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.

Bacteriophage Therapy for the Prevention and Treatment of Fracture-Related Infection Caused by Staphylococcus aureus: a Preclinical Study

“…From a therapeutic viewpoint, phage therapy can be considered a natural, specific and self-limiting strategy and is currently being revisited as a sustainable approach to target (multidrug) resistant bacteria and difficult-to-treat cases. Although several reports have shown promising clinical outcomes in patients with orthopedic device-related infections, ( 11 , 12 , 14 , 16 ), questions remain regarding the optimal application protocol, systemic effects of phage therapy and the impact of the immune response, specifically phage-neutralizing antibodies ( 17 , 23 ). This proof-of-concept study evaluated the application of phage therapy for the prevention and treatment of FRI in a clinically relevant rabbit model.…”

“…The therapeutic potential of phages to support treatment of challenging cases of orthopedic device-related infections has been demonstrated in a number of case reports and series over the past decade ( 10 – 16 ). However, many unanswered questions remain concerning the optimal application protocol ( 17 ). Phage therapy is most often applied locally to patients with a musculoskeletal infection, whereby phage suspensions are prepared in a buffered solution and applied directly into the wound ( 10 , 12 – 14 , 18 ).…”

Practical Assessment of an Interdisciplinary Bacteriophage Delivery Pipeline for Personalized Therapy of Gram-Negative Bacterial Infections

“…Guideline No. 8: Documentation During and After Phage Therapy Responsible: physicians Treating physicians must comprehensively document the communication about phage therapy with the patient, interdisciplinary expert discussions, treatment plans, adaptions to the intended treatments, all monitoring steps including (severe) adverse events (SAE) or reactions (SAR), and follow-up measures [67], particularly if treating under the umbrella of Article 37 of the Helsinki Declaration.…”

“…Guideline No. 9: Monitoring and Follow-Up Responsible: phage laboratory, physicians, diagnostic services Monitoring during phage therapy includes the following tasks: Monitoring of patient's parameters, i.e., the patient's clinical, psychological, and laboratory parameters are monitored closely, such as every other day [34,67]. A medical contact person is provided to the patient.…”

Phage Therapy for Multi-Drug Resistant Respiratory Tract Infections

“…Bretaudeau and colleagues (2020) describe this approach as tailored to treat individuals who have exhausted all other treatment options [ 80 ]. However, this framework has enabled the use of magistral preparations in clinical trials regulated on a national level, which has been recently performed by a multidisciplinary phage task force ( The PHAGEFORCE Study Protocol ) [ 82 ].…”