470. Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in Patients with Significant Drug Abuse: Outcomes from Global Phase 3 Studies of Delafloxacin (DLX)

BACKGROUND: Delafloxacin (DLX), an IV/oral anionic fluoroquinolone antibiotic, is approved for the treatment of ABSSSI including those due to MRSA and Gram-negative pathogens including P. aeruginosa. Two global phase 3 ABSSSI trials included patients with substance abuse including IV drugs. METHODS: Two multicenter, double-blind, double-dummy trials of adults with ABSSSI randomized patients 1:1 to receive either DLX monotherapy or vancomycin 15 mg/kg + aztreonam (VANAZ) for 5–14 days. Study 302 used DLX 300 mg BID IV only; study 303 used DLX 300 mg BID IV for 3 days with a mandatory blinded switch to DLX 450 mg oral BID. Key endpoints were Objective Response at 48–72 hours with ≥20% reduction in lesion size, and Investigator assessment of outcome at Follow-up (FU, Day 14), both in the Intent To Treat population. RESULTS: In the 2 studies, 620 patients with substance abuse, excluding alcoholism, including heroin, cocaine and methamphetamine abuse, were randomized in the United States. 71% were male with mean age 44 years. Average erythema area at baseline was ~230 cm(2). 16% percent had cellulitis, 30% abscesses, and 53% wound. S. aureus (SA) was the most frequent pathogen. DLX was non-inferior to VANAZ for the Objective Response: 85.9% DLX vs. 84.4% VANAZ [∆2.6 (95% CI −2.9, 8.1)] as well as the assessment of outcome at FU: 82.0% DLX vs. 79.3% VANAZ [∆3.2 95% (CI −3, 9.4)]. Micro success in evaluable patients with SA was seen in 99.1% DLX vs. 100% VANAZ as well as 98.2% DLX vs. 100% VANAZ in patients with MRSA. The overall % of patients with at least one adverse event (AE) was comparable for DLX (49.0%) compared with VANAZ (56.1%). The most frequent treatment-related AEs were gastrointestinal in nature, including nausea seen in 9.7% DLX and 5.8% VANAZ patients, primarily mild to moderate in severity. There were no cases of C.difficile diarrhea. Discontinuations due to treatment-related AEs were lower with DLX (0.3%) compared with VANAZ (2.2%). CONCLUSION: Fixed-dose monotherapyDLX was comparable to VANAZ in ...