1. ARGONAUT-IV: susceptibility of carbapenemase-producing Klebsiella pneumoniae to the oral bicyclic boronate β-lactamase inhibitor ledaborbactam combined with ceftibuten.
- Author
-
Jacobs MR, Good CE, Abdelhamed AM, Mack AR, Bethel CR, Marshall SH, Hujer AM, Hujer KM, Patel R, van Duin D, Fowler VG, Rhoads DD, Six DA, Moeck G, Uehara T, Papp-Wallace KM, and Bonomo RA
- Subjects
- Boronic Acids pharmacology, Humans, Klebsiella Infections drug therapy, Klebsiella Infections microbiology, Klebsiella pneumoniae drug effects, Microbial Sensitivity Tests, beta-Lactamases metabolism, Anti-Bacterial Agents pharmacology, Bacterial Proteins metabolism, beta-Lactamase Inhibitors pharmacology, Ceftibuten
- Abstract
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., Competing Interests: Robert A. Bonomo reports a grant from Entasis and grants from Merck, Wockhardt, and Shionogi outside the submitted work.
- Published
- 2024
- Full Text
- View/download PDF