María C. Cumplí-Gargallo, Department of pneumology, Hospital del Mar, Barcelona, Spain
Patrick J. Hurley, Department of pneumology, Hospital del Mar, Barcelona, Spain
Jose G. González-García, Department of pneumology, Hospital del Mar, Barcelona, Spain
Marisol Domínguez-Álvarez, Department of pneumology, Hospital del Mar; Department of Medicine and Life Sciences, Universitat Pompeu Fabra; Hospital del Mar Research Institute. Barcelona, Spain
This review explores the potential of bacteriophage therapy as an emerging strategy against mycobacterial infections, including Mycobacterium tuberculosis and non-tuberculous mycobacteria. Conventional treatments for these pathogens are prolonged, poorly tolerated, and increasingly ineffective due to multidrug- and extensively drug-resistant strains, highlighting the urgent need for innovative alternatives. Bacteriophages, viruses that specifically infect and lyse bacteria, offer a targeted and adaptable alternative or adjunct to antibiotics. The review summarizes the biology of mycobacteriophages, methods for their isolation and formulation, and mechanisms of bacterial lysis. It also compiles preclinical and clinical evidence supporting their efficacy in reducing bacterial burden, enhancing antibiotic susceptibility and improving outcomes, particularly in refractory Mycobacterium abscessus infections. Despite promising advances, challenges such as phage resistance, host immune responses, and regulatory inconsistencies remain. Well-designed clinical trials and standardized production protocols are essential to translate this therapy into clinical practice.