Linezolid vs vancomycin - Analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia

Objective: To assess the effect of baseline variables, including treatment, on outcome in patients with nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). Design: Retrospective analysis of data from two prospective, randomized, double-blind studies. Setting: Multinational study with 134 sites. Patients: A total of 1,019 patients with suspected Gram-positive nosocomial pneumonia, including 339 patients with documented S aureus pneumonia (S aureus subset) and 160 patients with documented MRSA pneumonia (MRSA subset). Interventions: Linezolid, 600 mg, or vancomycin, 1 g, q12h for 7 to 21 days, each with aztreonam. Measurements and results: Outcome was measured by survival and clinical cure rates (assessed 12 to 28 days after the end of therapy). Logistic regression analysis was used to determine the effect of treatment and other baseline variables on outcome. Kaplan-Meier survival rates for linezolid vs vancomycin were 80.0% (60 of 75 patients) vs 63.5% (54 of 85 patients) for the MRSA subset (p = 0.03). Logistic regression analysis confirmed that the survival difference favoring linezolid remained significant after adjusting for baseline variables (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.0 to 4.8; p = 0.05). Other baseline variables associated with significantly higher survival rates in MRSA pneumonia were serum creatinine levels less than or equal to two times the upper limit of normal and absence of cardiac comorbidities. Clinical cure rates for linezolid vs vancomycin (excluding indeterminate or missing outcomes) were 59.0% (36 of 61 patients) vs 35.5% (22 of 62 patients) for the MRSA subset (p < 0.01). Logistic regression analysis confirmed that the difference favoring linezolid remained significant after adjusting for baseline variables (OR, 3.3; 95% CI, 1.3 to 8.3; p = 0.01). Other baseline variables associated with significantly higher clinical cure rates in MRSA pneumonia were single-lobe pneumonia, absence of ventilator-associated pneumonia, and absence of oncologic and renal comorbidities. Conclusions: In this retrospective analysis, initial therapy with linezolid was associated with significantly better survival and clinical cure rates than was vancomycin in patients with nosocomial pneumonia due to MRSA.