Bacteriophage therapy in the era of antimicrobial resistance: clinical evidence, translational challenges, and emerging regulatory frameworks (2020–2026)

Abstract

Antimicrobial resistance has intensified the search for alternatives to conventional antibiotics, particularly against multidrug-resistant bacterial pathogens that increasingly compromise treatment outcomes in hospitals and community settings. This narrative review examines bacteriophage therapy as an alternative for combating multidrug-resistant bacteria. Recent literature is discussed thematically, with emphasis on original studies, clinical datasets, translational experiments, and regulatory documents. The current evidence base consists predominantly of compassionate-use reports, small cohorts, and early-phase trials, including CRISPR-enhanced and inhaled phage platforms, which report safety observations, compartment-specific responses, and microbiome effects in individual studies. Mechanistic considerations discussed in the review include route-specific delivery, phage–host ecological interactions, resistance trade-offs, and phage–antibiotic synergy. While microbiological and clinical responses have been reported in individual studies, no confirmatory randomized trial has demonstrated clinical efficacy for any phage therapy indication. Manufacturing, standardization, and regulatory pathways for scaled deployment also remain unresolved. Regulatory developments in Europe, the United Kingdom, the United States, and Australia remain heterogeneous and predominantly access-based or compassionate-use-based rather than approval-based. Specific technical challenges include incomplete standardization of susceptibility testing and the need for robust monitoring of immune neutralization, endotoxin burden, and long-term ecological effects. Routine clinical adoption of phage therapy will ultimately depend on outcomes of adequately powered confirmatory trials, alongside resolution of manufacturing, regulatory, and standardization challenges.