title: 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.
authors: Hospital Civil de Guadalajara, Guadalajara, Jalisco, Mexico. Electronic address: orca0059@prodigy.net.mx.
authors: Alejandro
authors: A
authors: Ortiz-Covarrubias
authors: Merck and Co, Inc., Kenilworth, NJ, USA.
authors: Edward
authors: E
authors: Fang
authors: Merck and Co, Inc., Kenilworth, NJ, USA.
authors: Philippe G
authors: PG
authors: Prokocimer
authors: Merck and Co, Inc., Kenilworth, NJ, USA.
authors: Shawn D
authors: SD
authors: Flanagan
authors: Bayer HealthCare, Beijing, China.
authors: Xu
authors: X
authors: Zhu
authors: Bayer HealthCare, Mexico City, Mexico.
authors: Jose Francisco
authors: JF
authors: Cabré-Márquez
authors: Bayer Yakuhin, Osaka, Japan.
authors: Toshiaki
authors: T
authors: Tanaka
authors: Cognigen Corporation, a subsidiary of Simulations Plus, Inc., Buffalo, NY, USA.
authors: Julie
authors: J
authors: Passarell
authors: Cognigen Corporation, a subsidiary of Simulations Plus, Inc., Buffalo, NY, USA.
authors: Jill
authors: J
authors: Fiedler-Kelly
authors: Facultad Ciencias Médicas, Universidad Nacional de Rosario, Sanatorio Británico, Rosario, Argentina.
authors: Esteban C
authors: EC
authors: Nannini
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007843:Latin America; D000069349:Linezolid / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010755:Organophosphates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D010080:Oxazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D017192:Skin Diseases, Bacterial / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D010755:Organophosphates; D010080:Oxazoles; D000069349:Linezolid; C515040:tedizolid phosphate
keywords: ABSSSI; Latino ethnicity; Oxazolidinone; Tedizolid