Determination of MIC Quality Control Ranges for Ceftibuten-Avibactam (Fixed 4 μg/mL), a Novel β-Lactam/β-Lactamase Inhibitor Combination

Abstract

Ceftibuten/ARX-1796 (avibactam prodrug) is a novel oral antibacterial combination in early clinical development for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis. ARX-1796 is the novel avibactam prodrug being combined with ceftibuten for oral dosing that is converted to active avibactam in vivo .

Antibacterial Prodrugs to Overcome Bacterial Antimicrobial Resistance

“…Ceftibuten ( 23 , Figure 8 ), an orally active 3rd generation cephalosporin, is already approved for the treatment of infections caused by H. influenzae , H. parainfluenzae , M. catarrhalis , and penicillin-susceptible S. pneumoniae , having already shown clinical efficiency in the treatment of uncomplicated UTIs. The addition of the β -lactamase inhibitor avibactam ( 24 , Figure 8 ) leads to the broadening of the spectrum of Gram-negative pathogens that are susceptible to the drug, including β -lactamase-producing Enterobacterales [ 27 , 29 , 30 ]. A study carried out by Sader et al [ 30 ] determined MIC 50 and MIC 90 values of 0.03 and 0.06 µg/mL, respectively, for the ceftibuten-avibactam combination against 3216 Enterobacterales.…”

“… Structure of TBP-PI-HBR ( 22 ), ceftibuten ( 23 ), and avibactam ( 24 ) [ 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. …”