Marc Siler

Writing 39C
R. Mykkanen
4/17/14
Antibiotic resistance has been an on-going battle since the beginning of pharmaceutical
medicines and is an issue of increasing importance with every passing year; it is imperative that
we work to solve this issue before it becomes even worse than it currently is. Upon initial
discovery, antibiotics were deemed wonder drugs and medical miracles. They helped to save
thousands of lives and increase human lifespan. However, as soon as antibiotics became
available for the public, bacteria were already developing resistance. And now, each year,
thousands of people die due to infections from antibiotic resistant bacteria. Humans have relied
on antibiotics to remedy symptoms of fevers and sore throats and coughs so much that many may
take antibiotics for granted. One must realize that antibiotics have existed for only less than a
century, and now we are running out of antibiotics.
In order to under antibiotic resistance, one must understand what antibiotics are, and how
they work. Alexander Fleming first discovered antibiotics in 1928, when he observed that a
strain of Penicillium mold inhibited the growth of certain harmful bacterium, and named it
penicillin. Although Fleming made this discovery, he was unable to isolate, purify, and
synthesize the strain. This did not discourage other scientists from working with penicillin;
eventually two scientists from Oxford, Howard Florey and Ernest Chain, were able to describe
procedures for purification in 1940. This led to production and distribution of penicillin in the
40s (Aminov, 8). Soon Pfizer, a pharmaceutical corporation, discovered a way of large-scale
production of penicillin by a process of deep tank fermentation [Flavell-While, 55]. Antibiotics
were now well on their way to the public.
On a superficial level, antibiotics are easy to define: opposing or against bacteria.
However, it is much more complex than that. There are many different types of infections caused
by different bacteria: strep throat by Streptococcus, staph infection from Staphylococcus, and
tuberculosis by Mycobacterium to simply name a few. It also depends on whether the bacteria
are gram-positive or gram-negative.

Figure 1. Outer Structure of Gram-positive Bacteria. (SEDICO, 2004-2014)

Figure 2. Outer structure of gram-negative bacteria. (SEDICO, 2004-2014)
Basically, bacteria have different cell wall structures, with gram-negative bacteria containing
lipopolysaccharides, porin channels, and murein lipoproteins that aid them against the
effectiveness of the antibiotics. Gram-positive bacteria have simpler cell wall structures made up
mostly of peptidoglycan, meaning that they are more susceptible to antibiotics [SEDICO
Pharmaceutical Company]. There are several ways antibiotics work, they can either: inhibit cell
growth, induce cell death, or weaken the bacterias cell wall. Antibiotics inhibit cell growth by
limiting the bacterias ability to synthesize DNA, RNA, or protein. This prevents certain
chemical reactions from taking place and hinders their ability to grow and multiply. Some
antibiotics work by destroying the cell walls because the bacteria cannot survive without a cell
wall, as it holds the cell together (Kohanski, Dwyer, Collins, 2-4). Because antibiotics were able
to destroy and inhibit harmful bacteria, it was believed that infectious diseases would be no
more; that is until it was observed that bacteria were developing resistances.
According to the Center for Disease Control and Prevention (CDC), antibiotic resistance
is defined as the ability of bacteria or other microbes to resist the effects of an antibiotic. This
concept is far from new. Less than 20 years after Fleming discovered the effects of Penicillium,
he warned about the threats of antibiotic resistance during his Nobel Prize acceptance speech.
Fleming stated that as beneficial as penicillin may be, There [is] a dangerin
underdosage...[and] non-lethal quantities of the drug make [the bacteria] resistant (Penicillin,
31-32). Underdosage and drug misuse are big factors in antibiotic resistance. If not all the
bacteria are killed off, some bacteria survive and mutate to diminish the effectiveness of the
drugs. Bacteria can resist antibiotics in various ways: neutralizing the antibiotic, pumping the
antibiotic out, mutating genetic material, or transferring of DNA codes for resistance. If one cell
of bacteria has survived through one of these methods, it can multiply and become resistant to a
specific drug. What makes antibiotic resistance an even more pressing issue is that bacteria can
develop resistance to multiple types of antibiotics. These bacteria are considered superbugs and
very dangerous.
Currently in our society, there is a paradox regarding antibiotic resistance. The battle with
drug-resistant bacteria has already lasted several decades and has progressively gotten worse
while the research and development of new antibiotics has dramatically decreased. Between
1950 and 1970, it was a time that was considered the golden era of discovering new drug
classes.

Figure 3. (Infectious Diseases Society of America, 2009)

Yet since then, the rate of discovery of novel drug classes suddenly dropped. In 1990, it was
reported that large pharmaceutical companies have stopped looking for new antibiotics or have
significantly reduced their efforts into research (Bad Bugs, No Drugs, 16) Figure 3 shows that
pharmaceutical companies have only developed five new antibiotic agents between 2003 and
2007. Also, there is a clear trend in the decrease of new antibiotics. Antibiotic resistance has had
a tremendous impact on the medical and pharmaceutical fields. And the cutback in research has
had a severe negative effect economically as well. In 1992, it was estimated that $1.3 billion
were spent trying to treat hospital-acquired infections from just six species of antibiotic-
resistant bacteria (Aminov, 12). $1.3 billion is a staggering number, and a number that has only
increased decades later. In fact, this number has grown to approximately $5 billion in the U.S
alone. Infections due to drug resistant bacteria have increased heath care costs because of longer
hospitalizations, extra physician visits, the higher cost of alternative antibiotics, more post-
hospital care, lost work days, and deaths The financial burden is not limited to only
hospitalization costs. Research and development of new antibiotics is very expensive and very
long. Its estimated that if a new research and development program were to start today, it would
cost anywhere from $800 million to $1.7 billion and take about 10 years to test for production of
a new drug (Bad Bugs, No Drugs, 15, 5). And there would be no guarantees that a new drug
would actually come into development. The return companies would receive from producing a
new antibiotic would not even come close to the amount of resources spent for research, so it
makes sense in a business standpoint that these pharmaceutical companies have stopped or
significantly decreased their research. Simultaneously, thousands of lives continue to be taken by
drug-resistant bacteria. The CDC estimates that almost at least 2 million people acquire serious
infections with bacteria that are resistant to one or more of the antibiotics designed to treat those
infections, [and] at least 23,000 people die each year as a direct result of these antibiotic-resistant
infections (Antibiotic Resistance Threats, 11). The Infectious Diseases Society of America
(IDSA) wants to change this. They released a report in 2004 that reiterated not only the impact
antibiotic resistant bacteria, but also the importance of reinvigorating research and
development of new antibiotics. They didnt stop there. They also lobbied the 109
th
congress
about antibiotic resistance, which led to the introduction of promising legislation in 2005 and
2006, however the legislation was not enacted (Bad Bugs, No Drugs: No ESKAPE!, 1). The
IDSA is making positive progress in attempting to broaden the awareness on antibiotic resistance
by increasing the political and legislative involvement within the issue.
While the IDSA believes the answer to antibiotic resistance is through continuing the
same process that currently exists to find new antibiotics, there are those that believe it is time to
look for alternative methods. Currently, scientists utilize a process of metagenomic analysis of
antibiotic producing microbes. This involves testing for antibacterial properties, and amplifying
the bacterias DNA through the use of primers and specific testing methods, and running the
found DNA sequence (AGTC strand) through a database to determine if the bacterium has
already been discovered. While there is a database of over 5000 known bacteria (helpful and
harmful), not all environments have been discovered, leaving the possibility of discovering new
antibiotics that could change the world of medicine. However, this process is long a tedious and
not yielded the same amount of results as in the past. Also, scientists have chemically altered
existing antibiotics, but bacteria have become resistant to those as well. Essentially, we are
running out of wonder drugs. One alternative to antibiotic resistance is bacteriophage therapy.
Bacteriophages are viruses that infect bacteria, and bacteriophage therapy is the use those viruses
to treat bacterial infections. Bacteriophage therapy has been known to have a relatively good
success rate in treating bacterial infections that showed no susceptibility to antibiotics (Golkar,
Bagasra, Pace). There is huge potential for the future of medicine with this type of therapy and
can be viewed as a valuable asset. While there is more testing that still needs to be done because
of possible safety issues, bacteriophage therapy cannot be ignored. Apart from bacteriophage
therapy, many believe that healthcare agencies and physicians have to be more watchful and
careful about antibiotics. The CDC has tried to improve its monitoring of antibiotics, but gaps in
knowledge about antibiotic resistance still exists. According to the CDC, there is no systematic
surveillance of antibiotic resistance threats, data on antibiotic use is not systematically collected,
and programs to improve antibiotic prescribing are not used in the United States (Antibiotic
Resistance Threats, 27). Overuse of antibiotics has played a significant role in bacteria becoming
resistant, and it is because prescription drugs are so readily available to people. A way to slow
antibiotic resistance as much as possible could be by limiting the amount of drugs prescribed.
There are numerous discussion about how to prevent antibiotic resistance and find solutions.
Regardless, antibiotic resistance wont pause and wait until we find a solution.
If you were to search the term antibiotic resistance on the internet, numerous
organizations pop up explaining how tremendous the issue of antibiotic resistance is. The Center
for Disease Control and Prevention (CDC). The World Health Organization (WHO). The Food
and Drug Administration (FDA). The National Institute of Allergy and Infectious Diseases
(NIAID). Those are only a few. Despite many organizations making efforts to control and limit
antibiotic resistance, the general public typically does not have an understanding of what it is.
This compounds the issue because of drug misuse and overuse. The enormous impact of
antibiotics cant be understated. Neither can the issue of antibiotic resistance. We have relied on
antibiotics for almost a century and have saved hundreds of thousands of lives. With the current
rate of antibiotic resistance, mankind is approaching a post-antibiotic era. With a lack of new
antibiotics and research, and limited amount of surveillance and programs regarding antibiotic
resistance, the issue will continue to get worse. Bacteria have been adapting to their
environments for thousands, if not millions, of years; antibiotic resistance cannot be stopped,
only slowed. Therefore we must keep pushing to develop antibiotics or other alternatives if we
want to continue to live and thrive in this world.

Works Cited
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