Program Schedule

254
In Vitro Activity of Ceftazidime in Combination with Avibactam versus 1825 Pseudomonas aeruginosa Clinical Isolates Obtained from across Canada as Part of the CANWARD Study, 2009-2013

Session: Poster Abstract Session: Antimicrobial Resistance: Novel Agents and Approaches to Gram-negative Infections
Thursday, October 9, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Posters
  • Walkty Ceftazidime-Avibactam Pseudo IDSA2014_October_Version 3.pdf (407.8 kB)
  • Background:  Avibactam is a non-beta lactam beta-lactamase inhibitor, with activity against molecular class A, class C, and some class D beta-lactamase enzymes.  The purpose of this study was to evaluate the in vitro activity of ceftazidime in combination with avibactam against a large collection of Pseudomonas aeruginosa clinical isolates obtained as part of the CANWARD study (2009-2013).

    Methods:  From January 2009 to December 2013, inclusive, 12 to 15 sentinel hospitals across Canada submitted clinical isolates from patients attending ERs, medical and surgical wards, hospital clinics, and ICUs (CANWARD).  Each center was asked to submit clinical isolates (consecutive, one per patient/infection site) from blood (100 to 165), respiratory (100), urine (25 to 50), and wound (25 to 50) infections.  Susceptibility testing was performed using broth microdilution as described by CLSI.  Doubling concentrations of ceftazidime were evaluated in combination with a fixed concentration of avibactam (4 μg/mL).

    Results:  1825 P. aeruginosa clinical isolates were obtained as a part of CANWARD. The antimicrobial susceptibility profile of these isolates is presented below.

    Antimicrobial

    MIC50

    (µg/mL)

    MIC90

    (µg/mL)

    Susceptibility Breakpoint

    (µg/mL)

    % Susceptible

    Amikacin

    4

    16

    ≤16

    93.0

    Ceftazidime

    4

    32

    ≤8

    82.7

    Ceftazidime-Avibactam

    2

    8

    Not defined

    No data

    Ciprofloxacin

    0.25

    4

    ≤1

    76.7

    Colistin

    1

    2

    ≤2

    94.6

    Gentamicin

    2

    16

    ≤4

    83.0

    Meropenem

    0.5

    8

    ≤2

    82.0

    Piperacillin-Tazobactam

    4

    64

    ≤16/4

    84.7

    Two-hundred and fifty-seven isolates (14% of the total) were multidrug-resistant (non-susceptible to at least one antimicrobial from 3 or more classes). Ceftazidime-avibactam demonstrated an MIC of ≤8 μg/mL (ceftazidime susceptibility breakpoint) versus 70.4% of MDR isolates. Further, 67.4% of ceftazidime non-susceptible isolates and 79.9% of meropenem non-susceptible isolates had an MIC of ≤8 μg/mL for ceftazidime-avibactam.

    Conclusion:  The combination of ceftazidime-avibactam demonstrated improved in vitro activity over ceftazidime alone versus P. aeruginosa clinical isolates obtained from patients across Canada (4-fold reduction in MIC90).  Over two-thirds of MDR isolates evaluated were inhibited by ≤8 μg/mL of ceftazidime-avibactam.

    Andrew Walkty, MD1,2, Melanie Decorby, MSc3, Heather J. Adam, PhD1,2, Philippe LagacÚ-Wiens, MD2,4, James Karlowsky, PhD2,4, Daryl Hoban, PhD1,2 and George Zhanel, PhD2, (1)Microbiology, Diagnostic Services of Manitoba, Health Sciences Centre, Winnipeg, MB, Canada, (2)Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada, (3)Department of Clinical Microbiology, Health Sciences Centre, Winnipeg, MB, Canada, (4)Microbiology, Diagnostic Services of Manitoba, St. Boniface Hospital, Winnipeg, MB, Canada

    Disclosures:

    A. Walkty, None

    M. Decorby, None

    H. J. Adam, None

    P. LagacÚ-Wiens, None

    J. Karlowsky, None

    D. Hoban, Abbot: Research relationship, Research support
    Astellas Pharma Canada: Research relationship, Research support
    AstraZeneca: Research relationship, Research support
    Cubist Pharmaceuticals: Research relationship, Research support
    Merck Canada Inc.: Research relationship, Research support
    Optimer: Research relationship, Research support
    Pfizer: Research relationship, Research support
    Sunovion: Research relationship, Research support
    The Medicines Company: Research relationship, Research support
    Theravance: Research relationship, Research support
    Triton Pharma: Research relationship, Research support
    Trius: Research relationship, Research support

    G. Zhanel, Abbot: Research relationship, Research support
    Astellas Pharma Canada: Research relationship, Research support
    AstraZeneca: Research relationship, Research support
    Cubist Pharmaceuticals: Research relationship, Research support
    Merck Canada Inc.: Research relationship, Research support
    Optimer: Research relationship, Research support
    Pfizer: Research relationship, Research support
    Sunovion: Research relationship, Research support
    The Medicines Company: Research relationship, Research support
    Theravance: Research relationship, Research support
    Triton Pharma: Research relationship, Research support
    Trius: Research relationship, Research support

    Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

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