2039. In Vitro Activity of Delafloxacin and Microbiological Response Against Fluoroquinolone Susceptible and Non-Susceptible S. aureus Isolates from two Phase 3 Studies of Acute Bacterial Skin and Skin Structure Infections (ABSSSI)
Session: Poster Abstract Session: Antimicrobial Resistant Infections: Treatment
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • IDWeek 2016 Micro Poster 2039.Final Update.10.6.pdf (150.1 kB)
  • Background: Delafloxacin (DLX) is an investigational anionic fluoroquinolone antibiotic with broad spectrum activity, including Gram-positive organisms, Gram-negative organisms, atypical organisms, and anaerobes. The in vitro activity of delafloxacin and percent microbiological response in subjects infected with fluoroquinolone non-susceptible S. aureus isolates was determined from two global Phase 3 studies of delafloxacin versus vancomycin plus aztreonam in ABSSSI.

    Methods: Patients were enrolled in 23 countries predominately in the US but also Eastern Europe, South America and Asia. The microbiological intent-to-treat population (MITT) included 1042 patients from which 1716 isolates were submitted for identification and susceptibility testing per CLSI guidelines at the central laboratory (JMI Laboratories, N. Liberty, IA). Comparator fluoroquinolone antibiotics included levofloxacin and ciprofloxacin. Non-susceptibility to these antibiotics was determined using CLSI breakpoints.

    Results: S. aureus isolates were 51% levofloxacin or ciprofloxacin non-susceptible (FQ-NS). Delafloxacin activity and percent microbiological response are presented below.

    Baseline Organisms (MITT; both treatment arms)

    Number of Isolates
    FQ-S/FQ-NS

    DLX FQ-S
    MIC50/90
     (µg/mL)

    DLX FQ-S
    Range
    (µg/mL)

    DLX FQ-NS
    MIC50/90
    (µg/mL)

    DLX FQ-NS

    Range
    (µg/mL)

    Number of Subjects with FQ-S/FQ-NS isolates
    (ME Inv-Assessed Endpoint at Follow-Up)

    Percent Microbiological Response for Subjects with FQ-NS isolates

    S. aureus1

    455/232

    0.008/0.008

    0.002-0.12

    0.25/0.25

    0.004-4

    168/81

    80/81 (98.8%)

    MRSA

    101/195

    0.008/0.008

    0.002-0.12

    0.25/0.25

    0.004-4

    37/71

    70/71 (98.6%)

    MSSA

    358/39

    0.008/0.008

    0.002-0.12

    0.12/0.25

    0.004-0.5

    132/10

    10/10 (100%)

    1Patients with MRSA and MSSA were counted only once in S. aureus.

    Conclusion: Delafloxacin demonstrated high rates of microbiological response against FQ-NS isolates. The data suggest that delafloxacin could be a good treatment option for S. aureus ABSSSI isolates where high rates of ciprofloxacin and levofloxacin non-susceptibility are observed including MRSA.

    Sandra Mccurdy, M.S.1, Laura Lawrence, B.S.1, Leah N. Woosley, B.S.2, Robert K. Flamm, Ph.D.2, Carol Tseng, Ph.D.3 and Sue K. Cammarata, M.D.1, (1)Melinta Therapeutics, Inc., New Haven, CT, (2)JMI Laboratories, Inc., North Liberty, IA, (3)H2O Clinical LLC, Hunt Valley, MD

    Disclosures:

    S. Mccurdy, Melinta Therapeutics, Inc.: Employee , Salary

    L. Lawrence, Melinta Therapeutics, Inc.: Employee , Salary

    L. N. Woosley, JMI Laboratories: Employee , Salary

    R. K. Flamm, JMI Laboratories: Employee and Shareholder , Salary

    C. Tseng, H2O Clinical LLC: Consultant , Consulting fee

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

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.