Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial

Summary Background New antibiotics are needed to treat infections caused by drug-resistant bacteria. Tedizolid is a novel oxazolidinone antibacterial drug designed to provide enhanced activity against Gram-positive pathogens. We aimed to assess the efficacy and safety of intravenous to oral tedizoli...

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Bibliographic Details
Published in:The Lancet infectious diseases 2014-08, Vol.14 (8), p.696-705
Main Authors: Moran, Gregory J, Prof, Fang, Edward, MD, Corey, G Ralph, Prof, Das, Anita F, PhD, De Anda, Carisa, PharmD, Prokocimer, Philippe, Dr
Format: Article
Language:English
Subjects:
Acetamides - administration & dosage
Administration, Intravenous
Administration, Oral
Adolescent
Adult
Aged
Aged, 80 and over
Anti-Bacterial Agents - administration & dosage
Antibacterial agents
Antibiotics
Antibiotics. Antiinfectious agents. Antiparasitic agents
Bacteria
Biological and medical sciences
Double-Blind Method
Female
Gram-positive bacteria
Humans
Infectious Disease
Infectious diseases
Linezolid
Male
Medical sciences
Middle Aged
Organophosphates - administration & dosage
Oxazoles - administration & dosage
Oxazolidinones - administration & dosage
Patients
Pharmacology. Drug treatments
Skin
Skin Diseases, Bacterial - drug therapy
Staphylococcus infections
Treatment Outcome
Young Adult
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Summary:Summary Background New antibiotics are needed to treat infections caused by drug-resistant bacteria. Tedizolid is a novel oxazolidinone antibacterial drug designed to provide enhanced activity against Gram-positive pathogens. We aimed to assess the efficacy and safety of intravenous to oral tedizolid for treatment of patients with acute bacterial skin and skin-structure infections. Methods ESTABLISH-2 was a randomised, double-blind, phase 3, non-inferiority trial done between Sept 28, 2011, and Jan 10, 2013, at 58 centres in nine countries. Patients (aged ≥12 years) with acute bacterial skin and skin-structure infections (cellulitis or erysipelas, major cutaneous abscess, or wound infection) that had a minimum lesion area of 75 cm2 and were suspected or documented to be associated with a Gram-positive pathogen, were randomly assigned (1:1), via an interactive voice-response system with block randomisation, 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. Randomisation was stratified by geographic region and type of acute bacterial skin and skin-structure infection. The primary endpoint was early clinical response (≥20% reduction in lesion area at 48–72 h compared with baseline), with a non-inferiority margin of −10%. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT01421511. Findings 666 patients were randomly assigned to receive tedizolid (n=332) or linezolid (n=334). 283 (85%) patients in the tedizolid group and 276 (83%) in the linezolid group achieved early clinical response (difference 2·6%, 95% CI −3·0 to 8·2), meeting the prespecified non-inferiority margin. Gastrointestinal adverse events were less frequent with tedizolid than linezolid, taking place in 52 (16%) of 331 patients and 67 (20%) of 327 patients in the safety population. Treatment-emergent adverse events leading to discontinuation of study drug were reported by one (
ISSN:1473-3099
1474-4457
DOI:10.1016/S1473-3099(14)70737-6