Phage Therapy in Cystic Fibrosis. Challenges and Perspectives

Multidrug-resistant Pseudomonas aeruginosa (MDR PA) produces biofilm thus causing colonization, pulmonary failure and death in patients with cystic fibrosis (CF). Despite prolonging CF survival, antibiotics fail to eradicate MDR PA. A therapeutic alternative is phage therapy (PT). During decades, although testing lytic phages improved their efficacy in vitro to lyse PA biofilm, how they can persistently act in vivo, even in personalized approaches, remain debatable. We report our appraised results from 22 papers on lytic phages tested in vitro and in vivo on pulmonary and non-pulmonary models infected by various PA strains. Challenges and perspectives on PT in CF to advance custom-based approaches to treat or prevent MDR PA, combined with or alternative to antibiotics, are then discussed. To overcome barriers in international regulatory bodies on phages as medicines, we claim a new definition of advanced phage biological therapy aiming to reach a global consensus thus advancing PT in CF.