1348. In vitro activity of plazomicin, a next-generation aminoglycoside, against carbapenemase-producing Klebsiella pneumoniae
Session: Poster Abstract Session: Novel Agents
Friday, October 5, 2018
Room: S Poster Hall
Posters
  • 1348_IDWPOSTER_PLAZOMICIN.pdf (829.1 kB)
  • Background: Plazomicin is a next-generation aminoglycoside with in vitro activity against multidrug resistant Gram-negative species, including carbapenem resistant isolates.  The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE) is a federally funded, prospective multi-center consortium of 20 hospitals from 9 US healthcare systems to track carbapenem-resistant Enterobacteriaceae.

    Methods: Minimum inhibitory concentrations (MICs) of plazomicin were determined by broth microdilution according to current CLSI guidelines against a collection of 697 carbapenem resistant Klebsiella pneumoniae with defined carbapenem resistance mechanisms, including KPC and OXA carbapenemases.  Isolates were submitted by participating CRACKLE centers.

    Results: Carbapenemases present in study isolates included KPC-2 (n=323), KPC-3 (n=364), KPC-4 (n=2), OXA-48 like (n=7) and NDM (n=1).  Plazomicin MICs ranged from ≤0.12 to >32 mg/L, with MIC50 and MIC90 values of 0.25 and 1 mg/L, respectively (Figure).   MICs of 689 (98.8%) isolates were ≤4 mg/L, while MICs of the remaining 8 isolates were >32 mg/L.  Plazomicin MICs were related to specific carbapenemases present in isolates: of 8 isolates with MICs >32 mg/L, 7 contained OXA-48 like and one contained KPC-3, suggesting that these isolates possess an aminoglycoside-resistance mechanism on the same plasmid as their carbapenemase gene, such as a 16S ribosomal RNA methyltransferase, against which plazomicin is not active.

    Conclusion: Plazomicin has good in vitro potency against a collection of carbapenemase-producing K. pneumoniae, with MIC90 value of 1 mg/L and MICs of ≤4 mg/L for 98.9% of isolates.

    Michael R. Jacobs, MD PhD1, Caryn E. Good, MA/MPH2, Ayman M. Abdelhamed, MD PhD3, Daniel D. Rhoads, MD3, Kristine M. Hujer, BS4,5, Andrea M. Hujer, BS4,5, Susan D. Rudin, BS4,5, T. Nicholas Domitrovic, MS4,5, Lynn Connolly, MD, PhD6, Kevin M. Krause, MBA6, Sandra S. Richter, MD7, David Van Duin, MD, PhD8, Barry N. Kreiswirth, PhD9, Robert A. Bonomo, MD4,5 and Antibiotic Resistance Leadership Group, (1)Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH, (2)Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH, (3)Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH, (4)Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, (5)Case Western Reserve University, Cleveland, OH, (6)Achaogen, Inc., South San Francisco, CA, (7)Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, (8)Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, (9)Public Health Research Institute, Rutgers New Jersey Medical School, Newark, NJ

    Disclosures:

    M. R. Jacobs, Achaogen: Investigator , Research grant . Shionogi: Investigator , Research grant .

    C. E. Good, None

    A. M. Abdelhamed, None

    D. D. Rhoads, None

    K. M. Hujer, None

    A. M. Hujer, None

    S. D. Rudin, None

    T. N. Domitrovic, None

    L. Connolly, Achaogen, Inc.: Consultant , Consulting fee .

    K. M. Krause, Achaogen: Employee , Salary .

    S. S. Richter, bioMerieux: Grant Investigator , Research grant . BD Diagnostics: Grant Investigator , Research grant . Roche: Grant Investigator , Research grant . Hologic: Grant Investigator , Research grant . Diasorin: Grant Investigator , Research grant . Accelerate: Grant Investigator , Research grant . Biofire: Grant Investigator , Research grant .

    D. Van Duin, achaogen: Scientific Advisor , Consulting fee . shionogi: Scientific Advisor , Consulting fee . Allergan: Scientific Advisor , Consulting fee . Astellas: Scientific Advisor , Consulting fee . Neumedicine: Scientific Advisor , Consulting fee . Roche: Scientific Advisor , Consulting fee . T2 Biosystems: Scientific Advisor , Consulting fee .

    B. N. Kreiswirth, None

    R. A. Bonomo, None

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