Phage Therapy: Various Perspectives on How to Improve the Art.

Use of phages as antibacterial agents has a long and, even, storied history. During that time much has been learned but, to a degree, also forgotten. As a consequence, today we experience a largely preclinical development of a field which already has been subject to substantial clinical practice. This development, as well, is now occurring within a much more rigorously regulated environment than previously had been the case. The consequence is not only a need to reinvent standards of practice but to do so within a more explicitly pharmacological context. Of particular concern is that the application of phages to bacterial infections does not always result in control of the latter, necessitating ongoing thought on how to refine treatment protocols. Here I consider a number of issues relevant to such refinement, focusing on areas which, in my opinion, phage therapy researchers-perhaps especially those new to the field-might struggle with. In order of presentation, I consider how best to describe phage therapy within publications toward achieving a more coherent literature, the importance of Poisson distributions along with killing titers toward understanding phage dosing, the associated importance of establishing sufficient phage numbers in situ to achieve adequate bacteria killing, various problems with the use of multiplicity of infection (MOI) as a description of phage dosing, how to anticipate the basic kinetics of phage-bacteria absorptive interactions, how to distinguish passive from active treatments, and basic approaches toward addressing disappointing efficacy outcomes.