Public aware of and accept use of bacteria-killing viruses as alternative to antibiotics, study shows

Peer-Reviewed Publication

UNIVERSITY OF EXETER

The public are in favour of the development of bacteria-killing viruses as an alternative to antibiotics – and more efforts to educate will make them significantly more likely to use the treatment, a new study shows.

The antimicrobial resistance (AMR) crisis means previously treatable infections can kill. This has revitalised the development of antibiotic alternatives, such as phage therapy, which was first explored over a century ago but abandoned in many countries in favour of antibiotics.

The study shows public acceptance of phage therapy is already moderately high, and priming people to think about novel medicines and antibiotic resistance significantly increases their likelihood of using it.

There is a higher acceptance of phage therapy when described without using perceived harsh words, such as “kill” and “virus” but instead “natural bacterial predator”.

Those who took part in the survey had a high awareness of antibiotic resistance – 92 per cent had heard of antibiotic resistance, but only 13 per cent reported that they had heard about phage therapy prior to the survey.

Success and side effect rate, treatment duration, and where the medicine has been approved for use, influenced their treatment preferences.

The study was conducted by Sophie McCammon, Kirils Makarovs, Susan Banducci and Vicki Gold from the University of Exeter.

Dr Banducci said: “While phage therapy remains poorly understood by the UK public our research suggests there is extensive acceptance and support for its development. Exposure to only very limited information about antibiotic resistance and alternative treatments to antibiotics greatly increases the public acceptance of phage therapy.”

Dr Gold said: “Those involved in the research wanted to know more about phage therapy and were inspired to research this topic after completing our survey. Exposure to only a very limited amount of information about phage therapy significantly increases acceptance.”

Researchers held a workshop with experts and a review of phage research. They also fielded a survey assessing the UK public’s acceptance, opinions and preferences regarding phage therapy. A total of 787 people completed the survey, distributed in December 2021.

One group was given two scenarios; in the first they presented with a minor infection, and in the second they presented with an infection that did not respond well to antibiotics for three months. In each scenario, the group ranked the selected attributes based on their importance in deciding whether to accept a treatment or not.

Participants were randomly assigned one of four descriptions of phage therapy and then surveyed to assess their acceptance of the treatment. The acceptance of phage therapy was high across the board. However, describing phage therapy using perceived harsh words, such as “kill and “virus”, resulted in lower acceptance rates than alternative descriptions. Additionally, participants who had recent exposure to information about antibiotic resistance and alternative treatments were more accepting of phage therapy.

From the 787 participants who completed the survey, 213 left written responses expressing their opinions on the potential of phage therapy. Of this group, 38 per cent showed a specific interest in phage therapy development, while a further 17 per cent supported the development of antibiotic alternatives generally.

Sophie McCammon said: “An advantage of phage therapy is often the minimal side effects. Emphasising this through education and marketing may increase public acceptance of phage therapy.

“Even though phage therapy may be some years away from routine clinical use in the UK, increasing pressures from the AMR crisis require evaluation of the UK public’s acceptance of alternative treatments.

“The public desire for increased education is apparent. Expanding schemes which are interactively involving children in phage research not only generates excitement for the therapy now, but also promotes awareness in the generation likely to be treated with antibiotic alternatives.”

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JOURNAL

PLoS ONE

DOI

10.1371/journal.pone.0285824 

METHOD OF RESEARCH

Meta-analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Phage therapy and the public: Increasing awareness essential to widespread use

ARTICLE PUBLICATION DATE

18-May-2023

TARGETING PHAGE THERAPY WORLD

 CONGRESS WILL BRING PHAGE

THERAPY UP TO ANOTHER LEVEL

 WITH MORE THAN 70

 COMMUNICATIONS

Meeting Announcement

MITOCHONDRIA-MICROBIOTA TASK FORCE

NEWS RELEASE 22-MAY-2023

 

IMAGE: 25+ MAJOR SPEAKERS WILL PRESENT OUTSTANDING COMMUNICATIONS DURING TARGETING PHAGE THERAPY 2023 view more 

CREDIT: TARGETING PHAGE THERAPY

The 6th World Congress on Targeting Phage Therapy 2023, being held on June 1-2 in Paris, will include more than 70 communications highlighting the most recent advances in phage and phage therapy. 

150+ attendees will gather to discuss the future potential of phage therapy. The most strategic question to discuss is: “how to bring phage therapy up to a new level?”.

Targeting Phages 2023 will address how phages play a strategic role to combat infection and antibiotic resistance. A special session will also be dedicated to how phages and phage therapy can modulate gut microbiota.

Get access to the final agenda and speakers.

 

Supporters

Armata Pharmaceuticals and BiomX will share the results of their latest clinical trials

Mina Pastagia, Armata Pharmaceuticals, USA

Safety, Pharmacokinetics, and Antibacterial Activity of AP-PA02 Multi-phage Cocktail in Patients with Cystic Fibrosis and Chronic Pulmonary Pseudomonas aeruginosa Infection (SWARM-P.a. Clinical Trial)

Iddo Nadav Weiner, VP of Research at BiomX, Israel

A Phase 1b/2a Randomized, Double-blind, Placebo-controlled Study Evaluating Nebulized Phage Therapy in Cystic Fibrosis Subjects with Chronic Pseudomonas Aeruginosa Pulmonary Infection

 

Cellexus will present the use of their CellMaker system in GMP production

Adam Ostrowski, Cellexus, United Kingdom

Implementating GMP Manufacturing for Phage Therapy

 

More than 25 posters will be presented by academics and industrials

Efficiency of innovative bacteriophage products: Bafacol®, Bafasal® and Bafador® in improving animals health in poultry farming and aquaculture

Proteon Pharmaceuticals (Poland)

Hierarchical classifier of 171 bacteriophage genera with related families and orders

Proteon Pharmaceuticals (Poland)

Selection of bacteriophages with therapeutic potential based on complete genome sequence analysis

JSC Biochimpharm (Georgia)

Propagation and purification of S. epidermidis-specific phage COP-80B for preclinical mouse model study

COBIK (Slovenia)

Check the list of posters of Phage Therapy 2023.

 

Come and Network with 150+ Attendees

Industrial participants: Phiogen (USA), Armata Pharmaceuticals (USA), BiomX (Israel), Cellexus (UK), , Aparon (UK), AusHealth (Australia), Biochimpharm JSC (Georgia), BIOCODEX (Paris), BIOMERIEUX SA (France), COBIK (Slovenia), ERYTECH Pharma (France), H Venture Partners (USA), Intralytix, Inc. (USA), MB Pharma s.r.o. (Czech Republic), Microbiotix Inc. (USA), Optipharm Inc. (Republic of Korea), Phage Consulting, Phagos (France), Pherecydes Pharma (France), Proteon Pharmaceuticals S.A. (Poland), R.E.D. Laboratories (Belgium), Resistell (Switzerland), Rime Bioinformatics (France), SET Medikal (Turkey), Vésale Bioscience (Belgium), Vitalis Phage Therapy (India), and others.

Academic participants: Adam Mickiewicz University, Agricultural University of Athens, Amrita University, Azabu University, Bacteriophage.news, Baylor College of Medicine, Bhabha Atomic Research Centre, Biological Research Centre, Szeged,Campus Universitaire de Maubeuge, Centre International de Recherche en Infectiologie, Chungnam Natl. Univ., Comenius University, Food and Drug Administration (FDA), Fundação Universidade Aberta Da Terceira,Fundación AZTI, G. Eliava Institute of Bacteriophages, microbiology and virology, Geneva University Hospitals, German Center for Infection Research (DZIF), German Federal Institute for Risk Assessment, Helmholtz Center Munich, Hirszfeld Institute of Immunology and Experimental Therapy, Hôpitaux Unversitaires de Genève, Hospices Civils de Lyon, IDADE, IIBR ,Ilia state university, INSERM, Institut Pasteur, Instituto de Biología Integrativa de Sistemas (I2SysBio) Universitat de València-CSIC, Kyorin University, Laboratoire ERRMECe, Laboratoire M2iSH, Lesaffre International,Louvain University, Masaryk University, Max Planck Institute for Medical Research, Medical center Francesc Macia, MPI, National Taiwan University, North-West Unversity, Pediatric Infectious Diseases Research Center, Phage Consulting,Phage Directory, Pharmabiotic Research Institute (PRI),Polish Academy of Sciences, Prof. Waclaw Dabrowski Institute of Agricultural and Food Biotechnology – State Research Institute, Queen Astrid Military Hospital, Queen Astrid Military Hospital, Burn Wound Centre, LabMCT, Brussels, Belgium, Sofia University, Stockholm University, TailΦr Labs, Baylor College of Medicine, and others.

 

Industrial Participation

25+ Industries will be present at Targeting Phage Therapy 2023 this June in Paris

CREDIT

Targeting Phage Therapy

Contributing partner

PHAGE Therapy, Applications, and Research Journal is the Official Partner of Targeting Phage Therapy 2023.

Attendees will have the chance to network with the Editor in Chief, Martha Clokie, during Targeting Phage Therapy 2023 and discuss about future collaboration.

 

For more information about the conference program, speakers, venue and more: www.phagetherapy-site.com

 

More about PHAGE: Therapy, Applications, and Research

PHAGE: Therapy, Applications, and Research is the only peer-reviewed journal dedicated to fundamental bacteriophage research and its applications in medicine, agriculture, aquaculture, veterinary applications, animal production, food safety, and food production. Under the distinct leadership of Editor-in-Chief Martha Clokie, PhD, University of Leicester, United Kingdom, the Journal showcases groundbreaking research, reviews, commentaries, opinion pieces, profiles, and perspectives dedicated to defining the roles of phages in all facets of microbiology and microbial ecology and exploring their potential to manipulate bacterial communities and treat infection.

PHAGE is the critical resource for molecular biologists, microbiologists, bacteriologists, bioengineers, immunologists, clinicians, and translational biologists, and aims to unify this evolving cluster of innovative researchers, industry leaders, clinicians, and policy makers. The Journal also advances knowledge and development in this re-emerging area of research and opens doors for new ideas and funding opportunities for researchers and clinicians in the field.

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Targeting Phage Therapy 2023: Where are we today and what's next?

Meeting Announcement

MITOCHONDRIA-MICROBIOTA TASK FORCE

 

IMAGE: THE 6TH WORLD CONGRESS ON TARGETING PHAGE THERAPY 2023 WILL BE HELD ON JUNE 1-2, IN PARIS, FRANCE. view more 

CREDIT: CREDITS TO TARGETING PHAGE THERAPY CONFERENCE

The 6th World Congress on Targeting Phage Therapy 2023 has returned to present all aspects related to phages and phage therapy on June 1-2 in Paris, France.

It will highlight the recent innovations and clinical applications of phages, validation and limitations. Paris Targeting Phage Therapy 2023 will also cover how phage will transform the medicine of tomorrow.

International phage therapy and infectious disease experts will cover the following points:

• Phage Therapy: Recent Advances & Challenges
• Bacteriophage Characterization & Isolation
• Co-Evolutionary Mechanisms of Bacteria and Phages
• Bacteriophages & Microbiota: On the Way to a Medical Revolution?
• Bacteriophage Prophylactic & Therapeutic Applications
• Phages, Radiotherapy & Wound Healing

 

Bacteriophages & Microbiota: On the Way to a Medical Revolution?

In collaboration with the International Society of Microbiota (ISM), a session will be dedicated to how phage will modulate the quality and quantity of microbiota. We will also discuss how to select the adequate phage to target microbiota dysbiosis in disease.

Session Details.

 

Paris Targeting Phage Therapy 2023 Speakers

Targeting Phage Therapy 2023 will gather a group of academic and industrial professionals worldwide to discuss their most recent research and data.

Academic Speakers:

Domenico Frezza, University of Roma Tor Vergata, Italy Phage Therapy: Vision and Gaps

Martha Clokie, University of Leicester, United Kingdom Phage Therapy & Its Applications: Where We Are Now and What’s Next?

William Summers, Yale University, USA  The History of Phage Therapy

Tristan Ferry, Hospices Civils de Lyon, France The Use of Bacteriophage Therapy for Complex Bacterial Infections: the PHAGEinLYON Experience

Anna Pistocchi, Università degli Studi di Milano, Italy Investigating the Therapeutic Potential of Phages as Antibacterials and Immunomodulators in a Zebrafish Model of Cystic Fibrosis

Rodrigo Ibarra Chavez, University of Copenhagen, Denmark Phage-inducible Chromosomal Islands Promote Genetic Variability by Blocking Phage Reproduction

Lilian Musila, U.S. Army Medical Research Directorate, Kenya Potential of Therapeutic Phages to Combat MDR ESKAPE Pathogens in Developing Nations

Jean-Paul Pirnay, Queen Astrid Military Hospital, Belgium Bacteriophages: It’s a medicine, Jim, but not as we know it

Aleksandra Petrovic Fabijan, Westmead Institute for Medical Research, Australia Therapeutic Monitoring of Phage Therapy

Noemi Poerio, University of Rome Tor Vergata, Italy A Novel Combined Host- and Pathogen-Directed Therapeutic Approach to Fight Infections by MDR- Klebsiella pneumoniae

Ryszard Międzybrodzki, Hirszfeld Institute of Immunology and Experimental Therapy PAS, Poland Phages in the Medical Research Activity in Poland

Anders S. Nilsson, Stockholm University, Sweden Novel Computer Program for Modelling Bacteriophage Infection Kinetics

Farzaneh Moghtader, Istinye University, Turkey Combined Therapies for Severely Infected Wounds: Multifunctional Bio-hybrids Composed of Gelatine Microspheres Carrying Bacteriophages and/or bFGF and their Aggregates with Mesenchymal Stem Cells

Willem-Jan Metsemakers, KU Leuven, Belgium The Use of Bacteriophage Therapy for Difficult-to-Treat Musculoskeletal Infections: the PHAGEFORCE Experience

Mzia Kutateladze, Eliava Institute of Bacteriophage, Georgia Phage Therapy: History in the Soviet Unions and Potential Treatment of Human Infections

Industrials:

Alexander Sulakvelidze, President and CEO of Intralytix, Inc., USA Modern Approaches for Optimizing Therapeutic Phage Preparations

Jessica Sacher, cofounder of Phage Directory, Australia Scaling Phage Therapy, Starting with Phage Australia

David Jernigan, PhagenCorp, LLC, USA Inducing Native Phages From the Human Virome to Address Targeted Infections

Pranav Johri, Founder of Vitalis Phage Therapy, India From Patient to Advocate – Introducing Phage Therapy to India

 

Present Your Innovations: 10 Minutes to Convince

During the Paris Targeting Phage Therapy 2023, a session will be dedicated to the latest innovations in the field of phages and phage therapy.

If you are academics, industrialists or representatives of startups, the scientific committee of Phage Therapy 2023 invites you to present your latest innovation in 10 minutes.

More information.

Tracks for abstract submission.

Abstract Submission Details.

 

Institutional Partners

This meeting is organized under the endorsement of the International Society of Microbiota (ISM).

 

Contact Us

In case you needed any further information on the registration, program, or abstract submission please visit our website.

You can also directly contact the organizing committee via email: contact@tid-site.com.

Find more information on our social media: LinkedIn and Facebook. 

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SOVIET SCIENCE

Case study highlights the potential—and challenges—of phage therapy

Chris Dall, MA

 

 

February 28, 2024

 

Antimicrobial Stewardship

For over two decades, Lynn Cole was in a protracted battle with bacteria and her own immune system.

Diagnosed as having the autoimmune disease Sjogren's syndrome in 1999, Cole suffered from pulmonary fibrosis, was oxygen dependent and highly susceptible to pneumonia, and frequently needed antibiotics for recurrent lung and urinary tract infections. Her daughter, Mya, was there for all of it.

"Most of my childhood was doctor's appointments, inpatient hospital stays, treatments…all that kind of stuff," Mya Cole told CIDRAP News.

But around 2010, Lynn Cole began to have recurrent bloodstream infections caused by the bacterium Enterococcus faecium. From 2013 to 2020, she underwent several hospitalizations at University of Pittsburgh Medical Center (UPMC) for E faecium bloodstream infections and received multiple courses of intravenous antibiotics. At some point in her complex medical history, the bacterium had colonized her gut and become the source of the recurrent infections.

Over that period, Cole, whose case was described in a recent report published in the journal mBio, would typically be sent home with a PICC (peripherally inserted central catheter) line to continue the antibiotic treatment. But within a few days of finishing the antibiotics and removing the PICC line, Cole's blood cultures would be positive for E faecium again.

"We just continued that cycle over and over again, which was frustrating," Mya Cole said.

The cycle continued, with increased frequency, into late 2020, when Cole experienced 26 days of persistent E faecium bacteremia despite treatment with multiple antibiotics that showed in vitro activity against the bacteria.

At that point Cole's treatment team suggested bacteriophages—bacteria-killing viruses—as a potential solution. Cole, after conferring with Mya and her partner, Tina Melotti, said yes.

"We did a little research, and then we talked as a family and agreed that if it could give us a chance, we would try it," Mya said.

A phage cocktail suppresses the infection

To find a phage that might work for Lynn Cole's infection, her doctors turned to researchers at UPMC's Van Tyne lab, which studies how bacteria evolve to resist antibiotics and develops new approaches to treat resistant infections. After receiving the request from Cole's doctors in June 2020, when it had become clear that antibiotics were not going to solve the problem, the lab set out to find a phage that matched the strain of E faecium that was causing the recurrent infections.

Phages aren't hard to find, because they're one of the most abundant organisms on the planet. They can be found in soil, plants, sewage water, and even in the human body. But unlike antibiotics, which work against a narrow or broad spectrum of bacteria, phages have to match the exact strain of bacterium they are targeting to have an effect. That requires testing isolates from a patient's infection to find a match.

Dan Higgins / CDC

Once a match is found, the identified phage then has to be grown, purified, and prepared for use in a patient. And that's only part of the lengthy process. Because phages are not approved for use in the United States, an Emergency Investigational New Drug (eIND) application for each individual case has to submitted to the US Food and Drug Administration to get the go-ahead. 

Ultimately, scientists at the University of Colorado found a phage—9184—that had activity against isolates collected from Cole's infection and sent it the Van Tyne lab, where it was propagated and purified. In December 2020, after spending 20 days in the intensive care unit, Cole began receiving three daily doses of the phage in combination with systemic antibiotics.

"And then, within 24 hours, the blood cultures were clear for the first time that month," said Madison Stellfox, MD, PhD, a member of the Van Tyne lab and co-author of the case report.

After being sent home from the hospital, Cole continued receiving antibiotics and the phage therapy through the PICC line under the supervision of Mya and Tina, both of whom work in healthcare. After a few breakthrough infections that were able to be managed at home, Stellfox and her colleagues added another phage—Hi3—to the treatment regimen.

We did a little research, and then we talked as a family and agreed that if it could give us a chance, we would try it.

Mya Cole

For several months, the phage cocktail appeared to be working. Later analysis of bloodstream isolates and rectal swabs by the Van Tyne lab would show that the abundance of E faecium in Cole's gastrointestinal tract—which the antibiotics alone could not tackle—decreased and remained suppressed when she began receiving the combination of the two phages and the antibiotics.

During that time, Cole was free of the bloodstream infections and able to travel. Her improvement enabled her doctors to step-down the antibiotic and phage regimen. Things were looking up.

"You could definitely tell that she was feeling better," Mya Cole said. "She had a lot more color in her face and a lot more personality."

An unforeseen immune response

If the story ended there, it would add to the list of successful compassionate-use cases whereby phages, in combination with antibiotics, have saved severely ill patients who have multidrug-resistant infections and have run out of options. That success has led to an increase in phage therapy requests.

But that's not where the story ends. On day 395 of her treatment, Cole suffered another E faecium bloodstream infection. At the Van Tyne lab, which had been regularly testing samples of Cole's blood serum that were collected by Mya and Tina to see if the cocktail was still working, they began to see a "precipitous decrease" in phage activity.

Lynn Cole (L), Tina Melotti (C), and Mya Cole (R)

When it became clear that the phage therapy was no longer suppressing the infection, Cole and her family decided to cut back on the treatment. She died of pneumonia in 2022, seven-and-a-half months after stopping phage treatment.

While Cole's infection had not become resistant to the phages or the phage-antibiotic combination, Stellfox explains, posthumous analysis of the isolates suggested that the addition of the second phage triggered an immune system response that may have blocked phage activity against the bacteria and resulted in a return of the recurrent bloodstream infections.

"We did see some binding of antibodies to those phages," Stellfox said. "I think that probably played some role."

Case highlights promise, pitfalls

In the paper, Stellfox and her colleagues note that Lynn Cole's experience may not be generalizable to a larger patient population. But she says the case nonetheless highlights both the potential and the pitfalls of phage therapy, which is being increasingly sought out with the emergence and spread of multidrug-resistant bacterial infections and the weak pipeline for new antibiotics.

One major point for her is that phage therapy is safe: The Van Tyne lab has now treated more than 20 patients with phages they've prepared, including 2 others with the same cocktail given to Lynn Cole, and they've seen no severe adverse events.

"I think it shows that if you take the time to do the matchmaking and find that right phage, [phage therapy] can really have a great role in the future," she said.

The challenge of working with phages, however, is that they are not chemicals with set structures, Stellfox noted. And the field lacks the kind of standardized procedures that exist with antibiotics and other approved drugs.

"They're living entities…they adapt, they change, and that's a great thing about them," she said. "But it can also make things trickier."

The immune system is one place where things can get tricky. That's because little is known about what kind of immune response phage therapy will provoke, says Steffanie Strathdee, PhD, co-director of the Center for Innovative Phage Applications and Therapeutics (iPATH) at the University of California, San Diego. For the most part, the focus has been on the interaction between the bacteria and the phage, with the human immune response the "missing part of the triangle."

They're living entities…they adapt, they change, and that's a great thing about them....But it can also make things trickier."

Madison Stellfox, MD, PhD

Strathdee, who co-authored the book The Perfect Predator, which describes her husband's life-threatening Acinetobacter baumannii infection and the phage cocktail that saved him, says that in the compassionate-use cases where phages are needed to save a patient's life, clinicians don't have the luxury of time.

"I don't think it's any surprise that we're going to see cases where antibody is generated against phage," Strathdee said. "But there's no time to say 'hold on, let's assess the patient's immune system to see if there are pre-existing antibodies directed against the phage.' "

Phage therapy 3.0

But just because phages can generate an immune system reaction isn't a reason to "throw out the baby with the bathwater," Strathdee adds, explaining that there have been some cases in which phage therapy has provoked an immune response that wasn't clinically relevant and the patient improved. In addition, she noted, the limitless supply of natural or genetically modified phages means researchers can source new phages that the human immune system hasn't seen yet.

Ultimately, Strathdee believes that what researchers learn from this case and others, along with clinical trials that are under way, will help inform the next stage of phage therapy, or phage therapy 3.0, as she calls it.

"Now we can get smarter about it," she said. "As phage therapy starts to become more mainstream, this issue of the human immune system and its role in phage therapy will become more important."

As phage therapy starts to become more mainstream, this issue of the human immune system and its role in phage therapy will become more important.

Steffanie Strathdee, PhD

Stellfox hopes the case report will help inform future phage research, and says some of the credit should go to Mya and Tina, whose regular collection of blood serum enabled her and her colleagues to get a better understanding of what happened and present their findings.

"They helped us so much, and we are indebted to them," she said.

Mya Cole says that although her mother knew there was no guarantee that phage therapy would cure her or prolong her life, she wanted people to know about and learn from her experience.

"She was very adamant that even though [a cure] couldn't be guaranteed, she wanted her story and her experiences to continue on, even if she did not, so that it could help other patients," she said.

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