Overcoming Antimicrobial Resistance: Phage Therapy as a Promising Solution to Combat ESKAPE Pathogens

This review highlights the renewed promise of bacteriophage (phage) therapy as an alternative to antibiotics in combating multidrug-resistant (MDR) ESKAPE pathogens—major drivers of hospital-acquired infections. It outlines phages’ unique antibacterial mechanisms, including targeted bacterial lysis, enzymatic biofilm disruption, and synergistic effects with antibiotics. The paper emphasizes the importance of advanced delivery systems (liposomes, hydrogels, nanofibers, nanoemulsions) and diverse administration routes (oral, topical, intravenous, intranasal, intravesical) to enhance phage stability and overcome physiological barriers. Innovations in phage engineering using CRISPR-Cas, synthetic biology, and continuous evolution are expanding host range and improving lytic efficiency. Early clinical evidence supports phage therapy’s safety and potential, though challenges remain—such as bacterial resistance to phages, regulatory hurdles, and scalability. Integrating microbiology, nanotechnology, and clinical medicine, phage therapy is emerging as a sustainable and versatile tool in the post-antibiotic era.