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.

Keywords: ABSSSI; Latino ethnicity; Oxazolidinone; Tedizolid.

Fig. 1

Proportion of Latino patients with clinical response at 48–72 h and clinical success at end of therapy and post-treatment evaluation visits (ITT analysis set). ITT: intent-to-treat.

Fig. 2

Boxplots of tedizolid AUC_0–24, C_max, C_min at steady-state in Latino and non-Latino patients. Boxes are 25th, 50th, and 75th percentiles with median as horizontal line; whiskers are 5th and 95th percentiles. Asterisks show data points outside of this range. The number of subjects is provided above each box. (A) AUC_(0–24),ss area under the concentration curve at steady state. (B) C_max,ss, maximum concentration at steady state. (C) C_min,ss, minimum concentration at steady state.