Hospital Acquired Pneumonia (Sub-Category)

Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study

RG Wunderink
MS Niederman
MH Kollef
AF Shorr
MJ Kunkel
et al



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 1,184 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.

PubMed Link to Article:

Wunderink RG, Niederman MS, Kollef MH, Shorr AF, Kunkel MJ, Baruch A, McGee WT, Reisman A, Chastre J. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis. 2012 Mar 1;54(5):621-9. doi: 10.1093/cid/cir895. Epub 2012 Jan 12. PubMed PMID: 22247123.