Personalized approaches in phage therapy of multidrug-resistant infections

The global spread of infections caused by multidrug-resistant microorganisms highlights the importance of seeking and developing new antimicrobial agents. One of the additional elements in the fight against antibiotic-resistant microorganisms could be bacteriophages, including strategies for their combined use with antibiotics. Bacteriophages have been used to treat infectious diseases since the early 20th century, but until recently, they received little attention as treatment options for infectious diseases. Research and development of various strategies for bacteriophage use have intensified due to the increasing spread of antibiotic resistance and the slowed pace of new antibiotic development. However, the application of phage therapy today faces several challenges, primarily related to the restrictions imposed by current medical regulatory requirements and the insufficient development of effective therapeutic practices based on the principles of evidence-based medicine. It is noteworthy that, despite over 100 years of clinical experience with bacteriophages, there are only a limited number of clinical studies addressing the safety and efficacy of phage therapy. Nonetheless, in recent years, the number of such studies has begun to grow. This article provides an overview of modern approaches to the therapeutic use of bacteriophages, including personalized phage therapy and the production of commercial phage cocktails. The advantages and disadvantages of both approaches are discussed, and the results of personalized phage therapy applications are presented. The article also outlines the requirements of medical regulatory bodies regarding the production and administration of phage therapeutic agents, as well as progress in resolving issues related to bacteriophages intended for the treatment or prevention of specific bacterial infections in humans within the EU. Additionally, the experience of implementing phage therapy in various countries is highlighted. To avoid past mistakes and ensure the widespread adoption of phage therapy in medicine, it is necessary to address several issues related to the biological properties of bacteriophages, the specifics of phage preparation production and standardization, the risk of microorganisms developing resistance to bacteriophages, and the successful conduct of randomized controlled clinical trials.