1830. In Vitro Activity of Meropenem-Vaborbactam Against Isolates of KPC-producing Enterobacteriaceae Collected Worldwide in 2014-2015
Session: Poster Abstract Session: Antibacterial Susceptibility Surveillance
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • MedCo_P16_IDSA 2016_vabor_v01_final.pdf (340.2 kB)
  • In Vitro Activity of Meropenem-Vaborbactam Against Isolates of KPC-producing Enterobacteriaceae Collected Worldwide in 2014-2015

    M. Hackel, R. Badal, D.  Sahm

    IHMA, Inc. Schaumburg, IL, USA

    Background: Vaborbactam (formerly RPX7009) is a novel β-lactamase inhibitor with potent activity against class A carbapenemases such as KPC. The meropenem-vaborbactam (MEM-VAB) combination is in Phase 3 clinical trials. The activity of MEM-VAB and comparator agents was evaluated against a recent global collection of KPC-producing Enterobacteriaceae.

    Methods:

    MICs of MEM alone or with VAB at fixed 8 µg/ml, tigecycline (TCG), polymyxin B (PMB), and gentamicin (GEN) were determined against 991 KPC-producing, OXA-48- and MBL-negative isolates following CLSI guidelines.  The study collection was comprised of 11 species and six KPC variants collected in 2014-2015 in Europe, North and Latin Americas, and Asia/South Pacific.

    Results:

    Cumulative % inhibited by MEM alone and with VAB are shown in the table below, with MIC90 values boxed and shaded.

     

     

    MIC (µg/ml)

    Organism (n)

     

    ≤0.03

    0.06

    0.12

    0.25

    0.5

    1

    2

    4

    8

    16

    32

    >32

    Enterobacteriaceae

    MEM

    0

    0

    0

    0

    0

    0

    4.1

    11.9

    24.5

    39.6

    53.7

    100

    (991)

    MEM-VAB

    46.3

    51.9

    57.7

    71.3

    85.4

    93.4

    97.4

    98.9

    99.5

    99.7

    99.7

    100

    Klebsiella spp.

    MEM

    0

    0

    0

    0

    0

    0

    2.3

    8.1

    20.3

    35.0

    49.6

    100

    (897)

    MEM-VAB

    43.3

    48.5

    54.0

    68.8

    84.2

    92.9

    97.1

    98.8

    99.4

    99.7

    100

    100

    E. coli

    MEM

    0

    0

    0

    0

    0

    0

    25.7

    65.7

    85.7

    94.3

    100

    100

    (35)

    MEM-VAB

    97.1

    97.1

    100

    100

    100

    100

    100

    100

    100

    100

    100

    100

    Enterobacter spp.

    MEM

    0

    0

    0

    0

    0

    0

    27.6

    44.8

    55.2

    86.2

    89.7

    100

    (29)

    MEM-VAB

    75.9

    86.2

    100

    100

    100

    100

    100

    100

    100

    100

    100

    100

    MIC50/90 for all strains for TGC, PMB, and GEN were 1/2, 0.5/16 and 1/>64 ug/ml, respectively.

    Conclusion:

    MEM-VAB showed excellent in vitro activity against KPC-producing Enterobacteriaceae, lowering the meropenem MIC50 and MIC90 from 32 to 0.06 µg/ml, and >32 to 1 µg/ml, respectively. There were no significant differences in activity between species or KPC variant type.  VAB restores the in vitro activity of MEM against this large collection of recent clinical isolates of KPC-producing Enterobacteriaceae.

    Meredith Hackel, PhD, MPH, Robert Badal, BS and Dan Sahm, PhD, International Health Management Associates, Inc., Schaumburg, IL

    Disclosures:

    M. Hackel, IHMA, Inc.: Independent Contractor , Research support

    R. Badal, IHMA, Inc.: Independent Contractor , Research support

    D. Sahm, IHMA, Inc.: Independent Contractor , Research support

    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.