Efficacy, safety, tolerability and population pharmacokinetics of tedizolid, a novel antibiotic, in Latino patients with acute bacterial skin and skin structure infections

Abstract

Acute bacterial skin and skin structure infections are caused mainly by Gram-positive bacteria which are often treated with intravenous vancomycin, daptomycin, or linezolid, with potential step down to oral linezolid for outpatients. Tedizolid phosphate 200mg once daily treatment for six days demonstrated non-inferior efficacy, with a favourable safety profile, compared with linezolid 600mg twice daily treatment for 10 days in the Phase 3 ESTABLISH-1 and -2 trials. The objective of the current post-hoc analysis of the integrated dataset of ESTABLISH-1 and -2 was to evaluate the efficacy and safety of tedizolid (N=182) vs linezolid (N=171) in patients of Latino origin enrolled into these trials. The baseline demographic characteristics of Latino patients were similar between the two treatment groups. Tedizolid demonstrated comparable efficacy to linezolid at 48-72h in the intent-to-treat population (tedizolid: 80.2% vs linezolid: 81.9%). Sustained clinical success rates were comparable between tedizolid- and linezolid-treated Latino patients at end-of-therapy (tedizolid: 86.8% vs linezolid: 88.9%). Tedizolid phosphate treatment was well tolerated by Latino patients in the safety population with lower abnormal platelet counts at end-of-therapy (tedizolid: 3.4% vs linezolid: 11.3%, p=0.0120) and lower incidence of gastrointestinal adverse events (tedizolid: 16.5% vs linezolid: 23.5%). Population pharmacokinetic analysis suggested that estimated tedizolid exposure measures in Latino patients vs non-Latino patients were similar. These findings demonstrate that tedizolid phosphate 200mg, once daily treatment for six days was efficacious and well tolerated by patients of Latino origin, without warranting dose adjustment.

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

“…A slightly higher incidence of drug-related TEAEs was observed with tedizolid than with linezolid treatment, which was attributed to the higher number of patients ( n = 8) experiencing phlebitis at the infusion site (without discontinuation and considered not serious events) than in the linezolid arm ( n = 0). This rate (20.9%) of drug-related TEAEs in the tedizolid arm of the current study was similar to that of the integrated ESTABLISH studies (22.4%) (27). Furthermore, the overall rates of GI TEAEs (including those related to study drug) and abnormal hematological findings were lower in both treatment arms than in the integrated data from the ESTABLISH studies (26).…”

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

“…Similarly to previously published data, the incidence of drugrelated AEs was also numerically lower in this study with tedizolid treatment compared with linezolid [46]. Linezolid, whilst generally well tolerated, may cause myelosuppression, in particular thrombocytopenia and anaemia requiring platelet or blood transfusion [22].…”

New Antibiotics in the Therapy of Osteomyelitis

“…Its spectrum covers Grampositive pathogens, including linezolid-resistant S. aureus [101] . It has been shown to be efficient, safe and well-tolerated in phase 3 studies and a post-hoc analysis for Latino patients [101][102][103] . Its efficiency has been studied in rat foreign-body osteomyelitis, but no data for human osteomyelitis exists [104] .…”