U1070 participates to the CO-ACTION, funded by the French ANR (Agence Nationale de la Recherche) within the framework of JPIAMR
The CO-ACTION project aims to develop and provide a framework for evaluating and validating the effectiveness of antibiotic and non-antibiotic combinations (COMs) in the preclinical setting based on pharmacokinetic/pharmacodynamic principles. The interaction between existing antibiotics from at least 6 different classes will be determined for Gram-negative multidrug-resistant strains and analysed by interaction modelling. Synergistic COMs will be further quantified using time-kill curves and applying mechanistic PKPD modelling to predict effective dosing regimens in vivo. Mechanisms of interaction and potential emergence of resistance will be explored. Effectiveness of the most promising 3-6 COMs will be determined in up to 5 available animal model systems. The potential of the COMs in patients will be evaluated by Monte Carlo Simulations using derived PKPD relationships, PD targets and suggest clinical breakpoints for COMs.
Collaborators: Johan Mouton (coordinator), Erasmus University, Lena Friberg, Uppsal University, Francoise van Bambeke, Université Catholique de Louvain, William Couet, Université de Poitiers and Inserm U1070, Alain Bousquet-Melou, National veterinary school INRA, Toulouse.