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Prokocimer P, De Anda C, Fang E, Mehra P, Das A. Tedizolid Phosphate vs Linezolid for Treatment of Acute Bacterial Skin and Skin Structure Infections: The ESTABLISH-1 Randomized Trial. JAMA. 2013;309(6):559–569. doi:10.1001/jama.2013.241
Author Affiliations: Trius Therapeutics Inc, San Diego, California (Drs Prokocimer, De Anda, and Fang); eStudySite, Chula Vista, California (Dr Mehra); and AxiStat Inc, San Francisco, California (Dr Das).
Importance Acute bacterial skin and skin structure infections (ABSSSIs), including cellulitis or erysipelas, major cutaneous abscesses, and wound infections, can be life-threatening and may require surgery and hospitalization. Increasingly, ABSSSIs are associated with drug-resistant pathogens, and many antimicrobial agents have adverse effects restricting their use. Tedizolid phosphate is a novel oxazolidinone in development for the treatment of ABSSSIs.
Objectives To establish the noninferiority of tedizolid phosphate vs linezolid in treating ABSSSIs and compare the safety of the 2 agents.
Design, Setting, and Patients The Efficacy and Safety of 6-day Oral Tedizolid in Acute Bacterial Skin and Skin Structure Infections vs 10-day Oral Linezolid Therapy (ESTABLISH-1) was a phase 3, randomized, double-blind, noninferiority trial that was conducted from August 2010 through September 2011 at 81 study centers in North America, Latin America, and Europe. The intent-to-treat analysis set consisted of data from 667 adults aged 18 years or older with ABSSSIs treated with tedizolid phosphate (n = 332) or linezolid (n = 335).
Interventions A 200 mg once daily dose of oral tedizolid phosphate for 6 days or 600 mg of oral linezolid every 12 hours for 10 days.
Main Outcome Measures The primary efficacy outcome was early clinical response at the 48- to 72-hour assessment (no increase in lesion surface area from baseline and oral temperature of ≤37.6°C, confirmed by a second temperature measurement within 24 hours). A 10% noninferiority margin was predefined.
Results In the intent-to-treat analysis set, the early clinical treatment response rates were 79.5% (95% CI, 74.8% to 83.7%) of 332 patients in the tedizolid phosphate group and 79.4% (95% CI, 74.7% to 83.6%) of 335 patients in the linezolid group (a treatment difference of 0.1% [95% CI, −6.1% to 6.2%]). The sustained clinical treatment response rates at the end of treatment (day 11) were 69.3% (95% CI, 64.0% to 74.2%) in the tedizolid phosphate group and 71.9% (95% CI, 66.8% to 76.7%) in the linezolid group (a treatment difference of −2.6% [95% CI, −9.6% to 4.2%]). Results of investigator-assessed clinical treatment success rates at a posttherapy evaluation visit (1-2 weeks after the end-of-treatment visit) were 85.5% (95% CI, 81.3% to 89.1%) in the tedizolid phosphate group and 86.0% (95% CI, 81.8% to 89.5%) in the linezolid group (a treatment difference of −0.5% [95% CI, −5.8% to 4.9%), and were similar for 178 patients with methicillin-resistant Staphylococcus aureus isolated from the primary lesion.
Conclusions and Relevance Tedizolid phosphate was a statistically noninferior treatment to linezolid in early clinical response at 48 to 72 hours after initiating therapy for an ABSSSI. Tedizolid phosphate may be a reasonable alternative to linezolid for treating ABSSSI.
Trial Registration clinicaltrials.gov Identifier: NCT01170221
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