Efficacy and Safety of Tedizolid Phosphate versus Linezolid in a Randomized Phase 3 Trial in Patients with Acute Bacterial Skin and Skin Structure Infection

Abstract

Tedizolid phosphate is approved for the treatment of acute bacterial skin and skin structure infection (ABSSSI) caused by Gram-positive bacteria in the United States, Europe, and other countries. In this multicenter, double-blind, phase 3 study, 598 adult ABSSSI patients in China, Taiwan, the Philippines, and the United States were randomized to receive 200 mg of tedizolid, intravenously (i.v.)/orally (p.o.), once daily for 6 days or 600 mg of linezolid, i.v./p.o. twice daily for 10 days. The primary endpoint was early clinical response rate at 48 to 72 h. Secondary endpoints included programmatic and investigator-assessed outcomes at end-of-therapy (EOT) and posttherapy evaluation (PTE) visits. Safety was also evaluated. In the intent-to-treat (ITT) population, 75.3% of tedizolid-treated patients and 79.9% of linezolid-treated patients were early responders (treatment difference, –4.6%; 95% confidence interval [CI], –11.2, 2.2). After exclusion of patients who never received the study drug (tedizolid, n = 8; linezolid, n = 1; modified ITT), comparable early response rates were observed (tedizolid, 77.4%; linezolid, 80.1%; treatment difference, –2.7%; 95% CI, –9.4, 3.9). Secondary endpoints showed high and similar clinical success rates in the ITT and clinically evaluable (CE) populations at EOT and PTE visits (e.g., CE-PTE for tedizolid, 90.4%; for linezolid, 93.5%). Both drugs were well tolerated, and no death occurred. Eight patients experienced phlebitis with tedizolid while none did with linezolid; hence, drug-related treatment-emergent adverse events were reported in a slightly higher proportion in the tedizolid (20.9%) arm than in the linezolid arm (15.8%). The study demonstrated that tedizolid in a primarily Asian population was an efficacious and well-tolerated treatment option for ABSSSI patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT02066402.)

Tedizolid Versus Linezolid for the Treatment of Acute Bacterial Skin and Skin Structure Infection: A Systematic Review and Meta-Analysis

“…The search program generated 313 reference; 105 articles were screened after excluding 208 duplicated articles. Finally, eight articles were identified for full-text review for eligibility and only four studies [9,10,11,13] designed to compare the clinical efficacy and safety of tedizolid and linezolid in the treatment of patients with ABSSSI were enrolled in this meta-analysis (Figure 1 and Appendix A). Overall, this meta-analysis included a total of 2056 patients (1048 in the tedizolid group and 1008 in the linezolid group).…”

“…Overall, this meta-analysis included a total of 2056 patients (1048 in the tedizolid group and 1008 in the linezolid group). Two studies [11,13] were primarily conducted in western countries, one [9] was primarily in Asian countries and one [10] was only in Japan (Table 1). Except for the Prokocimer et al study [13], which compared only the oral form of tedizolid and linezolid, the other three studies compared an initial intravenous injection followed by oral use.…”

“…Tedizolid—a novel oxazolidinone—represents one of the treatment options with favorable pharmacokinetic characteristics and a good safety profile [8]. However, the efficacy and safety of these new drugs are only reported in limited studies [9,10,11,12,13], and the experience in real-world clinical practice remains scarce. Moreover, it remains unclear whether the clinical efficacy and the risk of adverse events (AEs) of tedizolid is not inferior to those of the first oxazolidinone—linezolid or not.…”

Comparative in vitro potency and kill curve activity of tedizolid and linezolid against Gram-positive bacteria isolated from Chinese hospitalized patients in 2013–2016

“…At clinically relevant concentrations, tedizolid exerted a greater bactericidal effect in vitro than linezolid against a Chinese clinical PRSP strain and exerted a bacteriostatic effect against Chinese isolates of MRSA further supporting that tedizolid may be a suitable alternative to linezolid for the treatment of ABSSSI, nosocomial pneumonia and bloodstream infections caused by Grampositive bacterial pathogens. The efficacy and safety of tedizolid have been established in Chinese subjects with ABSSSI; 25 however, further clinical studies are required to prove its efficacy in other indications prior to use in patients.…”

“…23,24 Tedizolid has recently been approved in the USA, Canada, Europe, Japan and other countries for the treatment of acute bacterial skin and skin structure infections (ABSSSIs); its efficacy and safety have also been demonstrated in Chinese patients with ABSSSI. 25 The objective of this study was to evaluate 1) the susceptibility of selected clinical Gram-positive pathogens and 2) the in vitro time-kill activity of tedizolid and linezolid against MRSA and PRSP, which were isolated from patients in Chinese hospitals, at concentrations relevant to Chinese subjects based on previously established pharmacokinetic data.…”