Current State of Compassionate Phage Therapy

Abstract

There is a current unmet medical need for the treatment of antibiotic-resistant infections, and in the absence of approved alternatives, some clinicians are turning to empirical ones, such as phage therapy, for compassionate treatment. Phage therapy is ideal for compassionate use due to its long-standing historical use and publications, apparent lack of adverse effects, and solid support by fundamental research. Increased media coverage and peer-reviewed articles have given rise to a more widespread familiarity with its therapeutic potential. However, compassionate phage therapy (cPT) remains limited to a small number of experimental treatment centers or associated with individual physicians and researchers. It is possible, with the creation of guidelines and a greater central coordination, that cPT could reach more of those in need, starting by increasing the availability of phages. Subsequent steps, particularly production and purification, are difficult to scale, and treatment paradigms stand highly variable between cases, or are frequently not reported. This article serves both to synopsize cPT publications to date and to discuss currently available phage sources for cPT. As the antibiotic resistance crisis continues to grow and the future of phage therapy clinical trials remains undetermined, cPT represents a possibility for bridging the gap between current treatment failures and future approved alternatives. Streamlining the process of cPT will help to ensure high quality, therapeutically-beneficial, and safe treatment.

Keywords: antibiotic resistance; bacteriophage therapy; compassionate use.

Figure 1

General process and considerations for compassionate phage therapy (cPT). Required steps are shown in bold. Circular arrows indicate processes that are dynamic and do not occur necessarily in a chronological order. PRV: Phage-resistant variant. AB: Antibiotic.

Figure 2

Geographic distribution of organizations (grouped by type) that have either previously participated in cPT cases or demonstrated intent to do so in the future through registration with Phage Directory (numbers current as of January 2019). Phage organizations not having yet contributed to cPT are not listed here. SME: Small- and medium-sized enterprises.