1616. In Vitro Activity of Ceftolozane/Tazobactam (CXA-201) versus Pseudomonas aeruginosa Isolates Obtained from Patients in Canadian Hospitals: CANWARD 2011
Session: Poster Abstract Session: Novel Antimicrobial Agents
Saturday, October 20, 2012
Room: SDCC Poster Hall F-H
Posters
  • CeftolozanePseudomonas_CANWARD2011_Sept26_2012_version 2.pdf (333.5 kB)
  • Background:   Cephalosporin resistance among P. aeruginosa isolates is mediated, in part, by production of an AmpC beta-lactamase.  Ceftolozane, a novel anti-pseudomonal cephalosporin, demonstrates reduced affinity for AmpC beta-lactamases and improved binding to P. aeruginosa penicillin binding proteins relative to ceftazidime.  The purpose of this study was to evaluate the in vitro activity of ceftolozane in combination with tazobactam (ceftolozane/tazobactam: formerly CXA-201) versus P. aeruginosa clinical isolates obtained from patients in Canadian hospitals.

    Methods:   From January through October 2011, 15 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 (100), respiratory (100), urine (25), and wound/IV (25) infections.  Susceptibility testing was performed using CLSI broth microdilution.  Doubling concentrations of ceftolozane were evaluated in combination with a fixed concentration of tazobactam (4 µg/mL).

    Results:   In total, 330 P. aeruginosa 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)

    Range

    Susceptibility Breakpoint

    % Susceptible

     

     

     

     

     

     

     

     

     

     

     

     

    <>Amikacin

    4

    8

    ≤1 to >64

    ≤16

    94.6

    Cefepime

    4

    16

    ≤0.25 to >64

    ≤8

    86.1

    Ceftazidime

    2

    32

    ≤0.25 to >32

    ≤8

    85.2

    Ceftolozane/

    tazobactam

    0.5

    1

    ≤0.12 to >64

    Not defined

    Not defined

    Ciprofloxacin

    0.25

    4

    ≤0.06 to >16

    ≤1

    78.2

    Colistin

    1

    2

    0.25 to 16

    ≤2

    95.5

    Gentamicin

    1

    8

    ≤0.5 to >32

    ≤4

    88.2

    Meropenem

    0.5

    4

    ≤0.03 to >32

    ≤2

    84.2

    Piperacillin/

    Tazobactam

    4

    64

    ≤1 to >512

    ≤16/4

    84.6

     

     

     

     

     

     

    Twenty-three isolates (7.0%) were multi-drug resistant (MDR = resistant to at least 3 different antimicrobial classes).  The MIC90 values for ceftolozane/tazobactam, cefepime, and ceftazidime versus the MDR isolates were 8 µg/mL, 32 µg/mL, and >32 µg/mL, respectively.

    Conclusion:   Ceftolozane/tazobactam demonstrated improved in vitro activity (16-32 fold lower MIC90 value) over ceftazidime and cefepime versus a collection of 330 P. aeruginosa clinical isolates.  Over 90% of MDR P. aeruginosa isolates were inhibited by ≤8 µg/mL of ceftolozane/tazobactam.

    Andrew Walkty, MD1,2, Melanie Baxter, MSc1, Heather J. Adam, PhD1,2, Kim Nichol, MSc1, Philippe LagacÚ-Wiens1,3, James Karlowsky, PhD1,2, Daryl Hoban, PhD1,2 and George G. Zhanel, PhD4, (1)University of Manitoba, Winnipeg, MB, Canada, (2)Microbiology, Diagnostic Services of Manitoba, Health Sciences Centre, Winnipeg, MB, Canada, (3)Microbiology, Diagnostic Services of Manitoba, St. Boniface Hospital, Winnipeg, MB, Canada, (4)Medical Microbiology, University of Manitoba, 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. Hoban, Abbott Laboratories: Research relationship, Research support
    Achaogen, Inc.: Research relationship, Research support
    Affinium Pharmaceuticals: Research relationship, Research support
    Astellas Pharma Canada Inc: Research relationship, Research support
    AstraZeneca Pharmaceuticals LP: Research relationship, Research support
    Cubist Pharmaceuticals: Research relationship, Research support
    Merck Frosst Canada: Research relationship, Research support
    Pfizer Canada Inc: Research relationship, Research support
    Sunovion Pharmaceuticals Inc: Research relationship, Research support
    The Medicines Compancy: Research relationship, Research support
    Cerexa, Inc.: Research relationship, Research support

    G. G. Zhanel, Abbot Laboratories: Research relationship, Research support
    Achaogen, Inc.: Research relationship, Research support
    Affinium Pharmaceuticals: Research relationship, Research support
    Astellas Pharma Canada, Inc.: Research relationship, Research support
    AstraZeneca Pharmaceuticals LP: Research relationship, Research support
    Cubist Pharmaceuticals: Research relationship, Research support
    Merck Frosst Canada: Research relationship, Research support
    Pfizer Canada Inc: Research relationship, Research support
    Sunovion Pharmaceuticals Inc.: Research relationship, Research support
    The Medicines Company: Research relationship, Research support
    Cerexa, Inc.: Research relationship, Research support

    Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 17th with the exception of research findings presented at the IDWeek press conferences.