781. In Vitro Antibacterial Activity of Meropenem/RPX7009, (a Carbapenem/-lactamase Inhibitor Combination) against Contemporary Enterobacteriaceae (ENT) Isolated from Intra-abdominal (IAI) and Urinary Tract Infections (UTI) in the United States (USA)
Session: Poster Abstract Session: Antimicrobial Agents: Novel Agents
Friday, October 9, 2015
Room: Poster Hall
Posters
  • IDWeek15 Carbavance 781 Final.pdf (315.4 kB)
  • Background: We evaluated the in vitro activity of meropenem (MER) RPX7009 (RPX), a serine-β-lactamase inhibitor against consecutive clinical isolates of ENT obtained from IAI and UTI during 2014 in the USA. MIC testing included susceptible, carbapenem-resistant ENT (CRE), ESBL phenotype, and MER non-susceptible (NS) K. pneumoniae (KPN) isolates.

    Methods: 1755 ENT were tested for MICs against MER RPX (fixed 8 g/mL) and comparators using CLSI broth microdilution methodology.

    Results: Against 1273 ENT from UTI, MER and MER/RPX both displayed MIC50/90 values of ≤0.015/0.06 g/mL (MIC ranges were ≤0.015-32 and ≤0.015-0.5 g/mL, respectively). 100/100% of ENT from UTI were inhibited at ≤1/≤2 g/mL of MER (CLSI/EUCAST Susceptible [S] breakpoints) in the presence of 8 g/ml of RPX. Similarly, 99.4/99.6% of ENT from IAI (482) were inhibited at ≤1/≤2 g/mL of MER in combination with 8 g/mL of RPX. Against 16 isolates of CRE and 13 isolates of MER-NS KPN from UTI (Table), RPX in combination with MER restored MER MICs to ≤0.5 g/mL (MIC90 0.5 g/mL). Susceptibility rates for comparator compounds against CRE were 62.5, 0, 0, and 12.5% for minocycline (MIN), piperacillin/tazobactam (P/T), ceftazidime (CAZ), and levofloxacin (LVX), respectively. Susceptibility rates for comparator compounds against MER-NS KPN were 69.2, 0, 0, and 7.7% for MIN, P/T, CAZ, and LVX, respectively. Against ENT displaying an ESBL-phenotype, MER/RPX MIC90 values were 2-fold lower than MER and the highest MER/RPX MIC observed was 0.5 g/mL.

    Conclusion: MER/RPX shows high activity against clinical isolates from UTIs and IAIs including those caused by CRE, MER-NS KPN, and isolates demonstrating an ESBL-phenotype that are often resistant to multiple antimicrobial agents. Clinical trials are in progress.

    Organism group,

    (Infection type, no. tested)

    Antimicrobial

    agent

    MIC (g/mL)

    MIC

    range

    MIC50

    MIC90

    CRE, (UTI, 16)

    MER

    4->32

    16

    >32

    MER/RPX

    ≤0.015-0.5

    0.03

    0.5

    MIN

    1->8

    4

    >8

    P/T

    >64

    >64

    >64

    CAZ

    32->32

    >32

    >32

    LVX

    0.25->4

    >4

    >4

    ENT ESBL-phenotype

    MER

    ≤0.015-8

    ≤0.015

    0.06

    (UTI, 86)

    MER/RPX

    ≤0.015-0.5

    ≤0.015

    0.03

    MIN

    0.25->8

    1

    >8

    P/T

    1->64

    4

    32

    CAZ

    0.25-32

    16

    >32

    LVX

    ≤0.12->4

    >4

    >4

    MER-NS KPN

    MER

    4->32

    16

    >32

    (UTI, 13)

    MER/RPX

    ≤0.015-0.5

    0.03

    0.5

    MIN

    1->8

    4

    8

    P/T

    >64

    >64

    >64

    CAZ

    >32

    >32

    >32

    LVX

    0.25->4

    >4

    >4

    Michael D. Huband, BS, Robert K. Flamm, PhD, Paul R. Rhomberg, BS, Ronald N. Jones, MD and Mariana Castanheira, PhD, JMI Laboratories, Inc., North Liberty, IA

    Disclosures:

    M. D. Huband, The Medicines Company: Research Contractor , Research support

    R. K. Flamm, The Medicines Company: Research Contractor , Research support

    P. R. Rhomberg, The Medicines Company: Research Contractor , Research support

    R. N. Jones, The Medicines Company: Research Contractor , Research support

    M. Castanheira, The Medicines Company: Research Contractor , Research support

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