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Linezolid in Methicillin-Resistant Staphylococcus Aureus Nosocomial Pneumonia: A Randomized, Controlled Study (seen in 04/12 critical care pharmacology literature update)
Study Question: Compared to dose-optimized vancomycin, is linezolid superior in treating methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia?
Study Description: This article described a multicenter, double-blind trial evaluating clinical outcome at the end of the study (EOS) in 348 adult patients with MRSA pneumonia. Patients received either vancomycin (dose-adjusted for trough concentrations, goal trough not specified) or linezolid (600 mg IV every 12 h).
Results: At the EOS, there was a significant improvement in clinical cure for patients treated with linezolid compared to vancomycin (57.6% and 46.6%, respectively; p= 0.042), with similar results for microbiologic cure. Vancomycin trough levels were reported as medians of 12.3, 14.7, and 16.1 mcg/mL on days 3, 6, and 9, respectively. There was an increase incidence of nephrotoxicity in the vancomycin treated group (7.3% vs 3.7% with linezolid; p-value not reported), but overall no difference in the number of adverse drug events between groups and no difference in 60-day mortality.
Conclusion(s): Clinical response in patients treated with linezolid was significantly better at the EOS compared to vancomycin for the treatment of nosocomial MRSA pneumonia.
Perspective: This study had a number of notable limitations. A target vancomycin trough was never specified, and the median levels suggest that a significant number of patients had not achieved troughs that are acceptable by current standards (15-20 mcg/mL) even by day 6. Accordingly, the reader is left to wonder what the results would have been had patients randomized to vancomycin been treated more optimally. Although 1,225 patients were randomized, only 348 patients were evaluated for the primary outcome of clinical outcome at the EOS, and the results of an intention-to-treat evaluation of the primary outcome were not presented. While not apparently statistically significant, more patients who received vancomycin were receiving mechanical ventilation (73.9% vs. 66.9%) and had MRSA bacteremia (10.8% vs. 5.2%) at baseline.