Earlier this semester, my grandpa passed away at the age of 74.  A staph infection that was resistant to antibiotics weakened his immune system beyond repair and he soon died from an opportunistic infection.  My family felt helpless because his infection was resistant to antibiotics, so there was little the doctors could do to treat it.  Current data from the Centers for Disease Control and Prevention suggests that there are at least 2 million resistant infections in the US alone each year, about 1% of which are fatal.  Dr. Margaret Chan, director of the World Health Organization stated this April that “the world is heading towards a post-antibiotic era in which common infections will once again kill.”  We need to develop better treatments for resistant infections soon, not only for our grandparents, but for everyone alive today, and for the generations to come after us.  I would like to propose phage therapy as an effective and sustainable alternative to chemical antibiotics.  I first learned about phage therapy earlier this year when I presented an article as part of my pre-pharmacy coursework, and it frustrates me to think that phage therapy could have saved my grandpa and given us a few more years together.

Though you may be unfamiliar with it, I hope that after reviewing its advantages over traditional antibiotics, you will soon recognize phage therapy as the preferred solution for the global problem of antibiotic resistance.

Problems with Chemical Antibiotics

To reiterate, our problem is that many bacterial infections are becoming resistant to chemical antibiotics and are thus very difficult to treat.  Unfortunately, this resistance can arise relatively quickly.  In a study published in Science this September, researchers at Harvard Medical School were able to create highly resistant bacteria in less than two weeks.  Pharmaceutical companies have also begun to realize that their antibiotics become obsolete quickly and are thus reluctant to invest in developing new antibiotics.  Chemical antibiotics were effective in the short run, but we now need something better.

What Are Bacteriophages?

In order to understand my proposed solution to this problem, we must first understand what bacteriophages are.  Bacteriophages, or phages for short, are viruses that infect bacteria.  They are the most abundant life forms on the planet and are present wherever bacteria are present, including within our bodies.  In the phages life cycle, it attaches to the bacteria’s membrane, injects its genetic material, replicates inside of it, and the next generation bursts through the membrane, killing the bacterium.  Phage therapy utilizes this natural mechanism to destroy the bacteria that make up infections.  Phage therapy has been used safely and effectively to treat bacterial infections in Russia, Poland, and the Republic of Georgia for roughly 90 years, and research to develop therapies in the US has recently begun in response to the problem of antibiotic resistance.

Advantages For Treating Resistant Infections

Now that we know what phage therapy is, we can talk about its advantages for treating resistant bacteria, which I obtained from a 2016 review by Rehna et al.  The most important advantage is that phage therapy performs just as well against resistant infections as it does against bacteria that are sensitive to antibiotics.  Another important advantage is that there is a lower risk of bacteria developing resistance to phage therapy.  Phages evolve alongside bacteria and are able to counter advantages that bacteria develop.  When a bacteriophage treatment becomes obsolete, new effective therapies can be prepared to replace it in a matter of weeks because effective phages are easy to discover.  Lastly, phages have a very high specificity, so one strain of phage would target just one strain of bacterium.  This would prevent phages from killing the so-called “good bacteria” that are important for our health.

Concerns

Despite its advantages, some people do have concerns about phage therapy
Some are worried about the possibility of bacteriophages transferring genes between bacteria or they’re worried that patients will develop immune responses to the treatments.  However these concerns are largely theoretical, and it’s safe use in other countries over the last several decades raises no practical concerns.

But the main challenge facing phage therapy in the United States is the FDA’s current restrictions on the approval of antibiotics.   The FDA requires new clinical trials for a drug when it is altered in any way.  These regulations are incompatible with the dynamic nature of phages.  The FDA regulations are designed around chemical antibiotics, but as a 2012 article in the journal Frontiers in Microbiology states, efforts to treat resistance with chemical antibiotics are “static responses to a dynamic problem.”  We obviously want to maintain regulations that are important for our safety, but if we want the dynamic and sustainable solution to resistance that phage therapy affords, changes must be made.

What We Can Do

With the global crisis of antibiotic resistance looming, it is clear that the FDA must revise their restrictions on drug approval in order to accommodate phage therapy.   I have created a Change.org petition to an FDA official to make this change.  If you want to help save the lives of those we care about and improve the future of healthcare, please sign this petition.

What Reason Do We Have to Believe that the FDA Will Change Their Regulations to Accommodate Phage Therapy?

1. According to an article published earlier this November by NPR, President-Elect Donald Trump has promised to push the FDA to loosen their regulations in order to expedite the process of drug approval for life-saving medications.  This could involve modifications that would make phage therapy feasible within our health system.

2. According to a review published in 2012 in Frontiers in Microbiology, the FDA has made an exception in the past to their rule that any changes to a medication require a new set of clinical trials.  The FluMist® influenza vaccine is reformulated every year to target particular strains of influenza.  The FDA has validated their development system and does not require clinical trials every year.  This model could be applied to phage therapy to make development more feasible. 

3. Lastly, the FDA has already approved the use of bacteriophages as a food additive.  In 2006, the FDA approved a mixture of 6 different bacteriophage strains to prevent listeria contamination in meat and poultry products.  Because the preparation was considered a food additive and not a drug, it was not held to the same standards and was approved for use.  This example shows that the FDA is at least open to considering the potential that bacteriophages may have as an antibiotic.

Although there is still more research to be done to develop phage therapy in the United States, I hope that we will soon have access to a sustainable solution to the problem of antibiotic resistance.
With your help, we can make all bacterial infections treatable again.  

 
References:

1. Baym, Michael et al. “Spatiotemporal microbial evolution on antibiotic landscapes.” Science. 353 (6304) 1147-1151. 9 Sep. 2016. http://web.b.ebscohost.com.libraryproxy.uwp.edu:2048/ehost/command/detail?sid=69f466c4-d4b9-42c7-9e73-4db1da96d7a2%40sessionmgr103&vid=3&hid=123 Web. 19 Nov. 2016.

2. Centers for Disease Control and Prevention. “Antibiotic / Antimicrobial Resistance”. Centers for Disease Control and Prevention. US Department of Health and Human Services, 25 Oct. 2016. https://www.cdc.gov/drugresistance/ Web. 2 Dec. 2016.

3. Chan, Margaret. “WHO Director-General briefs UN on antimicrobial resistance”. World Health Organization. World Health Organization, 18 April 2016. http://www.who.int/dg/speeches/2016/antimicrobial-resistance-un/en/ Web. 2 Dec. 2016

4. Keen, EC. Phage therapy: concept to cure. Frontiers In Microbiology. Switzerland, 3, 238, July 19, 2012. ISSN: 1664-302X. https://www.ncbi.nlm.nih.gov.libraryproxy.uwp.edu:2443/pmc/articles/PMC3400130/ Web. 15 Nov. 2016.

5. Kelly, Amita and Barbara Sprunt. “Here Is What Donald Trump Wants To Do In His First 100 Days.” NPR. NPR, 09 Nov. 2016. http://www.npr.org/2016/11/09/501451368/here-is-what-donald-trump-wants-to-do-in-his-first-100-days Web. 17 Nov. 2016.

6. Rehna, A., et al. "Bacteriophage Therapy." International Journal Of Pharmaceutical, Chemical & Biological Sciences 6.2 (2016): 117-123. Academic Search Complete. http://web.a.ebscohost.com.libraryproxy.uwp.edu:2048/ehost/pdfviewer/pdfviewer?vid=2&sid=2860730e-e68e-4088-97f1-129ce8e7ef65%40sessionmgr4009&hid=4207 Web. 17 Nov. 2016.

7. U.S. Food and Drug Administration. “FDA Approval of Listeria-specific Bacteriophage Preparation on Ready-to-Eat (RTE) Meat and Poultry Products.” U.S. Food and Drug Administration. U.S. Department of Health and Human Services, 5 Nov. 2014. http://www.fda.gov/food/ingredientspackaginglabeling/ucm083572.htm Web. 20 Nov. 2016