Diazabicyclooctanes (DBOs): a potent new class of non-β-lactam β-lactamase inhibitors

The beta-lactams have been among the most successful classes of antibacterial agents for the past half century. However, a disturbing increase in resistance to beta-lactams has been noted among Gram-negative bacteria, which is attributable to p-lactamase enzymes not within the spectrum of currently marketed beta-lactams or beta-lactam/beta-lactamase inhibitor combinations. Diazabicyclooctanes (DBOs) were first investigated as beta-lactam mimics in the mid-1990s by chemists at Hoechst Marion Roussel (now part of Sanofi-Aventis) and proved to be a rich source of beta-lactamase inhibitors (BLI). Two members of this novel series of highly potent, broad spectrum BLIs are now in clinical development and their properties are reviewed here.