Safety and efficacy of phage therapy via the intravenous route

Abstract

Increasing development of antimicrobial resistance is driving a resurgence in interest in phage therapy: the use of bacteriophages to treat bacterial infections. As the lytic action of bacteriophages is unaffected by the antibiotic resistance status of their bacterial target, it is thought that phage therapy may have considerable potential in the treatment of a wide range of topical and localized infections. As yet this interest has not extended to intravenous (IV) use, which is surprising given that the historical record shows that phages are likely to be safe and effective when delivered by this route. Starting almost 100 years ago, phages were administered intravenously in treatment of systemic infections including typhoid, and Staphylococcal bacteremia. There was extensive IV use of phages in the 1940s to treat typhoid, reportedly with outstanding efficacy and safety. The safety of IV phage administration is also underpinned by the detailed work of Ochs and colleagues in Seattle who have over four decades' experience with IV injection into human subjects of large doses of highly purified coliphage PhiX174. Though these subjects included a large number of immune-deficient children, no serious side effects were observed over this extended time period. The large and continuing global health problems of typhoid and Staphylococcus aureus are exacerbated by the increasing antibiotic resistance of these pathogens. We contend that these infections are excellent candidates for use of IV phage therapy.

Editorial: Phage Therapy: Past, Present and Future

“…They have also been used therapeutically for ~100 years, with a good safety record (although their exploitation in this regard has lagged behind their use in molecular biology). Publications demonstrating the safety of phage applications (some of which include phase I safety trials) include (Rhoads et al, 2009; Wright et al, 2009; Miedzybrodzki et al, 2012; Sarker et al, 2012, 2016; Rose et al, 2014; Fish et al, 2016; Speck and Smithyman, 2016). Nonetheless, and despite a demonstrated need for new, safe antibacterial agents (Aminov, 2016), phage use by most Western physicians has not yet caught on, and this is due (presumably) to a lack of familiarity with phage therapy, but also because of a relative lack of regulatory approval.…”

A scaled‐down model for the translation of bacteriophage culture to manufacturing scale

“…With renewed interest and increasing levels of current research, phage therapies are emerging as potential tools against antimicrobial-resistant infections (Bragg, van der Westhuizen, Lee, Coetsee, & Boucher, 2014;Lin, Koskella, & Lin, 2017;Speck & Smithyman 2016).…”

“…With renewed interest and increasing levels of current research, phage therapies are emerging as potential tools against antimicrobial‐resistant infections (Bragg, van der Westhuizen, Lee, Coetsee, & Boucher, ; Lin, Koskella, & Lin, ; Speck & Smithyman ). However, in addition to the required improvements in phage purification, the standardization and phage production process has not been widely explored.…”

Use of bacteriophages in the treatment of colistin-only-sensitive Pseudomonas aeruginosa septicaemia in a patient with acute kidney injury—a case report

“…Historical reports show that they were efficaciously used via the intravenous route, especially in typhoid fever and Staphylococcus aureus bacteremia [3], but this is—as far as we know—the first contemporary report of intravenous bacteriophage monotherapy against P. aeruginosa septicaemia in humans.…”