Efficacy, safety and pharmacokinetics of tedizolid versus linezolid in patients with skin and soft tissue infections in Japan – Results of a randomised, multicentre phase 3 study

Mikamo, Hiroshige; Takesue, Yoshio; Iwamoto, Yoshiki; Tanigawa, Tetsuya; Kato, Masahiro; Tanimura, Yoko; Kohno, Shigeru

doi:10.1016/j.jiac.2018.01.010

Cited by 39 publications

(21 citation statements)

References 38 publications

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“…The favorable safety profile of i.v./p.o. tedizolid treatment at 200 mg once daily, for approximately 10 days, has recently been demonstrated in a phase 3 clinical study in Japanese patients with complicated skin and soft tissue infections in terms of hematological and GI drug-related TEAEs versus linezolid (38). Additionally, according to a case series publication, tedizolid treatment for an extended duration of 7 to 14 days in four severe and complex ABSSSI patients was effective and well tolerated without any reported adverse event (39).…”

Section: Discussionmentioning

confidence: 99%

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

Alder

et al. 2019

Antimicrob Agents Chemother

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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.)

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Section: Discussionmentioning

confidence: 99%

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

Alder

et al. 2019

Antimicrob Agents Chemother

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“…Clinical response as an exploratory end point was assessed at 7–4 days after the end of treatment. In the ITT population, clinical response rates were 77.8% (56 of 72) and 80.0% (28 of 35) in tedizolid-treated and linezolid-treated patients, respectively ( difference −2.2%, 95% CI −17.4% to 15.8%) 46…”

Section: Methodsmentioning

confidence: 98%

“…A phase III, randomized, controlled, open-label trial comparing tedizolid and linezolid for the treatment of ABSSSI was also conducted in Japanese patients 46. Clinical response as an exploratory end point was assessed at 7–4 days after the end of treatment.…”

Section: Methodsmentioning

confidence: 99%

<p>Tedizolid phosphate for the treatment of acute bacterial skin and skin-structure infections: an evidence-based review of its place in therapy</p>

Bassetti¹,

Castaldo²,

Carnelutti³

et al. 2019

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Introduction Tedizolid phosphate is an oxazolidinone approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) and active against methicillin-resistant Staphylococcus aureus . Aims The objective of this article was to review the evidence for the efficacy and safety of tedizolid phosphate for the treatment of ABSSSI. Evidence review Approval of tedizolid phosphate for the treatment of ABSSSI was based on the results of two phase III randomized controlled trials, ESTABLISH-1 (NCT01170221) and ESTABLISH-2 (NCT01421511), comparing 6-day once-daily tedizolid vs 10-day twice-daily linezolid. In ESTABLISH-1, noninferiority was met with early clinical response rates of 79.5% and 79.4% in tedizolid and linezolid groups, respectively (difference 0.1%, 95% CI –6.1% to 6.2%, with a 10% noninferiority margin). In ESTABLISH-2, noninferiority was met with 85% and 83% rates of early clinical response in tedizolid and linezolid groups, respectively (difference 2.6%, 95% CI –3.0% to 8.2%). Pooled data from ESTABLISH-1 and ESTABLISH-2 indicated a lower frequency of thrombocytopenia in tedizolid-treated than in linezolid-treated patients. Conclusion Tedizolid offers the option of an intravenous to oral switch, allows once-daily administration, and presents lower risk of myelotoxicity when a 6-day course is used for the treatment of ABSSSI. Greater economic cost associated with this antibiotic could be offset by its shorter treatment duration and possibility of oral administration in routine clinical practice, although either sponsored or nonsponsored postmarketing observational experience remains essential for ultimately confirming the effectiveness and tolerability of tedizolid outside clinical trials.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Lan

Lin

Chang³

et al. 2019

Antibiotics

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This meta-analysis aims to assess the efficacy and safety of tedizolid, compared to linezolid, in the treatment of acute bacterial skin and skin structure infection (ABSSSI). PubMed, Web of Science, EBSCO (Elton B. Stephens Co.), Cochrane Library, Ovid Medline and Embase databases were accessed until 18 July 2019. Only randomized controlled trials (RCTs) comparing the efficacy of tedizolid with linezolid for adult patients with ABSSSIs were included. The outcomes included the clinical response, microbiological response, and risk of adverse events (AEs). A total of four RCTs involving 2056 adult patients with ABSSSI were enrolled. The early clinical response rate was 79.6% and 80.5% for patients receiving tedizolid and linezolid, respectively. The pooled analysis showed that tedizolid had a non-inferior early clinical response rate to linezolid (odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.77–1.19, I2 = 0%). The early response rate was similar between tedizolid and linezolid among patients with cellulitis/erysipelas (75.1% vs. 77.1%; OR = 0.90, 95% CI = 0.64–1.27, I2 = 25%), major cutaneous abscess (85.1% vs. 86.8%; OR = 0.93, 95% CI = 0.42–2.03, I2 = 37%) and wound infection (85.9% vs. 82.6%; OR = 1.29, 95% CI = 0.66–2.51, I2 = 45%). For methicillin-resistant Staphylococcus aureus patients, tedizolid had a favorable microbiological response rate of 95.2% which was comparable to linezolid (94%) (OR = 1.19, 95% CI = 0.49–2.90, I2 = 0%). In addition to the similar risk of treatment-emergent AEs (a serious event, the discontinuation of the study drug due to AEs and mortality between tedizolid and linezolid), tedizolid was associated with a lower risk of nausea, vomiting and abnormal neutrophil count than linezolid. In conclusion, once-daily tedizolid (200 mg for six days) compared to linezolid (600 mg twice-daily for 10 days) was non-inferior in efficacy in the treatment of ABSSSI. Besides, tedizolid was generally as well tolerated as linezolid, and had a lower incidence of gastrointestinal AEs and bone marrow suppression than linezolid.

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Efficacy, safety and pharmacokinetics of tedizolid versus linezolid in patients with skin and soft tissue infections in Japan – Results of a randomised, multicentre phase 3 study

Cited by 39 publications

References 38 publications

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

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

<p>Tedizolid phosphate for the treatment of acute bacterial skin and skin-structure infections: an evidence-based review of its place in therapy</p>

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

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