Antibiotic resistance apocalypse? Not so Fast

Image Credit: Charlize Du Preez

As antimicrobial resistance rises and new antibiotic discoveries dwindle, researchers are exploring bacteriophages—viruses that target specific bacteria—as a promising alternative treatment for drug-resistant infections.

The World Health Organisation estimated that antimicrobial resistance caused 1.27 million deaths globally in 2019. Antimicrobial resistance occurs when bacteria are no longer affected by the antibiotics used to stop or kill them. With increasing antimicrobial resistance and few new antibiotic discoveries, researchers have started to look in new directions for the treatment of drug-resistant bacteria. One such area of research is bacteriophages. 

Bacteriophages, also called phages, are viruses that have co-evolved with bacteria and are their natural enemies.

Bacteriophages selectively infect bacteria, so using bacteriophages to treat infections, referred to as phage therapy, is a nascent but interesting field of medicine.

Phage therapy is not new. The term bacteriophage was coined by Félix d'Hérelle in 1917, even before the discovery of penicillin. People have been attempting to treat infection using phage therapy ever since. While phage therapy has been used for the last century in certain parts of the world, such as Georgia and Poland, it fell out of popularity in the Western world following World War II for multiple reasons including the discovery and rise of antibiotics, the Cold War and phage therapy’s association with the Soviet Union, and uncertainty regarding phage therapy’s effectiveness. 

So why has phage therapy come back in fashion in recent years? The big draw of phage therapy is the potential to treat multidrug-resistant (MDR) bacteria. You may have heard of Methicillin-Resistant Staphylococcus aureus (MRSA). MRSA commonly causes skin infections but can have complications such as blood, heart, lung and joint infections. MRSA is just one bacteria of many that have become resistant to multiple antibiotics. Bacteria are rapidly becoming resistant to more drugs, making infections increasingly difficult to treat, resulting in more illness and deaths. Phages can offer an alternative treatment method to this growing problem.

Bacteriophages seem to be generally safe to use with few side effects. Phages are everywhere in our environment, and we are constantly exposed to them without causing any harm. However, this does not mean there is no possibility of harmful effects; more investigation is needed.

We still have a relatively poor understanding of bacteriophages, especially how they may act when used as drugs.

However, their continued use in certain parts of the world and some recent studies have shown no signs of side effects, and more trials are underway.  

Phages are also quite specific in the bacteria they attack. This is beneficial because our bodies host many bacteria species, especially in the gut. These bacteria, called the microbiome or microbiota, have helpful jobs like producing necessary vitamins or preventing bacteria from growing too much, causing infection. Because phages can be specific, they can kill off the bacteria causing the infection without killing the wider microbiome. 

Selecting the bacteriophages to use for therapy can be difficult. While phages are easy to find, considering they live practically everywhere, phages like to attack specific bacteria, so you need to find the correct one to use. Like with antibiotics, bacteria can develop resistance to bacteriophages. Some research suggests that using a mix of many bacteriophages and using only deadly (to the bacteria) bacteriophages can prevent the development of resistance.

Some issues are unique to bacteriophages because they are viruses. Firstly, phages require direct contact with the bacteria to work, making administering them difficult. For example, it is easy to put medication on a skin infection, but it is much harder to get medication that reaches the brain. Another issue is that upon encountering the bacteria, the phages multiply. The initial amount of bacteriophages delivered is smaller than the amount that patients will end up with, and there is uncertainty whether large amounts of phages can cause harm. 

While the promise is great, there is still too little evidence of bacteriophages' effectiveness, and further research in the area will be needed to determine whether bacteriophages can revolutionise the future of antimicrobial medicine.