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

Taniborbactam, a bicyclic boronate β-lactamase inhibitor with activity against <i>Klebsiella pneumoniae</i> 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 <i>K. pneumoniae</i> and 197 multidrug-resistant (MDR) <i>Pseudomonas aeruginosa</i> to cefepime-taniborbactam and comparators was determined by broth microdilution. For <i>K. pneumoniae</i> (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 <i>K. pneumoniae</i> 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 <i>P. aeruginosa</i>, 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 <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i> isolates. Of all 108 carbapenem-intermediate/resistant <i>P. aeruginosa</i> 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 <i>in vitro</i> activity comparable to ceftazidime-avibactam and greater than meropenem-vaborbactam against carbapenem-resistant <i>K. pneumoniae</i> and carbapenem-intermediate/resistant MDR <i>P. aeruginosa</i>.