Risk of Bacteriophage Therapeutics to Transfer Genetic Material and Contain Contaminants Beyond Endotoxins with Clinically Relevant Mitigation Strategies.

Bacteriophage therapy is a promising adjuvant therapeutic in the treatment of multidrug-resistant infections and chronic biofilm infections. However, there is limited knowledge about how to best utilize these agents in vivo, leading to a wide range of treatment protocols. Moreover, while bacteriophages are similar to antibiotics in their antimicrobial effects, these are active viruses and are very different from conventional antibiotics. One main difference that clinicians should be cognizant about is the potential ability of these therapeutics to horizontally transfer genetic material, and the clinical ramifications of such events. In addition, while bacteriophage therapeutics are readily tested for sterility and endotoxins, clinicians should also be aware of other contaminants, such as exotoxins, pathogenicity islands and prophages, that can contaminate bacteriophage therapeutics, and their clinical ramifications. While the perception may be that these are only theoretical issues, regulatory agencies are starting to recommend their evaluation when using bacteriophage therapy and subsequently these topics are discussed herein, as are ways to test for and mitigate the adverse effects of these issues.