NXL104, un nouvel inhibiteur de β-lactamases à large spectre

NXL104 (Novexel) is a novel non-β-lactam inhibitor of β-lactamases. It displays a broad-spectrum inhibition profile including both enzymes of class A (penicillinases, extended-spectrum β-lactamases [ESBLs] and some carbapenemases) and class C (cephalosporinases). It is generally combined with third-generation cephalosporins, in particular ceftazidime. The combination ceftazidime-NXL104 is actually very active against enterobacterial isolates (MICs usually less than 1 mg/l), even in the presence of ESBL (including CTX-M), overexpressed cephalosporinase (associated or not with impermeability), or KPC- and OXA-48-type carbapenemases. The major limit is the absence of inhibition of metallo-β-lactamases (e.g. IMP, VIM, NDM). Interestingly, several murine models have confirmed the in vitro activity of the combination ceftazidime-NXL104 which is currently in phase II clinical trials for the treatment of complicated urinary tract and intra-abdominal infections. Although this novel β-lactamase inhibitor is very promising in vitro and in vivo in animal models, the results of clinical trials are awaited and will be decisive for the future of this molecule.