Citations 3
ARGONAUT-IV: susceptibility of carbapenemase-producing Klebsiella pneumoniae to the oral bicyclic boronate β-lactamase inhibitor ledaborbactam combined with ceftibuten
Jacobs, Michael R. , Good, Caryn E., Abdelhamed, Ayman M., Mack, Andrew R , Bethel, Christopher R. , Marshall, Steven H. , Hujer, Andrea M. , Hujer, Kristine M., Patel, Robin , Fowler, Vance G., Rhoads, Daniel D. , Six, David A. , Papp‐Wallace, Krisztina M. , van Duin, David , Rhoads, Daniel D , Six, David A , Moeck, Greg , Uehara, Tsuyoshi , Papp-Wallace, Krisztina M , Bonomo, Robert A , Patel, Robin , Hujer, Kristine M., Fowler, Vance G. , Uehara, Tsuyoshi , Bonomo, Robert A.
Antimicrobial Agents and Chemotherapy | October 30, 2024 | Volume: 68 | Issue: 12 | Pages: No page available
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.
ARGONAUT-III and -V: susceptibility of carbapenem-resistant Klebsiella pneumoniae and multidrug-resistant Pseudomonas aeruginosa to the bicyclic boronate β-lactamase inhibitor taniborbactam comb
Jacobs, Michael R. , Abdelhamed, Ayman M., Good, Caryn E., Mack, Andrew R , Bethel, Christopher R. , Marshall, Steven H. , Hujer, Andrea M. , Hujer, Kristine M., Patel, Robin , Fowler, Vance G. , Rhoads, Daniel D. , Six, David A. , Uehara, Tsuyoshi , Papp‐Wallace, Krisztina M. , van Duin, David , Rhoads, Daniel D , Six, David A , Moeck, Greg , Uehara, Tsuyoshi , Papp-Wallace, Krisztina M , Bonomo, Robert A , Patel, Robin , Fowler, Vance G. , Bonomo, Robert A.
Antimicrobial Agents and Chemotherapy | August 12, 2024 | Volume: 68 | Issue: 9 | Pages: No page available
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), MIC 90 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 , MIC 90 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 .
ARGONAUT II Study of the In Vitro Activity of Plazomicin against Carbapenemase-Producing Klebsiella pneumoniae
Good, Caryn E., Hujer, Andrea M. , Abdelhamed, Ayman M., Rhoads, Daniel D. , Hujer, Kristine M., Rudin, Susan D., Connolly, Lynn, Krause, Kevin M. , Patel, Robin , Arias, César A. , Kreiswirth, Barry N. , Rojas, Laura J. , D’Souza, Roshan , White, Richard C. , Brinkac, Lauren , Nguyen, Kevin , Singh, Indresh , Fouts, Derrick E. , Group, for the Antibacterial Resistance Leadership, Patel, Robin , Fouts, Derrick E , van Duin, David , Rhoads, Daniel D , Jacobs, Michael R. , Domitrovic, Tatiana , Arias, César A. , Kreiswirth, Barry N , Bonomo, Robert A. , Group, for the Antibacterial Resistance Leadership
Antimicrobial Agents and Chemotherapy | March 5, 2020 | Volume: 64 | Issue: 5 | Pages: No page available
Plazomicin was tested against 697 recently acquired carbapenem-resistant Klebsiella pneumoniae isolates from the Great Lakes region of the United States. Plazomicin MIC 50 and MIC 90 values were 0.25 and 1 mg/liter, respectively; 680 isolates (97.6%) were susceptible (MICs of ≤2 mg/liter), 9 (1.3%) intermediate (MICs of 4 mg/liter), and 8 (1.1%) resistant (MICs of >32 mg/liter). Resistance was associated with rmtF -, rmtB -, or armA -encoded 16S rRNA methyltransferases in all except 1 isolate.