Old and New Beta-Lactamase Inhibitors: Molecular Structure, Mechanism of Action, and Clinical Use

The beta-lactams have a central place in the antibacterial armamentarium, but the increasing resistance to these drugs, especially among Gram-negative bacteria, is becoming one of the major threats to public health worldwide. Treatment options are limited, and only a small number of novel antibiotics are in development. However, one of the responses to this threat is the combination of beta-lactam antibiotics with beta-lactamase inhibitors, which are successfully used in the clinic for overcoming resistance by inhibiting beta-lactamases. The existing inhibitors inactivate most of class A and C serine beta-lactamases, but several of class D and B (metallo-beta-lactamase) are resistant. The present review provides the status and knowledge concerning current beta-lactamase inhibitors and an update on research efforts to identify and develop new and more efficient beta-lactamase inhibitors.