Durlobactam is a new member of the diazabicyclooctane class of β-lactamase inhibitors with broad spectrum activity against Ambler class A, C, and D
serine β-lactamases.
Sulbactam is a first generation β-lactamase inhibitor with activity limited to a subset of class A
enzymes that also has direct-acting antibacterial activity against Acinetobacter spp. The latter feature is due to
sulbactam's ability to inhibit certain
penicillin-binding proteins, essential
enzymes involved in bacterial cell wall synthesis in this pathogen. Because
sulbactam is also susceptible to cleavage by numerous β-lactamases, its clinical utility for the treatment of contemporary
Acinetobacter infections is quite limited. However, when combined with
durlobactam, the activity of
sulbactam is effectively restored against these notoriously multidrug-resistant strains. This
sulbactam-durlobactam combination is currently in late-stage development for the treatment of Acinectobacter
infections, including those caused by
carbapenem-resistant isolates, for which there is a high unmet medical need. The following mini-review summarizes the molecular drivers of efficacy of this combination against this troublesome pathogen, with an emphasis on the biochemical features of each partner.