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Summary of the Wunderink 2012 Trial
In a cohort of patients with MRSA pneumonia, linezolid was shown to improve clinical cure rate and cause less nephrotoxicity than vancomycin, but it did not improve 60-day mortality. The findings of this study may have been confounded by unbalanced baseline characteristics.
Key Points from Wunderink 2012
- Prospective, randomized, double-blind study included 348 patients with HAP/VAP or HCAP with a positive culture for MRSA
- Randomized patients to linezolid 600 mg IV Q12h vs. vancomycin 15 mg/kg Q12h (dosing adjusted by a local pharmacist) for 7-14 days (21 days if concurrent bacteremia)
- Primary endpoint (clinical outcome at end of study [7-30 days] in per-protocol patients) was more common with linezolid (57.6% vs. 46.6%, p=0.042, NNT 9)
- Despite randomization, baseline characteristics were not balanced in the per-protocol cohort, with the vancomycin group having higher incidence of mechanical ventilation (66.9% vs. 73.9%), double the rate of bacteremia (5.2% vs. 10.8%), higher rate of diabetes (36.1% vs. 42.5%), and higher rate of baseline kidney disease (27.9% vs. 36.9%)
- 60-day mortality was not different between linezolid and vancomycin (28.1% vs. 26.3%)
- Nephrotoxicity (SCr increase of 0.5 mg/mL or increase of 50% if abnormal at baseline) was more common with vancomycin in the mITT group (8.4% vs. 18.2%). It is important to note that the study did not use the standardized RIFLE criteria for renal dysfunction or report rates of renal replacement therapy
Citation
Wunderink RG, Niederman MS, Kollef MH, et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis. 2012 Mar 1;54(5):621-9. PMID 22247123
