Non-tuberculous mycobacteria (NTM) can cause chronic lung infections in people with cystic fibrosis (CF). Mycobacterium abscessus (Mab) and M. avium (MAC) are the most frequently isolated species. The currently available treatments against NTM infections can be prolonged and complex, not always leading to NTMs’ eradication. NTMs form biofilms (i.e. a protective matrix containing aggregations of bacterial colonies) within the epithelia of the CF lung alveoli; wrapped inside the biofilm, NTMs do not replicate, resulting “dormant” and less sensitive to drugs. It is necessary to find drugs’ combinations that affect NTMs even when wrapped in biofilms, as well as in the replicative phase. In this project, models of NTM in the replicative and non-replicative phase will be created in vitro, through a collection from CF patients in 32 Italian laboratories: new drug combinations (from two to four compounds) will be tested against them. The goal is to find at least one combination that kills Mab and MAC in vitro at any stage, in order to clinically shorten the prolonged todays’ therapies. The compound will be tested in animal models and, since these are antibacterial molecules, already on the market, the transition to clinical trials may be somewhat quicker.