Xeruborbactam and Nacubactam, New Perspectives for β-Lactamase Inhibitors: A Narrative Review

The global spread of multidrug-resistant Gram-negative bacteria has increased the need for β-lactamase inhibitors with broader activity. This narrative review examines nacubactam and xeruborbactam, two emerging inhibitors with distinct pharmacological and microbiological profiles. Nacubactam combines serine β-lactamase inhibition with PBP2 binding and β-lactam-enhancing activity, whereas xeruborbactam provides broader enzymatic coverage, including several clinically relevant metallo-β-lactamases and OXA carbapenemases. Their clinical development is also at different stages, with phase III efficacy data already available for nacubactam-based combinations, while xeruborbactam remains supported mainly by preclinical and phase I evidence. Rather than being interchangeable, nacubactam and xeruborbactam may therefore occupy distinct and potentially complementary roles in the future treatment of multidrug-resistant Gram-negative infections.