Aztreonam-avibactam: an option against carbapenem-resistant Enterobacterales with emerging resistance.

The Enterobacterales are an order of Gram-negative bacteria comprising a few major human pathogens such as Escherichia coli and Klebsiella pneumoniae . However, carbapenem-resistant En-terobacterales (CRE) has risen as an urgent threat for human health, leading to high mortality with very limited antimicrobial options. The main mechanism mediating resistance to β - lactams including carbapenems in the Enterobacterales is production of β -lactamases, which are two categories of enzymes capable of hydrolyzing β -lactams: serine β -lactamases and metallo-β -lactamases (MBLs). Avibactam (AVI) is a non-β -lactam β - lactamase inhibitor able to inhibit almost all serine β -lactamases but not MBLs.AVI in combination with ceftazidime (CAZ) has been approved for treating infections caused by CRE but CAZ-AVI has no activities against those producing MBLs. Currently, no MBL inhibitors have been approved for clinical use. Aztreonam (ATM), a monobactam, is stable to the hydrolysis of MBLs,and AVI can protect ATM from the inactivation by serine β -lactamases. The ATM- AVIcombinationmaythereforebeaviablechoiceagainstCREpro-ducing