥15 mg/L may be an independent risk factor for nephrotoxicity highlights the need for additional studies to assess current recommendations for vancomycin dosing for ICU patients with pneumonia.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of Miami Miller School of Medicine and Jackson Memorial Hospital, Miami, FL, USA.
authors.forename: Ennie L
authors.initials: EL
authors.lastname: Cano
authors.forename: Nadia Z
authors.initials: NZ
authors.lastname: Haque
authors.forename: Verna L
authors.initials: VL
authors.lastname: Welch
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Cely
authors.forename: Paula
authors.initials: P
authors.lastname: Peyrani
authors.forename: Ernesto G
authors.initials: EG
authors.lastname: Scerpella
authors.forename: Kimbal D
authors.initials: KD
authors.lastname: Ford
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Zervos
authors.forename: Julio A
authors.initials: JA
authors.lastname: Ramirez
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Kett
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003404:Creatinine / Q000097:blood; D019992:Databases as Topic; D005260:Female; D006801:Humans; D015994:Incidence; D007362:Intensive Care Units; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D014640:Vancomycin / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D014640:Vancomycin; D003404:Creatinine