Clinical Response of Tedizolid Versus Linezolid in Acute Bacterial Skin and Skin Structure Infections by Severity Measure: Pooled Analysis of 2 Phase 3 Double-Blind Trials
Background: There is no consensus on defining disease severity in acute bacterial skin and skin structure infections (ABSSSI) trials. In two ABSSSI, noninferiority Phase 3 trials (ESTABLISH-1 and ESTABLISH-2), 6 days of tedizolid, a novel oxazolidinone antibacterial, demonstrated noninferior efficacy to 10 days of linezolid. In this prespecified subgroup analysis, the effect of different measures of disease severity at baseline (lesion size, fever, increased white blood cell count, System Inflammatory Response Syndrome [SIRS], lymphadenopathy, and presence of immature neutrophils [bands]) on clinical response was investigated.
Methods: Eligible patients were randomized 1:1 to receive 200 mg tedizolid once daily for 6 days or 600 mg linezolid twice daily for 10 days. ESTABLISH-1 patients received oral therapy, while ESTABLISH-2 patients received IV therapy with an optional switch to oral. The primary endpoint was early clinical response (≥20% reduction in lesion area compared to baseline at 48‐72 h after start of study drug). Investigator-assessed clinical response at the posttherapy evaluation (PTE; 7-14 days posttherapy) was a key secondary endpoint. Response rates to therapy were compared between tedizolid and linezolid with and without the presence of specified measures of disease severity at screening.
Results: Among the 1333 patients in the pooled intent-to-treat population, there was no difference in the specified measures of disease severity between patients randomized to tedizolid (n = 664) and linezolid (n = 669). Early clinical response rates were similar between the tedizolid and linezolid treatment groups across all evaluated severity subgroups (Figure 1). Similar response rates between the two antibacterials were also maintained for investigator-assessed clinical response at PTE across all evaluated measures of severity.
Conclusion: In the pooled data for these two phase 3 trials for ABSSSI, 6 days of TZD was consistently non-inferior to 10 days of LZD, regardless of the measure of disease severity used.
Figure 1. Early Clinical Response by Severity Measures
Cubist: Employee, Salary
E. Fang, Trius/Cubist: Employee, Salary
A. Das, Cubist: Consultant, Consulting fee
Cempra: Consultant, Consulting fee
Cerexa: Consultant, Consulting fee
Nabriva: Consultant, Consulting fee
Paratek: Consultant, Consulting fee
Trius: Consultant, Consulting fee
Achaogen: Consultant, Consulting fee
Durata: Consultant, Consulting fee
P. Prokocimer, Cubist: Employee and Shareholder, Salary
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