Scientists at the Ineos Oxford Institute (IOI) have found a new potential combination therapy to combat antimicrobial resistance (AMR) by targeting two key bacterial enzymes involved in resistance. The study, “The Triple Combination of Meropenem, Avibactam, and a Metallo-β-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different β-Lactamase Producers,” has been published in Engineering.
This new study looked at a combination of three drugs: the β-lactam antibiotic meropenem, a newly developed MBL inhibitor called indole-2-carboxylate 58 (InC58), and an SBL inhibitor called avibactam (AVI).
“This study builds on our previous work to develop broad spectrum metallo β-lactamase inhibitors. Here we combatted multiple resistance mechanisms simultaneously to great effect, and this is a great example of how chemistry and microbiology teams can collaborate to develop new potential therapies. This combination therapy works very well in the lab and the next challenge will be to show that this works in infection models and ultimately in a hospital setting,” said Dr Alistair Farley, IOI Scientific Lead and a co-author for the study.
The team tested the effectiveness of the combination of all three compounds, compared to a combination of meropenem with either InC58 or AVI alone, on 51 strains of meropenem-resistant bacteria. Researchers compared the minimum inhibitory concentration (MIC) of the different drug combinations. The study found that the triple-drug combination was more effective at stopping growth of bacteria in the lab than either of the dual-drug combinations.
By University of Oxford
Article can be accessed on: phys.org