Bacteriophage Pharmacology and Immunology

Abstract

The discovery of bacterial viruses approximately 100 years ago fairly quickly led to their use as antibacterial agents. For roughly two decades – early 1920s to early 1940s – bacteriophages represented the only means readily available to medicine by which many bacterial infections might be treated and cured. This near monopoly, however, came to a close as antibiotics became generally available. Antibiotics, especially as more broadly specific, selectively toxic antibacterials were both more easily developed and more easily used medicinals than phages. Phage therapy did not disappear from medical practice altogether, however, and increasingly is viewed as a viable alternative to antibiotics under circumstances where bacterial resistance to antibiotics is an issue. In addition are circumstances where a more selectively toxic antibacterial is desired, antibacterials that, for example, have less of a negative impact on nontarget members of a body’s microbiome. As for any drug, the successful development of phage therapeutics requires a pharmacological approach, whether implicit or, ideally, explicitly implemented. In this chapter, we consider pharmacokinetic and pharmacodynamic principles, body impact on drugs and drug impact on body, respectively, and both as they may be applied to the development of phage-based antimicrobials. As an important facet of both the pharmacokinetics and pharmacodynamics of phage therapy, we take a close look particularly at phage interactions with the mammalian immune system.