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. 2024 Dec 5;68(12):e0112724.
doi: 10.1128/aac.01127-24. Epub 2024 Oct 30.

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

Michael R Jacobs  1   2 , Caryn E Good  2 , Ayman M Abdelhamed  2 , Andrew R Mack  3   4 , Christopher R Bethel  4 , Steven H Marshall  4 , Andrea M Hujer  4   5 , Kristine M Hujer  4   5 , Robin Patel  6 , David van Duin  7 , Vance G Fowler  8 , Daniel D Rhoads  1   9 , David A Six  10 , Greg Moeck  10 , Tsuyoshi Uehara  10 , Krisztina M Papp-Wallace  1   4 , Robert A Bonomo  3   4   5   11   12
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ARGONAUT-IV: susceptibility of carbapenemase-producing Klebsiella pneumoniae to the oral bicyclic boronate β-lactamase inhibitor ledaborbactam combined with ceftibuten

Michael R Jacobs et al. Antimicrob Agents Chemother. .

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.

Keywords: Klebsiella pneumoniae; VNRX 7145; beta-lactamase inhibitor; bicyclic boronate; boronic acid; boronic acid inhibitor; ceftibuten; ledaborbactam.

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Conflict of interest statement

Robert A. Bonomo reports a grant from Entasis and grants from Merck, Wockhardt, and Shionogi outside the submitted work.

Figures

Fig 1
Fig 1
Histogram of ceftibuten-ledaborbactam MICs of K. pneumoniae by carbapenemase type. Upper panel shows MICs of isolates with KPC-2 and KPC-3. Lower panel shows MICs of isolates with other carbapenem resistance mechanisms.
See this image and copyright information in PMC

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