title: Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections.
abstract: OBJECTIVE
  Higher vancomycin concentrations are thought necessary for treatment of deep-seated methicillin-resistant Staphylococcus aureus (MRSA) infection, yet this may result in greater risk of nephrotoxicity. We evaluated the relationship of serum vancomycin trough concentration with clinical outcomes and nephrotoxicity for patients with deep-seated MRSA infection.
  
  
  METHODS
  A retrospective cohort study evaluated adults with MRSA pneumonia, endocarditis or osteomyelitis who received vancomycin for > or = 5 days from June 2005 to June 2007. Patients were stratified by mean vancomycin trough level [low (< 15 mg/l), high (> or = 15 mg/l)]. Outcomes were clinical response, mortality, length of stay (LOS) and nephrotoxicity. Three definitions of nephrotoxicity were used: i) rise in serum creatinine (SCr) > or = 0.5 mg/dl; ii) 50% increase in SCr; and iii) 25% decrease in estimated creatinine clearance.
  
  
  RESULTS
  Fifty-five patients experiencing MRSA pneumonia (n = 28), endocarditis (n = 9), osteomyelitis (n = 20) and multiple infections (n = 2) were stratified into low (n = 39) and high (n = 16) groups. High group patients were more likely to be septic (p = 0.01) and have a higher APACHE II score (p = 0.01). After adjustment for APACHE II score, clinical response rates among survivors did not differ significantly. Risk of death was not significantly different between the high (19%) and low (5%) group patients (p = 0.1). LOS did not differ significantly between groups (p = 0.7). Nephrotoxicity occurred in the low and high groups, respectively, for 10 and 31% (p = 0.04) with definition 1, 10 and 31% (p = 0.04) with definition 2, and 13 and 25% (p = 0.1) with definition 3. After adjustment for APACHE II score, odds of nephrotoxicity based on definitions 1 or 2 were increased among the high versus low groups (OR = 3.27, 95% CI: 0.7 - 15.25, p = 0.1), although not statistically significant.
  
  
  CONCLUSIONS
  Clinical outcomes did not differ significantly between high and low trough groups for deep-seated MRSA infections. Nephrotoxicity was consistently higher in the high trough group, regardless of the definition used.
authors.affiliation: The Nebraska Medical Center, Department of Pharmaceutical and Nutrition Care, 984031 Omaha, NE 68918-4031, USA. ehermsen@nebraskamed.com
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Hermsen
authors.forename: Monica
authors.initials: M
authors.lastname: Hanson
authors.forename: Jayashri
authors.initials: J
authors.lastname: Sankaranarayanan
authors.forename: Julie A
authors.initials: JA
authors.lastname: Stoner
authors.forename: Marius C
authors.initials: MC
authors.lastname: Florescu
authors.forename: Mark E
authors.initials: ME
authors.lastname: Rupp
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004697:Endocarditis, Bacterial / Q000188:drug therapy; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D007902:Length of Stay; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008875:Middle Aged; D010019:Osteomyelitis / Q000188:drug therapy; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy*; D016896:Treatment Outcome; D014640:Vancomycin / Q000009:adverse effects* / Q000097:blood*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D003404:Creatinine