Clinical and Translational Perspectives on Bacteriophage Therapy for Nontuberculous Mycobacterial Diseases

Abstract

Mycobacterium abscessus complex (MABC) infections are among the most intractable challenges in clinical mycobacteriology because of their extensive intrinsic and acquired antibiotic resistance. Recent studies on compassionate use and a systematic 20-patient cohort study demonstrated that bacteriophage therapy is safe and generally well-tolerated, and it has been proven capable of inducing clinically meaningful improvements. Nevertheless, patient outcomes remain heterogeneous, largely because of antibody-mediated neutralization during intravenous administration and morphotype-dependent susceptibility, with smooth variants exhibiting resistance to currently available phages. Notably, phage resistance has rarely been observed in treated isolates, suggesting that durable efficacy is achievable when guided by pretreatment susceptibility screening. Emerging strategies, including phage engineering, lytic enzyme application, and liposomal encapsulation, are being developed to overcome intracellular barriers and immune clearance, whereas phage-antibiotic combinations have displayed synergistic activity. POSTSTAMP, the first prospective clinical trial, is establishing a structured framework for standardized evaluation. Collectively, these findings suggest that current compassionate use cases and small-scale cohorts provide a foundation for integrating bacteriophage therapy as a complementary strategy alongside antibiotics in future MABC treatment regimens.