title: Platelet profile in patients with acute bacterial skin and skin structure infections receiving tedizolid or linezolid: findings from the Phase 3 ESTABLISH clinical trials.
abstract: Tedizolid, the active moiety of tedizolid phosphate, is a recently approved oxazolidinone antibacterial with activity against a wide range of Gram-positive pathogens, including resistant strains such as methicillin-resistant Staphylococcus aureus. To date, 6 days of 200 mg tedizolid once daily has been shown to be noninferior to 10 days of 600 mg linezolid twice daily in two randomized, double-blind phase 3 trials (ESTABLISH-1 and ESTABLISH-2) for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs). The intent of this study was to characterize the platelet profiles of patients receiving tedizolid relative to linezolid over the course of treatment using pooled data from these two trials. The occurrences of clinically defined and statistical analysis plan-specified reduced platelet counts were assessed at the study days 7 to 9 visit, the study days 11 to 13 visit, and the posttherapy evaluation (PTE) visit. At the study days 7 to 9 visit, incidences of reduced platelet counts were low and largely similar between the groups. The only notable difference was a lower incidence of thrombocytopenia (platelet counts, <150,000 cells/mm(3)) among patients who received tedizolid (3.2%) relative to those who received linezolid (5.6%). At the study days 11 to 13 visit, patients who received tedizolid had lower incidences of platelet counts of <150,000 cells/mm(3) (-5.9%), <112,500 cells/mm(3) (-2.4%), and <100,000 cells/mm(3) (-1.9%) than patients in the linezolid group. Similar differences were noted at the PTE visit. Findings across the two phase 3 ABSSSI trials suggest that 6 days of 200 mg tedizolid daily confers a low potential for reduced platelet counts among patients with ABSSSIs. (The ESTABLISH-1 and ESTABLISH-2 trials have been registered at ClinicalTrials.gov under registration numbers NCT01170221 and NCT01421511, respectively.).
authors.affiliation: Albany College of Pharmacy and Health Sciences, Albany, New York, USA thomas.lodise@acphs.edu.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Lodise
authors.affiliation: Clinical Development, Cubist Pharmaceuticals, San Diego, California, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Fang
authors.affiliation: Minassian Biostatistics, Inc., San Diego, California, USA.
authors.forename: Sonia L
authors.initials: SL
authors.lastname: Minassian
authors.affiliation: Clinical Development, Cubist Pharmaceuticals, San Diego, California, USA.
authors.forename: Philippe G
authors.initials: PG
authors.lastname: Prokocimer
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001792:Blood Platelets / Q000473:pathology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D000069349:Linezolid; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D023303:Oxazolidinones / Q000627:therapeutic use*; D010976:Platelet Count; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D013777:Tetrazoles; C546016:tedizolid; D000069349:Linezolid