The Safety and Toxicity of Phage Therapy: A Review of Pre-Clinical and Clinical Studies

Abstract

Increasing rates of infection by antibiotic resistant bacteria have led to a resurgence of interest in bacteriophage (phage) therapy. Several phage therapy studies in animals and humans have been completed over the last two decades. We conducted a systematic review of safety and toxicity data associated with phage therapy in both animals and humans reported in English-language publications from 2008 – 2021. Overall, 69 publications met our eligibility criteria including 20 animal studies, 35 clinical case reports or case series, and 14 clinical trials. After summarizing safety and toxicity data from these publications, we discuss potential approaches to optimizing safety and toxicity monitoring with the therapeutic use of phage moving forward. In our systematic review of the literature, we found few, but no serious, adverse events associated with phage therapy. Comprehensive and standardized reporting of potential toxicities associated with phage therapy has generally been lacking in the published literature. Structured safety and tolerability endpoints are necessary when phages are administered as anti-infective therapeutics.

The Microbiome in Pancreatic Cancer-Implications for Diagnosis and Precision Bacteriophage Therapy for This Low Survival Disease

“…Bacteriophages are viral predators of bacteria, whose actions are almost exclusively specific for their target host species ( Clokie et al., 2011 ; Batinovic et al., 2019 ). There have been extensive reports and reviews on the application of bacteriophages in clinical scenarios ( Genevière et al., 2021 , Liu et al., 2021b , Pirnay et al., 2022 ; Satta et al., 2022 ). More recently, bacteriophage therapy has been successfully applied in human clinical trials, and on compassionate grounds for critically ill patients with resistant and difficult to treat infections, in Western countries ( Vandenheuvel et al., 2015 ; Schooley et al., 2017 ; Dedrick et al., 2019 ; Maddocks et al., 2019 ).…”