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The Rise and (Hopeful) Fall of Antibiotic Resistance
Thomas Bina – ENGL 137
It is an understatement to say that it is difficult to conceive what life would be like
without certain technologies. Particularly in the realm of science, work has come incredibly far
in an incredibly short period of time. The developments that have come about even in the last
century are astounding. However, such rapid growth of knowledge also brings with it ignorance.
Such is the case with the discovery and development of antibiotics. Though the development of
that class of drug resulted in a shift of the entire human experience, we have rushed too fast into
it. And now, we face a health crisis which will require us to reconsider how we have been
dealing with antibiotics for the past 50 years.
To properly chronicle the history of antibiotics, it is necessary to begin with the discovery
that bacteria are disease causing agents. This revelation dates back to 1854. A doctor by the
name of John Snow was investigating a cholera outbreak in London. The outbreak was crippling
for the community as it faced a mortality rate exceeding 12.8 percent in some areas.14 At the
time, the dominant belief was that disease is caused by a “miasma” – bad air which arose from
sewage and other organic wastes. However, Snow’s observations were inconsistent with this
belief. Instead, he was able to link the disease to the town’s public water pump. Upon further
study, Snow found cholera bacteria in that water and was able to link the disease to it. Though
famed for this discovery in modern times, the idea was still unaccepted until after Snow’s death
when Louis Pasteur validated the germ theory of disease in the 1860s. While not hugely
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applicable to modern antibiotic resistance, this discovery by Snow and Pasteur’s following
research and experiments display a key facet of science. Factual evidence is the only necessary
catalyst required to change decades of previously held ideas.
Additionally, scientific discovery always builds upon itself. No discovery happens
independently. Sir Isaac Newton famously stated “If I have seen further than others, it is by
standing on the shoulders of giants.” And so, the true story of antibiotics begins 70 years after
Snow conjectured that bacteria were the cause of cholera. In fact, its beginning was rather
serendipitous. In 1928, Alexander Fleming returned from holiday to find mold on his petri
dishes, which were supposed to be growing Staphylococcus bacteria. This bacterium is a cause of
boils, sore throats, and abscesses. Shockingly, this mold – a strain of Penicillin notatum – created
a zone of growth inhibition around it. It prevented the harmful bacteria from growing. Upon
further experimentation, Fleming found this “mold juice” to be capable of killing a wide range of
harmful bacteria .12 However intriguing this discovery was at the time, the gravity of it was
largely unrecognized at the time of its publication. Not until 1941 was penicillin utilized for
medical purposes after the work of a number of other researchers.
The development of penicillin as a drug lined up almost perfectly with World War II. At
that time, WWII had been raging in Europe for the better part of two years. The number of
casualties was staggering. Many did not die in the fighting but rather by bacterial infections from
Staphylococcus, Streptococcus, and Pneumococcus – all bacteria which are killed by penicillin.
There was an incredible drive to produce penicillin for the war effort which led to great effect.
The death rate from bacterial infection fell to less than one percent. Compare that to the 18
percent it was during World War I.11 After learning of this new “miracle” drug, unsurprisingly
there was tremendous demand of penicillin for civilian usage. Though the drug was rationed
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during the war, production increased massively following it. Production of penicillin was at 21
billion units in 1943, and then 1,663 billion units in 1944 before jumping again to 6.8 trillion
units by 1945.12 These incredibly high levels of production met the understandably high demand.
There was no other alternative in medicine at the time. At that time 50 years ago, this drug
seemed to cure almost every ailment under the sun.
But think about today. No one goes to their doctor asking for penicillin. Why? Penicillin
seemed to be the answer to all medical woes. Well, quite simply, it does not work anymore.
Penicillin is no longer sufficient to combat modern bacteria. The reason behind that fact boils
down to a single idea: evolution. The use of antibiotics, such as penicillin, creates artificial
pressures upon bacteria. Most of the bacteria are killed by the antibiotic. But those that do resist
the antibiotic and survive long enough to reproduce give rise to a new strain, resistant to the very
antibiotic which was intended to kill them. Over time as the antibiotic is used more, that resistant
strain becomes more common and propagates more and more. And soon enough, the antibiotic
which was intended to kill the bacteria is entirely ineffective. The very use of antibiotics is what
eventually makes them obsolete, unable to kill bacteria. Now, if that does not sound too bad,
remember that the development of penicillin dropped the mortality rate of infections by about 20
fold. Life expectancies have jumped from 56.4 years to 80 in the years since antibiotics have
been introduced.15 Penicillin alone is estimated to have saved 200 million lives.2
Why has this problem not been addressed before? Scientists have predicted that it would
occur. Alexander Fleming himself spoke about the possibilities of resistance during his Nobel
Prize lecture:
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But I would like to sound one note of warning. Penicillin is to all intents and
purposes non-poisonous so there is no need to worry about giving an overdose and
poisoning the patient. There may be a danger, though, in underdosage. It is not difficult to
make microbes resistant to penicillin in the laboratory by exposing them to
concentrations not sufficient to kill them, and the same thing has occasionally happened
in the body.
The time may come when penicillin can be bought by anyone in the shops. Then
there is the danger that the ignorant man may easily underdose himself and by exposing
his microbes to non-lethal quantities of the drug make them resistant. Here is a
hypothetical illustration. Mr. X. has a sore throat. He buys some penicillin and gives
himself, not enough to kill the streptococci but enough to educate them to resist
penicillin. He then infects his wife. Mrs. X gets pneumonia and is treated with penicillin.
As the strep-tococci are now resistant to penicillin the treatment fails. Mrs. X dies.6
Essentially antibiotic resistance has been ignored because the problem has not been so severe as
to require action. It has been far easier to find a replacement drug than to address the root
problem behind the development of resistance. After bacteria became penicillin resistant,
scientists moved to streptomycin. When bacteria became resistant to that, scientists moved to
chloramphenicol. Then chlortetracycline, to rifampicin, to vancomycin, to ciprofloxacin, to
linezolid, to daptomycin, etc.10 As soon as bacteria became resistant to one class of antibiotic,
researchers moved on to the next and the next and the next for the last 50 years. However, this
model of development has reached its last breaths. Bacteria have a distinct advantage over
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researchers trying to develop antibiotics. The incredibly rapid reproduction rates of bacteria
mean that they can adapt to a new antibiotic far faster than scientists can develop the drug to
replace its predecessor. Resistant strains of bacteria are appearing far more rapidly than ever
before. While it took 22 years for penicillin resistant pneumococcus to develop, it took only a
single year before bacteria developed resistance to ceftaroline – an antibiotic developed in 2011.1
That change is reflected in the numbers of illnesses caused by antibiotic resistant bugs.
Each year in the United States, over two million illnesses and twenty three thousand deaths are
attributed to resistant bacteria.5 The widespread emergence of antibiotic resistance in the face of
these numbers is terrifying for those in healthcare professions. It has become incredibly difficult
to treat patients afflicted by bacterial diseases. Nowhere is the problem more prevalent than in
the intensive care unit (ICU). Antimicrobial resistance has emerged as one of the largest outcome
determining factors for patients in the ICU. Infections caused by antibiotic resistant bacteria
make it incredibly difficult to give patients proper treatment leading to longer hospital stays and
increased in-hospital mortality rates.7 The absolute worst case scenario is the development of a
“superbug” – a bacterium resistant to all known antimicrobials. Such a bug, if uncontained, could
result in a pandemic quite reminiscent of the Bubonic plague which afflicted Europe and killed
more than 20 million people, a third of the population at the time.4 Though that is certainly the
worst possible outcome, antibiotic resistance presents a very real challenge for modern day
medicine. Dr. Keiji Fukuda, the World Health Organization’s Assistant Director-General for
Health Security has stated, “Without urgent, coordinated action by many stakeholders, the world
is headed for a post-antibiotic era, in which common infections and minor injuries which have
been treatable for decades can once again kill.”16 Following the same practices as the last 50
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years will almost certainly do nothing to remedy this problem. So the question poses itself: what
is the solution to antibiotic resistance?
The Center for Disease Control and Prevention (CDC) has actually outlined four core
actions to prevent antibiotic resistance: preventing infections and the spread of resistance,
tracking, improving antibiotic prescribing/stewardship, and developing new drugs and diagnostic
tests.5 The first action is fairly simple: avoid infection to begin with. That means following
proper hygiene like washing hands and properly cooking food, things many people do anyway.
Tracking is simply keeping data on antibiotic resistant infections, both causes and risk factors.
The fourth core action is the same thing scientists have been doing for 50 years; continue
researching and developing new ways to combat bacteria. Though it seems obvious, this point
should not be dismissed. New antibiotics have become very hard to come by in recent years. 15
of the largest 18 pharmaceutical companies have completely abandoned the antibiotic field.15
Many researchers are looking for methods other than antibiotics to combat bacterial disease. But
the main focus should be on the third core action: improving antibiotic prescribing/stewardship.
Lack of awareness regarding the risks of using antibiotics has been the single greatest contributor
to the development of resistance. Though proper knowledge and awareness will not eliminate
antibiotic resistance, it can play a key role in slowing the development and spread of resistance.
Whether or not that will happen comes down to whether the public is able to change how they
view the use of antibiotics.
Previously, antibiotics have been used as a blanket answer to any illness a patient suffers
– whether the antibiotic will be effective or not. There are a number of situations where this is
the case. Many times antibiotics are subscribed at the patient’s behest simply because they feel
the need to do something when feeling sick. The antibiotics are essentially prescribed as a
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placebo. Even more nonsensically, there are times when patients have a viral infection and
antimicrobials are prescribed. This action does literally nothing as antibiotics are designed to
target bacteria and not viruses. But there is seemingly a large proportion of the populace which
does not understand that this is the case. In fact, there seems to be a shockingly large number of
people who do not follow the proper course of action against viruses by being vaccinated –
though that is an entirely different issue. However, the onus does not fall only on the patient.
Many times when a doctor is unable to identify the specific cause of an illness, he or she will
prescribe a broad spectrum antibiotic as a protective measure against any possible
complications.3 It is also possible that the doctor can miss on a number of details regarding a
prescription, from incorrect dosage, incorrect length of treatment, or incorrect antibiotic
altogether. In total, research has shown that prescribed antibiotics are ineffective in 30 to 50
percent of cases.15
These practices have led to unnecessarily high levels of antibiotic usage, which only
serve to promote resistance to those antibiotics. But antibiotic usage by humans is not the only
consideration to make when addressing this problem. Though approximately 23 x 106 kg of
antibiotics are used annually, less than half are provided to people.9 The remainder is
administered for agriculture. To preface this section, the impact of agricultural antibiotics on
human health has not been well established. However, it is strongly suspected that resistant
bacteria from animals can be conferred into the human body, mainly through consumption of
food. There have been several studies which have established links between antimicrobial use in
livestock and resistant infections in humans through studies of direct traces to meat and poultry
operations, studies of farmers, and studies of the transfer of commensal bacteria.13 Antibiotic
usage in agriculture is often even more common than in humans. 16 percent of dairy cows
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receive antibiotic therapy. 15 percent of beef calves receive antibiotics. 88 percent of growing
swine receive antibiotics for disease prevention.8 In many cases, managed livestock operations
present an ideal environment for pathogens to be transferred between organisms, picking up
antibiotic resistance genes along the way. However, resistant bacteria from livestock can also be
transferred into the environment. Up to 90 percent of the antibiotics which livestock receive are
excreted in waste by the animals, before being dispersed by groundwater and water runoff.15 This
usage of antibiotics further engenders the development of resistance and needs to be taken into
consideration.
In both public use and in agricultural use, there is a general ignorance towards the
consequences of antibiotic overuse. Though antibiotics have been in use for the better part of a
century, they have been used recklessly, without taking heed of the possible ramifications of
their use. And now, today’s scientists are facing the consequences of that overuse – which is still
continuing to this day. But there is hope in those who have realized the global threat which is
posed by the rise of antibiotic resistance. Now that the problem is known, the next step is to
make a shift in how antibiotics are used now to prevent the current situation from becoming
worse. There is more than enough evidence for the medical community to have changed its
standing beliefs. All that is left is whether the public will develop awareness of this issue and
make changes to prevent this problem from becoming a true crisis.
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References
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"About Antimicrobial Resistance." Centers for Disease Control and Prevention. Centers
for Disease Control and Prevention, 08 Sept. 2015. Web.
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"Alexander Fleming." New World Encyclopedia. New World Encyclopedia, 1 Nov. 2013.
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"Antimicrobial (Drug) Resistance." National Institute of Allergy and Infectious Diseases.
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<http://www.niaid.nih.gov/topics/antimicrobialresistance/understanding/pages/causes.asp
x>.
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"Black Death." History.com. A+E Networks, 2010. Web.
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Center for Disease Control and Prevention. Antibiotic Resistance Threats in the United
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and Prevention. Web.
6.
Fleming, Alexander. "Penicillin." Nobel Lecture. Stockholm. 11 Dec. 1945. Web.
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Unit." Annals of Internal Medicine 134.4 (2001): 298-314. 20 Feb. 2001. Web.
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Policy, and Potential.” Public Health Reports 127.1 (2012): 4–22. Print.
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Antimicrobial Chemotherapy 49.1 (2002): 25–30. Web. 1 Nov. 2016.
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Lewis, Kim. "Platforms for Antibiotic Discovery." Nature Reviews Drug Discovery 12
(2013): 371-87. Nature. Nature, 30 Apr. 2013. Web.
11.
Markel, Howard. "The Real Story behind Penicillin." PBS. PBS, 27 Sept. 2013. Web.
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12.
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Development of Penicillin. N.p.: Royal Society of Chemistry and American Chemical
Society, 1999. Print.
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"Science of Resistance: Antibiotics in Agriculture." Alliance for the Prudent Use of
Antibiotics. Tufts University, n.d. Web.
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Vachon, David. "Father of Modern Epidemiology." John Snow - Historical Giant in
Epidemiology. UCLA Department of Epidemiology, May-June 2005. Web.
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Ventola, C. Lee. “The Antibiotic Resistance Crisis: Part 1: Causes and Threats.”
Pharmacy and Therapeutics 40.4 (2015): 277–283. Print.
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to Public Health. Geneva: World Health Organization, 30 Apr. 2014. Print.