Bacteriophage Therapy and the Mutant Selection Window

We use kinetic models to investigate how to design antimicrobial phage therapies to minimize emergence of resistant bacteria. We do this by modifying the mutant selection window hypothesis in a way that accounts for the ongoing self-replication of the phage. We show that components of combination phage therapies need to be appropriately matched if treatment is to avoid the emergence of resistant bacteria. Matching of components is more easily achieved when phage dosages are high enough that ongoing phage replication is not needed for the clearance of the bacteria. Theoretical predictions such as ours need to be tested experimentally if applications of phage therapy are to avoid the problems of widespread resistance that have beset chemical antibiotics.