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

Mohamad Yasmin; Steven H Marshall; Liang Chen; Daniel D Rhoads; Michael R Jacobs; Laura J Rojas; Federico Perez; Andrea M Hujer; Kristine M Hujer; David van Duin; Vance Fowler; Henry F Chambers; Barry N Kreiswirth; Robert A Bonomo; Antibacterial Resistance Leadership Group

doi:10.1128/aac.00208-24

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

Antimicrob Agents Chemother. 2024 Oct 8;68(10):e0020824. doi: 10.1128/aac.00208-24. Epub 2024 Aug 20.

Authors

Mohamad Yasmin¹, Steven H Marshall¹, Liang Chen², Daniel D Rhoads³, Michael R Jacobs⁴, Laura J Rojas^{1

5

6}, Federico Perez¹, Andrea M Hujer^{1

7}, Kristine M Hujer^{1

7}, David van Duin⁸, Vance Fowler⁹, Henry F Chambers¹⁰, Barry N Kreiswirth², Robert A Bonomo^{1

5

6

7

11

12

13}; Antibacterial Resistance Leadership Group

Affiliations

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.
¹² Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
¹³ Department of Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

PMID: 39162528
PMCID: PMC11459940 (available on 2025-02-20)
DOI: 10.1128/aac.00208-24

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.

Keywords: Klebsiella pneumoniae carbapenemase; OmpK35; OmpK36; Vabomere resistance; antimicrobial resistance; meropenem; meropenem vaborbactam resistance; vaborbactam.

MeSH terms

Anti-Bacterial Agents* / pharmacology
Bacterial Proteins* / genetics
Bacterial Proteins* / metabolism
Boronic Acids* / pharmacology
Drug Combinations
Drug Resistance, Multiple, Bacterial / genetics
Heterocyclic Compounds, 1-Ring
Humans
Klebsiella Infections / drug therapy
Klebsiella Infections / microbiology
Klebsiella pneumoniae* / drug effects
Klebsiella pneumoniae* / genetics
Meropenem* / pharmacology
Microbial Sensitivity Tests*
Mutation
Porins / genetics
Porins / metabolism
Whole Genome Sequencing*
beta-Lactamases* / genetics
beta-Lactamases* / metabolism

Substances

Meropenem
beta-Lactamases
Anti-Bacterial Agents
Boronic Acids
Bacterial Proteins
meropenem and vaborbactam
Porins
vaborbactam
OmpK36 protein, Klebsiella pneumoniae
Drug Combinations
Heterocyclic Compounds, 1-Ring

Abstract

MeSH terms

Substances

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