A molecular analysis of meropenem–vaborbactam non-susceptible KPC-producing <i>Klebsiella pneumoniae</i>
We characterized the molecular determinants of meropenem-vaborbactam (MV) non-susceptibility among non-metallo-β-lactamase-producing KPC-<i>Klebsiella pneumoniae</i> (KPC-<i>KP</i>). 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 <i>bla</i><sub>KPC</sub> copy numbers. KPC-<i>KP</i> isolates with decreased susceptibility to MV were detected among a collection of isolates predating the availability of MV.
Authors
- Robert A. Bonomo (ORCID: https://orcid.org/0000-0002-3299-894X)
- Kristine M. Hujer
- Henry F. Chambers (ORCID: https://orcid.org/0000-0001-5317-4491)
- Andrea M. Hujer (ORCID: https://orcid.org/0009-0001-3543-1826)
- Barry N. Kreiswirth (ORCID: https://orcid.org/0000-0002-0243-131X)
- Vance G. Fowler (ORCID: https://orcid.org/0000-0002-8048-0897)
- Steven H. Marshall (ORCID: https://orcid.org/0009-0003-1811-2633)
- Daniel D. Rhoads (ORCID: https://orcid.org/0000-0002-7636-5191)
- David van Duin (ORCID: https://orcid.org/0000-0003-4784-3227)
- Michael R. Jacobs (ORCID: https://orcid.org/0000-0002-4235-7855)
- Mohamad Yasmin (ORCID: https://orcid.org/0000-0002-5859-1769)
- Liang Chen (ORCID: https://orcid.org/0000-0001-5845-2235)
- Laura J. Rojas (ORCID: https://orcid.org/0000-0003-4410-1658)
- Federico Pérez
Institutions
- University of North Carolina at Chapel Hill (US)
- Duke University (US)
- University of California, San Francisco (US)
- Cleveland Clinic Lerner College of Medicine (US)
- Clinical Research Institute (US)
- Louis Stokes Cleveland VA Medical Center (US)
- Hackensack Meridian Health (US)
- University School (US)
- Center for Discovery (US)
- Case Western Reserve University (US)
Publication Details
- Journal
- Antimicrobial Agents and Chemotherapy
- Published
- 2024-08-20
- DOI
- https://doi.org/10.1128/aac.00208-24
- Citations
- 6
- Primary Topic
- Antibiotic Resistance in Bacteria
- Type
- article
- Field-Weighted Citation Impact
- 1.02
Funders
- U.S. Department of Veterans Affairs
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases