Breadth of Depth of Bacteriophage Antibacterial Activity

Bacteriophages (phages) are viruses that specifically infect bacteria. Many phages are obligate killers of bacteria, making them valuable antibacterial agents that have been used clinically for over a century. However, bacterial resistance to phages remains a significant limitation of phage therapy. This resistance can be categorized into two distinct types: pre-existing resistance that must be addressed at treatment initiation, and resistance that evolves during ongoing therapy. Phage cocktails, combinations of multiple treatment phages, can address both forms of bacterial resistance. The “breadth of activity” of phage cocktails refers to their capacity to overcome phage resistance present at treatment outset, which is particularly important for empirical treatment of unidentified bacterial infections. Conversely, “depth of activity” describes a cocktail’s ability to combat bacterial resistance as it evolves throughout treatment. The concept of “breadth of depth” combines these two parameters by providing a comprehensive measure of a phage cocktail’s capacity to suppress resistance evolution across diverse bacterial strains, including those targeted empirically.