Beyond the Blue and White

Antibiotic Resistance: The Fight Against Microscopic

Organisms That Create Macroscopic Damage
Jessica Reyer
April 15, 2016

Antibiotics. They seem to be the solution to almost any disease, well, a bacterial
disease anyways. No one thought that such a great discovery could cause any
problems; however, this is not the case. Due to the extensive use of antibiotics in the
United States and around the world, resistant bacteria have begun to arise. The
existence of these resistant bacteria has started the crisis of antibiotic resistance. This
problem is developing and will continue to develop into a very dangerous worldwide
crisis. There are currently strains of Methicillin-resistant Staphylococcus aureus
(MRSA) and E. coli that are resistant to all modern medications used to treat them in
humans.1 Treating these resistant diseases can become very costly and potentially very
dangerous because medications from decades ago with harmful side effects are the
only ones that can treat them.2
With such as serious issue at hand, changes need to be made in order to slow down the
progress of antibiotic resistance. Currently there are solutions available but there must
be national support in order for them to work. Phage therapy is an effective
replacement to antibiotics for both humans and animals. Another piece to this solution
is placing restrictions on the amount of antibiotics used for livestock, especially when it
comes to use for production purposes. If a change is not made soon, the appearance
of several types of super-resistant bacteria is very likely, and that will be a much more
challenging situation to deal with then the current one.

What Are Antibiotics?

Antibiotics are a type of medicine that target bacteria and either kill them or prevent
them from reproducing.3 There are antibiotics that target a wide range of bacteria while

others will only target a few types. Each antibiotic may work differently depending on
the substance being used along with the type of bacteria that is being targeted. For
example, some antibiotics affect the function of bacteria, and some target the cell wall of
the bacteria.4
Antibiotics were first developed when Alexander Fleming observed that Penicillin
notatum was able to prevent the growth of the bacteria Staphylococcus in 1928. This
allowed for research to be done on Penicillin leading to the use of Penicillin to treat an
infection for a policeman in 1941.5 Since the development of Penicillin as an antibiotic,
countless other antibiotics have been developed and used to treat numerous diseases.
These drugs have saved so many lives and continue to do so everyday. They help to
save people whose bodies are going into sepsis or even help young kids get over ear
infections. Antibiotics have served as the foundation for medical treatment since they
gained popularity, but that popularity is also leading to deadly effects.

How Have Bacteria Become Resistant?

In order for these bacteria to become resistant, they must develop a mutation that
makes them different. Mutations can occur when the bacterial DNA is replicated. There
are different types of mutations that occur such as the deletion of one nucleotide in the
entire genome. There is also insertion of a single nucleotide, substitution of one
nucleotide for another, and a frame shift mutation, which usually occurs with an
insertion or deletion mutation.6 These mutations can change the genes that are
expressed by a certain bacteria or the bacteria it produces. Changing one protein of a
cell can alter its cellular membrane or its cell signaling.

Chart reproduced from: "How Antibiotic Resistance Happens." Digital image. Centers
For Disease Control and Prevention. April 17, 2015. Accessed April 8, 2016.
http://www.cdc.gov/getsmart/community/images/how-ar-happens.jpg.

Mutations
such as
these
occur
randomly
with in the
replication
of bacterial
cells. One
of these
could
change the
cell wall of
a bacterial

cells that prevents it from letting antibiotic particles into the cell. Antibiotics do not kill
these mutated cells, so the bacteria are then free to replicate in their host environment.7
From this environment they can be spread between host environments such as
humans. All different species of bacteria have been able to evolve in order to survive
the presence of antimicrobial drugs.

The Current Implications of Resistant Bacteria

The widespread use of antibiotics has allowed for resistant bacteria to evolve. Strains
of bacteria have become completely resistant to all modern antibiotics.8 Certain
diseases can now only be treated with medications that havent been used for decades
and have other potentially harmful implications. These treatments can also become
very expensive. With different strains of bacteria being resistant to drugs, it becomes
difficult to effectively treat some diseases. If multiple antibiotics are used to try to treat a
resistant strain then a patient may suffer from the effects of healthy bacteria being
killed off. With continued use of antibiotics throughout the United States and other
countries with modern medicine, resistant strains of all different bacterial diseases will
form. These diseases will not be able to be treated in the same ways as in the past.9
With completely resistant strains forming, there is also a high probability that these
strains will spread. Epidemics and possibly pandemics of diseases that were believed
to be curable could break out. These superbugs could lead to events similar to those
that happened with cholera and even viral infections. All of the modern medicine that
was believed to be so great would become completely useless. The idea of the world
returning to the days of widespread illness is an absolutely terrifying one. Without other
forms of medicine or restrictions on the current use of antibiotics to treat human
diseases, this issue will continue to progress with the possibility of reaching a point
where new treatments may not work.
Not only are antibiotics widely used to treat diseases in humans, but also they are used
even more when it comes to using them in the food industry. Eighty percent of the
antibiotics used in the Untied States are given to farm animals.10 The majority of the
antibiotics given to animals are given for medical purposes; however, antibiotics are
used for other purposes as well. In the agricultural industry, antibiotics can help to
increase growth rates for livestock and to increase the size of these animals so they
become more profitable.11 The large-scale use of these drugs for unnecessary purposes
is also contributing to the problem of antibiotic resistance.

Authors estimates based on: United States of America. Food and Drug Administration.
2012 Summary Report on Antimicrobials Sold or Distributed for Use in Food-Producing
Animals. September 2014. Accessed April 3, 2016.
http://www.fda.gov/downloads/ForIndustry/UserFees/AnimalDrugUserFeeActADUFA/UC
M416983.pdf.

Although not all bacterial diseases that infect animals have the ability to infect humans,
there is the possibility that a certain strain of bacteria could mutate to infect humans or
other animals. In addition the resistant bacteria may form within the livestock
themselves and create the same problems in agriculture as there are with humans and
resistant strains of bacteria.12 Because these mutant strains may form in livestock that
are used for food, the resistant bacteria could be transferred to humans. The reign of
antibiotics in medicine and in the agricultural industry needs to come to an end in order
to slow down the progression of antibiotic resistance.

Phage Therapy
One potential solution that could help to slow-down the progression of antibiotic
resistance is phage therapy. Phage therapy is an alternate form to kill bacteria by using
bacteriophages, also known as phages. Bacteriophages are viruses that infect bacteria
and replicate inside the cell. Eventually they lyse the cell, or break it open, and the
replicated phages infect other bacterial cells (image below). Then, this process repeats
until all of the targeted bacteria are killed.13 Phage therapy helps to kill off only the target
bacteria and not all of the healthy bacteria in the body unlike some antibiotics.
Antibiotics are considered a big hammer and phage therapy is a guided missile when



treating bacterial infections.14
Phages can also be found almost
anywhere in nature like in soil, in
lakes, on plants, etc. There is no
shortage on the amount of
bacteriophages present on this
earth.

Process by which Phages Infect and Lyse
Bacteria

When using phages to treat a

bacterial infection, a cocktail of
different phages are used. This
helps to kill mutant strains of
bacteria along with preventing
resistant strains of bacteria from
forming. With multiple types of
phage present, all of the bacteria
will be killed off. This prevents
Chart reproduced from: Bacterial Lysis through
Bacteriophages. Digital image. Microbial World. August 31,
mutant strains of bacteria from
2011. Accessed April 9, 2016.
becoming resistant. The use of a
http://microbialworld.blog.com/files/2011/08/f248049cfa.jpg.
cocktail of phages is very similar

for the use of a cocktail when
treating HIV because of its easy mutation. In addition, phages can be used to treat
antibiotic resistant bacteria and low dosages are needed when using phage therapy.15
With this crisis of antibiotic resistance occurring, phage therapy would be an almost
perfect solution to slow down and even end this crisis. It has been effectively used in
Russia to treat patients since it was first developed in the 1920s. It was even used in
the United States in the 1920s and some of the 1930s until the creation of antibiotics.
With the threat of antibiotic resistance, European countries have started to look to
funding clinical trials with phage therapy. In 2014, the European Commission talked
about giving $5.2 million towards funding Phagoburn. Phagoburn is the first large,
multi-center clinical trial of phage therapy to treat human infections in Switzerland.16
The United States cannot continue to use antibiotics as much as it currently does or has
in the past. The government should start funding clinical trials for phage therapy in the
U.S. in similar manner to the European Commission funding Phagoburn. If clinical trials
arent funded then there will be no chance for phage therapy to replace antibiotics. The
National Health Institute (NIH) would be the best possible way to start these clinical
trials. With being such a large research institute and having a large presence in
medicine, it could easily influence private institutions to start clinical trials as well. The

NIH successful background of bring new techniques and practices into United States
medical care would be the perfect stepping stool to bringing phage therapy into practice
in the U.S.17 After clinical trials have been down, phage therapy can start to be
integrated into hospitals and private practices as treatment.
Although funding clinical trials would help to start the use of the phage therapy in the
U.S., there would have to be additional funding or regulations in place to continue its
use. Phage therapy has very few disadvantages when it comes to the medical side,
however, there are a few more on the financial side. Because phages are naturally
occurring and the cocktails are created based on the disease and person being treated,
it is impossible for phages to be patented.18 It can also be expensive to create the
different cocktails, which would not be ideal for pharmaceutical companies. Having a
society so focused on prescription drugs and the pharmaceutical companies that create
them causes problems with developing new medication methods that these companies
wont make millions of dollars off of. Phage therapy needs national funding and support
in order for it to be successfully integrated into United States medical practice.
Another drawback of phage therapy is the ineffectiveness when dealing with emergency
situations. It takes too long to develop a phage serum when dealing with a patient
going into sepsis.19 Because of this, there would need to be regulations put in place to
limit the use of antibiotics to emergency situations like sepsis. A limit on the antibiotic
use to emergency situations would drastically reduce the ability of antibiotic resistance
to progress to an unmanageable point. Although phage therapy is not the most
financially efficient way to combat this crisis, it is an effective alternative that can be
instituted immediately. Phage therapy and limits on antibiotics for human use is only
one part of a solution that could slow the progression of this crisis.

Limits on Antibiotic Use with Livestock

The use of antibiotics for non-medical reasons in livestock is another large contributor to
the problem of antibiotic resistance. The FDA has started to put guidelines in place for
pharmaceutical companies regarding the sale of antibiotics. Their plan is to remove
antibiotics for production purposes by taking a collaborative approach.20 The issue with
this current approach is that it will cost pharmaceutical companies large profits by
stopping the sale of antibiotics for production purposes. In order for the FDA to
effectively carry out their goal of eliminating this use of antibiotics, they must put
regulations on antimicrobial drugs. The FDA must prevent the sales of antibiotics used
for production in order to completely end their use. With these restrictions in place,
antibiotics will not be able to be used for any purpose other than for medical reasons.

Creating a situation where the use of antibiotics for production purposes would slow the
progress of antibiotic resistance.
It will be difficult for pharmaceutical companies to stop celling antibiotics for production
purposes. These regulations must be placed directly on the pharmaceutical companies
that sell the antibiotics along with any farm that would use them. Creating a fine for
farms that give antibiotics to their livestock for production purposes would further reduce
the use of these drugs. The fine would need to be great enough that there would be
loss of profit for those who attempt to use antibiotics for non-medical reasons.
Otherwise, these farmers would find ways to use them in order to keep their production
at its current status. Without regulations and fines in place, the goal of completely
eliminating them will never come to fruition. Placing regulations on these antibiotics
may create a lot of backlash, but the benefits of something like this far outweigh the
drawbacks.
This issue is becoming a lot larger than what many people believe it to be. It will only
continue to grow if changes are not made now. With regulations such as these and
investment in phage therapy, the issue of antibiotic resistance in the United States will
not become the fatal problem that is has the potential to become. If these steps are
taken by the U.S. to help stop this crisis, other countries may follow in its footsteps to
prevent this from escalating to a deadly global crisis.

Endnotes
1 Gelband,

Hellen, Molly Miller-Petrie, Suraj Pant, Sumanth Gandra, Jordan Levinson,

Devra Barter, Andrea White, and Ramanan Laxminarayan. The State of the World's
Antibiotics 2015. Report. 2015. Accessed April 9, 2015.
https://cddep.org/sites/default/files/swa_2015_final.pdf.
2 https://cddep.org/sites/default/files/swa_2015_final.pdf.
3 " U.S. National Library of Medicine, MedlinePlus, Antibiotics, https://www.nlm.nih.gov/
medlineplus/antibiotics.html (accessed April 2, 2016).
4 NPS MedicineWise, NPS Medicine Wise, What are antibiotics and how do they
work? http://www.nps.org.au/medicines/infections-and-infestations/antibiotics/forindividuals/what-are-antibiotics-and-how-do-they-work (accessed April 3, 2016).
5 America Chemical Society, ACS: Chemistry for Life, Discovery and Development of
Penicillin, http://www.acs.org/content/acs/en/education/whatischemistry/landmarks/
flemingpenicillin.html (accessed April 2, 2016).
6 The University of California Museum of Paleontology, Understanding Evolution, DNA
and Mutations, http://evolution.berkeley.edu/evolibrary/article/mutations_01 (accessed
April 3, 2016).
7 https://cddep.org/sites/default/files/swa_2015_final.pdf.
8 Ibid.
9 Ibid.
10 GRACE Communications Foundation, GRACE Communications Foundation,
Antibiotics, http://www.sustainabletable.org/257/antibiotics (accessed April 4, 2016).
11 http://www.sustainabletable.org/257/antibiotics.
12 https://cddep.org/sites/default/files/swa_2015_final.pdf.
13 Sulakvelidze, Alexander, Zemphira Alavidze, and J. Glenn Morris. "Bacteriophage
Therapy." Antimicrobial Agents and Chemotherapy. March 2001. Accessed April 3,
2016. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90351/.
14 Reardon, Sara. "Phage Therapy Gets Revitalized." Nature 510, no. 7503 (June 5,
2014): 15-16. Accessed April 2, 2016. doi:10.1038/510015a.
15 Reardon, 510.
16 Ibid.
17 "What We Do | National Institutes of Health (NIH)." U.S National Library of Medicine.
Accessed April 6, 2016. http://www.nih.gov/about-nih/what-we-do.
18 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90351/.
19 Ibid.
20 "U.S. Food and Drug Administration." FDA's Strategy on Antimicrobial Resistance.
Accessed April 3, 2016.
http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforInd
ustry/ucm216939.htm.

Images
Bacterial Lysis through Bacteriophages. Digital image. Microbial World. August 31,
2011. Accessed April 9, 2016.
http://microbialworld.blog.com/files/2011/08/f248049cfa.jpg.
United States of America. Food and Drug Administration. 2012 Summary Report on
Antimicrobials Sold or Distributed for Use in Food-Producing Animals. September 2014.
Accessed April 3, 2016.
http://www.fda.gov/downloads/ForIndustry/UserFees/AnimalDrugUserFeeActADUFA/U
CM416983.pdf.
"How Antibiotic Resistance Happens." Digital image. Centers For Disease Control and
Prevention. April 17, 2015. Accessed April 8, 2016.
http://www.cdc.gov/getsmart/community/images/how-ar-happens.jpg.