Understanding bacteriophage therapy as a density-dependent kinetic process.

Studies of bacteriophage as therapeutic agents have had mixed and unpredictable outcomes. We argue that interpretation of these apparently paradoxical results requires appreciation of various density-dependent threshold effects. We use a mathematical model to delineate different categories of outcome, including therapy by simple inundation, by active biocontrol, and by delayed active biocontrol. Counter-intuitively, there are situations in which earlier inoculation can be less efficacious, and simultaneous inoculation with antibiotics can be detrimental. Predictions of therapeutic responses are made using formulae dependent on biologically meaningful parameters; experimental measurement of the parameters will be a prerequisite of application of the model to particular study systems. Such modelling can point to which aspects of phage biology might most fruitfully be engineered so as to enhance the viability of bacteriophage therapy.