Research Headlines – Phages, a bacteria killer with a twis…

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Putting a fresh spin on the proverb ‘the enemy of my enemy is my friend’, EU-funded researchers have developed and tested an innovative treatment for infections caused by antimicrobial-resistant bacteria, which have developed into a major public health threat. This new weapon is a cocktail of bacteria-killing viruses called ‘phages’.

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In this unique case, the enemy is bacterial, and the enemy’s enemy is a type of virus that destroys bacteria. The EU-funded project PHAGOBURN tested the effectiveness of using these tiny allies – known as lytic bacteriophages, or ‘phages’, for short – on burn wounds, which are highly susceptible to infection.

‘Phagoburn was the first international, randomised, controlled study with phages,’ says Guy-Charles Fanneau de La Horie, the CEO of French SME Pherecydes Pharma, which was a partner in the project. ‘It has given visibility and credibility to phage therapy, especially with patients.’

The project also paved the way for future trials by managing to show that all requirements for such trials could be handled successfully, he notes: clearing the various regulatory hurdles to get the study approved in three countries was an achievement in its own right.

New line of attack

Phage therapy is proposed as an alternative for the treatment of bacterial infections that do not respond to current antibiotics. Antimicrobial resistance is not new, but it has escalated into a major threat to public health in recent years, with more drug-resistant strains having begun to appear and adding to the burden of hospital-acquired infection. New treatment options are urgently needed.

While the idea of using viruses to kill bacteria may seem counter-intuitive, it harnesses the concept of using natural predators against pathogens. Phages are the most abundant species on Earth, and they are very specific – they target only bacteria, which makes them extremely safe to use.

Collective action

Infections caused by multidrug-resistant bacteria are estimated to cause 33 000 deaths annually in the EU alone. Healthcare expenditures and productivity losses due to antimicrobial resistance are thought to represent a cost of about €1.5 billion per year.

A common response to a public health issue of such magnitude called for close collaboration between medical stakeholders – doctors, pharmacists, and SMEs for example – but also the commitment of regulators and policymakers. PHAGOBURN’s clinical trials were carried out at 9 hospitals in Belgium, France and Switzerland, where about 30 burn victims were enlisted to test one potential phage-based treatment.

This treatment used a cocktail of phages targeting bacterial infections caused by Pseudomonas aeruginosa, a species that is often antibiotic-resistant and is especially dangerous to hospital patients with weakened immune systems.

The trial, coordinated by the Percy Military Hospital in France, began in July 2015 and ended in January 2017. While the findings fell short of the partners’ expectations, they did indicate that the treatment is effective if a patient’s bacterial strain is highly sensitive to the phage cocktail, says de La Horie, who adds that the treatment strategy has since been refined. He also notes that the phages caused no side effects and were very well tolerated by patients.

Armed and ready…

Pherecydes Pharma already holds very large collections of phages against Escherichia coli (E-coli), Pseudomonas aeruginosa and Staphylococcus aureus (golden staph). These three bacterial species alone are responsible for more than half of antibiotic-resistant infections in industrialised countries.

‘Phages are now recognised as a credible alternative to antibiotics in cases where antibiotic therapy is not recommended,’ says de La Horie. They are now authorised on a compassionate basis in France, for exceptional use in situations where established treatments have failed, he reports.

Along with raising awareness of the potential of phage therapy, Phagoburn has also boosted the visibility and recognition of Pherecydes Pharma, especially with health authorities, clinicians and investors, de La Horie observes. Pherecydes Pharma has launched preparations for a full-scale facility to produce pharmaceutical grade phages from 2021, an investment that benefits from EU support via a grant awarded by the European Commission’s SME Instrument.

Project details

  • Project acronym: PHAGOBURN
  • Participants: France (Coordinator), Belgium, Switzerland
  • Project N°: 601857
  • Total costs: € 4 920 436
  • EU contribution: € 3 838 422
  • Duration: June 2013 to February 2017

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