Bacteriophage Therapy for Difficult-to-Treat Infections: The Implementation of a Multidisciplinary Phage Task Force (The PHAGEFORCE Study Protocol)

Abstract

In times where only a few novel antibiotics are to be expected, antimicrobial resistance remains an expanding global health threat. In case of chronic infections caused by therapy-resistant pathogens, physicians have limited therapeutic options, which are often associated with detrimental consequences for the patient. This has resulted in a renewed interest in alternative strategies, such as bacteriophage (phage) therapy. However, there are still important hurdles that currently impede the more widespread implementation of phage therapy in clinical practice. First, the limited number of good-quality case series and clinical trials have failed to show the optimal application protocol in terms of route of administration, frequency of administration, treatment duration and phage titer. Second, there is limited information on the systemic effects of phage therapy. Finally, in the past, phage therapy has been applied intuitively in terms of the selection of phages and their combination as parts of phage cocktails. This has led to an enormous heterogeneity in previously published studies, resulting in a lack of reliable safety and efficacy data for phage therapy. We hereby present a study protocol that addresses these scientific hurdles using a multidisciplinary approach, bringing together the experience of clinical, pharmaceutical and molecular microbiology experts.

Keywords: bacteriophage therapy; difficult-to-treat infections; efficacy; patient registry; safety.

Figure 1

Flowchart of the PHAGEFORCE study. Patients are screened for eligibility by the CBL. Based on the availability of active phages, the patient can (phage treatment group) or cannot (control group) be treated with phage therapy. Regardless of which group the patient is in, all data related to the infection will be collected. CBL: Coordination group for Bacteriophage therapy Leuven; QAMH: Queen Astrid Military Hospital.

Figure 2

Depending on the result of the phagogram, the patient will follow either the phage therapy trajectory (green) or the control trajectory (orange). For each trajectory, there is a standard-of-care protocol. CBL: Coordination group for Bacteriophage therapy Leuven.