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Antimicrobial Resistance: Implications and Costs

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Infection and Drug Resistance

Porooshat Dadgostar Abstract: Antimicrobial resistance (AMR) has developed as one of the major urgent threats
to public health causing serious issues to successful prevention and treatment of persistent
Milken Institute of Public Health, George
Washington University, Washington, diseases. In spite of different actions taken in recent decades to tackle this issue, the trends of
DC, USA global AMR demonstrate no signs of slowing down. Misusing and overusing different
antibacterial agents in the health care setting as well as in the agricultural industry are
considered the major reasons behind the emergence of antimicrobial resistance. In addition,
the spontaneous evolution, mutation of bacteria, and passing the resistant genes through
horizontal gene transfer are significant contributors to antimicrobial resistance. Many studies
have demonstrated the disastrous financial consequences of AMR including extremely high
For personal use only.

healthcare costs due to an increase in hospital admissions and drug usage. The literature
review, which included articles published after the year 2012, was performed using Scopus,
PubMed and Google Scholar with the utilization of keyword searches. Results indicated that
the multifactorial threat of antimicrobial resistance has resulted in different complex issues
affecting countries across the globe. These impacts found in the sources are categorized into
three different levels: patient, healthcare, and economic. Although gaps in knowledge about
AMR and areas for improvement are obvious, there is not any clearly understood progress to
put an end to the persistent trends of antimicrobial resistance.
Keywords: antimicrobial resistance, AMR, implications, cost

Background
Antimicrobial Resistance (AMR) occurs when microorganisms including bacteria,
viruses, fungi, and parasites become able to adapt and grow in the presence of
medications that once impacted them.1,2 AMR is considered a significant threat to
the public health systems not just in developing countries but throughout the
world.1,3 The fact that infectious diseases can no longer be treated with antibiotics
depicts an unknown future in health care.4 Infection with AMR leads to serious
illnesses and prolonged hospital admissions, increases in healthcare costs, higher
costs in second-line drugs, and treatment failures.3,5,6 For instance, just in Europe, it
has been estimated that antimicrobial resistance has been correlated with more than
nine billion euros per year.3,7 Furthermore, according to the Centers for Disease
Control and Prevention (CDC), antimicrobial resistance adds a 20 billion dollar
surplus in direct healthcare costs in the United States, which is exclusive of about
35 billion dollars in loss of productivity annually.8
The daunting threat of antimicrobial resistance is of particular importance in the
Correspondence: Porooshat Dadgostar category of antibiotic resistance in bacteria.3 According to the CDC, more than
Milken Institute of Public Health, George
Washington University, Washington, DC, two million people in the United States become ill with antibiotic-resistant diseases
USA every year, resulting in a minimum of 23,000 deaths.8 Antibiotic resistance com-
Tel +1-206-696-6474
Email [email protected] promises a human immune system’s capacity to fight infectious diseases and also

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contributes to different complications in vulnerable prevalent.4,19 Such availability makes it accessible for
patients undergoing chemotherapy, dialysis, surgery, and patients to do self-treatment for diseases that do not neces-
joint replacement.8 Furthermore, people with chronic con- sarily need antibiotics for treatment.4,15
ditions like diabetes, asthma, and rheumatoid arthritis will Moreover, antibacterial resistance can develop because
be heavily impacted by antibiotic resistance.2 Since the physicians unnecessarily prescribe lengthy courses of
effectiveness of antibiotics will be reduced due to persis- antibiotics.20 Financial incentives play an important factor
tence in trends of AMR, physicians should use last-resort in overprescribing antibiotics. For example, Chinese hos-
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classes of medicine such as carbapenems and polymyxins, pitals incentivize physicians to prescribe antibiotics; as
which are not necessarily readily available in developing a result, they will receive more money from pharmaceu-
countries, have a high cost, and have many different side- tical companies.21,22 Another factor contributing to over-
effects.9 prescribing antibiotics by providers is patients’
One of the most well-known cases of AMR, expectations from them.23 Studies have implicated that
Methicillin resistance in Staphylococcus aureus (MRSA), clinicians consider the perceived patient request for anti-
has been associated with high mortality rates every year biotics as one of the major barriers to adhere to standard
across the globe.1 In addition, multi-drug resistant gram- guidelines for antibiotic prescriptions.23,24 Providers try to
negative bacteria (MDR-GNB) has made the treatment of avoid the dissatisfaction of their patients by meeting their
different infections like pneumonia and urinary tract infec-
demand for prescribing antibiotics.23
tions more challenging.10–12 Furthermore, drug resistance
For personal use only.

to tuberculosis, gonorrhea, and typhoid fever are increas-

Agricultural Use of Antibiotics
ing every year and substantially contribute to the high
Agricultural use of antibiotics is another prominent con-
costs of individuals’ health as well as the health care
tributor to the antimicrobial resistance in humans.25,26 For
systems around the world, particularly in developing
instance, just in the United States, approximately 80% of
countries.7 Currently, 4.1% of new tuberculosis cases are
the antibiotics sold are applied to food that animals eat.27
considered to be multi-drug resistant.13 In countries like
In 2010, 63,200 tons of antibiotics were used in livestock
India, the Philippines, Russia, and South Africa, which
production worldwide which is significantly more than
have always had a high number of TB cases compared to
human consumption.28 In addition to the utilization of
other parts of the world, multi-drug resistant TB is antici-
antibiotics to treat sick animals, antibiotics are largely
pated to escalate significantly by 2040.14
added to healthy animal feed and drinking water in order
to prevent sickness (prophylaxis) among animals to a large
Factors Accelerating the Rate of AMR
extent, to further grow herds at subtherapeutic levels, and
Misuse and Overuse of Antibiotics
From early days of discovery of antibiotics in the 1940s, to elevate feed efficiency.9,27,29,30 For instance, one of the
Sir Alexander Fleming warned the public about the high widely used antibiotics in animal farming worldwide to
demand for antibiotics in the future which could lead to further promote the growth of livestock, particularly pigs,
their overuse.15–17 Different surveys across the globe indi- is colistin, a critical last-line antibiotic to treat severe
cate that many patients firmly believe antibacterial agents infections in humans.31–33
would help with viral diseases like the common cold or
flu.9 Furthermore, in many developing countries where Increase in Income Levels
there are deficiencies in proper diagnostic tools, patient According to Klein et al, between 2000 and 2015, global
management is predominantly contingent upon the pre- antibiotic use elevated by 65%.34 This significant rise in
scription of medicine, particularly antibiotics.18 global antibiotic use is predominantly because of over-
Administering antibiotics when they are actually not consumption of antibiotics in developing countries which
needed for the treatment is another example of common is the direct result of rising incomes.18,34 In other words,
misuse of them.4,18 Moreover, many antibiotics are of poor the rise in Growth Domestic Product (GDP) as well as
quality and sold over the counter in the developing living standards in low and middle-income countries
countries.4 For instance, in India and Vietnam, where (LMICs) have shown to be positively correlated with
there is insufficient enforcement of regulatory policies on antibiotic consumption.34,35 Moreover, an increase in
prescribing medicine, over-the-counter antibiotics are income levels in developing countries has led to an

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increase in animal protein consumption which may require quality global surveillance systems are critical for determin-
more antibiotics to be added to the food animals eat.36 ing and providing warning bells of problems associated with
There has been a stark change in the pattern of anti- changes in antimicrobial exposure.47 They also help with
bacterial consumption across the globe within the past observing the efficacy of the interventions implemented to
decade.34,37 In 2000, the highest antibiotic consumption standardize the usage of antibacterial agents in order to
rate was in the United States, France, Spain, New Zealand, address the issue of AMR.48 Thus, the existing gap in
and Hong Kong; however, in 2015, four of the countries knowledge about antibiotic usage worldwide highlights the
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with the highest rate of antibiotic consumption were low- great importance of a successful approach in engaging coop-
middle income countries such as Turkey, Tunisia, Algeria, erative efforts among different international sectors such as
and Romania.34 Rate of antibiotics in LMICs is still lower human and veterinary medicine, agriculture, animal produc-
than the rate in high-income countries, due to continuous tion, and of course, informed consumers.9 Furthermore,
increase in income level and living standards; however, it there is a gap in awareness of people regarding the proper
is highly likely that in a few years this rate might even- use and the potential hazard of antibiotics.49,50 For instance,
tually converge or even surpass the antibiotic consumption results of national questionnaires in different developed and
rate in developed countries.34,35
developing countries, including Japan, Australia, the United
Easy Travel Routes States, Sri Lanka, and Gulf Cooperation Council countries
Studies have suggested that the modern and easy traveling demonstrate that most people generally have limited knowl-
edge about the correct use of antibiotics.50–53
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routes for people, animals, and goods have also substan-

tially contributed to the dissemination of antimicrobial
resistance across the globe.2,38 By being exposed to resis- Methods
tant pathogens, human travelers are highly likely to return
Search Strategy
colonized and infected to their country.39 For instance,
With a thorough literature review, crucial information was
Ruppe et al have shown that European tourists traveling
compiled, assessed, and used to understand the implications
to India who had absolutely no contact with the Indian
and costs of AMR across the globe. Google, Google Scholar,
health care system still tested positive for carbapenemase-
PubMed, Microsoft Academic, Scopus, Medline, Global
producing Enterobacteriaceae (CPE) after they came back
Health, and searches within the CDC, WHO, and compar-
from their trip.40
able health organizations and websites were utilized to
Biological Factors obtain information. The review solely included published
Antibiotic resistance may happen spontaneously through articles written in English. Search terms including “AMR
mutation and bacterial evolution.41 Furthermore, plasmids, and cost,” “Antimicrobial resistance implications” and
small circular fragments of DNA in bacteria, can obtain “AMR and disease burden” were utilized in order to gather
a great variety of resistance genes through transposons and information. Moreover, searches within these databases con-
insertion sequences.42–44 These plasmids can be trans- centrated on literature that dates back no further than 2012.
ferred to bacteria from other species and spread the anti- The search yielded 200 articles. The titles and abstracts
bacterial resistance in the bacterial population.45 In of these articles were reviewed in order to screen for
addition, exchanging resistance genetic factors between publications that addressed the drivers of AMR and dif-
bacteria through horizontal gene transfer further acceler- ferent implications and cost of AMR. After removing the
ates the spread of antibiotic resistance.25,45,46 duplicates and opinion articles, 78 articles were identified
as relevant and met the inclusion criteria for this critical
Gaps in Knowledge
analysis project. The study flow diagram is illustrated in
The numerous gaps in knowledge about antibiotic resistance
Figure 1.
contribute to the continuing trends of AMR since the statis-
tics and particulars about the use of different antibiotics in
both the health care setting and in animal production are not Findings
systematically gathered worldwide.26,47 For instance, cur- The literature review findings demonstrates that the cost of
rently, just 42 countries in the world systematically gather AMR can be categorized into three different levels: Patient
data regarding the use of antibiotics in livestock.26 High- level, Healthcare level, and Economic level.6

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Table 2 Mortality Rates by 2050 Due to AMR in Different

Records identified as Additional records
eligible through through other sources Regions66
database searching
(n=200) (n=0) Asia 4,730,000
Africa 4,150,000
Europe 390,000
Latin America 392,000
Records after duplicates removed North America 317,000
(n=125) Oceania 22,000
Infection and Drug Resistance downloaded from https://www.dovepress.com/ by 181.214.249.48 on 21-Dec-2019

Notes: Adapted from Antimicrobial resistance: tackling a crisis for the health and wealth
of nations. 2014. Available from: https://amr-review.org/sites/default/files/AMR
Records excluded Review Paper - Tackling a crisis for the health and wealth of nations_1.pdf.
(n=47) Accessed September 17, 2019. Creative Commons Attribution 4.0 International
125
Public License (https://creativecommons.org/licenses/by/4.0/legalcode).66

• Conference abstracts which had

no full description
(n=8)
• Opinion articles United States, 2 million people are affected every year by
(n=15)
78 studies • Non-peer reviewed journals AMR and about 23,000 deaths occur as a result.57 This
included (n=24)
number is roughly the same as the European Union which
Figure 1 A flow diagram of articles included in the review. has an annual mortality rate of 25,000.5,58 Despite the
difficulty of obtaining precise mortality rates, official
For personal use only.

reports have estimated that about 10 million people will

Patient Perspective die across the world by 2050 if strong and effective action
Morbidity and mortality are important consequences of against AMR is not taken.4,59
AMR affecting patients.1,6 Compared to non-resistant Antimicrobial resistance also sabotages decades of global
forms, resistant bacteria will double the chances of devel- fights against many infectious diseases like tuberculosis,
oping a serious health issue and triple the chances of HIV, and malaria.56 The number of HIV cases resistant to
death.54 Of course, these negative outcomes will be more medicine are on the rise, particularly in Sub-Saharan Africa
pronounced with elevation of the severity of the resistant where 60% of patients with HIV have developed resistance
infections and the susceptibility of the host.55 Table 1 to HIV medicine.60,61 Unsurprisingly, patients with resis-
shows the comparison between mortality rates due to tance to HIV drugs have a higher risk of dying from HIV.62
AMR and major causes of mortality worldwide by 2050. According to the HIV drug resistance report in 2017, such
Currently, across the globe, approximately 700,000 indivi- continuous trends in resistance to HIV medicine threaten the
duals lose their lives because of the drug-resistant infec- global goal of putting an end to AIDS by 2030.63 In addition
tions each year.56 Table 2 indicates the mortality rates due to tuberculosis and HIV, in the past 50 years, Plasmodium
to AMR by 2050 in different regions of the world. In the falciparum, the causative agent of malaria, has become resis-
tant to anti-malarial medicines and this trend is predomi-
nantly seen in southeast Asia.64 The increase in resistance
Table 1 Mortality Rates by 2050 by Condition66 to malaria drugs obstructs malaria control which attempts to
Cancer 8.2 Million decrease the average 445,000 deaths that take place annually
Cholera 100,000–120,000 due to this deadly disease.65
Diabetes 1.5 Million
Diarrheal Disease 1.4 Million
Measles 130,000
Healthcare Perspective
Road Traffic Accidents 1.2 Million
AMR has disastrous impacts on healthcare costs.6
Tetanus 60,000
Antimicrobial Resistance 10 Million
According to the CDC, in the United States alone, anti-
biotic resistance could add about $1,400 to the hospital bill
Notes: Adapted from Antimicrobial resistance: tackling a crisis for the health and wealth
of nations. 2014. Available from: https://amr-review.org/sites/default/files/AMR for treating patients with any bacterial infections.8,67 This
Review Paper - Tackling a crisis for the health and wealth of nations_1.pdf.
Accessed September 17, 2019. Creative Commons Attribution 4.0 International
additional cost could go up significantly to more than
Public License (https://creativecommons.org/licenses/by/4.0/legalcode).66 $2 billion every year.8 According to different studies, it

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is projected that AMR could cost from $300 billion to approximately 1% and there would be a 5–7% loss in
more than $1 trillion annually by 2050 worldwide.4,28 developing countries by 2050.71,72 This percentage ulti-
High costs associated with expensive and intensive treat- mately translates into $100-210 trillion.28,66 Multidrug-
ments and escalation in resource utilization are the direct resistant TB alone could cost the world $16.7 trillion by
monetary effects of AMR on health care.3,4 Treating 2050.73,74
patients with resistant infections by using a combination Furthermore, due to AMR, the gap between the devel-
of regimens may be ineffective; as a result, compared to oping countries and the developed countries will become
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other patients, they may need longer hospitalization stays more pronounced; as a result, inequity will substantially
as well as more intensive care units (ICUs) and isolation increase.28 Most of the people who are pushed into
beds in order to prevent the spread of the infection.55 Also, extreme poverty as a result of AMR will be specifically
nosocomial outbreaks with resistant pathogens may result from low-income countries.28 This highlights the fact that
in the closure of a wing of a hospital and the cancellation the underprivileged population of the world will even-
of elective surgeries, costing the hospital money.55 tually be affected the most because these countries are
In addition to direct monetary effects, AMR generates more contingent on labor income which will be reduced
a burden on the health care system through secondary if there is a high prevalence of infectious diseases.28
effects.68 These effects happen when the procedures that In addition to the direct impact on GDP, antimicrobial
utilize antibiotics, which are essential to decrease the risk resistance has a major influence on labor through the loss of
of any infection after surgery, cannot be successfully car- productivity caused by sickness and premature death.68
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ried out due to the prevalence of antimicrobial Deaths because of antimicrobial resistance decrease the
resistance.68 Furthermore, AMR will challenge performing workforce, which in turn negatively impacts the size of the
organ transplants because they expose the patients to dif- population as well as the quality of the country’s human
ferent infections.66,69 For instance, Santoro-Lopes and de capital.68,75 Taylor et al have created a theoretical model in
Gouvea performed a comprehensive review on different order to estimate the economic impacts of AMR on the labor
multi-resistant infections that may occur after liver force in the future. In their work, they have compared
transplantation.70 In their work, they have discussed that a baseline (absence of AMR) with the current trend in
multi-drug resistant pathogens can increase the likelihood AMR as well as worse alternatives that might happen if
of transplant failure and death.70 Another secondary effect appropriate measures are not taken. According to their
of antimicrobial resistance will be on cancer treatments.66 results, if there is no change in the current pattern of AMR,
Due to AMR, chemotherapy cannot be performed on in ten years, the world working-age population will decrease
patients with cancer.71 Chemotherapy impairs the immune by two years. This change will be more pronounced in
system and makes patients with cancer vulnerable to dif- Eurasia compared to the rest of the world.75 In addition, in
ferent infections.59 Thus, the prevalence of AMR prohibits terms of annual GDP loss, if there is no change in the trends
physicians from administering antibiotics to patients with of AMR, the world will lose about $28 billion in ten years.
cancer.3,66,68 There is limited data on the exact cost of According to this model, with a $20 billion loss in GDP, the
different secondary effects of AMR which limits our European Union and The Organization for Economic Co-
understanding regarding what we might stand to lose.66 operation and Development (OECD) countries stand to lose
more than the rest of the world.75
Economic Perspective The global trade will also be heavily affected by antimi-
The literature review findings indicate that the cost of crobial resistance if the continuous trends in AMR still
AMR across the globe is extremely high and different in persist.32 The World Bank report demonstrates that global
each country.66,72 The CDC estimated that the cost of exports might decrease significantly by 2050 due to the
antimicrobial resistance is $55 billion every year in the effects of antimicrobial resistance on labor-intensive
United States, $20 billion for health care and about sectors.28 Thus, it can be concluded that the undesirable
$35 billion for loss of productivity.3,8 Recent research by outcomes of AMR on the global economy are projected to
the World Bank indicates that antimicrobial resistance be even more severe than the global financial recession due to
would elevate the rate of poverty and impact low-income its long-term impacts on the economy.28
countries compared to the rest of the world.28 Studies Impacts of AMR on livestock output will also be
show that annual global GDP could decrease by significant.30 Just like humans, the effect of AMR on

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animals will be due to mortality and morbidity. The

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