Metallo-beta-lactamase inhibitors: promise for the future?

Carbapenem resistance continues to erode the effectiveness of antibiotics such as imipenem and meropenem in the clinic. Resistance mechanisms can include interplay between porin loss (membrane permeability), mutation of penicillin binding proteins necessary for cell division, and expression of class A, B and D beta-lactamases. Bacterial resistance to beta-lactams such as penicillin or amoxicillin has been overcome in the clinic using several strategies, including development of antibiotics not susceptible to hydrolysis by beta-lactamases, or co-administration of the antibiotic with beta-lactamase inhibitors. This overview will focus on progress since 2000 in identifying inhibitors of class B, or metallo-beta-lactamases with the aim of reversing carbapenem resistance.