The urgent need for metallo-ß-lactamase inhibitors: an unattended global threat.

ABSTRACT

Due to their superior tolerability and efficacy, ß-lactams are the most potent and prescribed class of antibiotics in the clinic. The emergence of resistance to those antibiotics, mainly due to the production of bacterial enzymes called ß-lactamases, has been partially solved by the introduction of ß-lactamase inhibitors, which restore the activity of otherwise obsolete molecules. This solution is limited because currently available ß-lactamase inhibitors only work against serine ß-lactamases, whereas metallo-ß-lactamases continue to spread, evolve, and confer resistance to all ß-lactams, including carbapenems. Furthermore, the increased use of antibiotics to treat secondary bacterial pneumonia in severely sick patients with COVID-19 might exacerbate the problem of antimicrobial resistance. In this Personal View, we summarise the main advances accomplished in this area of research, emphasise the main challenges that need to be solved, and the importance of research on inhibitors for metallo-B-lactamases amidst the current pandemic.