Analysis of the Phase 3 ESTABLISH Trials: Tedizolid Versus Linezolid in Acute Bacterial Skin and Skin Structure Infection.

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Analysis of the Phase 3 ESTABLISH Trials: Tedizolid Versus Linezolid in Acute Bacterial Skin and Skin Structure Infection.

Antimicrob Agents Chemother. 2014 Nov 24;

Authors: Shorr AF, Lodise TP, Corey GR, De Anda C, Fang E, Das AF, Prokocimer P

Abstract
Tedizolid, a novel oxazolidinone with activity against a wide range of Gram-positive pathogens, was evaluated in two noninferiority, phase 3, acute bacterial skin and skin structure infection trials. Data from individual trials showed noninferior efficacy to linezolid and a favorable tolerability profile. To evaluate potential differences, pooled data were analyzed. Patients received tedizolid 200 mg (once daily, 6 days) or linezolid 600 mg (twice daily, 10 days). Efficacy was evaluated at 48 to 72 h (primary end point), on days 11 to 13 (end of therapy [EOT]), and 7 to 14 days after EOT (posttherapy evaluation). Treatment-emergent adverse events and hematologic and clinical laboratory parameters were collected. Baseline characteristics were comparable between treatment groups--852/1333 (64%) patients were from North America; the majority of infections were caused by Staphylococcus aureus. Tedizolid was noninferior to linezolid (early clinical response, 81.6% versus 79.4%). Early response remained relatively consistent across various host/disease factors and severity measures. Nausea was the most frequently reported adverse event (tedizolid, 8.2%; linezolid, 12.2%; P = 0.02), with onset primarily during the first 6 days. Fewer tedizolid than linezolid patients had platelet counts <150,000 cells/mm(3) at EOT (tedizolid, 4.9%; linezolid, 10.8%; P = 0.0003) and during postbaseline period through last day of active drug visit (tedizolid, 6.4%; linezolid, 12.6%; P = 0.0016). Efficacy was achieved with 6-day once-daily course of therapy with the option of an intravenous/oral regimen; fewer low platelet counts and gastrointestinal side effects were reported with tedizolid than with linezolid, aligning well with antimicrobial stewardship principles.

PMID: 25421472 [PubMed - as supplied by publisher]