A molecular analysis of meropenem–vaborbactam non-susceptible KPC-producing Klebsiella pneumoniae

Author:

Yasmin Mohamad1ORCID,Marshall Steven H.1,Chen Liang2ORCID,Rhoads Daniel D.3ORCID,Jacobs Michael R.4ORCID,Rojas Laura J.156ORCID,Perez Federico1,Hujer Andrea M.17,Hujer Kristine M.17,van Duin David8ORCID,Fowler Vance9,Chambers Henry F.10,Kreiswirth Barry N.2ORCID,Bonomo Robert A.156711ORCID,

Affiliation:

1. Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA

2. Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA

3. Department of Pathology, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, USA

4. Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

5. Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

6. Case Western Reserve University–Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, Ohio, USA

7. Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

8. Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA

9. Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA

10. Department of Medicine, University of California San Francisco, San Francisco, California, USA

11. Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

Abstract

ABSTRACT We characterized the molecular determinants of meropenem–vaborbactam (MV) non-susceptibility among non-metallo-β-lactamase-producing KPC- Klebsiella pneumoniae (KPC- KP ). Whole-genome sequencing was performed to identify mutations associated with MV non-susceptibility. Isolates with elevated MV MICs were found to have mutations encoding truncated or altered OmpK36 porins and increased bla KPC copy numbers. KPC- KP isolates with decreased susceptibility to MV were detected among a collection of isolates predating the availability of MV.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

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