Cefepime-enmetazobactam: first approved cefepime-β- lactamase inhibitor combination for multi-drug resistant Enterobacterales

Cefepime-enmetazobactam is a β-lactam/β-lactamase inhibitor (BL/BLI) combination that has demonstrated potent activity against extended spectrum beta-lactamase (ESBL)-producing Enterobacterales, recently approved by the US FDA for the treatment of complicated urinary tract infections (cUTI) and by the European Medicines Agency and the UK Healthcare products Regulatory Agency for the treatment of cUTI, hospital-acquired pneumonia including ventilator-associated pneumonia and bacteremia in adults. Cefepime is a 4th generation cephalosporin with a broad spectrum bactericidal activity and enhanced stability to degradation by chromosomal and plasmid-mediated AmpC cephalosporinases as well as carbapenemase OXA-48 like enzymes. Enmetazobactam is a novel penicillanic acid sulfone β-lactamase inhibitor structurally similar to tazobactam with activity against CTX-M, TEM, and SHV ESBL, and other class A β-lactamases, that restores cefepime activity in vitro and in vivo against ESBLs-producing Enterobacterales. The targeted activity of cefepime-enmetazobactam against ESBLs infections which are resistant to common antibiotics, together with its superior results against piperacillin/tazobactam in a phase 3 trial make this new BL/BLI combination an effective carbapenem sparing option for the treatment of serious infections caused by ESBLs-producing Enterobacterales. In addition, if clinical data are supportive, cefepime-enmetazobactam has a potential role in the treatment of pathogens co-producing OXA-48 like enzymes along with ESBLs.