1360. Antimicrobial Activity of Cefepime in Combination with VNRX-5133 Against a Global Collection of Enterobacteriaceae Including Resistant Phenotypes
Session: Poster Abstract Session: Novel Agents
Friday, October 5, 2018
Room: S Poster Hall
Posters
  • VenatoRx_P92_FEP 5133 Global Ent_IDSA 2018_FINAL.pdf (218.9 kB)
  • Background: VNRX-5133 is a novel cyclic boronate-based broad-spectrum β-lactamase inhibitor with potent and selective direct inhibitory activity against both serine- and metallo-β-lactamases (Ambler Classes A, B, C and D). In this analysis, we evaluated the activity of cefepime (FEP) in combination with VNRX-5133 and comparators against 1,120 recent Enterobacteriaceae clinical isolates, including carbapenem-resistant strains.

    Methods: MICs of FEP with VNRX-5133 fixed at 4 µg/mL (FEP/VNRX-5133) were determined following CLSI M07-A10 guidelines against 1,120 Enterobacteriaceae from community and hospital infections collected globally in 2012-2013. Resistant phenotypes were based on 2017 CLSI breakpoints. As FEP/VNRX-5133 breakpoints have not yet been established, the FEP 2 g q8h susceptible dose dependent (SDD) breakpoint of ≤8 µg/mL was considered for comparative purposes.

    Results: FEP/VNRX-5133 showed potent in vitro activity against drug resistant subsets of Enterobacteriaceae, with MIC90 values ranging from 1 µg/mL against ceftazidime-, levofloxacin-, or piperacillin-tazobactam-nonsusceptible isolates, to 8 µg/mL against meropenem-nonsusceptible isolates. FEP/VNRX-5133 inhibited >93% of all resistant subsets at ≤8 µg/mL.

    Conclusion: Cefepime in combination with VNRX-5133 demonstrated potent in vitro activity against Enterobacteriaceae, including cephalosporin-, fluoroquinolone- and carbapenem-resistant (CRE) isolates. Because this drug combination exhibited substantial potential for the treatment of infections caused by isolates often resistant to first line therapy, further development is warranted.

    Meredith Hackel, Ph.D, IHMA, Inc., Schaumburg, IL and Dan Sahm, PhD, International Health Management Associates, Inc., Schaumburg, IL

    Disclosures:

    M. Hackel, IHMA, Inc.: Employee , Salary . VenatoRx: Consultant , Consulting fee .

    D. Sahm, IHMA, Inc.: Employee , Salary . VenatoRx: Consultant , Consulting fee .

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