DefinePK

Abstract

Phage therapy, the use of bacteriophages to combat bacterial infections, is experiencing a significant resurgence driven by the escalating crisis of antibiotic resistance. This review provides a comprehensive overview of the evolution of phage therapy, from its early 20th-century origins and subsequent decline to its current status as a promising alternative or adjunct to conventional antibiotics. We examine the fundamental mechanisms of phage action, highlighting their specificity for bacterial targets and their lytic capabilities against even multi-drug resistant strains, while often sparing the host microbiota. Current applications are explored across various domains, including the treatment of chronic and resistant infections in humans, personalised medicine approaches, veterinary uses, and food safety applications. Key innovations, fueled by advances in genomics and synthetic biology, such as phage engineering, cocktail formulations, phage-derived enzymes (e.g., endolysins), and novel delivery systems, are discussed as crucial enhancers of therapeutic potential. Despite its promise, phage therapy faces significant challenges, including complex regulatory pathways, manufacturing and standardisation hurdles, the potential for bacterial resistance to phages, and host immune responses. Addressing these limitations through rigorous clinical trials, standardized protocols, and continued research is essential. This review underscores the critical need to integrate phage therapy into modern medical paradigms as a vital tool in the global fight against antibiotic-resistant infections, outlining future directions for research and clinical implementation.