Overcoming antimicrobial resistance: Phage therapy as a promising solution to combat ESKAPE pathogens

The global escalation of antimicrobial resistance (AMR) has intensified the search for alternative therapies, with bacteriophage (phage) therapy re-emerging as a promising solution. This review aims to critically evaluate the therapeutic potential of phage therapy against multidrug-resistant (MDR) ESKAPE pathogens, which are major contributors to hospital-acquired infections. The review discusses the distinct antibacterial strategies of phage namely, targeted lysis, enzymatic biofilm disruption, and synergy with antibiotics.

A comprehensive literature review was conducted focusing on the mechanisms of phage antibacterial activity and the molecular regulation of lytic and lysogenic life cycles, highlighting the therapeutic importance of the lytic-lysogenic switch. It also explores the integration of nanotechnology-based delivery systems that enhances therapeutic efficacy. Recent advances in phage engineering, including CRISPR-Cas technologies and synthetic biology approaches, were also analyzed to understand their contribution to optimizing phage efficacy.

Phage therapy demonstrates multiple antibacterial mechanisms, including targeted bacterial lysis, enzymatic biofilm disruption, and synergistic interactions with antibiotics. Advanced delivery systems such as liposomes, hydrogels, nanofibers, and nanoemulsions enhance phage stability and retention by overcoming physiological barriers like gastric acidity, enzymatic degradation, and immune clearance. Clinical evidence from compassionate use cases and early-phase trials highlights the safety and therapeutic promise of phage therapy.

Phage therapy represents a versatile and sustainable approach to combat multidrug-resistant infections. While regulatory, resistance, and scalability challenges remain, continued integration of microbiology, nanotechnology, and clinical research may enable its transition from experimental to mainstream therapeutic application in the post-antibiotic era.