471. Safety and Efficacy of Oral and/or Intravenous Tedizolid Phosphate (TZD) in Adolescents with Acute Bacterial Skin and Skin Structure Tissue Infections (ABSSSI)

Background Tedizolid phosphate has activity against gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, and was approved for the treatment of ABSSSI in adults in 2014. This study compared the safety and efficacy of TZD with protocol-specified, active comparators for the treatment of ABSSSI in adolescents. Methods This was a randomized, assessor-blind, global, multicenter, phase 3 study of TZD vs. active comparator for the treatment of gram-positive ABSSSI in adolescents (aged 12 to < 18 years; NCT02276482). Enrolled patients were stratified by region and randomized 3:1 to TZD 200 mg (IV and/or oral) once daily for 6 days or investigator-selected active comparator per local standard of care (IV vancomycin, linezolid, clindamycin, flucloxacillin, or cefazolin, and/or oral linezolid, clindamycin, flucloxacillin, or cephalexin) for 10 days. The primary endpoint was safety. The percentages of patients with treatment-emergent adverse events (TEAEs) were documented; secondary efficacy endpoints included the blinded investigator’s assessment of clinical success at a test of cure visit (18–25 days after start of dosing) and early clinical response (≥20% reduction from baseline lesion area) at 48–72 h. No hypothesis testing was planned for the treatment groups. Results Of the 121 patients enrolled, 120 were treated (TZD, N = 91; comparator, N = 29). Median (range) age was 15 (12–17) years. Most patients were male (62.5%), white (86.7%), and enrolled in Europe (78.3%). Infections included major cutaneous abscess (42.5%), cellulitis/erysipelas (40.0%), and infected wound (17.5%). At baseline, the median (range) lesion surface area was 82.1 (14–978) cm2. Of those with gram-positive cultures (n = 64), S. aureus was most frequently isolated (n = 55 [85.9%]) with 3 isolates (4.7%) being methicillin resistant. TZD was well tolerated, and TEAEs were balanced between treatment arms (TZD, 14.3%; comparator, 10.3%). A total of 3 (3.3%) patients in the TZD group and 1 (3.4%) in the comparator ...