Avibactam
Avibactam is a non-β-lactam β-lactamase inhibitor developed by Actavis jointly with AstraZeneca. A new drug application for avibactam in combination with ceftazidime was approved by the FDA in 2015 for treating complicated Urinary [tract infection|urinary tract] and complicated intra-abdominal infections caused by antibiotic-resistant pathogens, including those caused by multidrug resistant Gram-negative bacterial pathogens.
Increasing resistance to cephalosporins among Gram-negative bacterial pathogens, especially among hospital-acquired infections, results in part from the production of β-lactamase enzymes that deactivate these antibiotics. While the co-administration of a β-lactamase inhibitor can restore antibacterial activity to the cephalosporin, previously approved β-lactamase inhibitors such as tazobactam and clavulanic acid do not inhibit important classes of β-lactamases, including Klebsiella pneumoniae carbapenemases, New Delhi metallo-β-lactamase 1, and AmpC-type β-lactamases. Whilst avibactam inhibits class A, class C, and some class D serine β-lactamases, it has been reported to be a poor substrate/weak inhibitor of class B metallo-β-lactamases, such as VIM-2, VIM-4, SPM-1, BcII, NDM-1, Fez-1.
For infections sustained by metallo-β-lactamases producing bacteria, a therapeutic strategy consists in administering avibactam as companion drug administered alongside aztreonam. In fact, although in theory aztreonam is not hydrolyzed by metallo-β-lactamases, many metallo-β-Lactamases-producing strains co-produce enzymes that could hydrolyze aztreonam, therefore avibactam is given to protect aztreonam exploiting its robust β-lactamases inhibition. Avibactam is available in a combination with aztreonam and with meropenem.