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The Role of Bacteriophage in the Fight Against AMR

Engagement Manager

No action today, no cure tomorrow

The overuse of antibiotics has led to the concomitant appearance of resistant bacterial strains. Currently, there is no new novel antibiotic discovery to counter these antimicrobial-resistant (AMR) strains. With no novel discovery, most of the present antibiotics are either modified or combined versions of previously known compounds, which only amplifies the number of resistant bacterial strains.  

By 2050, WHO predicts that 10 million people a year will die from AMR, outnumbering the death toll attributed to cancer. As the threat of AMR escalates, increasing numbers of scientists and clinicians are seeking out new innovations that can replace current antimicrobials, one of these being the long-forgotten phage therapy.

Bacteriophage (phage) are bacteria-infecting viruses and are the most abundant and ubiquitous organisms on earth. As such, they play a significant role in microbial population dynamics and evolutions, and fortunately, offer no threat to humans. Prior to the antibiotic era, phage had been used to treat a wide variety of bacterial infectious diseases, including cholera, dysentery, typhoid fever, skin and surgical site infection, peritonitis, septicaemia, and external otitis. Phage are composed of proteins that encapsulate a DNA or RNA genome. Phage are able to recognise a specific bacterial cell and inject their viral genome into the bacterial cell. The phage are then able to hijack the host bacterial machinery and lyse (kill) the bacteria. Due to their ability to lyse bacteria, phage therapy has come up as a potential method for the treatment of AMR bacterial infections. However, due to inconsistencies seen in the effectiveness of phage therapy, clinical interest began to fade when the discovery of penicillin was made in the 1940s, kick-starting the golden age of antibiotics.

The threat of returning to a pre-antibiotic era has resurfaced interest in the potential of phage. Phage possess different properties from broad-spectrum antibiotics and have the potential to be used in combination with antibiotics, as together they often provide synergistic effects, or in replacement of antibiotics.

To date, there are a number of studies that have been carried out in vivo and in vitro, which have confirmed the safety and efficacy of phage in the treatment of multi-drug resistant infections. Phage therapy has also been employed using the compassionate use rationale in Europe and the US, especially when AMR-bacteria-infected patients are without effective treatment options or are terminally ill. However, one of the main blockers of phage therapy being used in clinical practice is that more studies are required to understand the unique pharmacological properties of phage. The anecdotal-only evidence of phage therapy success has severely limited wider global implementation, despite successful outcomes for last-resort patients and continuing support from populations able to access phage therapy. For phage to be implemented into modern medicine, successful clinical trials must be completed to demonstrate the success of phage at treating infection, so that they can be considered an effective replacement for antibiotics.