Understanding bacteriophage therapy as a density-dependent kinetic process

Studies of bacteriophage as therapeutic agents have had mixed and unpredict able outcomes. We argue that interpretation of these apparently paradoxical results requires appreciation of various density-dependent threshold effec ts. We use a mathematical model to delineate different categories of outcom e, including therapy by simple inundation, by active biocontrol, and by del ayed active biocontrol. Counter-intuitively, there are situations in which earlier inoculation can be less efficacious, and simultaneous inoculation w ith antibiotics can be detrimental. Predictions of therapeutic responses ar e made using formulae dependent on biologically meaningful parameters; expe rimental measurement of the parameters will be a prerequisite of applicatio n of the model to particular study systems. Such modelling can point to whi ch aspects of phage biology might most fruitfully be engineered so as to en hance the viability of bacteriophage therapy. (C) 2001 Academic Press.