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)

Abstract

BackgroundDelafloxacin (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.MethodsTwo 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.ResultsIn 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 cm2. 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%).ConclusionFixed-dose monotherapyDLX was comparable to VANAZ in treatment of ABSSSI in patients with substance abuse based on the Objective Response as well as investigator-assessed outcome. DLX was also comparable to VANAZ in treating patients with SA and MRSA. DLX appears effective and well tolerated in patients with ABSSSI and significant substance abuse.Disclosures All authors: No reported disclosures.