Penicillin and the Rise of Antibiotic Resistances and Allergies

Kara Redcay

Elon University

COR397A: Preventing Pandemics

May 11, 2020

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Introduction

“Do you have any allergies to any medications?”

It is one of the most easily anticipated questions from a healthcare professional during any genre

of visit. It was one I also anticipated when I confided in Elon’s health services clinic in the

winter of 2018 while experiencing a severe sore throat. I responded by informing the doctor that

a few individuals in my family had allergies to amoxicillin, however I had not been one of them.

In turn, the doctor prescribed me penicillin to combat the streptococcal pharyngitis, also known

as strep, that I had been diagnosed with. This was not my first time with this diagnosis or

prescription, so I headed to the pharmacy, picked up my prescription, and I took the first dose

without any hesitation. The next morning, I woke up with a plethora of red dots all over my face,

neck and shoulders. Assuming it was a reaction to my makeup or lotion, I took my second dose

of antibiotics and went on with my day. That night, I began having a hard time breathing and the

rash had worsened. I immediately emailed my doctor and took Benadryl. A different doctor

responded to my message, informing me that I was having an allergic reaction, and that I needed

to stop taking the antibiotics immediately. The next day, I headed to the pharmacy again,

although my strep symptoms seemed to have almost disappeared. I had wondered how, after

nineteen years, I had developed an allergy to an antibiotic I had been prescribed multiple times.

Nonetheless, moving forward, I alerted every healthcare professional of this new found allergy. I

only began to doubt this diagnosis in February of 2020, when I started conducting research and

became aware of the issue of antibiotic resistances and allergies.

Antibiotics are commonly prescribed medications, best used to fight bacterial infections,

by either killing bacteria or prohibiting them from reproducing. The discovery of this breed of
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medicine has allowed for multiple industries to reach their current success. Antibiotics have

transformed surgeries that were once considered complex in the past, into now relatively minor

procedures. They have helped to ensure that patients do not contract infections during

hospitalization, lowered the risk of blood poisoning, and have helped us on a day-to-day basis.

The introduction of antibiotics has truly changed the way the world functions, and more

importantly, survives.

When applied correctly, antibiotics can affect bacterial cells in four specific ways;

distribute the cell wall synthesis, inhibit the RNA synthesis, inhibit protein synthesis, or inhibit

DNA replication. There are two different types of antibiotics-- highly specialized antibiotics and

broad-spectrum antibiotics. Highly specialized antibiotics are effective against only certain

bacteria, compared to broad-spectrum antibiotics, which attack a wide range of bacteria. A

negative side effect to the broad-spectrum antibiotics is how they may attack bacteria that is

considered beneficial to humans. An international research team conducted a study in 2018 to

observe how broad-spectrum antibiotic exposure could negatively impact humans. They found

that, after twelve healthy men were prescribed a four-day antibiotic regimen, the participants

were missing nine common beneficial bacteria in their guts up to (and beyond) six months had

passed. “Our findings suggest that exposure to broad-spectrum antibiotics may dilute the

diversity of the intestinal bacterial ecosystem” (Cook, 2018). Although these effects may be a

result of overuse or misuse, the emergence of antibiotics shows the positive impacts that this type

of medicine has had on society.

Most antibiotics are produced in labs, however, they are also often based on compounds

produced by bacteria and fungi that are found in nature by scientists. Antibiotics first became
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commercially available during the 1930s. Following the release and discovery of a few main

classes of antibiotics, including penicillin, an era often referred to as the “golden-era” of

antibiotics began. This golden-era began in 1940 and concluded in 1962. During this time, most

of the antibiotics we are familiar with today were discovered, and subsequently, introduced into

the market. These antibiotics were derived from bacteria found in soil and compost, “bug juice,”

chemical dyes, and other odd foundations.

The average human expectancy increased by eight years from 1945 to 1972, with

antibiotics being used to heal infections that had once been considered deadly. This showed the

immediate benefits of the accessibility of antibiotics. There are few antibiotics under

development today, despite the growing threat of antibiotic resistant. As a result of this issue,

antibiotics are becoming less effective and valuable, especially one of the most well-known

kinds-- Penicillin.

Penicillin is considered to be the first known antibiotic. It was discovered by Alexander

Fleming in London in 1928. Fleming had collected a variety of petri dishes that contained

colonies of ​Staphylococcus,​ a disease caused by bacterias’ production of toxins. He found that

one of the dishes had grown mold, which secreted something, later identified as ​Penicillium

Notatum,​ that, in turn, had inhibited the growth of the colonies. With this discovery, Fleming

worked alongside his assistants and colleagues to obtain a pure form of ​penicillium​ from the

secretions of mold. Unfortunately, his niche team did not find success. However, Fleming

published his findings and the potential benefits in the British Journal of Experimental Pathology

in 1929, which sparked a global interest in the cause. Scientists across the world raced to make

this near discovery a reality. A group working at Oxford University was the first to find success.
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In 1941, said team used penicillin on the first human recipient. Due to a lack of resources, the

team was unable to keep the patient alive, but they saw an immense amount of progress before

his passing. The group continued testing the antibiotic on patients, and observed consistent

success.

More than a decade after Fleming’s initial discovery, penicillin became available on a

large scale, and the drug is now credited for sparking the “golden-era” of antibiotics. Penicillin

falls within the broad-spectrum category of antibiotics, and it is used to treat a variety of

infections(American Chemical Society International Historic Chemical Landmarks, 1999).

Today, it is most often used to cure infections of the middle ear, sinuses, stomach, bladder, and

kidney, along with more serious infections such as pneumonia and meningitis. Along with the

discovery of this valuable medicine came a general awareness of germ resistance. The first

penicillin-resistant bacteria discovered was ​Staphylococcus Aureus,​ which was discovered only a

year after penicillin’s commercial release.

Problem

It is obvious that antibiotics have revolutionized medicine in countless ways, however the

use of these drugs have also introduced the rapid appearance of resistant strains of bacteria. As a

result of human error in use of antibiotics, and the natural selective development of tolerances

and genetic changes, antibiotic resistance has become a prominent public health issue today.

Bacteria contain defense strategies, also called resistance mechanisms, that help them

fight back and survive against antibiotics. There are many different types of defense mechanisms

which are found in the DNA of the bacteria. Germs can limit and change the number of
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entryways into the cell, making it harder for the antibiotic to enter the cell. For example,

gram-negative bacteria have an outer membrane which can selectively keep antibiotics from

entering the cells. If it does enter, some bacteria can pump the antibiotics out of their cells.

Bacteria can also change or destroy the antibiotic, bypass the effects of the antibiotic, or change

the target for the antibiotic. This can happen through the use of enzymes and the development of

new cell processes; both of which make an antibiotic ineffective.

In addition to these resistance mechanisms, bacteria also have the ability to acquire

antibiotic resistance through cell replication and horizontal gene transfer. During cell replication,

some germs can develop mutations, making them resistant to antibiotics. Once these resistant

cells are present in the body, they are more likely to survive and reproduce, filling the host with a

stronger bacteria. Horizontal gene transfer also provides an opportunity for bacteria to share

genes. This can happen in three different ways; conjugation, transduction, and transformation.

Conjugation occurs when two bacteria pair up and connect through structures in the cell

membranes, transferring DNA from one bacterial cell to another. Transduction occurs when

viruses called bacteriophages infect bacteria. The viruses can carry genes that they have come in

contact with during the infection of another bacteria. These genes can be incorporated into the

DNA of the new bacterial host. The final potential transfer of resistance is transformation, which

occurs when bacteria take up pieces of DNA directly from the environment around the cell.

Germs can also have multiple-drug resistance, which occurs when they are resistant to

more than one antibiotic. As years have passed since the release of antibiotics to the public, there

has been a constant exposure to different drugs, making multiple-drug resistance a rule, rather

than an exception among resistant bacteria.

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One potential cause of this issue, which is often overlooked, is the antibiotic’s use in the

food industry. According to the FDA, more than 20 million pounds of antibiotics were sold to

livestock farms in 2014, which equated to about 80 percent of all antibiotics sold that year

(FoodPrint 2020). These antibiotics, referred to as ‘non-therapeutic,’ were used to help animals

grow faster and gain weight in a more efficient manner. They were also used to prevent the

spread of disease in overpopulated, unsanitary farms. Approximately 80-to-90 percent of

ingested antibiotics are not broken down, therefore, they can pass through the body while

remaining intact. This can lead to bacteria’s exposure to antibiotics, eventually causing a

resistance. It was also discovered that some of these germs may be able to survive and grow in

sink drains. This means that antibiotics can enter the environment as waste, promoting antibiotic

resistance after entering soil or water, through the transmission of wastewater. Bacteria can also

be spread from animals to people, through contact or consumption.

Antibiotic resistance has become one of the biggest public health challenges of our time.

Every year, at least 2.8 million people get an antibiotic-resistant infection. According to the

Center for Disease Control and Prevention, more than 35,000 people die a year as a result. In

2013, the chief medical officer for England, Professor Dame Sally Davies, said the rise in

drug-resistant infections was comparable to the threat of global warming (Stephens, 2014).

This issue is a global threat because it is not the person that becomes resistant to the

antibiotic, but the bacteria. Antibiotic-resistant bacteria can impact any individual at any age.

Antibiotics are even called “societal drugs,” since resistance can pass from bacterium to

bacterium, and the resistant bacterial infections can pass from person to person. An

antibiotic-resistant infection can quickly affect an entire community. The seemingly invincible
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germs often lead to extended hospital stays, additional follow-up visits with doctors, and costly

and toxic alternatives. It may also have the ability to affect the healthcare, veterinary, and

agriculture industries, making the potential threat much worse.

This issue has become a growing concern because there has been a significant lack of

achievements in the effective prevention and control of resistant development, due to the public’s

lack of basic knowledge of antibiotics. Scientists and researchers have predicted that, soon,

reality will closely resemble that of the pre-antibiotic era, with more than 20,000 potential

resistant bacteria.

Similar to a growing concern of antibiotic resistance, there is also a growing awareness of

antibiotic allergies and the potential misdiagnosis of them. According to the British Society for

Allergy and Clinical Immunology, “drug allergy is an adverse drug reaction with an established

immunological mechanism” (Cramp, 2018). All forms of natural and semisynthetic drugs can

cause an allergy. One of the most common antibiotics, penicillin, has the most relevance to this

issue. Around 10 percent of people report an allergy to penicillin, however only 1 percent

actually have an allergy, and only 0.03 percent of individuals exhibit life-threatening reactions to

the drug. A more typical allergic response to this antibiotic includes hives, wheezing, and

swelling, particularly of the face. These reactions are the primary cause for many of the

misdiagnoses of the allergy. For example, oftentimes childhood viruses can be accompanied by a

rash, which could be confused for an allergy. Another source of confusion is that the word

‘allergy’ is sometimes used synonymously with intolerance or side effects, which are not the

same. There is also the misconception that this allergy is believed to be passed down genetically,

which can be true for some types of antibiotics, but penicillin is proven to not be one of them.
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These potential causes for misdiagnosis can pose a huge threat to individuals. An

individual who is labeled as having an allergy to an antibiotic, resultingly has limited options for

medicines. This can cause a doctor to consider the use of alternatives, which are often less

effective antibiotics, and may expose patients to unnecessary risks. Alternatively, these allergies

can also lead to an increase in the prescribing of broad-spectrum antibiotics, as discussed prior.

Also, if an individual is misdiagnosed with an allergy as a child, he or she is likely to continue to

include that in his or her medical profile moving forward. Of the 1% that truly do have a

penicillin allergy, half will grow out of it within five years, according to the American Academy

of Asthma, Allergy, and Immunology. Within ten years, eight out of ten will no longer have the

allergy at all. Individuals who are labeled with a penicillin allergy are exposed to a larger variety

of antibiotics putting them at risk for contracting a resistant bacterial infection (Crist, 2019).

Values

The issue of antibiotic resistances and allergies directly relates to the efficiency chapter in

​ fficiency is the ability to avoid wasting materials, money,

Deborah Stone’s ​Policy Paradox. E

time, energy, and effort in doing something or producing a desired result. This chapter discusses

potential motivating factors for individuals working to combat threatening public policy issues.

In simpler terms, this chapter explains why there are a lack of efforts being made currently to

combat the issue at hand.

Stone references a passage by Herbert Simon, which explains general ‘efficiency’ by

analyzing the efficiency of a public library– “A key to circulation is a lively, up-to-date stock of

books. New books cost money, which could be found by relocating funds in the budget” (Stone,
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2012 p.64). Similar to books, the discovery of antibiotics can be expensive, and it can also take

an extremely long time. During the golden-era of antibiotics, there was a greater emphasis on the

search for viable drugs. In terms of the library analogy, there had only been one or two books

written, therefore the world was eager for more. No one had questioned if researching new

antibiotics was a viable use of resources during that time period.

This issue is also affected by financial aspects, which is directly related to efficiency.

Stone defined efficiency as “achieving an objective for the lowest cost,” however, not many

people would be quick to buy an antibiotic that was the cheapest solution to an issue. If a

scientist was only willing to invest so much money into research before releasing a drug to the

public, there would be guaranteed risks. Financial investments, along with time, often result in

reliability.

The potential lack of income is not the sole financial aspect of the lack of efficiency.

“The cost of an activity, economists tell us, include not only the actual money outlays for it but

also the forgone opportunities that could have been accomplished with the same expenditure”

(Stone, 2012 p.65). One core challenge to the creation and development of new antibiotics is the

understanding that “expected revenues are insufficient to drive long-term investment” (Towse,

2017). There are other fields that have a lower risk, with more achievable aspects and rewards.

Because of this, professionals in the medical and research field may be attracted to alternative

focal points.

Simon also said, “many branch libraries had a staff of two or more professionals where

one professional with a paraprofessional could have worked. High-salaried professionals often

did clerical tasks” (Stone, 2012 p.64). A lot of medical professionals are motivated by fame and
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fortune; they are drawn to curing the incurable, and solving the impossible. Tackling the

discovery of an entirely new antibiotic is not even within those realms. As one could see from

Alexander Fleming’s failed attempts to be the sole individual responsible for penicillin, the

journey to discovering an antibiotic is long and complex, requiring a vast amount of research and

experimentation. Because of this, some doctors or researchers with the capabilities of impacting

the industry are not inclined to even try. They are tempted by more simple, guaranteed, and

approachable fields of study.

Solution

There is no one solution to resolving this public health issue. The problem of antibiotic

resistance and allergies cannot be cured with the discovery of a single drug. Rather, this is an

issue that must be addressed constantly, for there will always be a bacteria resistant to an

antibiotic. Ever since the creation of antibiotics, resistance has been prevalent, however in the

earlier years of antibiotic discovery, scientists were still motivated to save lives that had been

considered lost. But once the ground level of antibiotics was established and appeared to be solid

enough, scientists moved on to the next solutionless problem. In Stone’s efficiency chapter, she

says “some citizens might ask whether the book collection is really what matters about a library”

(Stone, 2012 p.65). When comparing this to the issue at hand, one may argue that finding new

antibiotics is not the only part of the solution that matters. The only way to combat these issues

would be to create an initiative which would involve multiple steps and initiatives.

According to the World Health Organization, an increasing number of governmental

parties around the world are devoting efforts to the ever growing issue of antibiotic resistance
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and allergy (Stephens, 2014). The first step in this proposed initiative is to educate the public on

antibiotics, and the threat that resistances and allergies have on the future. For example,

educating individuals about the potential misdiagnosis of an illness or an allergy may have

multiple benefits. For one, it would encourage the need for more certainty when labeling a

general rash as an antibiotic-related allergy. It would push individuals to express any uncertainty

with their healthcare providers, especially in terms of allergies or diagnoses. It could also help

people identify the truths from the misconceptions of antibiotics. In 2019, the FDA partnered

with the CDC to launch a campaign titled “Get Smart: Know When Antibiotics Work” (Center

for Disease Control, 2020). However, there is little information on antibiotic resistance and the

roots of the issue. This campaign focuses rather on what antibiotics are and how to properly use

them.

Educating the public would also help generate passion and awareness towards the issue,

which could lead to more financial support and verbal encouragement from the public. By

strengthening the global awareness and surveillance of the issue, organizations and facilities will

be forced to address their potential impacts and involvements.

The next step would be to hold these people accountable for their contributions. The

majority of antibiotic use occurs in an agricultural setting, however many individuals are not

aware of the ways that this industry has contributed to the issue of resistance. By requiring this

industry to eliminate their constant misuse of antibiotics, the rapidness of resistance may

decrease. In 2013, the Food and Drug Administration implemented a voluntary initiative to phase

out the use of certain antibiotics in enhanced food production. This voluntary plan will not

encourage the industry enough to be considered a solution, especially because the United States
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is the second highest user of antibiotics in food-producing animals. David Wallings, a Senior

Health Officer at the Natural Resources Defense Council said, “when you put those small steps

in context, they’re probably not going to make a whole lot of difference in terms of reducing the

enormous use of antibiotics in pork production, poultry production, and beef production” (Dall,

2017). Especially because there is a lot of uncertainty as to how many antibiotic-resistant

bacteria can be traced back to food production. More research needs to be conducted to

determine exactly how this industry is impacting the rise of resistance to an allergy, in order to

determine how much it must be augmented. After said data is gathered, it is critical that the FDA

takes a stricter approach by setting mandatory reduction targets. Reducing the usage and reliance

on antibiotics in livestock would result in a significant decrease in resistant microbes in animals

and meat within a year or two, according to Environmental Health Perspectives (Levy, 2014).

These steps have already been taken by governments in the Netherlands and Denmark and have

proven to be successful.

Denmark remains a few steps ahead of the United States, in terms of revolutionizing their

livestock management and antibiotic usage. The country banned the use of all non-therapeutic

antibiotics in pigs more than two decades ago. Since then, there has been a significant decline in

the levels of vancomycin-resistant enterococcus, or VRE, which is a type of antibiotic-resistant

bacteria (Levy, 2014). This success from Denmark shows the importance of creating strict

requirements for the agriculture industry.

The following step in this solution would be to reduce the misuses of antibiotics in the

medical industry. Research shows that at least a third of all prescriptions from antibiotics are not

needed. The most misdiagnosed infections include sore throats, ear infections, and sinus
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infections. Many campaigns have been created to encourage a limited use of antibiotics, with the

sole exception of serious and life-threatening infections. However, this shift would require

professionals to withhold beneficial antibiotics from patients with more bearable conditions. In

2015, the Obama Administration set goals to reduce inappropriate antibiotic use in hospitals and

outpatient settings by 20 percent and 50 percent respectively (Hyun, 2016). However, the

specific steps being taken by the FDA and other associations are rather minuscule.

For example, in 2015, health care professionals were encouraged to use certain antibiotics

only for patients who had limited and or no other treatment options. Once again, this optional

attempt to limit the distribution of antibiotics would not substitute as a solution. Similar to the

reduction targets needed in the agriculture industry, the CDC and FDA should enforce those

goals set by the Obama administration in 2015, making adjustments accordingly.

A critical step in the resolution of this issue would be to stress the importance of

researching and creating new antibiotic classes that vary from those available in today's market.

The Royal Pharmaceutical Society stated that no new class of antibiotics has been discovered

since 1987, mainly because the financial returns for this search are low (Stephens). As discussed

in Stone’s efficiency chapter, money is a huge motivating factor when addressing public health

issues. One way to emphasize the importance of the search would be to implement financial

incentives. In 1983, the Orphan Drug Act was created, which encouraged research into

therapeutic agents for rare conditions by giving manufacturers federal funding and research tax

credits, as well as enhanced market exclusivity rights. This act has already been applied to many

antibiotics and antimicrobials, however by increasing the funding and inclusion, more

individuals would be willing to dedicate the time and money to this critical search (Swann,
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(n.d.). The creation of similar acts would heavily influence the medical field and its driving

factors.

The final step would be to accept the issue as ongoing and create ways to limit the death

toll that antibiotic resistant bacteria will cause. The CDC launched an Antibiotic Resistance

Solutions Initiative, which was designated to detect, respond, contain, and prevent resistant

infections. The initiative includes ways to combat and slow the increase of the resistance, as well

as offering a gold-standard lab capacity to all United States state and regional labs, and expertise

and assistance in some countries abroad. This initiative also increased capacity in state and local

health departments for rapid detection and faster response to outbreaks and emerging resistance

to contain and control spread (Center for Disease Control and Prevention, 2020). Choosing to

ignore the issue or support the false beliefs about the cause of the issue will lead to anything but

a solution.

As one can see, there have been a few steps taken to approach the issue of antibiotic

resistance and allergy, however not enough considering the threat that this issue has on a global

scale. Measures must be taken to educate the public, address the industries involved, motivate

the search, and stop the spread.

Conclusion

In a time of uncertainty, like the one we are currently experiencing with COVID-19, one

could wonder what reality would look like if the issue of antibiotic resistances and allergies were

addressed earlier on. Would there have been a medication discovered with the potential to lessen

the impact? Although antibiotics could not have cured COVID because it is a virus, they are able
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to help with any bacterial infections that may occur as a result. This is a situation where the

presence of antibiotics is astounding. This is also a situation where antibiotic resistance and

allergy may actually be contributing to the death toll. Without a devotion to finding a solution to

antibiotic resistance and allergy, while also working to prevent further impact, the future of

medicine will hit a standstill. Losing the ability to properly combat minor injuries and common

infections with a slip of paper and a familiar name will lead to a lower life expectancy and high

death rate. This global threat has the potential to completely change the way the world works,

which must be recognized before it does.

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