Recent Emergence of Aztreonam-Avibactam Resistance in NDM and OXA-48 Carbapenemase-Producing Escherichia coli in Germany

The continuing surge of carbapenem-resistant Enterobacterales (CRE) worldwide is a challenging problem of antimicrobial resistance today. The introduction of ceftazidime-avibactam (CZA) was an important step in the treatment of infections caused by CPE. Avibactam restores ceftazidime activity against carbapenemase-producing Enterobacterales of Ambler class A (KPC) and of Ambler class D (OXA-48 and 48-like), which are all serine β-lactamases. However, avibactam as well as the other β-lactam inhibitors currently in clinical use do not inhibit metallo-β-lactamases (MBLs) such as the carbapenemases of Ambler class B. Aztreonam is stable to hydrolysis by MBLs, a unique feature compared with other β-lactams but is generally cleaved by other clinically relevant serine β-lactamases (1). Therefore, aztreonam/avibactam (ATM-AVI) is a drug combination currently undergoing clinical trials to assess its efficacy in treating infections with Gram-negative bacteria, including those that produce MBLs (2). As many Enterobacterales that produce an MBL often coproduce a serine-β-lactamase, a combination of aztreonam with avibactam offers an effective alternative to treating those CRE infections (3).