1856. 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-negative (GN) Pathogens
Session: Poster Abstract Session: Clinical Study with New Antibiotics and Antifungals
Saturday, October 7, 2017
Room: Poster Hall CD
Posters
  • IDWeek 2017 - Poster 1856 - DLX Gram-negative outcomes.pdf (84.2 kB)
  • Background: DLX, an anionic fluoroquinolone antibiotic is in development for treatment of ABSSSI. This analysis focuses on pts with Gram-negative pathogens from 2 phase 3 ABSSSI trials.

    Methods:

    2 double-blind trials of adults with ABSSSI randomized pts 1:1 to receive either IV/oral DLX monotherapy or VAN 15 mg/kg with AZ for 5 – 14 days, conducted in US, Europe, Latin America and Asia. Key endpoints were objective response at 48-72 hours and investigator assessment of outcome at Follow-up (FU day 14) and Late Follow-up (LFU day 21-28).

    Results:

    In the 2 studies, 1042/1510 pts enrolled had a pathogen at baseline (Micro Intent to Treat [MITT]). 197 pts (19%) had a GN pathogen isolated at baseline; most were part of a mixed infection. 66% were male, mean age 52 yrs. Median digital erythema area at baseline was ~227 cm2. 25% had cellulitis, 27% abscesses, and 47% wound infections.The most common location was the lower extremities. K. pneumoniae was the most frequent GN isolate. The MIC50, MIC90 and MIC range were 0.12, 0.25, 0.03-4 µg/mL for K. pneumoniae; 0.12, 2, 0.03->8 µg/mL for E. cloacae; 0.06, 4, 0.008-4 µg/mL for E. coli; and 0.25, 4, 0.12->8 µg/mL for P. aeruginosa. Key endpoints are shown below:

    Key Endpoints

    Phase 3 Pts with GN pathogens

    DLX

    VAN/AZ

    n/Total (%)

    n/Total (%)

    Objective response 48-72h (ME)

    77/90 (85.6)

    83/94 (88.3)

    Investigator-Assessed Success (FU ME)

    74/75 (98.7)

    80/82 (97.6)

    Investigator-Assessed Success (LFU ME)

    73/75 (97.3)

    76/78 (97.4)

    Micro Success (FU ME) for key GN organisms:

    K. pneumoniae

    17/17 (100)

    17/17 (100)

    E. cloacae

    11/12 (91.7)

    9/10 (90)

    E. coli

    11/11 (100)

    16/17 (94.1)

    P. aeruginosa

    11/11 (100)

    10/10 (100)

    In the overall population, the proportion of pts with at least one treatment-emergent AE (TEAE) was similar for DLX (45.1%) compared to VAN/AZ (47.7%). The most frequent treatment-related adverse events 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 who discontinued treatment due to treatment related AEs.

    Conclusion:

    GN pathogens are a consideration in ABSSSI antibiotic selection. Fixed dose DLX monotherapy was comparable to VAN/AZ in effects in pts with GN pathogens based on the early and investigator assessed response and micro response. DLX appears effective and well tolerated in pts with GN pathogens in ABSSSI.

    William O'Riordan, MD, eStudySite, San Diego, CA, Scott Overcash, MD, Estudysites, La Mesa, 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:

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

    S. Overcash, 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.