586. In Vitro Activity of Ceftazidime (CAZ) Combined with Avibactam (NXL104) versus Pseudomonas aeruginosa Isolates Obtained from Patients in Canadian Hospitals: CANWARD 2010
Session: Poster Abstract Session: Novel Antimicrobial Agents
Friday, October 21, 2011
Room: Poster Hall B1
Handouts
  • Walkty XL104 Pseudo IDSA2011_Sept22.pdf (364.4 kB)
  • Background:  Resistance to β-lactam antimicrobials among P. aeruginosa isolates is mediated, it part, by production of an AmpC β-lactamase (an Ambler class C enzyme).  Avibactam (NXL104), a novel non-β-lactam β-lactamase inhibitor, inhibits Ambler class A and C enzymes.  The purpose of this study was to evaluate the in vitro activity of ceftazidime (CAZ) in combination with NXL104 (ceftazidime-avibactam, CAZ104) in comparison with other antimicrobials versus P. aeruginosa clinical isolates obtained from patients in Canadian hospitals.

    Methods:  From January through November 2010, 14 sentinel Canadian hospitals submitted pathogens from patients attending hospital clinics, emergency rooms, medical and surgical wards, and intensive care units (CANWARD).  Each centre was asked to submit pathogens (consecutive, one per patient/infection site) from blood (165), respiratory (100), urine (50), and wound/IV (50) infections.  Susceptibility testing was performed using CLSI broth microdilution.  NXL104 was evaluated at a fixed concentration of 4 µg/mL in combination with doubling concentrations of ceftazidime.

    Results:  In total, 376 P. aeruginosa isolates were obtained as a part of CANWARD.  The antimicrobial susceptibility profile of these isolates is presented below.

     

     

     

     

     

     

    Antimicrobial

    Susceptibility

    %

    MIC50

    MIC90

    Range

     

    Breakpoint

    Susceptible

    (µg/mL)

    (µg/mL)

     

     

     

     

     

     

     

    Amikacin

     ≤16

    89.9 

    32 

    ≤1 to >64 

    Ceftazidime

    ≤8

    79.1

    4

    32

    ≤0.25 to >32

    CAZ104

    Not defined

    No data

    4

    8

    0.25 to >16

    Ciprofloxacin

    ≤1

    73.4

    0.25

    8

    ≤0.06 to >16

    Colistin

    ≤2

    95.2

    2

    2

    0.25 to >16

    Gentamicin

    ≤4

    75.0

    4

    16

    ≤0.5 to >32

    Meropenem

    ≤4

    88.0

    0.5

    8

    ≤0.03 to >32

    Piperacillin-Tazobactam

    ≤64/4

    94.4

    4

    32

    ≤1 to >512

    The percentage of isolates with a CAZ MIC of ≤8 µg/mL with and without NXL104 was 92.0% and 79.3%, respectively.  Twenty-six isolates (6.9%) were multi-drug resistant (MDR = resistant to at least 3 different antimicrobial classes).  The percentage of MDR isolates inhibited by a CAZ MIC of ≤8 µg/mL in the presence and absence of NXL104 was 50% (13/26) and 0%, respectively. 

    Conclusion:  Addition of NXL104 to CAZ lowered the MIC of this agent versus P. aeruginosa (including MDR isolates).  Fifty percent of MDR P. aeruginosa isolates were inhibited by ≤8 µg/mL of CAZ104.


    Subject Category: A. Antimicrobial agents and Resistance

    Andrew Walkty, MD1,2, Melanie Baxter, MSc1, Heather J. Adam, PhD3, Kim Nichol, MSc1, Philippe LagacÚ-Wiens1,4, James Karlowsky, PhD1, Daryl J. Hoban, PhD1,5 and George G. Zhanel, PhD1, (1)University of Manitoba, Winnipeg, MB, Canada, (2)Microbiology, Diagnostic Services of Manitoba, Winnipeg, MB, Canada, (3)Health Sciences Centre, Winnipeg, MB, Canada, (4)Microbiology, St. Boniface Hospital, Winnipeg, MB, Canada, (5)Department of Clinical Microbiology, Health Sciences Centre, Winnipeg, MB, Canada

    Disclosures:

    A. Walkty, None

    M. Baxter, None

    H. J. Adam, None

    K. Nichol, None

    P. LagacÚ-Wiens, None

    J. Karlowsky, None

    D. J. Hoban, Abbott Laboratories Ltd: , Research support
    Astellas Pharma Canada Inc: , Research support
    Bayer Schering Pharma AG: , Research support
    Merck Frosst Canada Ltd.: , Research support
    Pfizer Canada Inc.: , Research support
    Sepracor Pharmaceuticals Inc.: , Research support
    The Medicines Company: , Research support

    G. G. Zhanel, Abbott Laboratories Ltd.: , Research support
    Astellas Pharma Canada Inc.: , Research support
    Bayer Shcering Pharma AG: , Research support
    Merck Frosst Canada Ltd.: , Research support
    Pfizer Canada Inc: , Research support
    Sepracor Pharmaceuticals Inc.: , Research support
    The Medicines Company: , Research support

    Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.