Advancing Phage Therapy for Chronic Infections: From Experimental Evidence to Clinical Use

Advancing Phage Therapy for Chronic Infections: From Experimental Evidence to Clinical Use

Joana Azeredo, University of Minho, Portugal

Chronic infections caused are often caused by biofilms that promote antimicrobial tolerance and persistence, making complete eradication difficult and limiting treatment success. Within these structured communities, limited phage diffusion, physiological heterogeneity, and the presence of phage-tolerant subpopulations restrict complete eradication. Using in vitro biofilm models, we show that adapted phages to biofilms improve activity within structured communities. Importantly, phage exposure selects bacterial subpopulations with reduced virulence traits, a phenomenon observed both in vitro and in vivo, which may contribute to improved clinical outcomes. Clinical implementation has been enabled through a magistral phage preparation pathway developed in collaboration with the Queen Astrid Military Hospital. In more than 20 chronic, difficult-to-treat cases, including lung infections, sustained clinical improvement was observed even without complete bacterial clearance. Together, these findings highlight the translational potential of phage therapy as a supportive strategy for managing chronic biofilm-associated infections.