Antimicrobial resistance is quickly becoming a big problem in the field of medicine with antibiotics being less and less effective. These drug-resistant bacteria may require alternative antibiotics or higher dosages that can prove to be more expensive and/or toxic. These can be divided into three groups: MDR-multi-drug resistant; XDR-extensively drug resistant; and TDR-totally drug resistant, also known as “superbugs”. This resistance comes about through three different mechanisms including genetic mutations, the natural resistance of bacteria, and the acquisition of resistance from another. This is not only a problem with bacteria but also with fungal, viral, protozoal infections as well.

There are a number of ways to prevent or slow down this drug resistance such as limiting the use of antibiotics in humans and livestock, the improvement of wastewater treatment (side note: so much unused medications and meds that have passed through the body are flushed down the toilet and end up in the water because there is no effective way to remove them all at treatment plants), and making sure that more people know about the dangers of overuse of antibiotics (as well as antifungals, antivirals, and antiprotozoals). These methods will only slow down the progression towards antimicrobial resistance; it is only a matter of time before antibiotics in particular become completely ineffective.

It takes an estimated 10 years for a new drug to be developed and get Health Canada (or FDA) approval which means we desperately need a replacement therapy soon. One particular new method of fighting bacteria is actually something that was studied at the turn of the last century and has been rediscovered: bacteriophages. Bacteriophages, or phages, are viruses that infect and kill bacteria and more researchers are turning to them as a possible replacement for the more typical antibiotics.

Bacteriophages are more plentiful than any other organism on Earth and are among the most diverse. They are found wherever bacteria are such as soil and intestines of animals but seawater is probably the biggest source. Phages were first discovered (independently) by British bacteriologist Frederick Twort and French-Canadian Félix d’Hérelle working at the Pasteur Institute in Paris in 1915 and 1917, respectively. The onset of World War I put Twort’s research on hold because of the shortage of funding but d’Hérelle was able to continue his work. Much of what we know about phages comes from his ground-breaking research. He was even the first to see the implications of using them as a treatment.

During the 1920’s and 30s, Giorgi Eliava from Georgia built upon this knowledge and used bacteriophages to treat soldiers in the Red Army. Their use has continued within the ex-Soviet Union and elsewhere in Eastern and Central Europe but has been largely ignored in the West for a number of reasons. The easy access to antibiotics such as penicillin and sulfa drugs made the need of another possibility unnecessary; many of the studies done on phages were written in Russian or Georgian and would not be followed internationally until after the fall of the Iron Curtain; and there are some limitations for using bacteriophages as a treatment.

Phages are difficult to prepare cleanly. Scientists need to grow large quantities of the host bacteria first then infect it with the phages which in turn kill the bacteria. The difficulty comes with the removal of the phages from the dead bacteria corpses without leaving any residual bacteria which could cause sepsis in the recipient. The scientists also need to figure out the correct concentration to administer. Too little and they would be ineffectual. Another problem is one of time. It will take years to research each phage. Because one type of phage kills one type of bacteria, more research needs to be done to identify the right one for each bacterium.

As said previously, much of this research has been done in the former Soviet Union and France but widespread use in the rest of Western Europe and North America may be a few years away. There has been a recent investment of 5 million euros in Phagoburn, a project that uses phages in the treatment of skin infections in burn victims and there has been FDA approval for the use of food additive that contains phages to kill Listeria monocytogenes (one of the most virulent forms of food poisoning). Currently, studies are also being done using phages against the dreaded MRSA and drug resistant tuberculosis.

Although a Canadian may have been at the forefront of the study of phages at the turn of the last century, funding for research into phages has not been consistent. Surveillance of antimicrobial resistance is not uniform from province to province so there are no definitive numbers as to how many people die from these so-called “superbugs” each year in Canada. We should be taking a more active role in the study of phages because probably sooner than later, our conventional antibiotics will no longer work leaving us with a health crisis of epic proportions.

–Janice Willson

Photo Source: NIH (National Institutes of Health), scanning electron micrograph of MRSA

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