title: Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study.
abstract: BACKGROUND
  Post hoc analyses of clinical trial data suggested that linezolid may be more effective than vancomycin for treatment of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. This study prospectively assessed efficacy and safety of linezolid, compared with a dose-optimized vancomycin regimen, for treatment of MRSA nosocomial pneumonia.
  
  
  METHODS
  This was a prospective, double-blind, controlled, multicenter trial involving hospitalized adult patients with hospital-acquired or healthcare-associated MRSA pneumonia. Patients were randomized to receive intravenous linezolid (600 mg every 12 hours) or vancomycin (15 mg/kg every 12 hours) for 7-14 days. Vancomycin dose was adjusted on the basis of trough levels. The primary end point was clinical outcome at end of study (EOS) in evaluable per-protocol (PP) patients. Prespecified secondary end points included response in the modified intent-to-treat (mITT) population at end of treatment (EOT) and EOS and microbiologic response in the PP and mITT populations at EOT and EOS. Survival and safety were also evaluated.
  
  
  RESULTS
  Of 1184 patients treated, 448 (linezolid, n = 224; vancomycin, n = 224) were included in the mITT and 348 (linezolid, n = 172; vancomycin, n = 176) in the PP population. In the PP population, 95 (57.6%) of 165 linezolid-treated patients and 81 (46.6%) of 174 vancomycin-treated patients achieved clinical success at EOS (95% confidence interval for difference, 0.5%-21.6%; P = .042). All-cause 60-day mortality was similar (linezolid, 15.7%; vancomycin, 17.0%), as was incidence of adverse events. Nephrotoxicity occurred more frequently with vancomycin (18.2%; linezolid, 8.4%).
  
  
  CONCLUSIONS
  For the treatment of MRSA nosocomial pneumonia, clinical response at EOS in the PP population was significantly higher with linezolid than with vancomycin, although 60-day mortality was similar.
authors.affiliation: Department of Pulmonary and Critical Care, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. r-wunderink@northwestern.edu
authors.forename: Richard G
authors.initials: RG
authors.lastname: Wunderink
authors.forename: Michael S
authors.initials: MS
authors.lastname: Niederman
authors.forename: Marin H
authors.initials: MH
authors.lastname: Kollef
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Shorr
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Kunkel
authors.forename: Alice
authors.initials: A
authors.lastname: Baruch
authors.forename: William T
authors.initials: WT
authors.lastname: McGee
authors.forename: Arlene
authors.initials: A
authors.lastname: Reisman
authors.forename: Jean
authors.initials: J
authors.lastname: Chastre
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003428:Cross Infection / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid