ARGONAUT-IV: susceptibility of carbapenemase-producing Klebsiella pneumoniae to the oral bicyclic boronate β-lactamase inhibitor ledaborbactam combined with ceftibuten.

Autor: Jacobs MR; Case Western Reserve University, Cleveland, Ohio, USA.; University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA., Good CE; University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA., Abdelhamed AM; University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA., Mack AR; Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.; Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA., Bethel CR; Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA., Marshall SH; Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA., Hujer AM; Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.; Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA., Hujer KM; Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.; Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA., Patel R; Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA., van Duin D; Division of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina, USA., Fowler VG; Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA., Rhoads DD; Case Western Reserve University, Cleveland, Ohio, USA.; Department of Pathology, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, USA., Six DA; Venatorx Pharmaceuticals, Inc., Malvern, Pennsylvania, USA., Moeck G; Venatorx Pharmaceuticals, Inc., Malvern, Pennsylvania, USA., Uehara T; Venatorx Pharmaceuticals, Inc., Malvern, Pennsylvania, USA., Papp-Wallace KM; Case Western Reserve University, Cleveland, Ohio, USA.; Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA., Bonomo RA; Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.; Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.; Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.; Departments of Biochemistry, Pharmacology, Proteomics and Bioinformatics Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.; CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, Ohio, USA.
Jazyk: angličtina
Zdroj: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2024 Oct 30, pp. e0112724. Date of Electronic Publication: 2024 Oct 30.
DOI: 10.1128/aac.01127-24
Abstrakt: 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.
Databáze: MEDLINE