ARGONAUT-IV: susceptibility of carbapenemase-producing Klebsiella pneumoniae to the oral bicyclic boronate β-lactamase inhibitor ledaborbactam combined with ceftibuten.
Ledaborbactam (formerly VNRX-5236), a bicyclic boronate β-lactamase inhibitor with activity against class A, C, and D β-lactamases, is under development as an orally bioavailable etzadroxil prodrug (VNRX-7145) in combination with ceftibuten for the treatment of urinary tract infections. At ceftibuten breakpoints of ≤1 mg/L (EUCAST) and ≤8 mg/L (CLSI), 92.5% and 99.0%, respectively, of 200 carbapenem-resistant Klebsiella pneumoniae isolates, predominantly K. pneumoniae carbapenemase producing, were susceptible to ceftibuten-ledaborbactam (ledaborbactam tested at a fixed concentration of 4 mg/L) compared to 4.5% and 30.5%, respectively, to ceftibuten alone.
Authors
- Ayman M. Abdelhamed
- David A. Six (ORCID: https://orcid.org/0000-0002-9013-1711)
- Tsuyoshi Uehara (ORCID: https://orcid.org/0000-0001-6994-4286)
- Krisztina M. Papp‐Wallace (ORCID: https://orcid.org/0000-0002-9976-7898)
- Kristine M. Hujer
- Andrea M. Hujer (ORCID: https://orcid.org/0009-0001-3543-1826)
- Andrew R Mack (ORCID: https://orcid.org/0000-0002-0131-7996)
- 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)
- Greg Moeck (ORCID: https://orcid.org/0000-0001-7827-7227)
- Robin Patel (ORCID: https://orcid.org/0000-0001-6344-4141)
- David van Duin (ORCID: https://orcid.org/0000-0003-4784-3227)
- Michael R. Jacobs (ORCID: https://orcid.org/0000-0002-4235-7855)
- Robert A Bonomo
- Christopher R. Bethel
- Caryn E. Good
Institutions
- University of North Carolina at Chapel Hill (US)
Publication Details
- Journal
- UNC Libraries
- Published
- 2025-05-01
- DOI
- https://doi.org/10.17615/tde0-ye85
- Primary Topic
- Antibiotic Resistance in Bacteria
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Health and Human Services
- U.S. Department of Veterans Affairs
- Office of Research and Development
- Shionogi
- Wockhardt
- National Institutes of Health
- Biomedical Advanced Research and Development Authority
- Geriatric Research Education and Clinical Center
- National Institute of Allergy and Infectious Diseases
- NIH Clinical Center