A Phase 3, Randomized, Double-Blind Study Comparing Tedizolid Phosphate and Linezolid for Treatment of Ventilated Gram-Positive Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia.

BACKGROUND: Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are associated with high mortality rates. We evaluated the efficacy and safety of tedizolid (administered as tedizolid phosphate) for treatment of gram-positive ventilated HABP/VABP. METHODS: In this randomized, noninferiority, double-blind, double-dummy, global phase 3 trial, patients were randomized 1:1 to receive intravenous tedizolid phosphate 200 mg once daily for 7 days or intravenous linezolid 600 mg every 12 hours for 10 days. Treatment was 14 days in patients with concurrent gram-positive bacteremia. The primary efficacy end points were day 28 all-cause mortality (ACM; noninferiority margin, 10%) and investigator-assessed clinical response at test of cure (TOC; noninferiority margin, 12.5%) in the intention-to-treat population. RESULTS: Overall, 726 patients were randomized (tedizolid, n = 366; linezolid, n = 360). Baseline characteristics, including incidence of methicillin-resistant Staphylococcus aureus (31.3% overall), were well balanced. Tedizolid was noninferior to linezolid for day 28 ACM rate: 28.1% and 26.4%, respectively (difference, -1.8%; 95% confidence interval [CI]: -8.2 to 4.7). Noninferiority of tedizolid was not demonstrated for investigator-assessed clinical cure at TOC (tedizolid, 56.3% vs linezolid, 63.9%; difference, -7.6%; 97.5% CI: -15.7 to 0.5). In post hoc analyses, no single factor accounted for the difference in clinical response between treatment groups. Drug-related adverse events occurred in 8.1% and 11.9% of patients who received tedizolid and linezolid, respectively. CONCLUSIONS: Tedizolid was noninferior to linezolid for day 28 ACM in the treatment of gram-positive ventilated HABP/VABP. Noninferiority of tedizolid for investigator-assessed clinical response at TOC was not demonstrated. Both drugs were well tolerated. CLINICAL TRIALS REGISTRATION: NCT02019420.

Safety and Efficacy of Oral and/or Intravenous Tedizolid Phosphate From a Randomized Phase 3 Trial in Adolescents With Acute Bacterial Skin and Skin Structure Infections.

BACKGROUND: Tedizolid phosphate is an oxazolidinone prodrug approved in 2014 for treatment of adults with acute bacterial skin and skin structure infections (ABSSSIs); however, efficacy has not previously been evaluated in children. This study compared the safety and efficacy of tedizolid (administered as tedizolid phosphate) with active antibacterial comparators for the treatment of ABSSSIs in adolescents. METHODS: This was a randomized, assessor-blind, global phase 3 study of tedizolid versus active comparators for the treatment of Gram-positive ABSSSIs in adolescents (12 to <18 years of age; NCT02276482). Enrolled participants were stratified by region and randomized 3:1 to receive tedizolid phosphate 200 mg (oral and/or intravenous) once daily for 6 days or active comparator, selected by investigator from an allowed list per local standard of care, for 10 days. The primary endpoint was safety; blinded investigator's assessment of clinical success at the test-of-cure visit (18-25 days after the first dose) was a secondary efficacy endpoint. Statistical comparisons between treatment groups were not performed. RESULTS: Of the 121 participants enrolled, 120 were treated (tedizolid, n = 91; comparator, n = 29). Treatment-emergent adverse events were balanced between treatment groups (tedizolid, 14.3%; comparator, 10.3%). Overall, 3 participants (3.3%) in the tedizolid group and 1 (3.4%) in the comparator group experienced a single drug-related TEAE. Clinical success rates were high in both treatment groups: 96.7% and 93.1% at the test-of-cure visit for the tedizolid and comparator groups, respectively. CONCLUSIONS: Tedizolid demonstrated safety and efficacy similar to comparators for the treatment of ABSSSIs in adolescents.