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. 2024 Sep 4;68(9):e0075124.
doi: 10.1128/aac.00751-24. Epub 2024 Aug 12.

ARGONAUT-III and -V: susceptibility of carbapenem-resistant Klebsiella pneumoniae and multidrug-resistant Pseudomonas aeruginosa to the bicyclic boronate β-lactamase inhibitor taniborbactam combined with cefepime

Michael R Jacobs  1   2 , Ayman M Abdelhamed  2 , Caryn E Good  2 , Andrew R Mack  3   4 , Christopher R Bethel  4 , Steven 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
Affiliations

ARGONAUT-III and -V: susceptibility of carbapenem-resistant Klebsiella pneumoniae and multidrug-resistant Pseudomonas aeruginosa to the bicyclic boronate β-lactamase inhibitor taniborbactam combined with cefepime

Michael R Jacobs et al. Antimicrob Agents Chemother. .

Abstract

Taniborbactam, a bicyclic boronate β-lactamase inhibitor with activity against Klebsiella pneumoniae carbapenemase (KPC), Verona integron-encoded metallo-β-lactamase (VIM), New Delhi metallo-β-lactamase (NDM), extended-spectrum beta-lactamases (ESBLs), OXA-48, and AmpC β-lactamases, is under clinical development in combination with cefepime. Susceptibility of 200 previously characterized carbapenem-resistant K. pneumoniae and 197 multidrug-resistant (MDR) Pseudomonas aeruginosa to cefepime-taniborbactam and comparators was determined by broth microdilution. For K. pneumoniae (192 KPC; 7 OXA-48-related), MIC90 values of β-lactam components for cefepime-taniborbactam, ceftazidime-avibactam, and meropenem-vaborbactam were 2, 2, and 1 mg/L, respectively. For cefepime-taniborbactam, 100% and 99.5% of isolates of K. pneumoniae were inhibited at ≤16 mg/L and ≤8 mg/L, respectively, while 98.0% and 95.5% of isolates were susceptible to ceftazidime-avibactam and meropenem-vaborbactam, respectively. For P. aeruginosa, MIC90 values of β-lactam components of cefepime-taniborbactam, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam were 16, >8, >8, and >4 mg/L, respectively. Of 89 carbapenem-susceptible isolates, 100% were susceptible to ceftolozane-tazobactam, ceftazidime-avibactam, and cefepime-taniborbactam at ≤8 mg/L. Of 73 carbapenem-intermediate/resistant P. aeruginosa isolates without carbapenemases, 87.7% were susceptible to ceftolozane-tazobactam, 79.5% to ceftazidime-avibactam, and 95.9% and 83.6% to cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively. Cefepime-taniborbactam at ≤16 mg/L and ≤8 mg/L, respectively, was active against 73.3% and 46.7% of 15 VIM- and 60.0% and 35.0% of 20 KPC-producing P. aeruginosa isolates. Of all 108 carbapenem-intermediate/resistant P. aeruginosa isolates, cefepime-taniborbactam was active against 86.1% and 69.4% at ≤16 mg/L and ≤8 mg/L, respectively, compared to 59.3% for ceftolozane-tazobactam and 63.0% for ceftazidime-avibactam. Cefepime-taniborbactam had in vitro activity comparable to ceftazidime-avibactam and greater than meropenem-vaborbactam against carbapenem-resistant K. pneumoniae and carbapenem-intermediate/resistant MDR P. aeruginosa.

Keywords: Klebsiella pneumoniae; Pseudomonas aeruginosa; beta-lactamase inhibitor; bicyclic boronate; cefepime taniborbactam; taniborbactam.

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Conflict of interest statement

Robert A. Bonomo reports grants from Venatorx, Entasis, Merck, Wockhardt, and Shionogi outside the submitted work. David A. Six, Greg Moeck, and Tsuyoshi Uehara are employees of Venatorx Pharmaceuticals, Inc.

Figures

Fig 1
Fig 1
Histogram of cefepime-taniborbactam MICs of K. pneumoniae by carbapenemase type.
Fig 2
Fig 2
Histogram of cefepime-taniborbactam MICs of P. aeruginosa by carbapenem resistance mechanism.
See this image and copyright information in PMC

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