Carly Wheelans

Antimicrobial Resistance
Antibiotic not automatic: use with care
Carly Wheelans
Mr. Toole
Independent Study Unit
Friday, May 13, 2016
Table of Contents
Introduction...Page 3
Summary of Research methods....Page 9
Background...Page 10
ExpertPage 15
Role of Control..Page 20
Logic of Evil.........Page 23
Case Studies
1. Greater Mekong Region....Page 34
2. India..Page 40
3. Brazil.Page 45
International OrganizationPage 49
Canadian Connection....Page 55
SolutionsPage 60
Bibliography..Page 64
Appendix.......Page 66
Introduction
Lots of people think, well, were humans; were the most intelligent and
accomplished species; were in charge. [Microorganisms] may have a different
outlook: more bacteria live and work in one linear centimeter of your lower colon
than all the humans who have ever lived. Thats whats going on in your digestive
tract right now. Are we in charge, or are we simply hosts for bacteria? It all
depends on your outlook. 1
Neil deGrasse Tyson best explains the human ego. It is human nature to judge, but
people continuously underestimate that which is visually inferior based on ignorance,
corruption, greed, and pride. This concept has been demonstrated numerous times
throughout history, yet continues to repeat itself: Soviet Union underestimated the United
States during the cold war, Napoleons decision to invade Russia in 1812, and the
Egyptian Presidents decision to attack Israel during the Suez crisis. Complacency is
everywhere and humans continue to exercise this form of ignorance. People are inclined
to believe that nuclear weaponry, war, and homicide will lead to human extinction, while
few consider the fact that microscopic organisms have the ability to alter the human fiat.
This disregard towards microorganisms has enabled them to become a threat.
Microorganisms are always present, but rarely seen and this in itself is power over human
incompetence.
We inherit every one of our genes, but we leave the womb without a single
microbe. As we pass through our mother's birth canal, we begin to attract entire
colonies of bacteria. By the time a child can crawl, [they have] been blanketed by
an enormous, unseen cloud of microorganisms a hundred trillion or more. They
are bacteria, mostly, but also viruses and fungi (including a variety of yeasts), and
they come at us from all directions: other people, food, furniture, clothing, cars,
buildings, trees, pets, even the air we breathe. They congregate in our digestive
systems and our mouths, fill the space between our teeth, cover our skin, and line
1 DeGrasse Tyson, Neil. "Neil DeGrasse Tyson Quotable Quote." Goodreads. Neil
DeGrasse Tyson, Space Chronicles: Facing the Ultimate Frontier, Mar. 2013. Web.
4
our throats. We are inhabited by as many as ten thousand bacterial species; those
cells outnumber those, which we consider our own by ten to one, and weigh, all
told, about three pounds the same as our brain. Together, they are referred to as
our microbiome and they play such a crucial role in our lives that scientists like
[Martin J.] Blaser have begun to reconsider what it means to be human. 2
Dr. Specter thoroughly demonstrates the scale at which Microorganisms inhibit Earth,
while showcasing the consistent interaction between humans and these microscopic
beings. By definition the term microorganism describes any organism too small to be
viewed by the unaided eye. This encompasses a wide range of living entities: Bacteria,
Protozoa, Viruses, Fungi, and Algae. Based on a worldwide abundance, humans must
coexist with microorganisms. These miniscule organisms can be utilized to ones
advantage and have been proven essential in the sustenance of life; they produce essential
vitamins within the human digestive tract, create dairy products, act as decomposers in
the nutrient cycle, form symbiotic relationships with plants, clean up oil spills and much
more. Humans alone benefit from microorganisms in infinite ways.
Microorganisms have also proven to be harmful. Society currently understands
that certain strains of microorganisms are parasitic and pathogenic. Although, initially
people believed that disease, mold, and other growths appeared in a spontaneous nature
arising within air. The French chemist and microbiologist Louis Pasteur conducted
several experiments to prove these speculations dubious. Firstly, Pasteur compared vials
of sterile solutions. One vial was kept concealed, another was exposed to the gaseous
atmosphere at a low altitude where air contains a high concentration of particles, and the
final vial was exposed to the atmosphere at a high altitude where the air is purest. The
vial that was enclosed remained clear, while the vial exposed to high altitudes became
slightly clouded and the vial that accumulated the most growth from microorganisms was
exposed to low altitudes where the air is most contaminated. From these findings,
Pasteur came to the verdict that microorganisms only arise from existing microbes and
multiply exclusively when removed from the air and situated into a medium of suitable
conditions for reproduction. His discovery received much criticism. Do not let yourself
be tainted with a barren skepticism.3 Pasteur argued his critics, but accordingly he
2 Specter, Michael. "Michael Specter Quotable Quote." Goodreads. 2 Jan. 2013. Web.
revised his experiments in a manner relatable to the public. In 1845, silkworms became
infected with an unknown disease. Pasteur analyzed the organism and demonstrated that
this disease was induced by microorganisms that mass-produced within the silkworms
tissue. Ultimately, the silkworms bodily tissue provided a suitable medium for
reproduction. Through this experiment, Pasteur provided the first apparent evidence that
microorganisms cause disease.
Will you have some microbe? There is some everywhere. [Microbiology] is the
fashion, it reigns undisputed; it is a doctrine which must not even be discussed
[], the learned Monsieur Pasteur, has pronounced the sacramental words, I
have spoken. The microbe alone is and shall be the characteristic of a disease;
that is understood and settled; the Microbe alone is true, and Pasteur is its prophet.
3
This illustration of the publics enthusiasm regarding Louis Pasteurs discovery of

microbial contribution to infectious disease displays the effect to which this knowledge
influenced society and medical ideologies. With an improved understanding of the origin
of infections, medical professionals had a greater direction concerning an approach
toward treatment for infectious diseases. In the same manner that individuals harness the
benefits of microbes where appropriate, people now have the ability to fight
microorganisms when they cause harm.
In 1900, the four leading causes of death worldwide were a result of microbial
infections; pneumonia, tuberculosis, gastrointestinal infections, and diphtheria. People
continued to be afflicted by disease, until the insurgence of antimicrobials.
Antimicrobials are a medical agent used to kill and inhibit the growth of pathogenic
microorganisms. These drugs transformed medicine and the course of medical
treatments. Unfortunately, the discovery of antimicrobials is accompanied by a prompt
accumulation of resistant strains of microorganisms.
3 BSc Microbiology. School of Biosciences. Available

at<http://www.nottingham.ac.uk/biosciences/prospectivestudents/undergra
duate/courses/bscmicrobiology.aspx>17 Feb. 2012.
6
Antimicrobial resistance describes the resilience of a microorganism towards the
effects of a drug that could once prevent or treat diseases caused by that particular
organism. This microscopic evolution has sizable impacts on a global society.
Antimicrobial resistance threatens the effectiveness of treatments over an expanding
range of infections caused by bacteria, parasites, viruses and fungi. Through inhibiting
the effectiveness of treatments, patients remain infected for extended periods increasing
the chance that resistant microorganisms will spread between patients. Antimicrobials
challenge the protection and comfortable lifestyle of those with weakened immune
systems; cancer patients, transplant recipients, and premature babies. These individuals
have an increased chance of disability or death at the absence of antimicrobials. Medical
professionals lose the capacity to install foreign objects inside the body. A study in 2007
performed by the American Academy of Orthopaedic Surgeons allocates that 500,000
knee replacements and over 175,000 hip replacements take place annually in the United
States. Over the last decade an abundance of athletic baby boomers has caused a raise in
these numbers at 174% for hip replacements and 673% for knee replacements. An
analysis by the National Institutes of Health sector of Infectious Disease and Research,
following this initial study proved that one out of six of these patients receiving
transplants would die without antimicrobials. Routine medical procedures are
transformed into high risk treatments without the proceeded amounts of prophylactic
antimicrobials. The failure of antimicrobials also results in longer durations of illness,
treatment, and hospitalization. Antimicrobial resistance disturbs the control of infectious
disease.
Among human suffering from widespread disease, individuals frequently
overlook the broader social and economic effects. As infections become unmanageable
and widespread health care expenditures rise. For Canadians, inflation in health care
expenses results in raised taxes, while for a country such as the United States under
private health care and insurance, the price of hospital bills will rise. In terms of
economics, people may be affected differently, but there is no denying that antimicrobial
resistance will affect everyone. Dr. Martin Cetron explains the interconnected
circumstances, Infectious diseases know no borders. We breathe the same air. We drink
the same water. We fly on the same planes. And an infectious disease outbreak anywhere
is a potential risk and threat to all of us.4 Therefor, new resistance mechanisms emerge
in specific regions and are rapidly transmitted on a global scale. International trade and
travel are accountable for this international transfer of resistant strains of
microorganisms. Antimicrobial resistance is similar to the global economy, in that when
large economies suffer a recession the effects are felt worldwide. When disease
outbreaks affect mass populations the microorganisms responsible are exchanged across
the globe. Never before has the world been interconnected to the degree, which it
currently is. The World Trade Organization has declared that international trade has
increased 5.3% since 2014. As well, Air, aquatic, and terrestrial transport networks have
expanded in destinations, speed, and volume of passengers and goods being carried.
Ultimately allowing pathogens to travel further, faster, and in larger quantities. The
International Air Transport Association states that over the span of one year (2014 - 2015)
the number of individuals travelling by aircraft increased 5.9%. Further statements
concluded, 1 billion people currently travel by commercial aircraft annually. This
number is estimated to double over the next twenty years. Aircrafts have confined spaces
with mass populations and re-circulated air, providing microorganisms with a suitable
location for the exchange of resistant strains. The consequences of an expanding global
transport network include infectious disease pandemics and vector distribution.
Essentially, antimicrobial resistance is a threat to the health of the global public.
The development of antimicrobial resistance is a natural evolutionary
phenomenon. This biological process could not have been prevented, but the expansion
in resistant strains of microorganisms could have been reduced. Human activity has
contributed to an acceleration in the rate of antimicrobial resistance. Through the misuse
and indulgence of antimicrobials, microorganisms have been situated under a select
pressure to become accustomed to the effects of these drugs. The purpose of
antimicrobials has been abused in the food industry, agriculture industry, health and
pharmaceutical industries, and patient persistency. Corruption, pride, and personal greed
lead each of these sectors in society to indulge in the benefits of antimicrobial use, while
4 Branswell, Helen. "Public Health Watches Foreign Outbreaks as Diseases Spread." Global
News. The Canadian Press, 9 Jan. 2014. Web. <http://globalnews.ca/news/1073494/public-healthwatches-foreign-outbreaks-as-diseases-spread/>.
8
human ignorance and deception enable these same individuals to elude the consequences
of antimicrobial resistance.
Civilization has become dependant on antimicrobials. Studies show that,
Antimicrobials support almost all of modern life5. People are accustomed to rely on
the support of antimicrobials to ensure ones health, protection over agriculture, growth of
livestock, and profit in the pharmaceutical industry. Fear has lead people to overuse
antimicrobials as these drugs provide assurance and security. Ironically, the
repercussions of antimicrobial dependence are what should be feared. People will be
depleted of this comfort in the absence of antimicrobials effectiveness. Society will learn
to live in fear when the simplest of injuries can deprive one of their life. It has taken
seventy years for antimicrobial resistance to advance into its current state, but society
does not have this luxury of time to alter the expansion of antimicrobial resistance. If
people cannot halt their indulgence in the comfort of antimicrobials the victims of
infectious disease will escalate, economic stability will plummet, and medical
innovations will be set back decades.
5 What Do We Do When Antibiotics Dont Work Any More? Perf. Maryn McKenna. 2015.
Summary of Research Methods

This independent study unit discusses the expansion of antimicrobial resistance
and the mechanisms responsible for the steady increase in the global prevalence of
resistant strains. A variety of sources were utilized in the process of collecting the
information necessary to create this report. Numerous online websites were visited,
while collecting background information and statistics. The 2015 documentary, The Rise
of Superbugs Resistant to Antibiotics, described the, deadly misuse of antibiotics
threatening our world6 and provided regions to further investigate as a case study. Dr.
Stanley Falkow provided myself with two autobiographical reports, several biological
reports, and insight through email and phone interviews. All sources utilized were factual
and reputable.
Background
6 Rise of the Superbugs. Dir. Geoff Thompson. Perf. Pro. Lindsay Grayson. 2012.
10
February 12, 1941, a 43-year old policeman, Albert Alexander, became the first
recipient of the Oxford penicillin [fourth person to receive penicillin]. He had
scratched the side of his mouth while pruning roses, and had developed a lifethreatening infection. Huge abscesses [a swollen area within body tissue,
containing an accumulation of pus] developed affecting his eyes, face, scalp, and
lungs. He had already had an eye removed and abscesses drained; even his
remaining eye had to be lanced to relieve the pain of the swelling. Penicillin was
injected and within days he made a remarkable recovery. Supplies of the drug ran
out and efforts to recycle the penicillin by extracting it from his urine failed.
Albert Alexander died a few days later.7
Officer Alexanders death took place within the last days of the pre-antimicrobial era.
Similar experiences with disease were of frequent occurrence among populations in this
time period. For many people endured the unpleasant effect of infectious disease derived
from ordinary, simple tasks. Individuals who became infected were left with no options:
hope the bodys immune system would stimulate a recovery or die. Albert Alexander was
one of the final individuals to endure the unpleasant conditions of an era before
antimicrobials.
The term antimicrobials literally means against life; in this context, against
microscopic life that eradicate human existence. Statistic Canada states that in the
modern era the leading cause of death is cancer and heart disease, but throughout history
the majority of people did not die of these diseases because they did not live long enough
to develop these conditions. For the majority of human existence, infectious diseases
were the leading causes of human morbidity and mortality. Unfortunately, this fact may
not be abolished as, We stand today on the threshold of the post antibiotic era. In the
earliest days of a time when simple infections such as the one he [Albert Alexander] had
will kill people once again. In fact they already are.5 Doctor McKenna illustrates the
occurrence of a relapse in history, as medical advancements become ineffective. She
7 American Chemical Society International Historic Chemical Landmarks. Discovery and
Development of
Penicillin. http://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenici
llin.html (accessed Month Day, Year).
11
refers to the recurrence of a human state of vulnerability against disease, rather than the
resilience of microorganisms to medications. This is in account to the fact that microbial
resistance is not a recent concept. For the same duration that humans have had access to
antimicrobials, microorganisms have been adjusting to survive the unfavourable
conditions generated by these agents. The existence of resistant strains of
microorganisms has been present for centuries, while only recently gaining public interest
as a response to the accelerating potential threat.
Antimicrobial resistance is a result of the basic evolutionary mechanism natural selection.
This term describes the differentiation in survival and reproduction of individuals due to
benefits of ones phenotype. Natural selection is a form of adaptation, which alters the
characteristics of a population over generations in response to adjustments in
environmental conditions. This process occurs as a result of a struggle for resources,
where individuals with traits beneficial to their environment acquire an increased fitness.
In biological terms, fitness refers to an organisms ability to survive and reproduce. In
order for natural selection to occur a trait must be heritable and prove advantageous in the
struggle for resources, otherwise the trait will not remain in the gene pool. Traits of an
individual that prove to be advantageous to ones environment remain within a population
and are inherited by offspring. In 1809 Charles Darwin, often considered as the father of
evolutionary biology alluded to this concept, It is not the strongest of the species that
survives, nor the most intelligent, but the one most responsive to change.6
Microorganisms are no exception to Darwins theory. Antimicrobials alter ones internal
environment and place microorganisms under a selective pressure for survival. Each time
someone takes an antimicrobial they increase the exposure of internal microorganisms to
that medication, allowing more opportunity for pathogens to evolve. Microorganisms can
naturally possess resistance to certain antimicrobials, while other microorganisms can
develop resistance. Resistance can be acquired in two ways: a genetic mutation or
through the transfer of resistant strains. A
mutation is any change that occurs in the DNA of a cell. Microorganisms undergo
random mutations in their genetic structure, which contribute to variation among these
populations. A variation that enables a microorganism to become resilient to the drugs
once used to kill it has a positive effect on that microorganisms fitness. Antimicrobials
12
eliminate susceptible microorganisms, while microorganisms with a greater fitness
eventually obtain antimicrobial resistance. This process decreases competition for the
resistant strains of microorganisms, as they acquire ample space and resources to
reproduce and pass on the resistant strain. Once an attribute that allows for antimicrobial
resistance emerges within a species, microorganisms of that species distribute the
resistant gene throughout their population. Notably, bacteria are proficient in the transfer
of genetic material, Theyre the original life forms almost, so for thousands of millions
of years theyve had a chance to work out ways to survive and one of those is to borrow
genes from other bacteria to survive.8 explains Microbiologist, Doctor John Turnidge.
The transfer of genetic material between bacteria occurs in three different ways:
1. Conjugation
2. Transduction
3. Transformation
Firstly, bacterial conjugation refers to the transfer of genetic material in the form of a
plasmid (circular DNA) or transposons (chromosomal segment). This form of genetic
transfer requires the donor bacterium to establish a physical connection to the recipient
bacterium through a temporary cytoplasmic bridge. Conjugation enables various
distantly related bacteria to transfer genes. Secondly, transduction is the process by
which a vector is utilized to transfer genetic material from one bacterium (or any
microorganism) to another. Finally, transformation is a process where bacteria take
possession of naked DNA, which is abandoned or purified genetic information, most
likely from a dead organism. The bacterium will replicate the foreign DNA along with
their own DNA if the enzymes inside the host cells recognize the foreign DNA.
Microorganisms such as bacteria have developed an abundance of techniques for
distributing advantageous traits among populations. If environmental conditions remain,
over generations a beneficial trait, such as antimicrobial resistance becomes more
frequent in the population; eventually, all offspring will contain the resistant gene that
helps the population thrive.
The cycle of natural selection can only induce a shift in nature over the period of
many generations. However, over the span of seventy years microorganisms have
8 "How Bacteria Become Resistant." Millennium Bugs. 1999 Australian Broadcasting
Cooperation. Web.< http://www.abc.net.au/science/slab/antibiotics/resistance.htm>
13
evolved to inhibit the effectiveness of antimicrobials. This is a result of the fact that
microorganisms have condensed generations. Particularly, bacteria produce a new
generation every twenty minutes. This rate has not been matched by pharmaceutical
innovations, but rather accelerated by a mass consumption of antimicrobials.
Society was warned of the development and consequences of antimicrobial
resistance, yet human ignorance has lead to the indulgence of antimicrobials, ultimately
causing the pandemic of antimicrobial resistance. In 1928 Sir Alexander Fleming
accidentally discovered the worlds first antibiotic. He noticed a petri dish containing the
bacteria classified as staphylococcus had become contaminated by a mould that appeared
to inhibit bacterial growth. On December 11th, 1945, Sir Alexander Fleming along with
Ernest Boris Chain and Sir Howard Walter Florey were awarded the Nobel Prize in
Physiology or Medicine for the discovery of penicillin and its curative effects over
infectious diseases. Sir Alexander Fleming declared in his acceptance speech,
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 under-dose himself and by exposing his microbes to non-lethal
quantities of the drug, make them resistant.8
Fleming felt there was an essential need for the public to understand the influence of the
findings. Sir Alexander Flemings acceptance speech is labelled as the Nobel Lecture,
as he utilized the opportunity to caution society. He remained passionate about the
management of penicillin and continued to remind the public of the threat associated with
misusing antimicrobials. Although, apparent in his warning, Flemings advice has gone
ignored. That exact year penicillin resistance emerged, only after being publicly
available for two years.
Similar occurrences of resistance are notable throughout the history of
pharmaceuticals. The antibiotic Vancomycin created in 1972 to treat bacterial strains of
streptococcus and staphylococcus became ineffective for use of treatment in 1988,
sixteen years later. In 1985, Imipenem was produced and used to treat most bacterial
infections, until 1998 when bacteria stopped responding to the drug. Recently,
14
Daptomycin was constructed in 2003 to treat life-threatening infections caused by grampositive organisms; within a year resistant strains emerged. Each of these antimicrobials
were disabled from resistant mechanisms. Microorganisms have refined their ability to
adapt to antimicrobials, limiting human capacity to prevent infectious diseases that
people are naturally susceptible too.
The innate adaptability of microorganisms has enabled these organisms to evolve
to rapidly changing environments. Microorganisms natural instinct for survival, rapid
reproduction, abundance of mutations, and gene transfer has inevitably allowed drugs to
induce less of an effect. Over time, complex interactions have contributed to the
acceleration of antimicrobial resistance. The causes of the persistence of antimicrobial
resistance have been connected to biological, societal, industrial, and legislative factors.
Each perspective is not exclusively responsible for the perseverance of antimicrobial
resistance, but all must be considered. In order to conceive solutions for this issue,
individuals must first understand the mechanisms, which throughout history contributed
to the development and advancement of antimicrobial resistance.
Expert
15
Antimicrobial resistance has only recently gained awareness in the public, leading
to the misconception that society, altogether, was oblivious of this arising crisis. For
decades the topic of antimicrobial resistance has been of urgent priority for
microbiologists and pathologists. Numerous individuals have made inconspicuous
contributions to the field of microbiology and the stagnation of antimicrobial resistance.
Stanley Falkow is one of these individuals whom is unheard of, but influences the daily
lives of every individual with his work. Born in 1934, Stanley Falkow is a microbiologist
and a professor of microbiology and immunology at Stanford University. Dr. Falkow
retired in 2010, although stated, I still am engaged in thinking and writing on the
subject, during an interview between Dr. Falkow and myself. He pursued his passion
for microbiology at the University of Maine, where he received a bachelor of science and
graduated with honors. Dr. Falkow then furthered his education at the University of
Michigan and later at Brown University, followed by an independent researcher position
at Georgetown University. His accumulated experiences taught him the biochemical and
microbiological techniques necessary to deduce how bacteria transmit antibiotic
resistance to one another.
Stanley Falkow is often regarded as the father of microbiology in respect to his
revolutionary work on how pathogens and their host cells interact to cause disease at a
molecular level. He has been recognized for his accomplishments and contribution to
science on numerous occasions. Dr. Falkow has received many awards over the span of
his career, some of which include:
[] the Bristol-Myers Squibb Award for Distinguished Achievement in Infectious
Disease Research, the Altemeier Medal from the Surgical Infectious Diseases
Society of America, the Howard Taylor Ricketts Award at the University of
Chicago, and the Paul Ehrlich and Ludwig Darmstaedter Prize. In 2003, he
received the Abbott Lifetime Achievement Award from the American Society for
Microbiology and the Selman A. Waksman Award in Microbiology from the
National Academy of Sciences. He received the Robert Koch Award in 2000.9
An honorary achievement not mentioned above is Dr. Falkows election to the United
9 Cohen, Stanley, N. "SCIENCE, BIOTECHNOLOGY, and RECOMBINANT DNA: A
PERSONAL HISTORY." Copyright 2009 by The Regents of the University of California. Web.
<http://digitalassets.lib.berkeley.edu/roho/ucb/text/cohen_stanley.pdf>.
16
Kingdom Royal Society in 2007. In being elected to this board, he became one of less
than 150 foreign members of this appraised scientific body. Most recently, at the age of
eighty-one, Stanley Falkow has been awarded the 2015 National Medal of Science. The
White House announced this honor on December 22nd, 2015; the award was presented in
January 2016. Dr. Falkow is one of nine recipients of the award, whom are recognized
for their outstanding contributions to varying fields of scientific disciplines. Specifically,
Stanley Falkow is being recognized for his pioneering work in the study of how bacteria
causes human disease and in what manner antibiotic resistance spreads.10 Although, this
contribution is only one of his many contributions to society through his field of
expertise.
Dr. Falkow formulated the text Molecular Kochs Postulates Applied to Microbial
Pathogenicity, which has provided the foundation that conducted research and analysis of
pathogenic microscopic genes that contribute to disease. He also developed a vaccine
that treats whooping cough. Arguably, Stanley Falkows most significant contribution is
simply his perspective on infections. He altered the basis of microbiology and
immunology in claiming that infections are a process, which is ultimately mediated by
the host rather than the invading pathogen.
In regards to antimicrobial resistance, Dr. Falkow is acclaimed for his work on
extra-chromosomal elements referred to as plasmids. Furthermore, he is known for
examining the role of plasmids in antibiotic resistance and pathogenicity in humans and
animals. Dr. Falkow found as previous researches had, that some bacteria were resistant
to antibiotics to which they had never been exposed. Subsequently, he identified that
bacteria gain resistant strains by sharing their genes and that this process occurs more
prominently than had ever previously been considered. Dr. Falkow recognized the
overuse of antimicrobials in society stating, "The enemy is us.11 He noticed that human
behavior was accelerating the growth of resistant strains among antimicrobials and
warned the industries of malpractice. I was fortunate enough to communicate with Dr.
10 Lovell, Donna. "Stanford Scientists Albert Bandura and Stanley Falkow to Receive the
National Medal of Science." Standford News. 22 Dec. 2015. Web.
<https://news.stanford.edu/2015/12/22/national-medal-science-122215/>.
11 Sternberg, Steve. "'America's Nobel' Winner Stanley Falkow Knows Germs." American
Scientist. 12 Dec. 2015. Web. <http://usatoday30.usatoday.com/news/health/2009-01-11-falkowprofile_N.htm>.
17
Falkow by means of phone and email interviews. Through various exchanges, Dr.
Falkow shared insight on his expertise surrounding microorganisms and their resistant
mechanisms. The following is a condensed version of an interview between Dr. Falkow
and myself, regarding his experiences and opinions on antimicrobial resistance. (refer to
appendix #1).
1.
Do you believe that microorganisms would have reached their current state of
resistance without the misuse, overuse, and inadequate dosage of antimicrobials in

healthcare, plant and animal agricultural, industrialized chemicals, and aquaculture
sectors?
I do not believe that microbes would have reached their current state of resistance
without the overuse of antibiotics. Bacteria are masters at survival and transfer their
genetic material promiscuously. There is now a good deal of antibiotic in the
environment in water and in the soil. Consequently, there are more and more antibiotic
resistant organisms literally everywhere in bacteria of all kinds - both pathogenic and
non-pathogenic. The two major factors at play in the increase of antibiotic resistant
organisms, I believe, is 1. The inappropriate use of antibiotics for treatment of infections
in the community (and especially in our hospitals; about 1/2 of all prescriptions written
for antibiotics are inappropriate) and 2. The use of antibiotics in animal feeds for growth
promotion (70% of all antibiotic production in the USA is employed in agriculture.
2.
Modern society is dependent on antimicrobials. Do you believe that people can limit
their use, in order to decelerate antimicrobial resistance?

Yes. The Infectious Disease Society of America has instituted programs internationally
that call for "Antibiotic Stewardship". Committees at all major medical centers and most
community hospitals have set up committees to guide physicians in all specialties in
the appropriate use of antibiotics for therapy. It's already having a positive effect. Both
the WHO and the CDC have declared antibiotic resistance a major threat to our health
and security and have proposed ways to reduce antibiotic use while preserving them for
treatment. Antibiotics are, after all, a major resource. I also believe that more and more
vaccines will become available. The best way to defeat an infectious disease is to prevent
18
it, not wait until you get the disease and treat it with an antibiotic. Of course there are
those that think vaccines are dangerous but in my experience these individuals are
misguided by fear and ignore the facts.
3.
In the 1970s you urged Food and Drug Administration to remove antibiotics from
animal feed. How did the industry react to your request?

Well they were not happy. I testified before Congress about this issue, they listened
politely but in the end the Congress told the FDA to withdraw the proposal to ban
antibiotics in animal feed for growth promotion and they asked for more research. Well,
its 40 years later and the research is still overwhelming. Excessive antibiotic use is
agriculture for non-therapeutic uses like feed supplements lead to the glut of antibiotic
resistant organisms in the environment. However, the FDA has recently published
guidelines for industry for the voluntary withdrawal of antibiotics for growth promotion
in animal feeds. It took a long time. I was 43 years old when I testified before
congress and I'm now 82 years old. I understood in the 1970s and throughout all these
years that the issue is one of a potential hazard to human and animal health versus the
economic consequences for the nation and the world. It's a balance of an action, which
is for the good of the community but may not be best for individuals. This is a
common dilemma of humanity. It's also a common dilemma in Medicine.
4. In what ways do you wish to see science advancing in the future?
There will be plenty to do! I have lived and experienced wondrous things in science.
Currently, the most challenging is the enormous amount of information that is being and
will be generated from sequencing all of life on the planet. There is no doubt that the day
is coming where medicine will be personalized. I predict that within 20 years, diseases
like cancer will be manageable in the same way the HIV/AIDS and diabetes can be
managed. This will happen in the technically advanced nations of the world. However,
the bulk of the world,(antibiotics or not, and vaccines or not) still suffer from diseases we
have conquered long ago. The leading cause of death in the world is respiratory tract
infection like influenza and pneumonia. The second leading cause is diarrheal
disease. Tuberculosis is still widespread, Our nation and the rest of the developed world
19
suffers from an inability to get the right resources to the right place in time to make a
difference. So the greatest advance in the future will be to cure poverty. It will take
science and the combined will of good, well meaning people. To see starving children
dying from disease that is preventable changes your entire perspective. More money is
spent worldwide in buying and selling military weapons than is spent on preventing
disease.
5. What advice do you have for youth following similar career paths to yourself?
I have taught a great number of students in my life. I still teach every week and I'm asked
this question often. The answer is simple, "Follow-your heart and your dream if that is
what feels right".
Role of Control
Control, although a critical determinant of organizational success often leaves too
much power in the hands of one individual or group. With ample opportunity, individuals
can become tempted to take advantage of ones power through the improper use of
20
authority. In complex issues such as antimicrobial resistance, there is an existing
hierarchy of control. This is often the reason why world issues are difficult to regulate; it
involves various parties all being controlled by another party.
When it comes to controlling the acceleration of antimicrobial resistance,
individuals with authority over the development of new antimicrobials have the greatest
influence. Limiting the expansion of resistant strains of antimicrobials is an intricate
process, which involves many parties. Initially, it seems that drug developers are in
control. However, after further investigation one discovers that researchers and
developers must submit an Investigational New Drug (IND) application to their
commanding national association.12 Each country has a distinct body of control, however
each national organization has similar regulations outlined by Mr. Mcclellan the United
States Congress of senate,
Under our laws, drugs must be demonstrated to be safe and effective to be legal.
No assumptions allowed by law. Other developed countries have similar laws. For
example when you walk into a drug store in Canada that serves Canadians, you
can be very confident that youre getting a product that is safe and effective.13
Examples of these national institutes are: Food and Drug Administration (FDA) in the
United States, Food and Drug Administration in China, and Health Canada within
Canada.
Historically, the largest government investments in basic drug discovery research
were made through various National Institutes of Health (NIH). Each convention takes a
maximum of thirty days to review a single Investigational New Drug submission. The
fundamental purpose for this tedious procedure is for the protection of volunteers
participating in clinical trials. These national federations have regulatory jurisdiction
over food, drugs, biologics, medical devices, electronics, cosmetics, tobacco, and
veterinary products. These institutes also have an integral association with facets in
12 "The Drug Development Process." U.S. Food and Drug Administration Protecting and
Promoting Your Health. 23 Nov. 2015. Web.
<http://www.fda.gov/ForPatients/Approvals/Drugs/ucm405622.htm>.
13 "THE SAFETY OF IMPORTED DRUGS." FDA.gov. 2015. Web.
<http://www.fda.gov/ohrms/dockets/dockets/04n0115/04n-0115-c000011-03-Appendix-QuotesFDA-vol11.pdf>.
21
advertising, water regulation, vaccines for animals, pesticides, meat and poultry, drug
abuse, alcohol, and consumer products. These institutes appear to be in control, but can
only operate with authority from their constitution.
Drug development is a global enterprise. Developers have the ability to choose
which drugs to develop and can establish the price of these drugs. However, developers
are dependant on government grants and patents to carry out the actual process of
development. Government funding has a significant impact on the prioritization of the
development of drugs. The cost of developing a new drug has been estimated to be more
than one billion dollars and in Canada, the government provides four hundred million
dollars to initiatives for advancements in healthcare, $1.4 billion for research machinery
and equipment, and two million one hundred sixty seven thousand dollars towards
centers for drug research and innovation.14 Specifically, The Centre for Drug Research
and Development (CDRD) received half of the government money granted for drug
research, declaring that:
Funding has enabled us to expand our capacity to develop and commercialize
innovative immunotherapy treatments for human disease. Not only has this
created highly skilled jobs, it provides Canadian researchers access to new
commercialization opportunities in this exciting and rapidly expanding area of
drug development.15
Karimah Es Sabar, president and CEO of the Centre for Drug Research and Development
illustrates the dependence of researchers on government funding. Drug development
consists of three stages: research, pre-clinical trials, and registration. The government is
the primary funder for the initial phase, while the government and pharmaceutical
companies equally fund the registration phase.
Drug development is a process, which the government regulates through registration,
requirements, and legislation. The government manages the registration of drugs with
14 "Federal Government Support." Government of Canada. 10 Jan. 2013. Web.
<https://www.ic.gc.ca/eic/site/lsg-pdsv.nsf/eng/h_hn01725.html>.
15 Karimah Es Sabar, President and CEO, The Centre for Drug Research and
Development (CDRD) <http://www.cdrd.ca/news/harper-government-supportsinnovation-in-immunotherapy-treatments/#sthash.n8X37Ma6.dpuf>
22
Investigational New Drug applications. These applications present difficulties for
developers such as; additional costs, time, and resources. The increase in adversities
discourages many researchers and companies from entering the antimicrobial
development pipeline. Governments also implement strict requirements for the execution
process of drug development. These requirements result in increased cost and clinical
trial time. Finally, legislation has been enforced restricting the development, sales, and
advertising of drugs. In general, the government has established that individuals
cultivating new drugs must be surveyed through each phase of development.
Antimicrobial resistance is a complex issue impacted through different sectors of society,
but the primary body of control is that which controls society. The government will
continue to have control over the acceleration of antimicrobial resistance as long as the
constitution regulates law and funding surrounding drug development.
Logic of Evil
In spite of human imperfection, people generally acknowledge that there are
moral boundaries, which should never be crossed and humans are more than capable of
abstaining from evil acts. We are all susceptible to unethical thoughts, but ultimately the
outcome of any action relies on the choice one makes to acknowledge or dismiss corrupt
thoughts. Individuals make decisions everyday based on incentive and desire and behind
each of these decisions (honorable and malicious) is a justification, otherwise known as
logic. The choices people make are a question of ones morals. Unfortunately, every man
has his price; good people are willing to violate the rules of decency and morality when
enough money is involved. In the means of antimicrobial resistance, antimicrobials were
intended to save lives and that is exactly how they were utilized, initially. Eventually, a
combination of greed, fear, and ignorance lead to the excessive use of antimicrobials.
23
Once individuals discovered they could exploit human vulnerabilities for wealth, people
then had the motivation and opportunity to misuse antimicrobials.
The causes of the persistence of antimicrobial resistance have been connected to
biological, societal, industrial, and legislative factors. Antimicrobial resistance has
progressed at its current rate as a result of complex interconnected components, which
did not solely contribute to this pandemic. Each different perspective must appropriately
be addressed in a holistic manner to effectively contain and address the persistence of
antimicrobial resistance. 16 In spite of the complexity of this concern, the publics
attention has been directed at a sole aspect of this issue. Corruption of economic,
environmental, social, and governmental factors has impaired the publics ability to
evaluate numerous aspects of antimicrobial resistance. For decades the topic of
antimicrobial resistance was exclusively discussed among experts in medical and
microbiological professions; recent progression of the threat, officials have been
compelled to broaden the publics awareness of antimicrobial resistance in an attempt to
hinder contradicting advancements. This sudden disclosure has gained public trust, as
people believe they are obtaining a legitimate disclosure regarding the details of the
situation. Ultimately, the public have been misled by numerous parties contributing to
the issue, through deception and propaganda of antimicrobial resistance.
An effective way to prevent adverse reactions from the public is to convince
people that they are unintentionally responsible for the evolution of antimicrobial
resistance. Officials have done precisely this; directed the publics attention towards
themselves. A joint statement was issued concerning antimicrobial resistance from
twenty-five national health organizations and centers for disease control and prevention
expressing that, Antimicrobials are a shared resource, and it is every individuals
responsibility to consider how each prescription or use of antimicrobials affects the
overall effectiveness of the [drug] arsenal. 17 Independently each organization (refer to
appendix #2) advocates this same philosophy, but united, the statement contained a
16 Nordberg, Per. "Antimicrobial Resistance." A Public Health Approach to Innovation. 2004.
Web. <http://apps.who.int/medicinedocs/documents/s20248en/s20248en.pdf>.
17 "Joint Statement on Antibiotic Resistance from 25 National Health Organizations and the
Centers for Disease Control and Prevention." Emerald Tufts. 2013. Web. 2016.
<http://emerald.tufts.edu/med/apua/policy/apua_action_34_1441267921.pdf>.
24
greater impact. This statement was one of many that urged individuals to take
accountability and act on this preceding threat. Through the use of assertive language
this statement provokes guilt and fear within readers. The author refers to the current
accumulation of pharmaceuticals as an arsenal, implying that civilization is at war against
microorganisms and patients are at fault for the inoperative defenses. The above
statement neglects to mention the quantity of mis-prescribed antimicrobials and the
current state of pharmaceutical innovations. Patients are condemned for ignorance of the
medical system. Unfortunately, for too many patients, the healthcare system is
unfavourably against them. Pharmaceutical industries, Healthcare professionals, and the
government have misled the public through deception and corruption within a
jurisdiction.
The pharmaceutical industries have neglected to contribute to the drug pipeline in
decades. The drug pipeline is a term devoted to a set of potential drugs that a
pharmaceutical company has under discovery or development at any given point in time.
Since 2011, no fabricated pharmaceutical advancements have taken place. A surge of
drug inventions arose between the years 1930 and 1962, as more than twenty classes of
antibiotics were developed. From 1962 to 2011, only two classes of drugs were
derived15. Over the years drug innovations have slowed to a halt. Prescriptions recently
introduced to the market are perceived as new, while actually, only alternate versions of a
pre-existing drug. When a microorganism becomes resistant to one version of a drug it
has an increased resilience to any version of that particular drug. Dr. Spellberg
commented on the release of a recent drug in 2005, Tigecycline is the first drug in the
glycylcycline class of antibiotics. If we did not have this new drug, Tigecycline,
infections would be essentially untreatable.18 Dr. Spellberg was used to increase the
credibility of this publication for Tigecycline. An additional tactic Pharmaceutical
companies utilize in the promotion of their products is double speak. In the above
statement the word new is applied in the context of modified. Tigecycline is not original,
18Buhner, Stephen Harrod. "Herbal Antibiotics, 2nd Edition: Natural Alternatives for Treating
Drugs." Googlereads. Web. 2016. <https://books.google.ca/books? when did Tigecycline come
onmarket&source=when did Tigecycline come on market >.
25
but rather a broad-spectrum antibiotic that has been available since the mid-1900s.19 It is
a derived form of minocycline with alterations to the molecule. Tigecycline was claimed
to have a decreased susceptibility to resistance, but this accusation was based purely on
the fact that microorganisms had less exposure to the drug. After two years of being on
the market resistant strains emerged and Tigecycline was found ineffective. Ambiguous
marketing is a common occurrence within the advertising of prescription products.
Under Canadas Food and Drugs Regulation act, prescription pharmaceutical companies
are prohibited from directing advertisements at consumers.20 However, industry
discovered a loophole in the interpretation of this piece of legislation. The act allows the
marketing of a products name, as long as the use of the product is not overtly stated. For
example, TV ads for the erectile dysfunction drug Viagra don't name its purpose. As well,
the act allows for the mention of a medical condition in publications for what is referred
to as "help seeking" purposes, so long as the product is not directly mentioned. In
Canada, a 2004 print advertisement for the cholesterol-lowering drug Lipitor depicted the
corpse of a fifty two year old woman who was not obese with a tag that listed the cause
of death as heart attack.21 Theres a strong correlation between the amount of money
pharmaceutical companies spend on advertising and what drugs patients are most often
requesting from physicians,22 accentuates the spokesperson for DTC advertising.
Patients have begun to demand medication that is not appropriate for their specific
condition. The manipulation of patients through advertisements has become so effective
that choices concerning a patients medication are impacted more by the attractiveness of
an advertisement than the medical merit of ones doctor.
19 Greer, Nicki, D. "Tigecycline (Tygacil): The First in the Glycylcycline Class of Antibiotics."
National Library of Medicine and National Institutes of Health. Apr. 2006. Web. 2016.
<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1426172/>.
20 "Food and Drug Regulations." Justice Laws Website. Web. 2016. <http://lawslois.justice.gc.ca/eng/regulations/c.r.c.,_c._870/FullText.html>.
21 Mintzes, Barbara, PhD. "Direct-to-Consumer Advertising of Prescription Drugs in Canada."
Health Council of Canada. Jan. 2007. Web. 2016. <http://www.healthcouncilcanada.ca/tree/2.38hcc_dtc-advertising_200601_e_v6.pdf>.
22 "Misprescribing and Overprescribing of Drugs." Worst Pills, Best Pills. 2016. Web. 2016.
<http://www.worstpills.org/public/page.cfm?op_id=3>.
26
Pharmaceutical corporations have been one of the most profitable industries
worldwide for a consecutive amount of years. In 2016 the world health organization
calculated that,
The global pharmaceuticals market is worth US$300 billion a year, a figure
expected to rise to US$400 billion within three years. The 10 largest drug
companies control over one-third of this market, several with sales of more than
US$10 billion a year and profit margins of about 30%. Six are based in the United
States and four in Europe. It is predicted that North and South America, Europe
and Japan will continue to account for a full 85% of the global pharmaceuticals
market well into the 21st century.23
The pharmaceutical industry has become an empire, as the operative goal of the industry
is to remain prosperous. Rather than investing in research, individual companies utilize
the wealth of the industry to further promote their products. The amount of money spent
on marketing ranges at 54 billion dollars a year. This does not include the abundance of
industry sponsored education, drug information conferences, and hospitality targeted
towards doctors. These questionable consulting and educational activities help to
influence the decisions of medical professionals and can lead to non-rationalized
prescriptions. The World Health Organization clarifies that pharmaceutical companies
spend one third of their revenue on marketing products, doubling the amount of revenue
spent on research. In the words of the director general of the World Health Organization,
Dr. Margret Chan, [there is] an inherent conflict of interest between the legitimate
business goals of manufacturers and the social, medical and economic needs of providers
and the public to select and use drugs in the most rational way.19 Many allegations have
been made against the pharmaceutical industry, in regards to advertising and promotional
tactics. For this reason, legislation was created to restrict the governing abilities of the
pharmaceutical industry over the public. One example is the Drugs and Magic Remedies
Act, which was established by the Indian government with the intent to control the
advertising of drugs. In violation of the guidelines of this act, the owner of Qadri
23 "Pharmaceutical Industry." World Health Organization. 2016. Web. 2016.
<http://www.who.int/trade/glossary/story073/en/>.
27
Dawakhana pharmaceutical firm, Hamdard Dawakhana was asked to recall 40 different

types drugs, in 1954.24 Mr. Dawakhana instead, filed a writ in Supreme Court. In 1959,
he successfully won his case on the terms that his right to free speech and right to carry
on trade and business were violated.25 The pharmaceutical industry quickly discovered
loopholes in legislation and became proficient in undermining the laws, as companies
continued with unethical advertising practices. The Drugs and Magic Remedies Act was
then amended in 1961, 1967 and in 1992, each time with the intent to oppose the subvert
strategies of the pharmaceutical industry. Similarly, the World Health Organization
developed the Ethical Criteria for Medicinal Drug Promotion in 1988. The guidelines of
this Act were disregarded based on a lack of strict regulation. The industry exploited
loopholes in the law that did not require proof of superiority over existing drugs for
approval. The ability of the cooperation appeared to intimidate the Food and Drug
Administration (FDA) into approving record numbers of drugs that offer no significant
benefit over drugs currently on the market, in addition to inducing adverse side effects.21
The pharmaceutical industry is the primary culprit in promoting the overuse and mis-use
of antimicrobials. Essentially, pharmaceutical companies continue to utilize deceptive
marketing and product revision because it proves to be the most efficient way for the
industry to acquire and secure mass profits. However, pharmaceutical industries are not
held accountable for the misleading marketing of drugs, but instead a lack of innovation
and contribution to the drug pipeline.
The malpractice of established practitioners is a primary cause of the
inappropriate use of antimicrobials. Antimicrobials are categorized to treat a specific
microorganism. For example antivirals treat viruses, antibiotics treat bacteria, and
antifungals are used against fungi. In prescribing antimicrobials professionals must be
precise; under-dosages and over-dosages causes redundant exposure of microorganisms
to antimicrobials, allowing for resistance. However, after a minimum of ten years of
medical school doctors, are expected to perform each task with accuracy.
24 "The Drugs and Magic Remedies." Objectionable Advertisements. Web. 2016.
<http://www.rfhha.org/images/pdf/Hospital_Laws/Drugs_magic_remedies_( advertisement)_act.p
df>.
25 "Health Care Case Law in India." A Reader. Ed. Mihir Desai. 2007. Web. 2016.
<http://www.cehat.org/humanrights/caselaws.pdf>.
28
The Center for Disease Dynamics, Economics & Policy, 2015 report found a
correlation between the spread of seasonal infections such as influenza and increases in
antibiotic use. Analysis of previous reports dated back to the year 2000, display a pattern
in the maximum antibiotic use and flu season to specific geographical regions. Antibiotic
use culminated persistently in North America and Western Europe from December
through to February, in South America in June and July, and in most of the tropics from
August to September.26 These patterns are consistent worldwide during winter months
universally known as the flu season, despite the fact that antibiotics cannot treat the
influenza. Antibiotics are used against bacteria, where as influenza is caused by a virus.
Antibiotics are routinely prescribed for infections precipitated by vectors other than
bacteria: malaria (Means et al. 2014), acute diarrhea (Kotwani et al. 2012), influenza
(Misurski et al. 2011), uncomplicated viral respiratory tract infections (Kotwani et al.
2012), and other viral infections. Medical professionals are driving the mis-use of
antimicrobials in the community by annually prescribing antibiotics to treat viral
infections.
In health care facilities, patients are routinely mis-diagnosed or the parasitic
culture is unidentified. In Vietnam, one-third of hospital prescriptions are inappropriate.
As a result, patients are prescribed what is known as broad-spectrum antibiotics. A
broad-spectrum antibiotic refers to a medical agent that is effective in treatment against a
wide range of pathogenic bacteria. Since, broad-spectrum antibiotics work against a wide
range of pathogens, in a sense acting as multiple drugs, these prescriptions provide the
opportunity for microorganisms to gain resistance to multiple drugs. This process
expands the growth of resistant strains by 42.9%27, contributing to the spread of resistant
strains between organisms not intentionally targeted. Trials have proven that the side
effect of resistant growth is more prominent than the actual effectiveness of broadspectrum antibiotics.28
26 GELBAND, HELLEN. "THE STATE OF THE WORLDS ANTIBIOTICS." Center for
Disease Dynamics, Economics & Policy. 2015. Web. 2016. <http://thewire.in/wpcontent/uploads/2015/09/State-of-the-Worlds-Antibiotics_proof_9.11.15-1.pdf>.
27 Du, Bin. "Management of Severe Sepsis in Patients Admitted to Asian Intensive Care Units:
Prospective Cohort Study." National Library of Medicine National Institutes of Health. 13 Jan.
2011. Web. 2016. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113333/?tool=pmcentrez>.
28 E. A. Martin (2003). Oxford Concise Medical Dictionary (6th ed.). Oxford University Press.
29
The application of antimicrobials is an essential portion of surgical procedures.

Individuals undergoing surgery are most often prescribed antimicrobials prior to the
operation to prevent the development of an infection following the procedure. These
medications must be applied before a surgery for efficiency. Patients prescribed
antimicrobials following procedures must increase their dosage for the same protection
over infection. Pre-surgical antimicrobials are an evidence verified standard in countries
of minimal corruption, for preventing postsurgical infections, although in countries of
high to middle corruption they are commonly prescribed after surgical procedures. In
post antimicrobial prescriptions, the risk of surgical site infections is increased. Francis
Mah, MD, a specialist in refractive surgery at Scripps Health System in San Diego says,
Theres definitely a need for change in the dynamic of what were doing to manage
complications post-surgery, 29 referring to the inappropriate application of Prophylactics
following operations. Eighty percent of antimicrobials prescribed post surgery, which
increases medical costs and contributes to the potential for antimicrobial resistance.
Finally, antimicrobial resistance has been detected to differentiate between
countries. This variation has been attributed to the deviation in the wealth (GDP), level
of health expenditure, quality of available health services, environmental factors such as
sanitation, and level of education of a country.30 However, several studies have amounted
to the same conclusion, in which these factors do not adequately explain the
differentiation between the level of antimicrobial resistance in varying countries. In
particular, the Australian study titled Antimicrobial Resistance: The Major Contribution
of Poor Governance and Corruption to This Growing Problem, published in March 2015,
investigated the impact of governmental corruption on antimicrobial resistance. This
recently published paper by Australian National University (ANU) proved that 28% of
the total antibiotic resistance variation in Europe could be connected to usage patterns
alone. Analysts then broadened this category to include time dependant factors, such as
29 Kent, Christopher. "Antibiotics & Cataract Surgery: New Frontiers." Review of
Ophthalmology. 15 Apr. 2015. Web. 2016.
<http://www.reviewofophthalmology.com/content/c/54133/#sthash.LEBB3TcA.dpuf>.
30 Carlet, J. "The Global Threat of Antimicrobial Resistance: Science for Intervention." National
Center for Biotechnology Information, U.S. National Library of Medicine. 17 Apr. 2015. Web.
2016. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446399/>.
30
global shocks. This resulted in the percentage of resistance caused by usage patterns to
increase to 33%, leaving the primary cause for resistance unexplained. The authors Peter
Collignon, Premachandra Athukorala, Sanjaya Senanayake and Fahad Khan discovered,
The general perception of antibiotic resistance is that it is almost entirely related
to the amounts of antibiotics used, not only in the broad sense of comparative
usage by different countries but also in individuals. However, the available
empirical evidence suggests that these two variables are not perfectly correlated at
national levels and across countries. We believe that other factors are as
important, or even more important, to account for the variations in resistance
observed between regions and countries. In particular, we wished to look at the
contribution of corruption.31
To accomplish their examination of corruption, these researchers conducted a
multivariate analysis of the variation of antimicrobial resistance between twenty-eight
European countries, covering the resistance of seven common human infections and
twenty-five pathogenic antibiotic combinations from 1998 to 2010. Europe was utilized
for research, as it provided a region where data for all parameters of the study are
available for multiple countries.28 Data indicated that the income level and gross tertiary
education enrolments of a country appeared to have no effect on resistance rates. This
comprehensive analysis transformed the ideology that wealth and relative education of a
country was a contributing factor to antimicrobial resistance.
Corruption occurs to varying degrees in all countries; through financial, economic
and social facets, but is especially detrimental in the development of a nations health
care sector. The authors further justify that government corruption is the socioeconomic
aspect most responsible for the acceleration of antimicrobial resistance throughout the
report. In the limitation of economic growth, influence in the spending of revenue,
lenient legislative control, and excellence of health care facilities, the authors, support
the hypothesis that poor governance and corruption contributes to antibiotic resistance
31 Collignon P, Athukorala P, Senanayake S and Khan F 2015, Antimicrobial Resistance: The
Major Contribution of Poor Governance and Corruption to This Growing Problem, Australian
National University.
31
and correlate better than antibiotic usage volumes with resistance rates.30 The
international Country Risk Guide was utilized in this report to determine the ranking of
government by control of corruption (Refer to appendix #3).
A nations corruption limits their economic growth. This is primarily a result of
uncertainty between major corporations. While particular multinational corporations
might gain a contract or tax breakthrough bribery, private organisations view corruption
as an additional risk to their investments, generally reducing the overall quantity of
investments made with particular countries.32 Poor trade and business result in a decline
in economic growth for the country. Essentially, decreased government revenue limits
the money available for investment and the health sector usually gets neglected. The
Australian paper exposed that infrastructure investments have greater potential for
compensation in legal dealings. For this reason, corrupt governments are more likely to
invest their revenue within intensive infrastructure projects in the divisions of transport or
military. If infrastructure is invested within the healthcare sector such as; hospitals and
equipment, while in themselves beneficial these entities cannot be prioritized above
primary health care and education. Limited available resources for health budgets results
in decreased salaries, education, and funding for operations. Ultimately, reducing the
services, access, and quality of care in health sectors.
The countries with higher levels of corruption were found to have less rigorous
and transparent legislation concerning the use and maintenance of medications. An
example that is not outlined within the study is the drug policy in India. In 1986, the drug
policy titled Measures for Rationalisation, Quality Control and Growth of Drugs &
Pharmaceuticals industry, although leniently enforced, was revised under the leadership
of Shri Rajiv to ensure an abundant availability of treatment for the people of India.33
The disregard for drug regulations generates inaccurate diagnosis and inadequate
prescription of antimicrobial treatments. Ineffective control over regions persistent with
the use of antimicrobials includes: inadequate dosages and improper preservation
32 Mauro P, 1995, Corruption and growth. The Quarterly Journal of Economics 110.3, 1995,
pp681-712.
33 "Drug Policy in India." India Network for Health. 2015. Web. 2016.
<http://www.medindia.net/buy_n_sell/pharm_industry/ph_drugpolicy.asp>.
32
antimicrobials and/or the surrounding environment. Disposing of antimicrobials in the
surrounding environment allows resistant strains to spread through water, food, human
transport, and poor infection control.
After completing the Australian report, data suggested that countries with more
corruption have a higher antimicrobial usage than the governments record. In correlation
to initial data of the Australian study on the variation of antimicrobial resistance amongst
different countries, researchers concluded that governmental corruption accounts for
absent 67%. Therefore, government corruption has a significantly larger impact than the
actual use of antimicrobial drugs in explaining variations in drug resistance between
countries.
Corruption occurs within multiple facets, each of which are not exclusively
responsible for the perseverance of antimicrobial resistance, but all must be considered.
In order to conceive solutions for this issue, individuals must first understand the
mechanisms, which throughout history contributed to the development and advancement
of antimicrobial resistance. Antimicrobial resistance should not be regarded as an
inevitable consequence of financial hardship for a country. Fortunately, antimicrobial
resistance can fluctuate and a reduction in government corruption results in a reduction in
the level of resistant pathogens. The ways in which governments manage corruption, not
only in the health sector, but across all aspects of society, will help achieve better public
health outcomes and reduce antimicrobial resistance.
33
Case Study: Greater Mekong Region

The Greater Mekong subregion is an internationally acclaimed region bound together by
a geographic feature: the Mekong River, situated in Southeast Asia. The Greater Mekong
subregion (GMS) of the Asia Pacific includes the countries of Cambodia, China (Yunnan
Province), Lao Peoples Democratic Republic (PDR), Myanmar, Thailand, and Vietnam.
This region combined has an area of 2.6 million square kilometers and a population of
approximately 326 million. In 1992, the ADB (Asian development bank) assisted six
countries with entering into a program of sub-regional economic cooperation, designed to
enhance economic relations among the countries. Greater Mekong is of the natural
ability for economic prosperity. Rich in human and natural resources, endowments of the
Mekong region have made a new frontier for Asian economic growth. Indeed, the
Greater Mekong region has the potential to be one of the world's fastest growing areas.
Unfortunately, antimicrobial resistance threatens the growth and survival of the entire
region.
The Greater Mekong region has become the epicenter for artemisinin resistance.
Isolated and derived from the plant Artemisia annua, or sweet wormwood, this
medication is known for its ability to rapidly reduce the number of Plasmodium parasites
in the blood of patients with malaria.34 Artemisinin is a terpene based anti-malarial,
prevalent in Chinese medicine. Qinghaosu, as artemisinin is informally referred to, is
currently the most effective anti-malarial. In addition to vector control, these medications
have led to significant declines in malaria morbidity and mortality. Artemisinin is a
broad-spectrum drug, in the means that the drug treats a broad range of parasites, acts as
multiple drugs, and prevents against different stages of the parasite. For this reason, the
34 "Q&A on Artemisinin Resistance." World Health Organization. 2015. Web. 2016.
<http://who.int/malaria/media/artemisinin_resistance_qa/en/>.
34
spread of artemisinin resistance has resulted in the resistance of medications which
chemical compound is mimicked within the molecular structure of artemisinin. Along
the Cambodia-Thailand border, parasites have become resistant to almost all of the
available antimalarial medications.34 In the beginning of 2014, 392 million treatments for
malaria were rendered ineffective because of multidrug resistance.34
Malaria is categorized as an acute febrile illness, simply meaning a feverish
sickness. Therefore initial symptoms include: fever, headache, chills and vomiting.
Symptoms may occur mildly at first, but if not recognized and immediately treated as
malaria within 24 hours, malaria can progress to severe illness, often leading to
death. The expansion in artemisinin resistance has lead to an increase in the number
of individuals affected by malaria. In the Greater Mekong region there are 160,000
deaths annually. Dr Pascal Ringwald of WHO, spoke at the ASTMH session in
November of 2009 stating, The loss of artemisinin derivatives to resistance has a
devastating effect on health in tropical countries, and threatens current global efforts
to eliminate malaria, as there are very few innovative replacement therapies in the
pipeline at the late stage of development.34 Dr Ringwald highlights the impact
artemisinin resistance has on the amount of individuals affected by this fatal disease.
The number previously mentioned is increasing, as the cost in human mortality raises
across the globe reversing any progress that antimalarial efforts have made in
attempts to eliminate malaria.35
Artemisinin resistance has caused, not only health implications, but rather
affected the entire economic structure of the greater Mekong region. With
artemisinin resistance prevalent throughout the region, malaria has become more
frequent throughout the population. Many factors contribute, but reports consider the
economic impact of malaria to be so high that it is considered the major cause of
poverty. To an individual, the cost can accumulate in the expense of medical
treatment, travel to clinics and dispensaries, prevention methods and equipment, loss
of income from days away from work and school, and burial upon death. As well,
35 Laxminarayan R. ACT Now or later: the economics of malaria resistance. Resources for the
future. 2003. Discussion Paper.
35
malaria has even been implicated in learning disability in children by which the
effects cannot be calculated in the effect of malaria on an economy. Each country
within the greater Mekong region spends $2.14 per person on malaria control
annually. This is a number that is estimated to rise if the spread of artemisinin
resistance is not neutralized, causing huge debt on the countrys economy.35 Once
examined, governments sustain costs in health care facility maintenance, drugs and
supplies, insecticide spraying, and bednet distributions. They also sustain loss of
income from sick workers, economic ventures, and lack of tourism, all resulting from
widespread disease. Within the same study mentioned before it was determined that
the economy of malaria endemic countries is 1.3% lower than countries without
malaria.36 The richest countries in Africa are free of malaria and located in the
northern and southern extremes of the continent. The gross domestic product of
malarial countries within Africa in 2000 was $1,526 compared to $8,268 in countries
without malaria.36 This statistic is relevant to the fact that the GDP of a country is
positively correlated with the standard of living for that country. For people living in
a malaria endemic area, the standard of living can remain low because of this disease.
However, even with the high cost associated with antimalarial resistance, in the long
run treating sick people so that they can return to work and school will help the
economy and translate into economic growth and poverty reduction.
The initial signs of artemisinin resistance appeared in the late 1950s in Southeast
Asia and spread across South Asia to East Africa by 1978.37 Subsequently the resistance
spread across the continent, leading to catastrophic increases in child morbidity and
mortality in sub-Saharan Africa. Artemisinin resistance has followed a geographic
pattern, causing a persistent parasite pool that is harder to eliminate. The incidence of
severe or prolonged illness and mortality has increased, particularly in low transmission
36 The economic burden of malaria. Gallup JL, Sachs JD Am J Trop Med Hyg. 2001 Jan-Feb;
64(1-2 Suppl):85-96.
37 Severe malaria not responsive to artemisinin derivatives in man returning from Angola to
Vietnam.Van Hong N, Amambua-Ngwa A, Tuan NQ, Cuong do D, Giang NT, Van Dung N, Tinh
TT, Van Tien N, Phuc BQ, Duong TT, Rosanas-Urgell A, D'Alessandro U, Van Geertruyden JP,
Erhart A. Emerg Infect Dis. 2014 Jul; 20(7):1199-202.
36
areas with reduced population immunity to malaria.38 This is due to the fact that regions
with less transmission among the population have minimal immunity, thus parasite
infections lead to acute symptomatic disease that get treated with low pressure dosages.
Under selective pressure, drug resistance is likely to propagate rapidly due to high drug
pressure on existing parasites. Artemisinin resistance has occurred as a consequence of
several factors: poor treatment practices, inadequate patient adherence to prescribed
antimalarial regimens, and the widespread availability of artemisinin-based monotherapies and substandard forms of the drug. All across the Greater Mekong region,
national antimalarial treatment policies have been slow to implement at the country level
and therefore have not been very effective in relieving the burden of disease.
A weak healthcare system and lenient drug policies within the Greater Mekong
region are believed to have accelerated the spread of artemisinin resistance. In order to
alter this epidemic the government must put in place strict drug policies. However, the
Greater Mekong region is known to have corrupt governance and because of this, the
public is reluctant to cooperate and accept policies put in place by the government.
Implementing national malaria drug policies occurs in a social context where selfmedication, mistrust of government officials, and lack of compliance are common. These
factors result in a difficult transition into more sustainable healthcare practices. The
changes are introduced by the Ministry of Health of various governments, which are
often not trusted. In Tanzania, one of six countries in the Greater Mekong region, the
government introduced policy changes through the ministry of health urging the public to
substitute artemisinin with sulphadoxine-pyrimethamine.39 The community was reluctant
as artemisinin was quicker and more effective than this new medication. Health care
practitioners in the region had developed a certain attachment to artemisinin. As well,
these policy changes only provoked patients into accumulating artemisinin for future use,
as it became scarce on the market. Ultimately, this policy change lead to suspicion,
noncompliance, and continued use of artemisinin. In many countries drugs with mass
38 Public health impact of drug resistant Plasmodium falciparum malaria.Bjrkman A, Bhattarai
A. 2016< http://www.ncbi.nlm.nih.gov/pubmed/15893289> Acta Trop. 2005 Jun; 94(3):163-9.
39 Uncertainty in malaria control in Tanzania: crossroads and challenges for future

interventions. Mboera LE, Makundi EA, Kitua AY. Am J Trop Med Hyg. 2007 Dec; 77(6
Suppl):112-8.
37
resistance are still used and this is a health policy failure, however, policy changes have
been significantly associated in terms of cost with retraining health care workers, printing
new drug regimens, and stocking new drugs. With the increase of transmission and drug
failures, medical care needs increase.
Efforts are underway to halt the spread of artemisinin resistance, including
coordination of activities and funding, and identification of areas of suspected artemisinin
resistance, through the use of newly identified molecular markers. However, targeting
resources for the containment of resistant parasites has proven inefficient and monitoring
the impact is challenging, while results in no advancements. In the Greater Mekong subregion the most sustainable solution to date has been to focus efforts toward a rapid
elimination of all parasites from the GMS.40 This strategy is more efficient for several
reasons. Firstly, a sub-regional strategy can build upon existing national programs and
political support for elimination of malaria, which by the public is more readily seen as
the issue rather than the resistance of antimalarial medications. The public has
contributed a greater amount of support towards these projects as they are in line with
their current commitment of malaria elimination. Second, the challenge of human
mortality is sub-regional in the means that it varies between countries, but for maximum
impact a harmonized elimination strategy is required. This has ultimately united the
countries within the sub-regional economic cooperation program. Finally, with a singular
goal across the sub-region, each country has been able to combine and utilize existing
regional bodies to catalyze political and funding support, and also leverage funding
already in place for success.
Although each country has their own policies, international organizations have
provided an alternate perspective by viewing the issue as a whole. One organization in
particular to participate in the efforts to reduce the impact of artemisinin resistance on the
greater Mekong region is the World Health Organization (WHO). In May 2007, the
World Health Assembly discussed malaria-endemic countries and solutions to
progressively cease the provision of artemisinin-based monotherapies. From this, WHO
40 Hwang, Jimee. "The Challenge of Artemisinin Resistance Can Only Be Met by Eliminating
Plasmodium Falciparum Malaria across the Greater Mekong Subregion." National Center for
Biotechnology Information, U.S. National Library of Medicine. 13 Jan. 2014. Web. 2016.
38
released the Global plan for artemisinin resistance containment, calling on all
stakeholders to maximize efforts to protect the efficacy of artemisinin, in January 2011.40
The global plan contains a comprehensive set of technical recommendations on how to
contain existing resistance and prevent it from emerging elsewhere, from which minimal
gains were made. WHO officials regrouped and in April 2013 launched the Emergency
response to artemisinin resistance in the Greater Mekong subregion, Regional framework
for action 2013-15.41 The framework urges national malaria partners to coordinate
programs in a manner, which aims at providing malaria interventions to any at-risk
groups, achieve tighter coordination and management of field operations, obtain better
information regarding the contamination of artemisinin resistance, and strengthen
regional procedures and support. Through these efforts, a regional hub has been
established in Phnom Penh, Cambodia to support and help coordinate activities. Efforts
to contain and eventually eliminate parasite resistance are still ongoing. WHO received
support from AusAID and the Bill & Melinda Gates Foundation, helping to strengthen
the coordination and technical support of activities in the Greater Mekong subregion.
The urgency of this situation has overlapped onto the agenda of various
already existing programs within the World Health Organization. The goal of the
2013-2015 regional framework is being implemented by the WHO Global Malaria
Program, the WHO Regional office for South-East Asia, the WHO Regional office
for the Western Pacific and WHO country offices. Each program is raising
awareness, although additional financing is still required for full implementation of
the regional elimination strategy. Outlined in a feasibility study created by WHO in
September 2014, elimination of antimalarial resistant parasites in the GMS would
cost over US$ 3 billion between 2015 and 2030. In 2013, the Global Fund to Fight
AIDS, Tuberculosis and Malaria committed US$ 100 million for 3 years to help the
affected GMS countries intensify malaria efforts. Recently, this donation has expired
and new financial and political commitments are required to help move the GMS
malaria agenda forward.
41"Status Report on Artemisinin Resistance." World Health Organization. Jan. 2014. Web. 2016.
<http://www.who.int/malaria/publications/atoz/status_rep_artemisinin_resistance_jan2014.pdf>.
39
Case Study: India

India, officially known as the Republic of India is a nation located in South Asia.
It is the seventh largest country by area with 2,864,021 km2 of land. India is bordered by
Pakistan to the west, China, Nepal, and Bhutan to the north, and Myanmar and
Bangladesh to the east. The country has a population of 1.2 billion people, making it the
most populous democracy and second most populous country in the world.
Unfortunately, these crowded conditions have, Proven to be a superbugs perfect petri
dish.42, stated Professor Lindsay Grayson highlighting the conditions of India, which
have lead to the spread of antimicrobial resistance.
Poor sanitation, lenient policies, and overcrowding have made India a fertile
ground for the development and expansion of resistant microorganisms. Many factors
have accelerated the rate of resistance for this nation, but the overuse of antimicrobials is
prevalent as there is no anti biotic policy within India. Antimicrobials are mass produced
and readily available over counter at an inexpensive cost without prescription. This can
be viewed positively as, more Indians are able to access antimicrobials, which are
particularly important for those who previously died of easily treatable infections.
However, the massive increase in use, both appropriate and inappropriate, is leading to
increases in drug resistance, which results in a reoccurring surge of untreatable infections.
India is the largest national consumer of antibiotics worldwide, with a sixty two percent
increase from their 2010 consumption of 12.9 billion units of antibiotics. The previous
number does not include all forms of antimicrobials.43
In the private healthcare sector, many doctors are poorly trained or unlicensed.
The lack of availability of some medicines because of irregular supply and problems
related to monitoring the external and internal drug quality has further increased the
problem, for doctors then turn to antimicrobials as a backup medication. Inappropriate
and irrational use of medicines provides favorable conditions for resistant
42 Rise of the Superbugs. Dir. Geoff Thompson. Perf. Pro. Lindsay Grayson. 2012.
43 Plump, Wendy. "Study Shows Significant Increase in Antibiotic Use across the World." News
at Princton. 10 July 2014. Web. 2016.
<http://www.princeton.edu/main/news/archive/S40/49/22E65/index.xml?section=topstories>.
40
microorganisms to emerge and spread.44 In India the infectious disease burden is among
the highest in the world. The poor sanitation from waste made by pharmaceutical
manufactures contaminating soil and waterways, and malnutrition exacerbates these
conditions.45
In 2009, the first superbug was identified when a fifty nine year old Swedish man
of Indian descent began visiting a hospital in rebro, Sweden, a small city 160 km away
from Stockholm. The patient, a diabetic male, needed treatment for abscess and urinary
tract infection. He recently returned from India, where abscesses developed inside and
surrounding his thighs and gluteal, resulting in hospitalization, first in Ludhiana and later
in Delhi. He underwent a surgery in Delhi, recovered and returned to Sweden.46 The
development of the abscess wasn't particularly unique, but his infection was. All
antimicrobials were ineffective and useless in treatment including carbapenems, the
strongest class of antibiotics currently known to mankind. Through further investigation,
doctors analyzing the case discovered, using a routine urine test, that the bacterium
responsible for the infection, was the commonly known Klebsiella pneumonia. This
bacterium frequently precipitates pneumonia and blood stream infections, however this
sample contained an unusual gene.
Doctors continued to study the bacterium for the following year and determined
that it originated in India. This gene, unknown, was later named NDM-1 (New Delhi
Metallo-beta-lactamase-1) or more commonly referred to as India-1, after the city where
the patient had been contaminated by the bacterium. NDM-1 is a bacterium, which
contains a specific enzyme that manipulates its ability to impede the effects of antibiotics.
This resistant parasite is referred to as the most dangerous superbug the world has ever
seen by most scientists, as the bacterium can eject its resistant genes into its surrounding
environment for other bacteria to collect. NDM-1 has the ability to convert all healthy
bacteria in ones body into superbugs, resistant to all antibiotics currently on the market.
44 Gupta, U. "Rationalizing Antibiotic Use to Limit Antibiotic Resistance in India." National
Center for Biotechnology Information, U.S. National Library of Medicine. Sept. 2011. Web.
2016. <http://www.ncbi.nlm.nih.gov/pubmed/21985810>.
45 "Global Antibiotic Resistance Partnership." Disease Dynamics, Economics, and Policy. 13
Apr. 2011. Web. 2016. <http://www.cddep.org/garp/home>.
46 Toleman, Mark, A. "Unique Genetic Structure in Klebsiella Pneumoniae Sequence Type 14
from India." National Center for Biotechnology Information, U.S. National Library of Medicine.
21 Sept. 2009. Web. 2016. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2786356/>.
41
Not only does NDM-1 impair the effectiveness of treatments against infections, it
transfers quickly from one bacterium to another, and rapidly increases the amount of
infectious resistance within the region.
Three months after naming this resistant parasite, more patients carrying the gene
were discovered in India. The Indian Government, however, dismissed any suggestions
of a corrupt system within the nation. Insulted, Legal professionals, government
personnel, and healthcare professionals claimed that the naming of the bacterial gene was
a plot against the country's lucrative medical tourism industry. Strict laws were installed,
regarding the ability of scientists to take biological samples out of India. It appeared,
however, the laws announced were aimed chiefly at British and Scandinavian researchers
who had named the bacterial gene, after smuggling water samples out of the country.
The democratically elected government of India attempted to oppress knowledge
of the emergence of NDM-1. A country like India, limited in healthcare facilities and an
unsustainable doctor patient ratio of one doctor to every 1,700 patients, the emergence of
super bugs is disastrous. Therefore, when Indian Scientists realized the threat of NDM-1
was legitimate, officials attempted to prevent scientists from notifying the public.
International medical literature was the first released report to cover the pathogenic
situation written by an Indian researcher. Immediately upon release, Dr. Vishwa Katoch,
the Indian governments secretary personnel for health research stated, India has a
problem like other countries, and naming the parasite after New Delhi is a conspiracy to
hurt Indias medical tourism.44 This was stated in an attempt to undermine the severity of
the problem. Government authorities were persistent and strived to intimidate the
researchers through letters validating that the report was conducted under illegal
circumstances. In one letter from the health ministry it was stated that, Permission is
required to be obtained from the relevant authorities.47 Despite many government
efforts and hate mail referring to the Indian scientists as, A devil, which consumes
children47, the report remained publicly accessible.
Accepting reality, the Indian government is now attempting to legitimize the
situation. With twenty nine percent of the population languishing below the poverty line,
experts say,
47 Shah, Sonia. Pandemic: Tracking Contagions, from Cholera to Ebola and Beyond. Print.
42
[India] has a high background rate of infections, we rely on antibiotics more than
developed countries do. Therefore, the impact of super bugs is likely to be much
greater for many in our country who cannot afford the newer, more powerful
antibiotics. Think of it as the price of fuel or kerosene going up. The rich will
manage wherever they are, but the poor will be hit hard.48
This is the one of many media conferences used to give reason to Indias current position
as the highest global consumer of antimicrobials. These frequent excuses have been of
greater occurrence than active restriction practices. The reluctant acceptance of the Indian
government to NDM-1, has allowed the gene the necessary time to develop and expand.
Within a year's time from the initial discovery of NDM-1, patients with this bacterial
gene were discovered in the US, UK, Canada, Japan and China. Similar cases have been
reported in more than 70 countries. Some of which, the patients had recently travelled to
the Indian Subcontinent and been exposed through medical treatment and hospital stays,
while many affected had never been to India. This occurrence suggests local
transmission within secondary countries affected.
Experts fear that India's excessive antibiotic usage is now leading to a powerful
mutation within bacteria. Easy availability and higher consumption of medicines have
lead to a disproportionately higher incidence of inappropriate use of antibiotics and
greater levels of resistance compared to any other country. However, in this position
globally, the Indian government continues to progress slowly. Presently, under various
national health programs, definite policies or guidelines are implemented for the
appropriate use of antimicrobials in certain situations such as Integrated Management of
Neonatal and Childhood Illness (IMNCI) in diarrheal diseases and respiratory infections.
Unfortunately, these regulations are not available for other diseases of public health
importance like common fever, which generates a higher income in means of
antimicrobial sales.
Antimicrobial resistance is a multifaceted problem, related mainly to existing
health care delivery systems of the country. In India, only 5% of GDP is spent on health,
out of which public health sector contributes to 0.9% and the remaining portion is
48 Biswas, Ranjita. "India: A Race to the Bottom with Antibiotic Overuse." Inter Press Service
News Agency. Web. 2016. <http://www.ipsnews.net/2014/08/india-a-race-to-the-bottom-withantibiotic-overuse/>.
43
covered by the private health sector. However, over 80% of the revenue contributed by
the private health sector comes from expenditures on medicines.48 The money being
generated for improvements to the healthcare system comes from the sales of excess
antimicrobials. This contradicting corruption has lead India into an epidemic of
resistance, plundering the countries social and economic health. The wellbeing of India
and the global public health, rely on the ability for countries to eliminate failure in
healthcare policies. Although small advancements have been made, Winning the fight
against infectious bacteria requires staying ahead of the organisms' ability to evolve.49
Since bacteria possess the ability to evolve rapidly, change must occur now for an
outcome in the favor of society.
Case Study: Brazil

Brazil, officially known as the Federative Republic of Brazil, is the largest sovereign state
in Latin America, characterized by diverse geographic and economic variations. Located
in the eastern portion of South America, Brazil borders nine countries and the Atlantic
49 Hede, Karyn. "Antibiotic Resistance: An Infectious Arms Race." Nature. Web. 2016.
<http://www.nature.com/nature/journal/v509/n7498_supp/full/509S2a.html>.
44
Ocean. Brazil is a federal republic with three political levels: the federal government, 26
states and a federal district, and 5563 municipalities. The health system is a complex
network formed by three interconnected subsectors; the public subsector Unified Health
System (SUS), the private subsector, and the private health insurance subsector. The
country has a population of 192 million inhabitants and is the fifth largest country by
both land area and total population. So Paulo is the largest and most populated city in
Brazil. Located in the southeast region of the country with 20 million people, this city is
known for its abundance of the countries major medical schools. These are top ranked
education facilities, where outstanding education has translated to exceptional healthcare
treatments and facilities. Despite its medical centers of excellence, antimicrobial
resistance in Brazilian hospitals poses as a major problem and challenge in treatments.50
Brazil, in general, has higher levels of bacterial resistance amongst the countries
key pathogens, compared to Europe and the United States. Although, top ranked in
medical education, corruption within Brazil has tainted the efficiency of its community
medical facilities. Transparency International's Corruption perception Index, as
preciously reviewed in this report, identifies Brazil as 69th out of 178 countries in means
of the country with the most corruption. Corruption costs Brazil almost $41 billion a year
alone, with 69.9% of the country's industries identifying the issue as a major constraint in
success of their business.51 In the healthcare industry corruption has occurred in many
different facets, which lead to an increase in antimicrobial resistance.
Brazil has a high consumption of last-resort drugs, such as colistin, which is quite
frequent in Brazilian intensive care units (ICUs). Through overuse, many isolates have
developed resistance to almost all currently available drugs.52 Evidence proves that the
total consumption of antimicrobials is a critical factor in select resistance. Paradoxically,
the under-use or inadequate dosage of prescribed medications, poor adherence, and
substandard antimicrobials contributes as much as over-use in causing resistance. A major
50 Rossi, Flvia. "The Challenges of Antimicrobial Resistance in Brazil." Clinical Infectious
Disease. Web. 2016. <http://cid.oxfordjournals.org/content/52/9/1138.full>.
51 "Brazil: Corruption Costs $41 Billion". Latin Business Chronicle. Archived from the original
on 21 March 2013. Retrieved 22 March 2013.
52 Furtado GHC, d'Azevedo PA, Santos AF, Gales AC, Pignatari AC, Medeiros EA. Intravenous
polymyxin B for the treatment of nosocomial pneumonia caused by multidrug-resistant
Pseudomonas aeruginosa. Int J Antimicrob Agents 2007;30:315-9.
45
problem in the development of resistant parasites in Brazil is the fact that antibiotics still
can be bought over-the-counter. This healthcare policy failure leads to self-medication,
contributing to the growth of antimicrobial resistance.
Brazil does not have a central microbiology reference laboratory, therefore
gathering data on the national state of antimicrobial resistance is difficult because the lack
of official publications. Recently, the local hospitals have had an increasing tendency to
consolidate microbiology laboratory services, transferring them off site. This has resulted
in a longer turnaround time for the culture and antimicrobial susceptibility test results.
Even with antimicrobial stewardship groups in the majority of the hospitals, delay of
microbiology reports may impair specific prescriptions, which in turn, contributes to a
higher selective pressure because of the large use of broad-spectrum antimicrobials.
Broadspectrum antimicrobials are a form of antimicrobial, which can treat multiple
infections with the purpose of managing infections that cannot be identified.
Unfortunately, the use of broad-spectrum antimicrobials has led to the development of
Multi Drug Resistance (MDR). This is a form of antimicrobial resistance shown by a
species of microorganism to multiple antimicrobial medications, which has become
prevalent in Brazil. WHO comments on this prevalence, stating that at its current state,
antimicrobial resistance in Brazil, will affect everyone, regardless of where they live [in
the country], their health or economic circumstances, lifestyles or behaviours.53
Antibiotic resistance is not just a medical issue, but also an ecological matter. Since
human populations are dependent on aquatic environments, the propagation of medical
waste within these sites represents a serious threat to public health. To understand the
process by which resistance propagates, it is necessary to consider not only hospital
settings, but evaluate resistant microorganisms in an ecological environment. Exposure
to antimicrobials is a major factor contributing to the development of resistant strains;
when hospital waste pollutes surrounding waters antimicrobial compounds exert a
selective pressure that promotes the dissemination of the genes of environmental
microorganisms, responsible for spreading resistance. When an ecosystem is altered by
different elements such as pollution, microorganisms react with drastic changes to the
53 "Antimicrobial Resistance." World Health Organization. 2015. Web. 2016.
<http://www.who.int/drugresistance/AMR_DRAFT_GAP_1_Oct_2014_for_MS_consult
ation.pdf>.
46
functioning of that ecosystem, the composition of the species, and abundance of the
species. This is an example of how microorganisms can evolve and acquire resistance.
Brazilian scientists evaluated six aquatic regions affected by pollution and concluded that
environments with higher levels of pollution had greater amounts of resistant
microorganisms than many of the regional hospitals.54 The data indicates that the
dissemination of resistant bacteria in aquatic ecosystems is compromising the
effectiveness of that drug. Also, these results are further evidence that precarious
conditions of basic sanitation and low efficacy of hospital effluent treatment plants can
contribute to the spread of multi-resistant bacteria into aquatic ecosystems, compromising
the effectiveness of medical treatments for an entire region.
In coordinating national action against Antimicrobial Resistance, the responsibility is
with Agencia Nacional de Vigilancia Sanitaria (Anvisa), a government agency, which
controls the field of communicable disease prevention and control, and pharmaceutical
regulations. In 2002, the agency commenced their efforts towards the reduction of
antimicrobial resistance within the nation by gathering a group of specialist together at a
national assembly to discuss possible guidelines for the prevention and control of the
continuously developing resistance. The group highlighted the necessity for creating a
surveillance network, leading not only to the implementation of a national Antimicrobial
Resistance surveillance network, but multiple prevention activities. Two years after the
meeting, in 2005, Anvisa officially created the national AMR surveillance network Rede
RM, composed by sentinel hospitals, public health laboratories, local and regional
sanitary surveillance centers, and local and regional commissions for control of infection.
The primary objective of Rede RM being, make health assistance more effective through
rational use of antimicrobials, as well as prevention, detection and control of AMR in
Brazilian health settings.55 Although successful, the crisis, which had evolved in Brazil
required more than surveillance that had ultimately made no reduction in the expansion
of resistant strains. This realization prompted the development of national legislation.
54 Coutinho, Felipe Hernandes. "Antibiotic Resistance in Aquatic Environments of Rio De
Janeiro, Brazil." INTECH. Web. 2016. <http://www.intechopen.com/books/perspectives-in-waterpollution/antibiotic-resistance-in-aquatic-environments-of-rio-de-janeiro-brazil>.
55 Lobosco, Hanna. "Implementation of International Strategies against Antimicrobial
Resistance." Institutionen Fr Hlsovetenskap Department of Health Sciences. June 2012. Web.
2016. <http://www.diva-portal.se/smash/get/diva2:536157/FULLTEXT01.pdf>.
47
The CCIH (Comissao de Controle de Infeccao Hospitalar/ Commission for Control of

Infection) coordinated various activities to promote legislation required for the rational
use of antimicrobials. In 2010, legal regulation made it mandatory to provide alcohol
solutions for hand disinfection in all health care settings in the country to promote
sanitation.56 The same year, another regulation was issued to control the sale of
antimicrobials, which can no longer be purchased without a special prescription.56
Brazil, is taking in the process of preventing Antimicrobial Resistance, with several good
intentions documented and many of the necessary tools in place, such as networks and
legal framework. Project Rede RM seems the most ambitious of current projects and has
provided a strong framework for the Brazilian community, in their fight against
Antimicrobial Resistance. However, it is limited, focused only on health care settings, an
area where improvements have already been made. Although mentioned briefly in one of
the intervention actions, society role has not been properly addressed and considered
within the project.55 Animal husbandry, corruption of the food industry, and effects of
pollution on the ecosystem are not dealt with by Anvisa in documentation. Therefore,
more work must be done on the entirety of antimicrobial resistance before Brazil can be
considered to have met WHO's idea of a comprehensive national plan, bringing together
all recommended interventions.
International Organization
Many International agencies such as: World Health Organization, European
Centre for Disease Control, and World Health Assembly have recognized and prioritized
antimicrobial resistance as a pressing public health issue, but still the containment of
resistant parasites has proven to be a challenge. The advancing threat of ineffective
antimicrobials is a global issue, which is best dealt with at a national level. One
organization, in particular, coordinating national efforts to alter the expansion of
resistance is the World Health Organization. Informally recognized by the acronym
WHO, the World Health Organization aims to improve public healthcare systems,
56Lobosco, Hanna. "A Review of Scientific Literature and the Case of Brazil." Institutionen Fr
Hlsovetenskap Department of Health Sciences. 2010. Web. 2016. <http://www.divaportal.se/smash/get/diva2:536157/FULLTEXT01.pdf>.
48
policies, and overall health of patients at an international level. As stated in the official
mission statement, World Health Organization
seeks to publish and disseminate scientifically rigorous public health information
of international significance that enables policy-makers, researchers and
practitioners to be more effective; it aims to improve health, particularly among
disadvantaged populations.57
This has been the goal of the organization since April 7th, 1948, when the constitution was
officially established. WHO headquarters originated in Geneva, Switzerland and
preceded the health organization, an agency of the League of Nations. At the time, the
organization involved sixty-one countries, but currently has restriction in one hundred
and fifty countries with a total of six regional offices. The World Health Organization is
a specialized agency of the United Nations, which is concerned with international public
health. WHOs current priorities include: the eradication of communicable diseases,
specifically HIV/AIDS, Ebola, malaria, and tuberculosis. However, the development of
antimicrobial resistance has reversed and threatens to diminish the remaining efforts
made by WHO to eradicate communicable diseases. For this reason, antimicrobial
resistance has become a major priority for the World Health Organization. It is
considered, the single greatest challenge in infectious diseases today58 for the WHO,
which has initiated several systems to combat the expansion of antimicrobial resistance.
To combat advancement in antimicrobial resistance, WHO first analyzed the situation
with the Antimicrobial Resistance Global Report on Resistance in 2013. The survey
warns of a, post antimicrobial era.57 It is also the first report on antimicrobial resistance
to survey one hundred and thirty three countries and capture each governments opinion
on the state of resistance within their country. In completing this section of the report,
WHO discovered a significant discrepancy between the actual and perceived state of
resistance. The report served as a successful tool in identifying the current state of the
situation, allowing organizations to understand what needs to be done next. While
57 "Bulletin of the World Health Organization." World Health Organization. 2016. Web. 2016.
<http://www.who.int/bulletin/mission_statement/en/>.
58 "WHO Report Finds Systems to Combat Antibiotic Resistance Lacking." World Health
Organization. 29 Apr. 2015. Web. 2016.
<http://www.who.int/mediacentre/news/releases/2015/antibiotic-resistance-lacking/en/>.
49
antimicrobial resistance is best dealt with at a national level, only thirty-four out of one
hundred and thirty three countries surveyed have a comprehensive national plan to
combat resistance.58 As well, there is a widespread leniency surrounding the surveillance
and policies regarding the use of antimicrobials. The majority of the countries have
continual sales of antimicrobials without prescriptions, poor laboratory capacity,
infrastructure, and data management of resistant strains; a lack of public knowledge. This
report allowed for a publicly accessible resource outlining areas requiring improvement
for the reduction of antimicrobial resistance.
In May 2015, the World Health Organization endorsed the Global Action Plan on
antimicrobial resistance at the sixty-eighth World Health Assembly. The development of
this plan was guided by the 2013 report, and advice from national and regional
stakeholders from multi-stakeholder consultations at various levels of government.
Through the course of development, WHO officials considered the structure of already
existing plans, activities, and initiatives. The goal of the World Health Organization is to
ensure, for as long as possible, successful treatment and prevention of infectious disease
through the responsible use of safe and effective medications, which are made available
to all who may require them. For this goal to be achieved, the plan has been categorized
into five strategic objectives, which are as follows;
1.
2.
3.
4.
5.
Improve awareness and understanding of antimicrobial resistance;

Strengthen knowledge through surveillance and research;
Reduce the incidence of infection;
Optimize the use of antimicrobial agents; and
Develop the economic case for sustainable investment that takes account of the
needs of all countries, and increase investment in new medicines, diagnostic tools,
vaccines and other interventions.59
The objectives divide efforts between various sectors, which require attention: human and
veterinary medicine, agriculture, finance, environment, and informed consumerism. As
well, The World Health Organization is combining its effort with various organizations to
regulate different societal facets. WHO is working with United Nations to treat
antimicrobial resistance at a political level and continues to work with FAO and OIE
59 "Global Action Plan on Antimicrobial Resistance." World Health Organization. 2016. Web.
2016. <http://www.who.int/drugresistance/global_action_plan/en/>.
50
regarding the economic aspects of the issue. The crisis continues to be managed with
urgency, for if not
This will be the end of modern medicine as we know it. If current trends
continue, sophisticated interventions, like organ transplantation, joint
replacements, cancer chemotherapy, and care of pre-term infants, will become
more difficult or even too dangerous to undertake. Adoption of the WHO
Global action plan on antimicrobial resistance at the May World Health
Assembly has given concrete expression to this growing level of concern.60
Dr. Margaret Chan, director of WHO, speaks out about the significance of global
participation in the action plan at the Geneva Convention of 2015. The plan has
improved the awareness and understanding of antimicrobial resistance through
effective communication, education and training. To date, this action plan has been
successful in providing the framework necessary for countries to develop unique
plans of action to combat antimicrobial resistance at a national level. Countries such
as Thailand and even Cambodia have developed a national assembly devoted to
reducing the expansion of resistant strains and if the rate of success continues, it is
estimated that each country involved under WHO will have an individualized action
plan in place by 2017.
Finally, the World Health Organization created the initiative World Antibiotic
Awareness Week from November 16th to 22nd. World Antibiotic Awareness Week
aims to increase awareness of global antibiotic resistance and to encourage best
practices among the general public, health workers and policy makers to avoid the
further emergence and spread of antibiotic resistance.61 This campaign has only
operated twice, the most recent year being called Antibiotics: handle with care. The
theme of the campaign reflects the underlying message that antibiotics are a precious
60 Chan, Margaret, Dr. "WHO Director-General Addresses G7 Health Ministers Meeting on
Antimicrobial Resistance." World Health Organization. 2015. Web. 2016.
<http://www.who.int/dg/speeches/2015/g7-antimicrobial-resistance/en/>.
61 "World Antibiotic Awareness Week." World Health Organization. 22 Nov. 2015. Web. 2016.
<http://www.who.int/drugresistance/en/>.
51
resource, which is essential to preserve. The week initiative emphasized that

antimicrobials, in particular antibiotics should be used to solely treat bacterial
infections and only when prescribed by a certified health professional, medication
should never be shared, and the full course of treatment should be completed, rather
than saved for the future. The World Health Organization encourages all Member
States, health partners, and community organizations to join this campaign and help
raise awareness of this issue. In doing so, WHO provides a variety of resources, made
available to support local campaigns with factsheets, infographics, posters and multimedia materials.
The European Centre for Disease Prevention and Control, an independent
agency of the European Union, has made additional efforts to reduce the spread of
resistant parasites across Europe. Although, in realizing that microorganism are
transmitted through travel, ECDC expanded antimicrobial resistant initiative on an
international level. Ultimately, since being established in 2004 in Solna, Sweden, the
mission of the European Centre for Disease Prevention and Control is to strengthen
defenses against infectious diseases. In regards to antimicrobial resistance, the
ECDC believes that the public is accountable for altering the advancements of
resistance strains, however the general public is unaware of the issue altogether. To
resolve this problem, the ECDC decided that the initial step to targeting the problem
was to increase awareness and from which the public can then alter their everyday
lives accordingly. The European Centre for Disease Prevention and Control has
created an infographic that depicts the various facets which antimicrobial resistance
spreads in society (refer to appendix #4). The infographic further explains how each
societal factor, specifically contributes to the spread of resistance. This infographic,
which has been translated into all EU official languages, is distributed in hospitals
across Europe to increase patient awareness.62 Following the European distribution,
62 "New EAAD Infographic on the Spread of Antibiotic Resistance Now Available in All the
Official EU LanguagesEuropean Centre for Disease Prevention and Control. 5 Nov. 2015. Web.
2016. <http://ecdc.europa.eu/en/press/news/_layouts/forms/News_DispForm.aspx?
ID=1312&List=8db7286c-fe2d-476c-913318ff4cb1b568&Source=http://ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/Pages/inde
x.aspx>.
52
the ECDC administered copies of the infographic to all international partners, one of
which being the World Health Organization. Pleased with the success of the
infographic, WHO included the sheet within its resource packages to support local
campaigns. Through the development of this inforgraphic, international awareness
has increased.
The Infectious Disease Society of America (IDSA) represents physicians,
scientists, and various health care professionals specializing in infectious disease.
This board was funded in 1963 and currently involves over 9,000 members. IDSA
has created an innovative campaign to direct liability onto individuals. A stewardship
commitment form, when signed obligates an individual to practice safe and
appropriate use of antimicrobials. IDSA is cooperating over this campaign with
various national institutes to achieve international change. Antibiotic stewardship
involves making a commitment to use antibiotics only when necessary, choose the
appropriate drugs, and always administer the medication at the proper dosage and
duration.63 This particular stewardship program has been signed by the White House,
who intend to lead a nationwide effort to elevate antimicrobial stewardship. This
Antibiotic stewardship program has improved the methods utilized to treat patients,
shorten antimicrobial use, and reduce health care facilities pharmacy costs. A review
of the program from 1996 to 2010 demonstrated that the antimicrobial stewardship
program achieved a 38% reduction in defined daily dose (DDD) per 1,000 patient
days.64 The results of this ongoing program included significant reductions in total
antibiotic consumption, duration, and inappropriate use, proving to be successful.
In conclusion, it is international organizations that create initiatives as
mentioned which will help eradicate the expansion of resistance. Although, these
initiatives are only successful with local participation and support. Antimicrobial
63 Centers for Disease Control and Prevention Office of Infectious Disease. Antibiotic
resistance threats in the United States, 2013. Apr, 2013. Available at:
<http://www.cdc.gov/drugresistance/threat-report-2013.> Accessed February 20, 2015.
64 Seven ways to preserve the miracle of antibiotics. Bartlett JG, Gilbert DN, Spellberg B. Clin
Infect Dis. 2013 May; 56(10):1445-50.<
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195192/>
53
Resistance is an international problem and by addressing the issue at this level,

quicker progression is made within the process of eradication.
Canadian Connection
Antibiotic resistance has increased dramatically, as the morbidity, mortality and economic
burden of infections with multiple drug resistant organisms, for which there are no
effective therapies, pose an increasing burden for health care systems worldwide; Canada
is no exception. However, Canadas susceptibility is not necessarily due to inadequate
healthcare and policy failures. As of April 3rd, 2016 WHO ranked Canada thirty, out of
one hundred and ninety countries in terms of best healthcare systems. The World Health
Organizations national ranking system is based off of five factors: overall health, overall
responsiveness, health equality, responsiveness equality, and fair financial contribution of
the nation. The analysis provides a framework that allows countries with weak
healthcare systems the ability to compare their structure to countries with thriving
healthcare systems.
In October 1994, the search for an appropriate structure of healthcare in Canada
began. The Canadian prime minister called on the National Forum on Health, in search
of innovative ways to improve the healthcare system at the time. The report summarizing
the forum, concluded that the main objective should be the rapid development of an
54
evidence based healthcare system in which decisions are made by health care providers,
administrators, policy makers, patients and the public on the basis of appropriate,
balanced and quality evidence.65 As a result, the National Forum on Health
recommended the development of a nationwide health information system and Health
Canada was created. Health Canada remains the federal department responsible for
maintaining and improving the health of Canadians since its formal establishment in
1996. While the provinces and territories are responsible for the delivery of healthcare
and resources to Canadians, the federal government is said to have the final say over the
majority of areas that affect health and healthcare.
Health Canada is the federal department that links provincial and federal efforts.
The federal and provincial governments have very different responsibilities in health
care. In general, the federal government cannot establish and maintain various policies in
national health care because provincial governments regulate the delivery and treatment
of health care to individuals, under the Canadian Constitution and its interpretation by the
courts. Therefore, health care is a field primarily under provincial jurisdiction. However,
Health Canada ensures the commitment of a strong, publicly funded healthcare system
guided by the principles of the Canada Health Act of 1984. This legislation allows the
government control over the healthcare system through what is known as constitutional
spending power.66 This enables the federal government to make a financial contribution
to certain programs under provincial jurisdiction, generally subjecting provincial
compliance to certain policies and requirements. The Canada Health Act is structured
with nine requirements that provincial governments are required to meet through
Canadas public health care insurance plan in order to qualify for the full federal cash
contribution under the Canadian Health Transfer (CHT). These nine requirements include
five criteria, two specific provisions and two conditions. The five criteria are often
referred to as the national principles, which are specifically: public administration,
comprehensiveness, universality, portability, and accessibility. The two specific
provisions relate to user charges and extra-billing for insured health services, while the
65 "History." Health Canada. 5 June 2012. Web. 2016. <http://www.hc-sc.gc.ca/hcs-sss/ehealthesante/infostructure/hist-eng.php>.
66 "THE CANADA HEALTH ACT: OVERVIEW AND OPTIONS." Parliament of Canada.
May 2006. Web. 2016. <http://www.lop.parl.gc.ca/content/lop/researchpublications/944-e.htm>.
55
two conditions pertain to the provision of provincial information and recognition of

federal contributions. Both sections connect the federal government to the healthcare
system through insured health services and extended health care services. Ultimately, the
federal government remains in control of health sectors through financial funding. To
utilize this control and commence a broader, more cohesive plan of action against
antimicrobial resistance, the Government of Canada is presenting Antimicrobial
Resistance and Use in Canada: A Federal Framework for Action.
On December 12th, 2013 a seventy five year old man, residing in the prairie region
of Manitoba, was infected with a common infection. Michael, as he has chosen to only
be referred to by his first name in any articles relating to the situation, frequently visited a
local hospital, because his wife was receiving a hip replacement and was quarantined for
five days. During this period, Michael had been prescribed a weeks dosage of
Amoxicillin, an antibiotic used to treat sinus infections. Several days after his wife was
discharged Michael began to experience severe fever, diarrhea, and stomach cramps.
Following various diagnostic tests, doctors concluded that he had been infected with a
resistant form of C. difficile bacteria, which is an infectious bacterium commonly found
in hospitals and healthcare institutes across Canada. As symptoms progressed, Michael
was eventually hospitalized and two weeks following his hospital admission, he passed
away. Although Michael was of an additional risk because of the fact that he was taking
antibiotics and is of older age, acquiring resistant forms of infection is becoming
increasingly popular within Canada. According to Health Canadas Report on nationwide
antibiotic and drug resistance rates, one in 23 hospitalized Canadians will become
infected with the superbug known as MRSA.67
Recent Canadian data shows that antibiotics have the leading amount of resistance
for antimicrobials. In Canada, 51% of antibiotics are being prescribed for patients with
upper respiratory tract infections, the common cold and other viral infections for which
antibiotics are ineffective. Each occasion in which these medications are misused, allows
bacteria the opportunity to evolve into a superbug. This healthcare system failure needs
67 "Canadian Antimicrobial Resistance Surveillance System Report 2015." Government of
Canada. Web. 2016. <http://healthycanadians.gc.ca/publications/drugs-products-medicamentsproduits/antibiotic-resistance-antibiotique/antimicrobial-surveillance-antimicrobioresistanceeng.php#a8>.
56
to be addressed; Superbugs have already cost Canadians $1-billion in medical care. Over
the last several years national reports noted a fourteen percent increase in the use of lastline antibiotics used to treat difficult infections. As a result, more than 18,000 patients in
Canada annually acquire multi-drug-resistant strains of bacteria.
In Canada, systematic efforts for controlling antibiotic resistance began in 1997
following a consensus conference entitled Controlling Antimicrobial Resistance: An
Integrated Action Plan for Canada.68 Unfortunately, this conference resulted in minimal
improvements of Canadian surveillance and action plans to reduce the growth and
expansion of antimicrobial resistance. A union, unique to Canada in opposing the
emergence of resistant parasites is the Canadian Antimicrobial Resistance Alliance
(CARA). This group is dedicated to the study of medical microbiology and infectious
diseases issues with a special interest in infections caused by antimicrobial resistant
pathogens and antimicrobial usage in Canada.69 CARA headquarters are located in
Ottawa, but researchers and board members reside all across Canada contributing to
additional programs such as: CANWARD, CANWARD Anaerobe, CANICU, NAUTICA,
and CROSS. In early 2007, this federally funded alliance launched a website campaign
designed to assist and educate Canadian healthcare providers and patients on the
escalating issue of antimicrobial resistance. George G. Zhanel describes the current state
and role of this website as,
The official website of the Canadian Antimicrobial Resistance Alliance (CARA),
which focuses on both community and hospital (e.g. ICU, nosocomial, respiratory,
urinary, fungal and MDR) infections. The website continues to grow under my
leadership. As Editor-in-Chief, I will continue to work with a multidisciplinary
group of Canadian experts to improve this unique, multipurpose, multidisciplinary
infectious diseases and medical microbiology content based website, which
addresses Canadian issues in antimicrobial and antifungal resistance and usage.69
68 Controlling antimicrobial resistance. An integrated action plan for Canadians. Health Canada
and The Canadian Infectious Disease SocietyCan Commun Dis Rep. 1997 Nov; 23 Supple 7
<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2094896/>
69 Zhanel, George G. "About Us." Canada Antimicrobial Resistance Alliance. Web. 2016.
<http://www.can-r.com/aboutUs.php>.
57
Zhanel explains how this online research portal addresses the problem with the unique
approach of collaborating with the multiple societal sectors, which experience or
contribute to antimicrobial resistance. Members of the alliance conduct various studies
and update all of the data collected onto this website for public use. With the goal to
provide current and comprehensive information, the online portal includes a variety of
features and tools on antimicrobial resistance in Canada including: national surveillance
of pathogens and infections, surveillance of antimicrobial resistance rates, antimicrobial
usage data, updates regarding investigational and new antimicrobials, research presented
at public and confidential conferences, and videos explaining antimicrobial mechanisms
of action and how one can assist in elimination efforts. Through a genuine approach
CARA created a useful tool for researchers, medical care providers, and the media in
understanding the rise of antimicrobial resistance in Canada and how this issue can be
managed.
Canadian governments and researchers have recognized that with decisive action,
the escalating rate of antimicrobial resistance can be minimized. Accordingly, appropriate
programs have been implemented and as a result Canada has one of the lowest rates of
resistance globally.70 Although, minor aspects of the Canadian healthcare system require
reform, overall access, quality, and satisfaction in Canada is high. As well, healthcare
expenditures are relatively well controlled, all of which contributing to the minimization
of inappropriate use of antimicrobial treatment, patients not finishing prescription
regimens, and improper use in livestock or crops. The structure of the Canadian
healthcare system is built on recognition of the limits of markets in distribution of
necessary medical care.
70 Deber, Raisa Deber, Phd. "Health Care Reform: Lessons From Canada." National Center for
Biotechnology Information, U.S. National Library of Medicine. Jan. 2004. Web. 2016.
58
Solutions
Effective antibiotics have been one of the pillars allowing us to live longer, live
healthier, and benefit from modern medicine. Unless we take significant actions to
improve efforts to prevent infections and also change how we produce, prescribe
and use antibiotics, the world will lose more and more of these global public
health goods and the implications will be devastating.71
Through linguistic studies, both the World Health Organization and various national
institutes concluded that failing to respond to the growth of Antimicrobial Resistance will
have detrimental impacts on the future international state. Specifically, both studies
demonstrated that if current trends are not altered in societies favour by 2050, depending
on the scenario, the world population is estimated to be 444 million lower than it would
otherwise be in the absence of AMR.72 Furthermore, the reduction in population and the
morbidity impact also reduces the level of world Gross Domestic Product (GDP). RAND
Europe estimates that by 2050 the world economy would be smaller, between 0.06% and
3.1%. Since, the losses of GDP are compounded annually over time, the result is
calculated as a cumulative loss that ranges between $2.1 trillion and $124.5 trillion.
71 "WHOs First Global Report on Antibiotic Resistance Reveals Serious, Worldwide Threat to
Public Health." World Health Organization. 30 Apr. 2014. Web. 2016.
<http://www.who.int/mediacentre/news/releases/2014/amr-report/en/>.
72 "Estimating the Economic Costs of Antimicrobial Resistance." RAND Europe. 2016. Web.
2016. <http://www.rand.org/randeurope/research/projects/antimicrobial-resistance-costs.html>.
59
However, these statistics are simply predictions for a future where Antimicrobial
resistance is not managed. Any alteration to diminish the current state of resistance is
productive. There is an abundance of solutions and while some countries have taken
appropriate steps to address the problem, every country and individual must contribute
more.
In order to eliminate Antimicrobial Resistance, several options have displayed
considerable effectiveness. First, the issue can be addressed by national healthcare
systems, with reform in the prescription, education, innovation, and public awareness of
antimicrobials. Alternatively, a major impact can be made on the expansion of resistance
through the restriction of the non-medical use of antimicrobials. Finally, strict legislation
regarding the sales, use, and transmission of antimicrobials can be implemented to further
reduce the expansion of this issue.
The education and overall awareness of the general public, concerning
antimicrobial resistance has a major impact on the state of the issue. In countries where
antimicrobials are purchased without a prescription, unnecessary use of antimicrobials is
rampant. The widespread use of these medications is largely due to the general
populations lack of knowledge about how antimicrobials work, and limited awareness of
the consequences of resistance mechanisms in public health. Once aware, individuals can
engage in sustainable practices such as only consuming antimicrobials when prescribed
by a doctor, completing the full prescription and taking the full dosage, even under the
circumstances that one may feel better; never share antimicrobials with others or use
leftover prescriptions. In this scenario, prescribers have appropriate knowledge of
general medicine, microbial virulence, immunological, genetic host factors, properties of
medications, and basic knowledge of epidemiology, but once prescribed, physicians have
little control over the ways in which patients apply and use the recommended amounts of
antimicrobials. For this reason, the prescribers of antimicrobials such as physicians and
pharmacists encounter dual, contradictory responsibilities. They must provide optimal
therapy for their patients and this responsibility, which tends to promote an overuse of
antimicrobials as a secure treatment method. For example, 50% of the antibiotic
prescriptions globally, both in the community and in hospitals, can be considered
60
inappropriate.73 In France, the top rank healthcare system in the world, only 21% of the
primary care physicians follow the guidelines in prescribing antibiotic treatment for
urinary tract infection.74 On the other hand, they have a responsibility to patients and to
public health in sustaining and ensuring the optimal health of all individuals. This task
can be best achieved through educating patients on daily practices that ensure optimal
health of that individual, but this responsibility is sometimes ignored. When
implemented, improved understanding and knowledge of the situation can reduce the
amount of resistance. Through increased awareness and use of simple and effective daily
practices such as good hand hygiene the public plays a primary role in not only resistance
reduction, but within infection prevention and control. Much of the success of
antimicrobial resistance elimination programs depends on educating the clinicians,
especially on making everyday treatment decisions.
Another solution is to restrict antimicrobial use for only the appropriate medical
purposes. Currently, 80% of the total antimicrobial use worldwide is imploded within
animal husbandry. The spread of resistance, affecting the lives of people globally, has
greater connection to the food industry and animal use of antimicrobials, rather than the
human consumption of these medications. This concept is unacceptable, and because of
poor sanitation and high stress among food animals in crowded farm environments,
antibiotics are utilized to prevent bacterial infections, support the animals weakened
immune system, and are considered useful for intensive breeding of animals. Although,
some antibiotics are designed exclusively for veterinary use, most of the antimicrobials
being used in veterinary medicine and animal husbandry belong to the same classes of
antimicrobials as those used for human diseases. The increased use of human
antimicrobials, allows pathogens greater exposure to medications, increasing the change
of resistance developing. Instead of antimicrobial use, improving environmental hygiene,
utilizing enzymes, probiotics, prebiotics, acids, bacteriocins, anti peptides, and
bacteriophages are all alternative methods to improve health and promote growth in food
73 Infectious Diseases Society of America and the Society for Healthcare
Epidemiology of America guidelines for developing an institutional program to

enhance antimicrobial stewardship.
74 Lee, Chang Ro. "Strategies to Minimize Antibiotic Resistance." National Center for
Biotechnology Information, U.S. National Library of Medicine. 12 Sept. 2013. Web. 2016.
61
animals, while decreasing infectious diseases, and substituting for antimicrobial use.75
Whichever the method, the use of antimicrobials in veterinary medicine, agriculture,
animal husbandry, and aquaculture needs to be reduced. Antimicrobials must be treated
as the valuable and limited resource in which they are.
Finally, it is worthwhile to formulate internationally acceptable standard protocols
about the use of antimicrobials. In particular, legislation would be beneficial in animal
husbandry, to ensure proper use and surveillance of medications in the social sector. In
addition, legislation could be enacted in respect to the transmission of resistant strains of
parasites. It is easiest to manage antimicrobial resistance in a single region, therefore the
more resistant strains travel and spread, the harder it becomes to contain these strains.
Legislation should be enacted to ensure individuals are tested prior to travel, and in the
case that test results confirm positive, that individual should be prevented from traveling,
quarantine within the original region. If Governments of individual countries, global and
community level organizations, the media, and microbiological experts must accept
responsibility in the development and implementation of policies designed to mitigate
this brewing global health crisis, for if system reform fails, the legal structure is present
to rely on.
Even though treatments of most human diseases have improved over time, the
treatment conditions for infectious diseases have gradually worsened, because of
antibiotic resistance and the lack of new drugs. Antimicrobial resistance has gradually
increased over the past two decades and is now widespread all over the world.76 Complete
eradication of antimicrobial resistance should not be the goal, but instead individuals
should focus efforts on healthy practices, awareness and understanding, restriction of
unnecessary antimicrobial use, and the implementation of international policies
concerning inappropriate antimicrobial use. Although, antimicrobial resistance has never
been eliminated, it can be controlled to prevent a return to the pre-antibiotic era.
75 Probiotics, prebiotics and competitive exclusion for prophylaxis against bacterial disease.
Callaway TR, Edrington TS, Anderson RC, Harvey RB, Genovese KJ, Kennedy CN, Venn DW,
Nisbet DJ Anim Health Res Rev. 2008 Dec; 9(2):21725.<http://www.ncbi.nlm.nih.gov/pubmed/19102792>
76 Lee, Chang Ro. "Strategies to Minimize Antibiotic Resistance." National Center for
Biotechnology Information, U.S. National Library of Medicine. 12 Sept. 2013. Web. 2016.
62
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Stefani, Stefania, ed. Global Antimicrobial Resistance 3.4 (December 01, 2015). Web.
Yang, Jennifer. "Spread of 'Superbugs' Growing Global Concern." Toronto Star. 01 May 2014:
A.16. SIRS Issues Researcher. Web. 14 Feb. 2016.
65
Appendix
1. Complete email exchange between Dr. Stanley Falkow and myself.
Canadian Inquiry on Antimicrobial Resistance
falkow@stanford.edu
Dear Stanley Falkow,
My name is Carly Wheelans and I am a grade eleven student currently attending Innisdale
Secondary School in Barrie, Ontario. I have been given the pleasure of being selected as a
member of the Simcoe County Youth Ambassadors group. This is a group of twenty-seven
students who travel to Germany and Cuba as Canadian representatives. As a member of this
group I will be conducting an independent research assignment regarding a contemporary global
issue. I am interested in science and health, so it only seemed appropriate to choose antimicrobial
resistance as my independent study topic. Since I am apart of an international ambassadors
program I will be approaching this issue through a global perspective. I will be including your
contributions to molecular microbial pathogenesis within my report. I was hoping that I could
email you, simply regarding yourself: what you consider to be your greatest accomplishment and
what inspired you to pursue microbiology? I would also appreciate receiving your expertise on
the impact of antimicrobial resistance and the urgency of this issue. As well, I am interested in
your predictions regarding resolutions that must take place to curb the progression of resistant
strains of microorganisms and whether these solutions are sustainable for the public. I understand
that you are a busy man and I am thankful for your time. I would be grateful to have the
opportunity to email an accomplished individual as yourself, specific questions regarding your
opinions on the pandemic of antimicrobial resistance. Thank you for your time I look forward to
hearing back from you.
Sincerely,
Carly Wheelans
Dear Carly:
I would be glad to receive E-mail questions from you and, within reason, I will answer them
promptly. You are taking on a formidable scientific problem and public policy question that I
worked on from 1958 until my retirement in 2010. I still am engaged in thinking and writing on
66
the subject ,although, fortunately, a good deal more of my time is devoted to walks and
conversations with a 6 year old Golden Retriever named Honey.
I will look forward from hearing from you.
Best,
Stanley
Dear Mr. Falkow,
Thank you for the prompt response. I am thrilled to have the opportunity to communicate
with you. Below is a list of questions I have composed. Please answer at your own
convenience. I also had a Golden retriever and found they are quite the compassionate breed of
dog. Enjoy your walks with honey. Thank you again for your time. I look forward to hearing
from you.
Regards,
Carly Wheelans
Questions:
What inspired you to become a microbiologist?
What do you consider to be your greatest accomplishment in life?
Modern society is dependant on antimicrobials. Do you believe that people can limit their use, in
order to decelerate antimicrobial resistance?
Do you believe that microorganisms would have reached their current state of resistance without
the misuse, overuse, and inadequate dosage of antimicrobials in healthcare, plant and animal
agricultural, industrialized chemicals, and aquaculture sectors?
Do you think society will ever discover a permanent cure for infectious disease, or do you believe
in order to keep up with microscopic evolution people will continuously revise the current
methods of treatment?
Why should people be aware of the imposing threat of antimicrobial resistance?
What mechanisms do you think are responsible for turning antimicrobial resistance into a global
issue, rather than a regional issue?
What advice do you have for the youth following similar career paths to yourself?
In what ways do you wish to see science advancing in the future?
What do you think needs to be done to combat the current crisis of antimicrobial
resistance? What do you think needs to be done to ensure future epidemics of resistance do not
occur?
Besides health, what do you think is the greatest impact of antimicrobial resistance on society?
In the 1970s you urged Food and Drug Administration to remove antibiotics from animal feed.
How did the industry react to your request?
67
Wow Carly. That's quite an assignment but I'll answer all your questions. I've actually written
two biographical sketches of my professional life.that answers some of your inquiries. I can send
them as PDF files or you tell me what format you want them in.
This is finals week for the medical students so it's a bit of a turmoil but I will answer your
questions as I get more free time next week.
Stanley
Dear Mr. Falkow,
Thank you for getting back to me. I would appreciate receiving those files in PDF format. As
well, I understand you are a busy man, so get back to me at a time convenient for yourself. I
look forward to hearing from you and reading your research.
Regards,
Carly Wheelans
Dear Carly:
Here are two articles I published that are autobiographical. I recognize that a good deal of this
may be too technical bit it answers your questions about I got started in bacteriology and about
my early life as a not too distinguished student.
Hope these help. Now I will get busy answering some of your other questions.
Best,
Stanley
Dear Mr. Falkow,
I would like to thank you for sending me those two autobiographical articles. The articles were
very helpful. I have just recently returned from one of the international ambassador trips through
the city program I am involved in. I would have responded sooner if I were not in Cuba. I
respect your busy schedule; would there be any way you could respond via email to some of the
previous questions asked. I do not need an elaborate response, whatever you feel appropriate.
Below are some of the questions I felt most important. Thank you again, hope you are still
enjoying your walks with Honey.
Best Regards,
Carly Wheelans
1. Do you believe that microorganisms would have reached their current state of resistance
without the misuse, overuse, and inadequate dosage of antimicrobials in healthcare, plant and
animal agricultural, industrialized chemicals, and aquaculture sectors?
2. Modern society is dependent on antimicrobials. Do you believe that people can limit their
use, in order to decelerate antimicrobial resistance?
68
3. In the 1970s you urged Food and Drug Administration to remove antibiotics from animal
feed. How did the industry react to your request?
4.
In what ways do you wish to see science advancing in the future?
2. What advice do you have for the youth following similar career paths to yourself?
Dear Carly:
I apologize for not answering sooner. If you would like, I could answer more of your questions
over a phone interview (617-621-7722). I envy you your trip to Cuba. I never made it there.
Honey and I thank you for remembering about our walks. It's never enough. There is never
enough time in one's life to have as many doges as you would like. I think Will Rogers said that if
there were no dogs in heaven, he'd like t go where the dog went.
My answers to your questions follow. Hope they are helpful.
2. Twenty-five national health organizations and centers for disease control and
prevention in a joint statement on antimicrobial resistance:
Alliance for the Prudent Use of Antibiotics, American Academy of Paediatrics, American
Academy of Physician Assistants, American Academy of Urgent Care Medicine,
American Medical Directors Association, American Public Health Association, American
Society of Health System Pharmacists, Association for Professionals in Infection Control
and Epidemiology, Inc., Association of State and Territorial Health Officials, Center for
Disease Dynamics, Economics & Policy, Centers for Disease Control and Prevention,
Consumers Union, Council of State and Territorial Epidemiologists, Infectious Diseases
Society of America, Institute for Healthcare Improvement, National Association of
County and City Health Officials, National Association of Directors of Nursing,
Administration in Long Term Care, National Association of Public Hospitals, Paediatric
Infectious Disease Society, Public Health Foundation, Robert Wood Johnson Foundation,
Society of Hospital Medicine The Pew Charitable Trusts, The Society for Healthcare
Epidemiology of America, The Society of Infectious Diseases Pharmacists, Trust for
Americas Health.
d
3. The updated version of the Data utilized in the Australian study connecting
government corruption to antimicrobial resistance:
d 4. The EAAD Infographic on the Spread of Antibiotic Resistance:
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