title: Risk factors for treatment failure in patients receiving vancomycin for hospital-acquired methicillin-resistant Staphylococcus aureus pneumonia.
abstract: BACKGROUND
  The rate of vancomycin failure in patients with hospital-acquired pneumonia (HAP) caused by methicillin-resistant Staphylococcus aureus (MRSA) has exceeded 40% in several studies. This observation was attributed initially to the lack of weight-based dosing and targeting of lower trough concentrations. However, a subsequent study demonstrated no additional benefit in patients who achieved trough vancomycin concentrations >15 mg/L compared with patients with concentrations between 5 and 15 mg/L. We sought to identify contributors to vancomycin failure in patients with MRSA HAP.
  
  
  METHODS
  This was a retrospective study of patients in a surgical intensive care unit with MRSA HAP who received vancomycin between January 1, 2005, and July 31, 2007. Clinical outcomes, microbiological data, prior antibiotic exposure, ventilator days, co-morbidities, and demographics were compared in patients with clinical success and those with treatment failure. Their characteristics were compared using a two-sided Fisher exact test or Mann-Whitney U test, as appropriate for nominal or continuous data.
  
  
  RESULTS
  More patients in the treatment failure group had received one or more doses of vancomycin within 90 days leading up to MRSA HAP (84% vs. 47%; p = 0.04). In addition, the duration of prior vancomycin exposure was significantly longer among patients in the treatment failure group (6 vs. 0 days; p < 0.05). There were no statistically significant differences in the percentages of patients who achieved a vancomycin trough concentrations > or =15 mg/dL within the first 48 h (28% vs. 17%; p = 0.69), 72 h (44% vs. 39%; p = 1.0), or 96 h (56% vs. 44%; p = 0.74) after starting treatment. Patients in the failure group had a significantly higher overall mortality rate (32% vs. 0; p = 0.02).
  
  
  CONCLUSIONS
  These data suggest that patients who have recent exposure to vancomycin are at high risk for vancomycin failure and may benefit from an appropriate alternative when a diagnosis of MRSA HAP is made.
authors.affiliation: Department of Pharmaceutical Services, Vanderbilt University Medical Center, 1211 Medical Center Dr., Nashville, TN 37232-7610, USA. jon.aston@vanderbilt.edu
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Aston
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Dortch
authors.forename: Lesly A
authors.initials: LA
authors.lastname: Dossett
authors.forename: C Buddy
authors.initials: CB
authors.lastname: Creech
authors.forename: Addison K
authors.initials: AK
authors.lastname: May
mesh_terms: D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003422:Critical Care; D003428:Cross Infection / Q000188:drug therapy* / Q000382:microbiology*; D004363:Drug Utilization / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000302:isolation & purification*; D008875:Middle Aged; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000382:microbiology*; D012189:Retrospective Studies; D012307:Risk Factors; D017211:Treatment Failure; D014640:Vancomycin / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin