The Potential of Bacteriophage Therapy as an Alternative Treatment Approach for Antibiotic-Resistant Infections

Nike Walter, Mohammadali Mirzaei, Li Deng, Christian Willy, Volker Alt, Markus Rupp

This study aimed to provide a comprehensive overview of the current state of the literature on the therapeutical application of bacteriophages. First, a bibliometric analysis was performed using the database Web of Science to determine annual number of publications and citations. Second, a systematic literature review was conducted on randomized-controlled trials (RCTs) of phage therapy in PubMed. Over the past decade the number of publications on bacteriophage therapy increased more than fourfold with 212 articles in 2011 and 739 in 2022. The systematic search in PubMed yielded 7 RCTs eligible for inclusion reporting on a total of 418 participants. Identified indications in this study included bacterial diarrhea, urinary tract infections, infected burn wounds, chronic otitis, chronic venous leg ulcers, and chronic rhinosinusitis. In three studies, mild to moderate adverse events were reported in 10/195 participants (5.1%). Three of the studies reported a statistically significant difference in outcomes comparing phage therapy with standard of care or placebo. Phage therapy has gained increasing interest over the years. RCTs on different indications suggest the safety of phage therapy, however reasons why phage therapy is not yet well accepted are limitations in the study designs. For a successful translation into clinical practice researchers and clinicians should learn from the earlier experiences and consider issues such as the quality of phage preparation, sensitivity testing, titer and dosages, as well as access to the infection site and stability for standardized protocols and future trials.