1200. Activity of the novel extended-spectrum β-lactamase inhibitor AAI101 in combination with cefepime towards a challenge panel of Acinetobacter baumannii
Session: Poster Abstract Session: Expanded Spectrum - New Antimicrobial Susceptibility Testing
Friday, October 6, 2017
Room: Poster Hall CD
Posters
  • Allecra_P113_AAI101 Cefepime A baumannii_IDSA 2017_FINAL.pdf (798.4 kB)
  • Background: AAI101 is a novel extended-spectrum β-lactamase inhibitor (BLI), active against ESBLs and a broad array of other BLs. AAI101 in combination with cefepime (FEP) is in Phase 2 development. Infections caused by A. baumannii, a pathogen endemic to the southern US and other global regions, are very challenging to treat, and often require combination therapy. This study examined the activity of FEP/AAI101 against a challenge set of A. baumannii clinical isolates enriched with OXA carbapenemase producers.

    Methods: BLs in A. baumannii were identified by genotyping. Broth microdilution MICs and susceptibilities were obtained following CLSI methods and breakpoints (BPs), except for ceftazidime-avibactam (CAZ/AVI) where FDA P. aeruginosa BPs were used. CLSI FEP BPs were used for FEP/AAI101.

    Results: All OXA-51 producers had the ISAba1 promoter. MIC90 data and % susceptibilities (%S) for FEP/AAI101 and comparators are shown in the Table. FEP/AAI101 was highly active against meropenem-susceptible (MPMs) isolates. FEP/AAI101 (AAI101 fixed at 8 µg/ml) covered 67% of OXA-51 and 53% of OXA-58 strains. Lower susceptibilities were obtained for OXA-23 and OXA-24/40 producers. FEP/AAI101 was the most active β-lactam product. Colistin (COL) was the only agent with consistently high activity against all A. baumannii isolates.

    Group

     

    FEP

    FEP/

    AAI101 [4*]

    FEP/

    AAI101 [8*]

    CAZ/

    AVI

    [4*]

    AMP/

    SUL [2:1*]

    PIP/

    TAZ

    [4*]

    COL

    MPMs

    (N = 17)

    MIC90

    64

    8

    0.06

    64

    32

    256

    1

    %S

    70.6

    94.1

    100

    58.8

    82.4

    70.6

    100

    OXA-23

    (N = 30)

    MIC90

    >128

    >128

    >128

    >128

    128

    >256

    0.5

    %S

    0

    0

    0

    3.3

    0

    0

    96.7

    OXA-24/40 (N = 30)

    MIC90

    >128

    >128

    >128

    64

    128

    >256

    4

    %S

    3.3

    3.3

    6.7

    6.7

    3.3

    0

    86.7

    OXA-51

    (N = 30)

    MIC90

    >128

    >128

    >128

    >128

    >128

    >256

    0.5

    %S

    0

    36.7

    66.7

    3.3

    16.7

    0

    100

    OXA-58

    (N = 30)

    MIC90

    >128

    128

    64

    >128

    64

    >256

    1

    %S

    13.3

    33.3

    53.3

    16.7

    6.7

    0

    100

    All

    (N = 137)

    MIC90

    >128

    >128

    >128

    >128

    128

    >256

    1

    %S

    12.4

    27.7

    40.1

    13.9

    16.1

    8.8

    96.4

    AMP, ampicillin; SUL, sulbactam; PIP, piperacillin; TAZ, tazobactam

    *BLI at fixed concentration in µg/ml or ratio as indicated

    Conclusion: FEP/AAI101 was the most potent β-lactam product tested against clinical isolates of A. baumannii producing OXA-51 and OXA-58 β-lactamases. Infections by this difficult pathogen often require combination therapy, of which FEP-AAI101 may be a component.

    Ian Morrissey, PhD1, Sophie Magnet, PhD2, Stephen Hawser, PhD3, Stuart Shapiro, PhD4, Harald Seifert, MD5 and Paul Higgins, PhD5, (1)IHMA Europe Sàrl, Monthey, Switzerland, (2)IHMA, Inc, Monthey/VS, Switzerland, (3)IHMA Europe Sàrl, Monthey/VS, Switzerland, (4)Allecra Therapeutics, Saint Louis, France, (5)Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany

    Disclosures:

    I. Morrissey, None

    S. Magnet, None

    S. Hawser, None

    S. Shapiro, Allecra: Employee , Salary

    H. Seifert, None

    P. Higgins, None

    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.