Linezolid in Methicillin-Resistant Staphylococcus aureus Nosocomial Pneumonia: A Randomized, Controlled Study
Top Cited Papers
Open Access
- 12 January 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Clinical Infectious Diseases
- Vol. 54 (5), 621-629
- https://doi.org/10.1093/cid/cir895
Abstract
(See the Editorial Commentary by Torres, on pages 630–2 .) 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.Keywords
This publication has 25 references indexed in Scilit:
- Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children: Executive SummaryClinical Infectious Diseases, 2011
- Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: A systematic review and meta-analysis*Critical Care Medicine, 2010
- Relationship between Initial Vancomycin Concentration‐Time Profile and Nephrotoxicity among Hospitalized PatientsClinical Infectious Diseases, 2009
- Pneumonia Caused by Methicillin‐ResistantStaphylococcus aureusClinical Infectious Diseases, 2008
- Health Care-Associated Pneumonia and Community-Acquired Pneumonia: a Single-Center ExperienceAntimicrobial Agents and Chemotherapy, 2007
- Linezolid (PNU-100766) versus Vancomycin in the Treatment of Hospitalized Patients with Nosocomial Pneumonia: A Randomized, Double-Blind, Multicenter StudyClinical Infectious Diseases, 2001
- Surveillance of Antimicrobial Use and Antimicrobial Resistance in United States Hospitals: Project ICARE Phase 2Clinical Infectious Diseases, 1999
- APACHE IICritical Care Medicine, 1985
- Nonparametric Estimation from Incomplete ObservationsJournal of the American Statistical Association, 1958