Engineering the Phage Revolution: Advances in Bacteriophage Therapy for the Antimicrobial Resistance Era

The global antimicrobial resistance (AMR) crisis has accelerated the search for novel antimicrobial solutions. Bacteriophages are gaining renewed attention for their host specificity, self-replication, and proven efficacy against multidrug-resistant and biofilm-associated infections. AMR caused an estimated 1.27 million deaths in 2019, projected to exceed 10 million people per year by 2050 if unchecked. This review highlights recent progress in phage biology, engineering, and clinical translation. Synthetic biology tools, including CRISPR-based editing and AI-assisted genome design, are expanding phage host range and safety. However, pharmacokinetic challenges like rapid systemic clearance call for advanced delivery platforms such as liposomal and polymeric carriers. Ongoing Phase 2/3 clinical trials targeting Pseudomonas aeruginosa and carbapenem-resistant Klebsiella pneumoniae demonstrate therapeutic potential, particularly when used with antibiotics. Regulatory bodies, including the US FDA, the European Medicines Agency and the European Directorate for the Quality of Medicines & HealthCare, are developing frameworks and standards to support clinical adoption. Together, these advances position bacteriophages as promising next-generation tools for targeted antimicrobial therapy and highlight the importance of global collaboration to transform personalized treatments into scalable and standardized clinical applications.