1857. Outcomes with IV/oral Delafloxacin (DLX) Compared to Vancomycin/Aztreonam (VAN/AZ) in Treatment of Patients (pts) with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) and Gram-positive (GP) Pathogens
Session: Poster Abstract Session: Clinical Study with New Antibiotics and Antifungals
Saturday, October 7, 2017
Room: Poster Hall CD
Posters
  • IDWeek 2017 - Poster 1857 - DLX Gram-positive outcomes REVISED 9292017.pdf (427.1 kB)
  • Background:

    DLX, an novel anionic fluoroquinolone antibiotic, is in development for treatment of ABSSSI. This analysis focuses on the outcome in patients with Gram-positive (GP) pathogens including MRSA from 2 global phase 3 ABSSSI trials.

    Methods:

    Two double-blind trials of adults with ABSSSI randomized pts 1:1 to receive either q12h DLX IV/oral monotherapy or VAN 15 mg/kg with AZ for 5 – 14 days. Key endpoints were objective response at 48-72 hours; and investigator assessment of outcome based on resolution of signs and symptoms at Follow-up (FU day 14) and Late Follow-up (LFU day 21-28).

    Results:

    1042/1510 pts enrolled had a baseline pathogen. 987 (95%) of pts with a baseline pathogen had a GP pathogen; 14% of pts had a mixed infection. Median erythema area at baseline was ~195 cm2. 30% had cellulitis, 31% abscesses, and 38% wounds. S. aureus was the most frequent isolate. The MIC50, MIC90 and MIC range for key pathogens were 0.008, 0.03, 0.002-0.5 µg/mL for MSSA; 0.12, 0.25, 0.002-4 µg/mL for MRSA; 0.015, 0.06, 0.008-0.06 µg/mL for S. pyogenes. Key endpoints are shown below:

    Key Endpoints

    Phase 3 Patients with GP pathogens

    DLX

    VAN/AZ

    n/Total (%)

    n/Total (%)

    Objective response 48-72h (micro evaluable [ME])

    405/461 (87.9)

    388/446 (87.0)

    Investigator-Assessed Success (FU ME)

    381/389 (97.9)

    361/368 (98.1)

    Investigator-Assessed Success (LFU ME)

    377/388 (97.2)

    358/367 (97.5)

    Micro Success (FU ME) for key GP organisms:

    S. aureus

    244/248 (98.4)

    233/239 (97.5)

    MSSA

    140/142 (98.6)

    136/140 (97.1)

    MRSA

    106/108 (98.1)

    97/99 (98.0)

    S. pyogenes

    18/19 (94.7)

    15/15 (100)

    In the overall population, the proportion of pts with at least one treatment-emergent adverse event (AE) was similar for DLX (45.1%) compared to VAN/AZ (47.7%). The most frequent treatment-related AE were gastrointestinal in nature including nausea seen in 6.1% and 4.3%, and diarrhea seen in 6.1% and 2% of DLX and VAN/AZ pts, respectively. There were 0.8% of DLX pts and 2.4% VAN/AZ pts discontinued treatment due to treatment-related AEs.

    Conclusion: GP pathogens, particularly MRSA, are the most frequent pathogens in ABSSSI. Fixed dose DLX IV/oral monotherapy was comparable to VAN/AZ in pts with GP pathogens including MRSA based on the early objective response as well as investigator assessed response and microbiologic response. DLX appears effective and well tolerated in pts with GP pathogens in ABSSSI.

    Scott Overcash, MD, Estudysites, La Mesa, CA, William O'Riordan, MD, eStudySite, San Diego, CA, Laura Lawrence, BS, Melinta Therapeutics, Inc., New Haven, CT, Sandra P. McCurdy, M.S., Melinta Therapeutics, Lincolnshire, IL, Carol Tseng, Ph.D., H2O Clinical LLC, Hunt Valley, MD and Sue K. Cammarata, MD, Melinta Therapeutics, Inc., Lincolnshire, IL

    Disclosures:

    S. Overcash, Melinta: Investigator , Research grant

    W. O'Riordan, Melinta: Investigator , Research grant

    L. Lawrence, Melinta: Employee , Salary

    S. P. McCurdy, Melinta Therapeutics: Employee , Salary

    C. Tseng, Melinta: Consultant and Research Contractor , Consulting fee

    S. K. Cammarata, Melinta Therapeutics: Employee , Salary

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 4th with the exception of research findings presented at the IDWeek press conferences.