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Lancet Infect Dis. 2014 Aug;14(8):696-705. doi: 10.1016/S1473-3099(14)70737-6. Epub 2014 Jun 5.

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.

Author information

1
Department of Emergency Medicine and Division of Infectious Diseases, Olive View-UCLA Medical Center, CA, USA.
2
Clinical Development, Cubist Pharmaceuticals, CA, USA.
3
Division of Infectious Diseases, Duke University Medical Center, NC, USA.
4
Biometrics, InClin, CA, USA.
5
Clinical Development, Cubist Pharmaceuticals, CA, USA. Electronic address: philippe.prokocimer@cubist.com.

Abstract

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 cm(2) 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 (<1%) patient in the tedizolid group and four (1%) patients in the linezolid group.

INTERPRETATION:

Intravenous to oral once-daily tedizolid 200 mg for 6 days was non-inferior to twice-daily linezolid 600 mg for 10 days for treatment of patients with acute bacterial skin and skin-structure infections. Tedizolid could become a useful option for the treatment of acute bacterial skin and skin-structure infections in the hospital and outpatient settings.

FUNDING:

Cubist Pharmaceuticals.

Comment in

PMID:
24909499
DOI:
10.1016/S1473-3099(14)70737-6
[Indexed for MEDLINE]
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