A hot topic in the global health scene, antimicrobial resistance is a major concern for both humans and animals alike. The World Health Organization defines antimicrobial resistance as “when microorganisms such as bacteria, viruses, fungi and parasites change in ways that render the medications used to cure the infections they cause ineffective” (1). Now, this process is a natural evolutionary function, but due to misuse and over-prescribing, we have sped up the rate at which it occurs. A popular example of this phenomenon is antibiotic resistance, when bacteria have evolved to outlast the medicines used to treat them. Some scientists threaten that we have entered the “post-antibiotic era”, a time when our antibiotics will no longer be effective and diseases which have been controlled will be life-threatening once again (2). But is it an empty threat? Already illnesses such as tuberculosis, pneumonia, and gonorrhea have shown signs indicating a level of antibiotic resistance as they become more challenging if not impossible to treat (3). So where do we go from here? How can we escape the “post-antibiotic era” and what alternatives are available? Responsible antibiotic stewardship is a great step forward and is a concept that is heavily enforced in medical pursuits, but is there something else out there that could be used to alleviate the burden on antibiotics? There could be, and it is called phage therapy.
Surprisingly, phage therapy is not a novel concept and was developed by Felix d'Herelle in Soviet Russia, but was discarded as non-viable by Western Medicine due to the lack of supporting research (4). It was tabled until the early 2000s as concerns about antibiotic resistance arose and alternative therapies needed to be explored. But what is a bacteriophage and how do we find them? Bacteriophages are a type of virus existing everywhere bacteria is present. In an interview with Dr. Lucy Grist regarding her research on phage therapy, I learned that phages are collected from cultures from different samples including soil and sewage. The cultures are analyzed to differentiate the phages and identify the more lytic, more effective at killing bacteria, strains (5). Now that we have a general understanding of how phages are collected, we can better understand this treatment. The key principle of phage therapy is the utilization of virulent bacteriophages to attack and kill bacteria in a host (6). This process entails collecting and culturing a sample from the patient, then once the pathogenic bacteria is identified from the culture, the isolate is tested for sensitivity to phages (2). Based on results from the culture and sensitivity, a decision about whether or not to use this treatment can be determined. Since phages can be administered via many different routes, identifying the proper route is essential.
The key to phage therapy is understanding that it is a very targeted and specific treatment, and so commercial production of these phages is not viable. While this is a disadvantage as it is not a one-size-fits-all approach, by creating a phage library and using combinations of phages some of the issues inherent in this therapeutic approach can be overcome. Scientists recommend building a library of these phages not only to simplify which phage to use for a certain bacteria, but also to identify any overlap where one phage can treat multiple bacterial pathogens, thereby allowing utilization of combined phage therapy (2). This treatment can be used on its own or in addition to antibiotic therapy with success. It should also be noted that phage resistance can occur, so treatments should be monitored and samples should be consistently collected and tested for resistance (2). To help mitigate this risk, Dr. Grist recommends using a phage cocktail (5). However, despite its shortcomings, there is evidence supporting a promising future for this therapy. Studies have shown that phage therapy is particularly helpful in controlling multi-drug resistant organisms and the ESKAPE pathogens including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (7).
Phage therapy is a relatively new alternative to antibiotics using lytic bacteriophages to kill specific, sensitive bacterial pathogens. Success for this therapy requires building a phage library and using mixtures of phages to treat susceptible infections. While these phages cannot be produced on a commercial level and resistance can develop, utilizing the library and consistently monitoring treatment can mitigate these disadvantages. While there is still much research needed in this field, there is a promising future for phage therapy and escape from the “post antibiotic era” world we find ourselves in. By having a viable therapeutic alternative, we can reduce the burden on antibiotics and ultimately lessen the development of antibiotic-resistant strains. This means having the ability to control and treat diseases that could be life-threatening and also maintaining the ability to perform essential medical procedures such as organ transplant and surgery. Fighting antibiotic resistance is a global endeavor ensuring the effectiveness of modern medicine, and is something we all need to recognize.
To learn more about antibiotic resistance and what research is being done in this field, check out the World Health Organization link below!
References
Who.int. 2017. Antimicrobial resistance. [online] Available at: <https://www.who.int/news-room/q-a-detail/antimicrobial-resistance> [Accessed 1 March 2021].
Cui, Z., Guo, X., Feng, T. and Li, L., 2019. Exploring the whole standard operating procedure for phage therapy in clinical practice. Journal of Translational Medicine, [online] 17(1). Available at: <https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-2120-z>.
Who.int. 2020. Antibiotic resistance. [online] Available at: <https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance> [Accessed 1 March 2021].
Chanishvili, N., 2012. Advances in Virus Research. 83rd ed. Elsevier, pp.3-40.
Grist, L., 2021. A Discussion on Phage Therapy.
Marza, J., Soothill, J., Boydell, P. and Collyns, T., 2006. Multiplication of therapeutically administered bacteriophages in Pseudomonas aeruginosa infected patients. Burns, [online] 32(5), pp.644-646. Available at: <https://www.sciencedirect.com/science/article/abs/pii/S0305417906000428?via%3Dihub>.
El Haddad, L., Harb, C., Gebara, M., Stibich, M. and Chemaly, R., 2018. A Systematic and Critical Review of Bacteriophage Therapy Against Multidrug-resistant ESKAPE Organisms in Humans. Clinical Infectious Diseases, [online] 69(1), pp.167-178. Available at:
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