Capsid and Tail
A weekly phage periodical
April 18, 2019
Issue 24: Compassionate phage therapy

Compassionate phage therapy

Where is the world at with compassionate phage therapy? This week, Dr. Shawna McCallin highlights a new review (co-authored with us at Phage Directory and with Dr. Ben Chan at Yale) of phage case reports published to date.

While the initiation and development of clinical trials is time-consuming, compassionate use cases of phage therapy for end-of-the-line treatment of patients with antibiotic-resistant infections have picked up the pace over the last few years. There have been 29 documented case reports since 2000, as well as many unpublished treatments, which we have reviewed here.

What’s New

TU Delft has just opened a new phage library (Fagenbank) for phage therapy. If you have phages you’d like to see used in medical treatments, reach out to Fagenbank by email at [email protected]. This library is an initiative by Dr. Stan Brouns, and Fagenbank is already in collaboration with UMC Utrecht, which has applied for a phage clinical trial for CF patients. Read more here!

Phage BankPhage Therapy

virMine is a new phage bioinformatics tool by Andrea Garretto and colleagues at Loyola University of Chicago. Use virMine to identify viral genomes from raw reads representative of viral or mixed (viral and bacterial) communities. Paper | Github

Bioinformatics ToolMicrobiomeVirome

We’ve been interviewed on the What Matters with Steven Brantley podcast! We talk antibiotic resistance, phage therapy, and Phage Directory. Listen here (64 min).

PodcastPhage TherapyPhage Directory

Sooyeon Song and colleagues have published a new paper showing that E. coli employs both active (lytic and temperate) and inactive phages (a cryptic prophage) to discriminate between nearby strains and control cell-cell contact according to whether a nearby strain is kin or non-kin. Journal article | News article

ResearchPhage Biology

A Canadian cystic fibrosis patient is looking to become the first in Canada to receive phage therapy. He currently seeks phages for his Burkholderia cepacia infection, and his doctors will have to convince Health Canada to give this a try. Read the story here.

Phage TherapySpecial Access ProgrammeCanada

Latest Jobs

Postdoctoral position: Bacteriophage biology
Monash University, The Barr Lab, Melbourne, Australia
Dr. Jeremy Barr

The Barr Lab research group is studying bacteriophages within the context of their bacterial and mammalian hosts. We are offering an excellent opportunity to engage in an exciting post-doc position that combines microbiology, cell biology, genetics, evolution and microscopy within both in vitro and in vivo model systems. A number of research project are available within the lab for the right applicant, including, but not limited to:

  • Interaction of temperate phages within the human gut microbiome and characterising the tripartite symbioses they form with bacterial and animal hosts.
  • Phage therapy with a focus on identifying mechanism of phage infectivity and translation of results into the clinic.
    Applicants are encouraged to read through the Barr lab website, including research directions and expectations, for further information on how to apply.
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Postdoctoral position: Phage development and therapy
Baylor College of Medicine, Texas Medical Center, Houston, TX
Dr. Barbara Trautner, Dr. Anthony Maresso and Dr. Frank Ramig

We have an exciting new postdoc training and research opportunity recently made possible via the acquisition of a VA Merit Award to discover and develop therapeutic phages to treat E. coli infections in a murine model of CAUTI (catheter associated urinary tract infection). This is a unique opportunity to engage a growing phage therapy presence and group at Baylor (Department of Molecular Virology and Microbiology) and the Texas Medical Center in Houston, Texas.

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Community Board

April 18, 2019
Seeking collaborator for phage and host sequencing
Name: Irshad Ul Haq, PhD, Assistant Professor
Location: Khyber Pakhtunkhwa, Pakistan
Organization: University of Haripur

We are seeking help/collaboration on phage and host sequencing. We don’t have any resources to do the sequencing of these, and therefore would like to connect with someone who would want to collaborate. Please email me at [email protected].

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Compassionate phage therapy

Shawna McCallin, PhD
LinkedIn
ORCID

Last week, our review on compassionate phage therapy was published in Viruses. Our goal with this review was to summarize compassionate phage therapy cases worldwide, outline the general process of compassionate phage treatment, and highlight areas in need of improvement.

For a digestible summary of the main points, please read on. If you’ve got more time, feel free to check out the full-length review!

Phage accessibility can help patients

In the best of worlds, phage products would be readily available for treatment of bacterial infections for patients in need. The way to achieving such accessibility is through marketing authorizations granted by health agencies, such as the FDA or EMA. These authorizations are granted based on sound results from clinical trials.

Not everyone has time to wait for phage clinical trials

None of the three trials for phage products completed to date have resulted in marketing authorizations, and there has not yet been a single phase lll trial. Only one phase ll trial is actively recruiting patients.

The reality is that phage products are at least several years out from attaining a marketing authorization, while antibiotic resistant infections continue to complicate and prolong treatments, or ultimately, take the lives of patients.

In the meantime: compassionate phage therapy

In the interim, compassionate use of phage therapy has been used increasingly frequently on a patient-to-patient basis, to varying degrees of success.

Our recently published review of compassionate phage therapy includes nearly 30 published reports, including >2000 patients where phages have been used to treat antibiotic resistant infections with different pathogens, via different administration routes, and in different countries.

The problem: reporting is scarce and variable

The variability between different clinical indications, results, and reporting criteria in these reports makes it nearly impossible to draw cumulative conclusions, but knowledge of how phages are being used in human therapy is undeniably important for its future development.

Information such as PK/PD data, bacterial load, adverse effects, beneficial combinations with antibiotics, or the appearance of phage-resistant variants can help to refine and improve treatment protocols, establish safety, and substantiate claims of antimicrobial activity.

No centralized reporting requirements for compassionate phage therapy

The fact is, however, there are currently no requirements for publicly reporting compassionate phage treatments, with many cases being published years later, or not being published at all.

Published reports range from thoroughly-investigated to second-hand accounts of the clinical result. It is also becoming more common for patient treatments to be announced via less formal channels of communication than scientific peer-reviewed journals, such as press releases and youtube.

A missed opportunity?

The question is then, is this lack of centralized reporting a missed opportunity, both for better patient treatment and for advancing phage therapy?

We argue that yes, a lack of formal reporting of case reports of compassionate phage therapy is a missed opportunity.

Increased reporting would create opportunities for more systematic comparison between cases, as well as to prevent biases for positive outcomes.

However, a balance needs to be struck between reporting and protecting the know-how of phage biotechs, while at the same time not compromising the true intention of compassionate treatment, which is to provide maximum benefit to the patient.

How do we put this into practice?

The questions that remain are the ‘who, where, what, and how’ about facilitating and encouraging compassionate phage use reporting. The reality is that while there have been many reviews and expert opinions addressing different aspects of phage therapy, these reviews and opinions rarely translate to actionable steps or policy changes. Indeed, we received an apt and appreciated comment from a reviewer on the lack of a practical formulation of our proposals.

Going forward, we are exploring possible actions we can take. One option is to make available a continually up-to-date list of compassionate phage therapy case reports. Ideally, with support from the phage community, we can collectively work toward creating a set of reporting standards for compassionate phage use.

Main Source:

McCallin, S., Sacher, J. C., Zheng, J., & Chan, B. K. (2019). Current State of Compassionate Phage Therapy. Viruses, 11(4), 343. https://doi.org/10.3390/v11040343

Shawna McCallin, PhD

LinkedIn
ORCID

Swiss Federal Institute of Technology in Lausanne (EPFL)

Shawna McCallin is a scientist at the Swiss Federal Institute of Technology in Lausanne (EPFL), Switzerland who has previously been involved in two phage clinical trials for E. coli diarrhea and S. aureus carriage. She has extensively studied commercial phage preparations from Russia and Georgia, with a focus on S. aureus phage diversity. As of recently, she is working on clinical and regulatory aspects of phage therapy and expanding her phage research to the microbiome. She is a member of the editorial board of the new scientific journal PHAGE: Therapy, Applications, and Research, and a member of the executive board of the ISVM.

For every issue of Capsid & Tail, we are committed to getting our facts straight, but we’re not experts in the information we’re bringing to you. If you feel that we’ve missed an important viewpoint, or if you have something to add, please reach out to us by emailing [email protected]. We’d love to hear from you, and we’d be happy to revisit topics we’ve covered (ideally with added information and viewpoints from community members like you!).

Lastly, please reach out if you’re interested in writing for us, or have suggestions for future issues!