Translating phage therapy into the clinic: Recent accomplishments but continuing challenges

Abstract

Phage therapy is a medical form of biological control of bacterial infections, one that uses naturally occurring viruses, called bacteriophages or phages, as antibacterial agents. Pioneered over 100 years ago, phage therapy nonetheless is currently experiencing a resurgence in interest, with growing numbers of clinical case studies being published. This renewed enthusiasm is due in large part to phage therapy holding promise for providing safe and effective cures for bacterial infections that traditional antibiotics acting alone have been unable to clear. This Essay introduces basic phage biology, provides an outline of the long history of phage therapy, highlights some advantages of using phages as antibacterial agents, and provides an overview of recent phage therapy clinical successes. Although phage therapy has clear clinical potential, it faces biological, regulatory, and economic challenges to its further implementation and more mainstream acceptance.

Schlesinger Nailed It! Assessing a Key Primary Pharmacodynamic Property of Phages for Phage Therapy: Virion Encounter Rates with Motionless Bacterial Targets

“…Schlesinger’s theorizing, as based on the work of Smoluchowski [ 18 ], therefore seems to represent a successful application of mathematics to our understanding of phage biology. This, by extension, should be relevant to our ability to predict important aspects of the pharmacology of phage therapy, with a greater understanding of phage therapy pharmacology likely relevant to more widespread of adoption of this important antibacterial strategy [ 2 ].…”

“…Hitting a target-here, the bacterium-intuitively thus should be a function of the area of a target rather than just its radius. Area in this case could be either that of a circle as a cross section of a sphere (πR 2 ) or instead the surface of that sphere (4πR 2 ), thus being functions of R 2 rather than of just R (=R 1 ). In addition, note that the calculation for k as provided in Equation (1) also includes the terms 4π [18], further confounding the issue of why R 1 rather than R 2 is being used in that equation.…”

“…Phage therapy is the use of bacterial viruses to treat infections caused by bacteria [1][2][3]. We can consider this phage therapy from the perspective of pharmacology [4], with pharmacology traditionally differentiated into what is labeled as pharmacokinetics vs. pharmacodynamics.…”

Isolation and characterization of lytic bacteriophages from various sources in Addis Ababa against antimicrobial-resistant diarrheagenic Escherichia coli strains and evaluation of their therapeutic Potential

“…Bacteriophage lytic and lysogenic cycles [130] Figure 3 Major breakthroughs in the elds of phage therapy and science: JAMA, Journal of the American Medical Association; IV, intravenous; GMP, good manufacturing practice [112].…”

Lytic bacteriophages interact with respiratory epithelial cells and induce the secretion of antiviral and proinflammatory cytokines

“…Phage therapy is a re-emerging therapeutic alternative to treat multidrug resistant (MDR) infections that relies on the use of bacteriophages (or phages) that infect and kill specific bacterial strains (1). Even though phage therapy is increasingly being used in clinical trials and compassionate use cases (via Emergency Use Authorizations) in the United States (2), there are decades of experience with phage therapy in Georgia, Poland, and Russia (3), where it is routine medical practice to prescribe phages for difficult-to-treat infections (4). Thanks to the success of phage therapy in Western Europe and the research from the Eliava Institute of Bacteriophages, Microbiology and Virology (Tblilisi, Georgia) and the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy (Wroclaw, Poland), there has been a renewed interest in this therapeutic strategy in the Western world.…”