Phage Therapy: Eco-Physiological Pharmacology

Abstract

Bacterial virus use as antibacterial agents, in the guise of what is commonly known as phage therapy, is an inherently physiological, ecological, and also pharmacological process. Physiologically we can consider metabolic properties of phage infections of bacteria and variation in those properties as a function of preexisting bacterial states. In addition, there are patient responses to pathogenesis, patient responses to phage infections of pathogens, and also patient responses to phage virions alone. Ecologically, we can consider phage propagation, densities, distribution (within bodies), impact on body-associated microbiota (as ecological communities), and modification of the functioning of body “ecosystems” more generally. These ecological and physiological components in many ways represent different perspectives on otherwise equivalent phenomena. Comparable to drugs, one also can view phages during phage therapy in pharmacological terms. The relatively unique status of phages within the context of phage therapy as essentially replicating antimicrobials can therefore result in a confluence of perspectives, many of which can be useful towards gaining a better mechanistic appreciation of phage therapy, as I consider here. Pharmacology more generally may be viewed as a discipline that lies at an interface between organism-associated phenomena, as considered by physiology, and environmental interactions as considered by ecology.

Phage therapy of pulmonary infections

“…These inundative densities may be attained particularly in the course of more "passive" phage therapy strategies [16][17][18][19][20][21] versus dosing strategies that rely instead on active, in situ phage replication to achieve inundative phage densities. Contrasting topical phage dosing, parenteral or per os dosing can be more reliant on the latter, that is, so-called "active" treatment strategies, since achievement of inundative phage densities "passively" can be difficult without direct physical application of phages to target bacteria.…”

Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review

“…Fundamentals of phage pharmacokinetics in animals and humans are different from those of chemical drugs. They integrate the classical view of antibacterial pharmacokinetics with ecological aspects of phages as a self‐replicating element of microbial communities within the body, along with characteristic responses of the body to virions . Moreover, bacteriophage is a universal name applying to the apparently most diverse entities in the world .…”

Phage therapy for severe bacterial infections: a narrative review

“…A good understanding of the non‐linear kinetics of bacteriophage distribution in blood and tissues is necessary to maximise efficacy of future therapeutic protocols . Usually applied to ecological rather than pharmacological systems, the phage replication cycle is generally held to follow classic Lotka–Volterra dynamics of predator (phage) and prey (bacteria), based on population sizes and interactions between them .…”