No in vitro activity of cefiderocol against OXA-427-producing Enterobacterales

The prevalence of carbapenem resistance in Enterobacterales is increasing worldwide due to a rapid spread of plasmid-mediated resistance mechanisms. Although new agents have been developed, such as β-lactam/β-lactamase inhibitor combinations, most of these agents have almost no activity against metallo-β-lactamases (MBLs) and limited activity against class D β-lactamases.1 Cefiderocol is a parenteral siderophore cephalosporin with activity against carbapenem-resistant Gram-negative bacteria, including Enterobacterales and non-fermenters.2–6 In contrast to the aforementioned novel agents, the chemical structure of cefiderocol is intrinsically stable against a broad range of resistance mechanisms, such as Ambler class A, B, C and D β-lactamases, including MBLs and oxacillinases (OXA enzymes).2–6 Therefore, cefiderocol has broader activity against MDR Enterobacterales compared with new β-lactam/β-lactamase inhibitor combinations. In 2017, a novel type of carbapenem-hydrolysing class D β-lactamase, OXA-427, was identified in different Enterobacterales.7 It confers resistance to penicillins and extended-spectrum cephalosporins, and reduced susceptibility to carbapenems.8...