CO-PROTECT is a French-German project on antimicrobial resistances which aims to associate novel beta-lactam/beta-lactamase inhibitors (ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam) with other last resort antibiotics (colistin, eravacycline, fosfomycin, plazomycin) to prevent the emergence of resistances in multi-drug resistant Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia. Semi-mechanistic PK/PD modelling, integrating sequencing and metabolomics insights, will allow further characterization of combination therapies and guide the selection of best combination regimens.