Linezolid in Methicillin-Resistant Staphylococcus aureus Nosocomial Pneumonia: A Randomized, Controlled Study

作者：Richard G. Wunderink, Michael S. Niederman, Marin H. Kollef, Andrew F. Shorr, Mark J. Kunkel, Alice M. Baruch, William T. McGee, Arlene L. Reisman, Jean E. Chastre · 发表于：Clinical Infectious Diseases · 年份：2012 · DOI：10.1093/cid/cir895 · 被引用次数：579 · 研究领域：Antimicrobial Resistance in Staphylococcus、Nosocomial Infections in ICU、Infection Control in Healthcare

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-c...