Antibiotic Resistance: Killer Virus to the Rescue?19 November 2013
IRELAND - A long forgotten therapy may be about to come to our salvation in the fight against antibiotic resistance, according to Dr John Rae of TEAGASC. He says the treatment has been around for nearly a century but that we in the English-speaking world have overlooked it for the past 60 years.
Called phage therapy, it has been in continuous use across Eastern Europe and Russia since the 1920s, according to Dr Rae.
Phage therapy gets its name from bacteriophages, tiny viruses that kill only bacteria.
Bacteriophages, or phages for short, are the most abundant organisms on the planet.
These viruses attack bacteria by injecting their genetic material into the bacterial cells.
The virus’ genetic material takes complete control of bacteria’s biochemical pathways, producing many more copies of the virus.
Finally the cells burst, releasing numerous viruses to go on the attack again.
Where antibiotics act like a nuclear bomb wiping out everything, phages are so specific that they only infect individual strains of bacteria, making phage treatments a silver bullet targeting only the problem bacteria, like MRSA.
This specific targeting is a very exciting aspect of the therapy, and offers a significant improvement on the mode of action of antibiotics, which alter the normal balance of bacteria in our body and can sometimes cause super-infections like C.diff.
Where Have They Come From?
Phages were first properly described in 1916 by Canadian microbiologist Felix d'Hercelle, according to Dr Rae. He would go to on develop phage treatments in collaboration with the Pasteur Institute in France and then in partnership with a Georgian scientist, George Eliava, setting up the Eliava Institute in Tbilisi, Georgia, which is still in operation today.
Phage treatments expanded greatly around this time, right around the world. Even US pharmaceutical companies like Eli Lily and the origins of Abbott became involved.
However, the treatments fell into disrepute due to a number of negative scientific reviews and the exaggerated claims by some manufacturers.
The advent of commercially available antibiotics in the 1940s and 50s was the death-knell for phage therapy, in the West at least.
However, behind the Iron Curtain in Eastern Europe, work on phage therapy continued unabated with, at its height, the Eliava Institute employing over 1,200 personnel producing over two tons of phages per week, the majority of this going to the Soviet army.
The West has woken up to phage therapy again as antibiotic resistance is dramatically on the rise, enviously turning its eye to the treasure throve of potentially life-saving treatments available in the former Soviet bloc countries.
But while the rush is on for new therapies, there are still a number of significant obstacles that need to be overcome.
Bumpy Road Ahead
Many of the problems of producing commercially available phage treatments in the West stem from the approach to medicine in this region, Dr Rae says. Much of the pharmaceutical drive has been to develop effective medicines that can be patented, and therefore profit-making.
The problem with phage therapy from a commercial point of view is that it is based on naturally occurring viruses and thus there is a lack of potential patents.
Another obstacle is the cost of getting therapies approved. Extensive research and human trials are required, and the costs of these can run from hundreds of millions to a billion dollars.
Other obstacles include potential unknown consequences by using live viruses. This can be somewhat mitigated by the knowledge that these treatments have been in use for nearly a century in other parts of the world without any indication of potential problems.
No cases of anaphylaxis, an extreme allergic reaction, have been reported, and this is thought to stem from the fact that we have co-existed with phages throughout human evolution.
Due to the rapid action of phages in killing and bursting bacterial cells, in the process they release all of the cells contents including toxins.
The sudden release of endotoxins could result in the patient going into toxic shock. However, comfort can be taken from the fact that this has not been reported to any great extent in Eastern bloc medicine.
There also is a known risk when using certain phages, known as temperate phages. These viruses do not burst the bacterial cell but instead merge their genetic code with that of bacteria.
There is a fear that this could make bacteria more infectious and indeed could pass antibiotic resistance to other bacteria.
However, this is easily overcome by avoiding the use of temperate phages in preference for lytic phages, which kill bacteria by bursting or lysing the cells.
Finally, no double blind trials that would meet Western standards have been reported in the history of phage treatment in the Eastern bloc. However reports in the literature especially from Poland have been very promising.
In present day Poland and Georgia, clinics exist to treat people with antibiotic resistant infections.
According to Dr Rae, the Hirszfeld Institute in Wroclaw, Poland opened its doors in 1952. It has reported impressive infection cure rates of between 75 to 100 per cent in over 1,500 patients since 1980, all with infections that routine antibiotic therapy failed to cure.
While the Eliava Institute in Tbilisi, Georgia, has a reputed 1,500 phage treatments.
American companies are now lining up to collaborate with these clinics, some arranging for treatment of US patients with antibiotic-resistant infections.
However the cost of a course of treatments is not cheap ranging from $8,000 to $22,000.
Today in Georgia and Russia phage treatments are available to the public without prescription.
With names like ‘Intestiphage’ and ‘Pyophage’, they contain a mixture of up to 20 phages targeting common infections. These phage mixtures are regularly updated at a frequency of six months and are region-specific.
First Treatments Here
Dr Rae says recent announcements by the University of Leicester of a phage that targets Clostridium difficile ('C. diff') are encouraging and already an FDA-approved phage treatment for Listeria on deli meats and other ready-to-eat foods is commercially available in the US through a company called Intralyix.
However, the first human treatments to arrive on these shores could be more than a decade away.
But they will arrive and it may only be a matter of time before we see phage-based probiotic drinks available in pharmacies here, aimed at improving gut health, by eliminating infections such as Salmonella and other diarrhoea causing bacteria.
The return of phage therapy to the West is timely, according to Dr Rae. It may well offer us the lifeline we need to fight the menace of antibiotic resistance, helping us maintain the hard-won achievements of modern medicine.