In a world of increasing resistance, discovery of antibiotics acting on new, unexploited targets is an important medical need. In coworking with groups active in pharmaceutical chemistry or in pharmacognosy (within the institute or outside), we evaluate the activity of new compounds and try to decipher their mode of action. In this context, we have discovered with the CMFA group new inhibitors of peptidoglycan synthesis and with the GNOS group, agents reversing resistance to b-lactams in Staphylococcus aureus or active against Leishmania Mexicana Mexicana and Trypanosoma brucei brucei.
In collaboration with the team of JM Bolla at the Université Aix-Marseille (France), we are also evaluating the activity of original compounds originally designed as inhibitors of efflux but showing much broader synergistic effects with antibiotics, in our models of infections, including intracellular infections and activity against strains that show resistance to other antibiotic classes or mutations in their efflux systems.
Our clinical research aims at optimizing the scheme of administration of antibiotics in terms of ease of administration, safety, and efficacy, taking into account their pharmacodynamic properties.
At the present time, we are evaluating administration by continuous infusion or prolonged infusion of beta-lactams. More specifically, we perform pharmacokinetic studies in specific patients populations (like haemodialysis patients, critically-ill patients or children) in order to propose optimize therapeutic doses. We investigate the parameters that can affect protein binding of drugs, as only the unbound fraction is thought to be important for activity.