Guidelines to Compose an Ideal Bacteriophage Cocktail

Properly designed bacteriophage therapeutics are the cornerstone for a successful outcome of bacteriophage therapy. Here we present an overview of the different strategies and steps that can be taken to develop a bacteriophage cocktail that complies with relevant quality and safety requirements. It is based on empirical bacteriophage therapy knowledge from over a century of experience, more recently performed studies, and emerging technologies. We emphasize the selection of adequate bacteriophages and describe a modified Appelmans' method to improve the overall performance of therapeutic bacteriophages individually and collectively in the cocktail. We present two versions of the method, which differ from each other by the employed techniques to evaluate phage activity and synergy: photometric assessment of bacterial growth versus measurement of bacterial respiration via the Omnilog® system.