Phage-host-immune system dynamics in bacteriophage therapy: basic principles and mathematical models

Abstract

Phage therapy is progressively being recognized as a viable alternative to conventional antibiotic treatments, particularly in the context of multi-drug resistant bacterial challenges. However, the intricacies of the pharmacokinetics and pharmacodynamics (PKPD) pertaining to phages remain inadequately elucidated. A salient characteristic of phage PKPD is the inherent ability of phages to undergo replication. In this review, I proffer mathematical models that delineate the intricate dynamics encompassing the phage, the host organism, and the immune system. Fundamental tenets associated with proliferative and inundation thresholds are explored, and distinctions between active and passive therapies are accentuated. Furthermore, I present models that aim to illuminate the multifaceted interactions amongst diverse phage strains and bacterial subpopulations, each possessing distinct sensitivities to phages. The synergistic relationship between phages and the immune system is critically examined, demonstrating how the host's immunological function can influence the requisite phage dose for an optimal therapeutic outcome. A profound understanding of the presented modeling methodologies is paramount for researchers in the realms of clinical pharmacology and PKPD modeling interested in phage therapy. Such insights facilitate a more nuanced interpretation of dose-response relationships, enable the selection of potent phages, and aid in the optimization of phage cocktails.