SLR - December 2014 - Sam Bazrafshan
Tedizolid for 6 Days Versus Linezolid for 10 Days for Acute Bacterial Skin and Skin-Structure Infections (Establish-2): A Randomized, Double-Blind, Phase 3, Non-Inferiority Trial
Reference: Moran GJ, Fang E, Corey GR, Das AF, De Anda C, Prokocimer P. Tedizolid for 6 Days Versus Linezolid for 10 Days for Acute Bacterial Skin and Skin-structure Infections (ESTABLISH-2): A Randomized, Double-blind, Phase 3, Non-inferiority Trial. Lancet Infect Dis. 2014 Aug;14(8):696-705.
Scientific Literature Review
Reviewed By: Sam Bazrafshan, DPM
Residency Program: Bethesda Hospital Inc.
Podiatric Relevance: As podiatric surgeons, polymicrobial skin infections in diabetics are commonly encountered. With increasing resistance to antibiotics, new line therapy is essential to the prompt and proper treatment of these infections. This study provides an alternative source to treating acute bacterial infections, specifically gram-positive infections that are resistant to vancomycin and linezolid.
Methods: The authors performed a randomized, double-blind, phase 3, non-inferiority trial between 2011 and 2013 on 666 patients. Patients greater than 12 years of age at 58 centers in nine countries were included in this study. Inclusion criterion was based on the presence of gram-positive suspected acute bacterial skin infections, wound infection, cutaneous abscess, cellulitis and erysipelas, which were stratified based on geographic region and type of infection. The bacterial infection had to comprise a minimum of 75 cm². An interactive voice-response system with block randomization was utilized to randomly assign patients to receive intravenous once-daily tedizolid (200 mg for 6 days) or twice-daily linezolid (600 mg for 10 days), with optional oral step-down. Improvement was determined when 20 percent reduction in lesion area was noted at 48–72 hours.
Results: Three-hundred-thirty-two patients received tedizolid and 334 received linezolid, which was randomly assigned. The non-inferiority margin was met in both groups, as early clinical response was noted in 283 (85 percent) patients in the tedizolid group and 276 (83 percent) in the linezolid group (2·6 percent, 95 percent CI –3·0 to 8·2). Sixteen percent of patients in the tedizolid group experienced gastrointestinal adverse events compared to 20percent who experienced these symptoms in the linezolid group, 4 (1 percent) of which had to discontinue the study drug due to emergent adverse effects.
Conclusions: This study demonstrated that intravenous to oral once-daily tedizolid 200 mg for six days was equally efficient as twice-daily linezolid 600 mg for 10 days for treatment of patients with acute bacterial skin infections. Tedizolid can be considered as an alternative treatment to gram positive acute bacterial infection in both hospital and outpatient setting. Particularly, this treatment could be used with MRSA infections resistant to vancomycin and linezolid.