Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study.
Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study.
- 2012
Available online from MWHC library: June 1997 - present, Available in print through MWHC library: 1999 - Winter 2007
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. 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. 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%).
English
1058-4838
*Acetamides/tu [Therapeutic Use]
*Anti-Bacterial Agents/tu [Therapeutic Use]
*Cross Infection/dt [Drug Therapy]
*Methicillin-Resistant Staphylococcus aureus/de [Drug Effects]
*Oxazolidinones/tu [Therapeutic Use]
*Pneumonia, Staphylococcal/dt [Drug Therapy]
Acetamides/ad [Administration & Dosage]
Acetamides/ae [Adverse Effects]
Adult
Aged
Anti-Bacterial Agents/ad [Administration & Dosage]
Anti-Bacterial Agents/ae [Adverse Effects]
Cross Infection/mi [Microbiology]
Cross Infection/mo [Mortality]
Female
Humans
Male
Middle Aged
Oxazolidinones/ad [Administration & Dosage]
Oxazolidinones/ae [Adverse Effects]
Pneumonia, Staphylococcal/mi [Microbiology]
Pneumonia, Staphylococcal/mo [Mortality]
Treatment Outcome
MedStar Washington Hospital Center
Medicine/Pulmonary-Critical Care
Clinical Trial, Phase IV
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Available online from MWHC library: June 1997 - present, Available in print through MWHC library: 1999 - Winter 2007
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. 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. 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%).
English
1058-4838
*Acetamides/tu [Therapeutic Use]
*Anti-Bacterial Agents/tu [Therapeutic Use]
*Cross Infection/dt [Drug Therapy]
*Methicillin-Resistant Staphylococcus aureus/de [Drug Effects]
*Oxazolidinones/tu [Therapeutic Use]
*Pneumonia, Staphylococcal/dt [Drug Therapy]
Acetamides/ad [Administration & Dosage]
Acetamides/ae [Adverse Effects]
Adult
Aged
Anti-Bacterial Agents/ad [Administration & Dosage]
Anti-Bacterial Agents/ae [Adverse Effects]
Cross Infection/mi [Microbiology]
Cross Infection/mo [Mortality]
Female
Humans
Male
Middle Aged
Oxazolidinones/ad [Administration & Dosage]
Oxazolidinones/ae [Adverse Effects]
Pneumonia, Staphylococcal/mi [Microbiology]
Pneumonia, Staphylococcal/mo [Mortality]
Treatment Outcome
MedStar Washington Hospital Center
Medicine/Pulmonary-Critical Care
Clinical Trial, Phase IV
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't