NXL04, a novel β-lactamase inhibitor with broad-spectrum activity

NXL104 (Novexel) is a novel non-beta-lactam inhibitor of beta-lactamases. It displays a broad-spectrum inhibition profile including both enzymes of class A (penicillinases, extended-spectrum beta-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-beta-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 beta-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. (C) 2010 Elsevier Masson SAS. All rights reserved.