Summer 2019

The State of
Antibiotic
Resistance in
Cambodia
Mariah Menanno
Drexel University, Philadelphia, USA
Table of Contents
INTRODUCTION ....................................................................................................................................... 3

BACKGROUND STATISTICS ................................................................................................................. 3

GLOBAL RESISTANCE .................................................................................................................................... 4

RESISTANCE IN ASIA AND SOUTHEAST ASIA ................................................................................................ 5
RESISTANCE IN CAMBODIA ........................................................................................................................... 5

CASE STUDIES .......................................................................................................................................... 5

CASE #1 ......................................................................................................................................................... 6
CASE #2 ......................................................................................................................................................... 6
CASE #3 ......................................................................................................................................................... 6
CASE #4 ......................................................................................................................................................... 6

SOCIAL, ECONOMIC, AND POLITICAL REASONS FOR INCREASED ANTIBIOTIC

RESISTANCE IN CAMBODIA ................................................................................................................ 6

SOCIAL ATTITUDES TOWARDS ANTIBIOTICS ................................................................................................ 7

FAMILY ECONOMICS ..................................................................................................................................... 7
POLITICAL REASONS FOR THE RISE IN ANTIBIOTIC RESISTANCE ................................................................. 8

CLINICAL REASONS FOR ANTIBIOTIC RESISTANCE IN CAMBODIA .................................... 9

LACK OF MICROBIOLOGICAL FACILITIES ..................................................................................................... 9

POOR KNOWLEDGE AND UNDERSTANDING OF ANTIBIOTICS ....................................................................... 9
LACK OF APPROPRIATE PRESCRIBING OR DISPENSING GUIDELINES .......................................................... 10
POOR CLINICAL INFECTION CONTROL ........................................................................................................ 10

CURRENT INTERVENTIONS: WHAT IS BEING DONE TO PREVENT FURTHER

RESISTANCE? ......................................................................................................................................... 10

CONCLUSIONS ....................................................................................................................................... 12

REFERENCES .......................................................................................................................................... 13

2
Introduction
Antibiotic resistance is a critical threat to global health. It occurs when bacteria evolve via
random mutation, gene transfer, or selective pressure in the face of antibacterial drugs [1]. When
an antibiotic is unable to kill or halt the replication of a certain type of bacteria, the resistant strain
is allowed to flourish and pass on resistant genes. Bacterial reproduction is a fairly rapid process.
The doubling time of Escherichia coli (E. coli), or time it takes the population to double in size, is
40 hours in the human intestinal tract, but can be around 22 minutes in the laboratory setting [2,3].
Thus, antibiotic resistance can occur and spread quickly throughout the bacterial community. The
problem is propagated by several populations: clinicians, patients, pharmacists, the general public,
and the agriculture industry all play a role in increasing resistance rates [4-6].
Antibiotic resistance is part of a broader issue, antimicrobial resistance (AMR). AMR
refers to the survival of all types of microbes when exposed to the drugs meant to kill or neutralize
them. This includes bacteria such as E. coli, parasites such as those which cause malaria, fungal
infections such as Candida, and even viruses such as HIV. In contrast, antibiotic resistance only
refers to infections caused by bacteria.
Another important differentiation is between the terms resistance and susceptibility, which
are essentially opposites. Resistant bacteria cannot be killed by a particular antibiotic, while
susceptibility means that an antibiotic is effective against bacteria. When microbiology
laboratories test whether an antibiotic will work to treat a patient, they often test for the
susceptibility of the bacteria to various antibiotic drugs.
Three of the biggest reasons for the rise in antibiotic resistance are over the counter
availability of antibiotics, incorrect dosing, and the widespread use of broad-spectrum antibiotics.
Throughout Cambodia, patients are able to walk into a pharmacy and receive antibiotics without
answering additional questions or showing proof of prescription. Incorrect dosing can occur when
a patient obtains an incomplete course from the pharmacy, or when the provider prescribes an
insufficient dose. Taking only one or two doses of an antibiotic can lead to resistance by
introducing enteric bacteria (bacteria that live in the human gut) to these drugs without killing
them. Likewise, using broad-spectrum antibiotics such as cephalosporins have created resistance
in the same way, by exposing bacteria to drugs but not killing them. While all bacteria have the
potential to become resistant to antibiotics, some are more likely to develop resistance due to
infection patterns, typical antibiotic treatments, or bacterial properties, such as doubling time.
Although enteric bacteria such as E. coli found naturally in the human body are beneficial, some
strains are quickly becoming resistant. Their constant presence in our bodies means they are
exposed to antibiotics whenever we are.

Background Statistics
The World Health Organization (WHO)’s Global Antimicrobial Resistance Surveillance
System (GLASS) has identified eight organisms it has classified as “selected priority bacteria” [7].
The list includes the following:

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 Bacteria Name
All Acinetobacter species
(spp.)
Escherichia coli
Klebsiella pneumoniae
Neisseria gonorrhoeae
Salmonella spp.
Shigella spp.
Staphylococcus aureus
Streptococcus pneumoniae
Common Name Disease or Symptoms
N/A Pneumonia, sepsis, wound
infections
E. coli Diarrhea, urinary tract
infections, kidney failure
Klebsiella Urinary tract infections,
sepsis, infection of many
organs
Gonorrhea Gonorrhea
Salmonella, Typhoid Food poisoning, typhoid
fever, paratyphoid
N/A Bloody diarrhea
Staph, MRSA (methicillin- Skin infections
resistant S. aureus)
N/A Pneumonia

All listed bacteria have already exhibited high rates of resistance or are quickly developing
resistance to common antibiotics. In addition to the eight key GLASS pathogens, bacteria relevant
in Cambodia specifically include Burkholderia pseudomallei, Salmonella enterica serovar
Choleraesuis and Streptococcus suis [8].

Global Resistance
The burden of antibiotic resistance globally is difficult to measure accurately as
surveillance (disease monitoring) systems such as GLASS are still fairly new. It is estimated that
in Europe and the United States, 50,000 deaths occur annually due to AMR. Low estimates state
the global number of deaths attributed to AMR could be close to 700,000 per year. Models
predicting the future impact of AMR project that without intervention by 2050, up to 4.7 million
annual deaths due to antimicrobial resistance could occur throughout Asia alone [9]. However,
these statistics include deaths due to resistant malaria and fungal infections, not soley antibiotic
resistance.
The failure of many common antibiotic treatments is expected to have far-reaching
economic consequences beyond healthcare [9]. For example, family members frequently take off
work to care for sick loved ones, meaning the illness or hospitalization of just one person decreases
productivity. Additionally, increasing antibiotic resistance will have large effects on the
agricultural sector, currently estimated to account for 70-80% of global antibiotic consumption
[6]. Primarily, farmers use antibiotics to prevent rather than treat disease in their livestock, which
increases resistance due to bacterial exposure to antibiotics. Resistance to antibiotics used in
agriculture could mean a future shortage of meat and animal products. Additionally, there is
evidence that bacteria from animal food products can enter humans, posing a threat for human
health [10].
In the first year of GLASS reporting (2017-2018), more than 1.7 million patients were
identified by the surveillance. Globally, the most commonly found resistant pathogens were E.
coli, K. pneumoniae, Salmonella spp., Acinetobacter spp., S. aureus, S. pneumoniae, N.
gonorrhoeae, and Shigella spp., in descending order of prevalence. This number represents only a

4
small portion of cases with resistant bacterial infections; not all countries reported data, including
Cambodia, and only a small number of health centers were involved in each country.

Resistance in Asia and Southeast Asia

Reports of resistance in Asia are alarmingly high. A study of 8 countries in East and
Southeast Asia found that 78% of Shigella samples were resistant to multiple antibiotics [11]. Even
within Southeast Asia, rates of resistance can vary widely. For example, resistance rates of
Campylobacter (a common cause of diarrhea) to the drug ciprofloxacin were around 77% in
Thailand, but only around 7% in Vietnam between 1996 and 1999 [12]. Similarly, a study from
1999 in Vietnam found that 28% of S. pneumoniae samples from children in Ho Chi Minh city
were penicillin resistant, while the rate was only 3% in rural children. Additionally, rates of
resistance to antibiotics such as erythromycin and co-trimoxazole were significantly higher among
urban-dwelling children [13].

Resistance in Cambodia
In Cambodia specifically, samples from 10 laboratories revealed 70-90% multiple drug
resistance among isolates of S. typhi (the bacterium which causes typhoid fever), 20-40%
methicillin resistance among S. aureus (MRSA), and 30-50% extended spectrum beta-lactamase
(ESBL) production in E. coli [8]. ESBL positive E. coli is particularly concerning because bacteria
which produce ESBL enzymes are resistant to several classes of antibiotics, not just one or two
individual drugs [14].
In one case-control study examining diarrhea among children under 5 years in Phnom
Penh, isolates from both cases and controls showed a Salmonella multidrug resistance rate over
33% and nearly 100% resistance of Shigella samples to the drugs streptomycin, sulfisoxazole,
trimethoprim, and tetracycline [15]. Another study found 48% of E. coli isolates from adults with
bloodstream infections in Cambodia were ESBL positive and a 22% MRSA presence among S.
aureus isolates [16].
Resistance in Cambodia is not only found in humans. A 2016 study of 150 raw meat
samples from two different markets in Phnom Penh found 17% of the samples were contaminated
with ESBL positive Salmonella and 62% contained ESBL positive E. coli [17, 10]. Researchers
also compared the genes of ESBL producing E. coli from the market to E. coli from the guts of
women living near the market. Almost half of the women’s samples were related to the isolates
from the market meat. Additionally, researchers found that women whose guts colonized ESBL
positive E. coli were more likely to eat sundried poultry products [10]. These findings are
concerning because they demonstrate a potential pathway for bacteria from animals and food to
enter the human population. This indicates the impact that antibiotic overuse in agriculture can
have on human health and the medical field.

Case Studies
Antibiotic resistance is not an issue of the future; it is one that has already reached
Cambodia. The following four case studies outline the treatment course of patients at a clinic in
Phnom Penh for their symptomatic and resistant bacterial infections. In some cases, thousands of
dollars were spent on successful treatment. In other cases, the patients still have the infection,
which cannot be cured. These patients do not have much in common – they all have different jobs,

5
are different ages and nationalities, and live in different parts of the city. Yet, they all had bacterial
infections that proved resistant to multiple treatments the cultures showed sensitivity to. In many
cases, the patients do not know how they contracted the bacteria.

Case #1
A South African woman, 53, presented with a urinary tract infection. A urine culture showed an
E. coli infection which was sensitive to more than 10 antibiotics. She was treated with
ciprofloxacin, a common antibiotic, which demonstrated sensitivity. A month later, she was tested
again, and her urine contained resistant ESBL positive E. coli. She was treated again with
intravenous (IV) meropenem antibiotics. The full course cost over $600. Almost two months later,
her urine culture grew E. coli again. She was treated twice with ciprofloxacin and amikacin,
respectively. The efficacy of the final treatment is pending.

Case #2
A North African woman, 42, had urine which contained ESBL positive E. coli and was treated
with clamovid (amoxycillin and clavulanic acid), which showed sensitivity. She also had heavy
growth of Klebsiella. About a month later, her urine culture still showed ESBL positive E. coli,
and she was treated with IV meropenem. After another month, the E. coli was no longer ESBL
positive, but after treatment with levofloxacin, her urine culture grew ESBL positive E. coli once
again. Eventually, she had to have a second course of expensive IV antibiotics to be cleared of the
E. coli. Her infection with other bacteria continues.

Case #3
A 78-year-old man had a urine culture containing Klebsiella. He has been treated with
levofloxacin, cefixime, and clamovid, all of which showed sensitivity. However, after several
rounds of treatment, his urine culture still grew Klebsiella. His infection is ongoing and has been
active for almost a year.

Case #4
A 28-year-old Indonesian man presented with bloody ejaculate (semen). He tested positive for
syphilis and was treated with ceftriaxone, which showed sensitivity. Almost a year later, his
symptoms returned, he tested positive for syphilis, and he was treated with doxycycline,
ciprofloxacin, and a longer course of ceftriaxone. The titer of the infection was the same as the
first time, meaning the number of antibodies in his blood was the same. After treatment was
completed, he not only tested positive, but the syphilis titer rose, meaning the infection became
more severe. He then began extencilline (long-acting penicillin) weekly injections for treatment.
In total, he had 3 courses of extencilline. After all treatment courses were completed, he still tested
positive for syphilis and developed lesions on his penis. His syphilis cannot be treated.

Social, Economic, and Political Reasons for Increased Antibiotic

Resistance in Cambodia
In Cambodia, the general flow of medical care for acute, infectious conditions contributes
to the rise of antibiotic resistance observed in the country. Generally, when people begin to feel

6
sick, they visit a local pharmacy and self-prescribe. If symptoms persist or worsen, patients will
seek care at a public or private clinic, from a village healthcare worker, or at a hospital if the
symptoms are severe. At the point of care, if a patient believes the treatment given is ineffective,
they will visit several healthcare providers, a practice known as doctor shopping [5]. Patients will
continue visiting providers until receiving a treatment they think will help their illness. Since
injected medicine is viewed as more potent, treatment considered effective is often something
injectable [4].
When patients follow this sequence of care, the first point of contact is the pharmacy. At
the pharmacy, sometimes patients will request only one or two pills of antibiotics, such as
ampicillin or amoxycillin, just enough to relieve symptoms. Because of widespread use, the
general public knows antibiotics such as ampicillin, tetracycline, and co-trimoxazole by the
nicknames “ampi,” “tetra,” and “cotrim,” respectively [5]. This demonstrates the normality of
antibiotic use in daily life.

Social Attitudes Towards Antibiotics

Social attitudes and common beliefs help to propagate antibiotic resistance. Many people
believe illnesses arise from internal inflammation or wounds. Knowledge of antibiotic use in the
treatment of external wounds is widespread; thus, antibiotics are seen as a cure of illness by healing
the wound inside the patient [5]. There are at least four other common misconceptions about
antibiotics in Cambodia: first, antibiotics help reduce inflammation; second, antibiotics can reduce
congestion and relieve symptoms of colds; third, antibiotics have a “cooling effect” in reducing
temperature; and fourth, antibiotics are capable of relieving pain [5]. These conflated
misunderstandings possibly stem from the frequency that antibiotics are taken with pain relievers
such as paracetamol (also known as acetaminophen), or anti-inflammatory drugs such as
ibuprofen, both of which reduce fever.
Furthermore, patients often want a speedy recovery that does not disrupt their daily lives
[4]. In search of faster and more affordable treatments, people will avoid visiting a doctor, opting
instead to self-medicate, or to visit healthcare providers that are less reliable but more accessible.
The desire for a quick recovery is partially why patients fail to finish the entire course of
antibiotics. Since medication is viewed as something taken when a person feels sick, medicine is
taken quickly and briefly. Once symptoms subside, many people do not see the need to continue
taking antibiotics. It is believed the illness is gone when symptoms disappear and medicine is no
longer taken. This is dangerous because partial courses of antibiotics give bacteria exposure to
drugs without killing them, allowing bacteria to evolve resistance.
At the clinical point of care, patients also request stronger or more advanced antibiotics.
They are often under the impression that these drugs are more potent and will make them feel
better more quickly. Due to the overuse of injectable antibiotics and intravenous fluids, there is a
perception that injections are better medicine, shortening symptom time and length of clinical care
[4]. Because injectable antibiotics are typically more advanced second or third-line treatment
options, these drugs should not be used very often. To preserve efficacy, they should be reserved
for bacteria already exhibiting resistance.

Family Economics
For many families, it makes more economic sense to purchase medicine directly instead of
paying for a doctor visit first. Patients will prioritize buying medication because they believe it
will make them feel better. The amount of medicine purchased often depends on how much money

7
is available at the time. As one patient in a qualitative study said, “If I have money I buy medicines,
to take two doses. But if I don’t have money I can only buy medicines to take once only” [5].
However, purchasing and taking only one or two doses of an antibiotic increases the risk of
resistance and the likelihood that patients will need a harsher, more expensive antibiotic for
treatment. Additionally, when experiencing familiar symptoms, patients will purchase the same
antibiotic given for past illnesses without knowing the cause [5]. For something like diarrhea which
is caused by bacteria, viruses, parasites, and protozoa, this can be dangerous.
Instead of going into the clinic or hospital, sometimes patients request a nurse to visit and
provide in-home services, including injectable antibiotics [5]. This saves time, and sometimes
money, for the family. In hospital settings, family members help provide care, food, and basic
cleaning for their loved ones. A hospital admission affects multiple members of a family, which
can prevent their ability to work and make money [4]. This deters some patients from seeking
hospital-based care.

Political Reasons for the Rise in Antibiotic Resistance

Politically, the problem of antibiotic resistance is fueled by a lack of enforcement for
existing regulations, the minimal nature of prescription drug laws, and continued reliance of rural
populations on unlicensed village health workers called pett phum.
In 1996, the government of Prince Sihanouk passed a law titled “Management of
Pharmaceuticals,” which was amended in 2007. Some provisions of the law are that pharmacists
must have a diploma approved by the Ministry of Health, that the Ministry must have knowledge
of pharmacies opening, and establishes a 2-10 million riel fine for distributing counterfeit
pharmaceuticals [19]. More recently, regulations were passed stating that pharmacies cannot give
antibiotics without a doctor’s prescription, and that pharmacies must give full courses of antibiotics
lasting at least 5 days. However, these laws have not been strongly enforced. While some
pharmacies do make an attempt to follow the regulations, the degree of compliance varies.
The lack of prescription drug laws and enforcement feeds into the use of both broad- and
narrow-spectrum antibiotics among the general public, the phenomenon of self-prescribing, and
the presence of unlicensed pharmacists throughout the country. By regulating the supply chain of
antibiotics and educating pharmacists, a large factor contributing to antibiotic resistance in
Cambodia could be reduced.
During the Cambodian Civil War, the Khmer Rouge forced doctors to flee, hide, complete
hard labor in the countryside, or face execution. Before the rise of the Khmer Rouge, there were
approximately 550 doctors in Cambodia [20]. When the Vietnamese swept into the country in
1978-1979, it is estimated that only between 10 and 48 doctors survived [20, 21]. This left gaping
holes in the country’s medical system. On the cooperatives (population-level rice growing
operations), the primary people providing health care had no medical training. Often, they taught
themselves medicine as patients came. In the country’s few hospitals, healthcare providers were
sometimes children as young as 10 or 12. Many of their parents were rural farmers, or part of the
“old people,” as they were viewed as the purest ideological group [21]. This history created a
culture where pett phum came to be trusted in communities, especially in rural areas. They are still
a valuable and essential resource in healthcare access for rural communities, but also lack modern
knowledge in medicine and pharmacology, including antibiotics and disease transmission. They
rely on treating symptoms based on observed drug reactions rather than treating diseases based on
formal medical training.

8
Clinical Reasons for Antibiotic Resistance in Cambodia
In clinical practice, some factors leading to inappropriate use of antibiotics include the lack
of microbiological facilities in clinics and hospitals, low levels of physician knowledge about
antibiotics, lack of appropriate prescribing guidelines, and poor clinical infection control. These
factors are associated with the numerous ways patients receive care, including public clinics,
private clinics, hospitals, home visiting nurses, and pett phum.

Lack of Microbiological Facilities

Many low and middle-income countries such as Cambodia lack resources and diagnostic
tools in healthcare centers. For instance, microbiology labs are not found in many hospitals and
clinics, which limits the type of care and treatment that can be offered. While using microbiology
labs increases diagnostic accuracy and the likelihood of effective treatment, it also makes medical
care slower and more expensive. In a culture that values speed and low costs in healthcare, lab
services are less attractive.
As a result, many diagnoses are made empirically, meaning that diagnosis and treatment
are given based upon physical symptoms rather than evidence from tests. One doctor estimated
that up to 70% of diagnoses in Cambodia are made this way [22]. Assessing a patient empirically
makes it more difficult to assign a correct diagnosis and treat appropriately. For example, some
conditions such as diarrhea have multiple causes. Treating diarrhea properly without lab evidence
relies on the physician’s knowledge and experience and on clear communication between patient
and provider. This leaves more room for error in treatment and diagnosis.
Even among hospitals containing microbiology labs, only 58% of physicians in a national
survey indicated frequent use and 33% said they used labs occasionally [18]. Perhaps more
worrying, in a focus group, one physician stated that they provide antibiotics “blindly.” If a doctor
is unsure what is causing disease, broad-spectrum antibiotics are given. These drugs reduce the
chance of error and treatment failure compared to an incorrect narrow-spectrum antibiotic [4]. This
demonstrates the preference of healthcare providers to treat empirically with broad-spectrum
antibiotics to save cost, time, and sometimes reputation. However, this habit is concerning. As
antibiotic resistance spreads, the need to treat patients again using more toxic and expensive drugs
will increase.

Poor Knowledge and Understanding of Antibiotics

A second problem is that even physicians and pharmacists do not fully understand proper
antibiotic use. A survey of 681 physicians across Cambodia showed 86% would prescribe
antibiotics such as amoxicillin, erythromycin, or azithromycin for a patient with symptoms of the
common cold (caused by a virus) [18]. Similarly, interviews with nurses and pharmacy attendants,
both trained and untrained, showed that antibiotics were prescribed for throat and respiratory tract
inflammation, despite the fact that most upper respiratory tract infections are viral [5, 23]. The
belief that antibiotics reduce inflammation is still widespread in the Cambodian medical
community. Additionally, 36% of physicians surveyed would prescribe antibiotics for children
under 5 with diarrhea, preferring to give the drugs cotrimoxazole and metronidazole [18]. This
conflicts with a 2011 study which demonstrated the most common cause of diarrhea in Cambodian
children under 5 was rotavirus, which is not bacterial [15].
Given examples of cases, physicians often selected antibiotics that bacteria already
exhibited resistance to, such as typhoid fever to ciprofloxacin. This reveals a lack of current

9
knowledge in the state of antibiotic resistance for specific bacteria [18]. These trends are
particularly dangerous in health centers that treat empirically, regardless of a correct diagnosis.
Without testing the resistance of bacteria to various antibiotics, physicians must rely on their prior
knowledge, which may no longer be accurate or effective.

Lack of Appropriate Prescribing or Dispensing Guidelines

A third way clinical environments contribute to antibiotic resistance is the lack of
appropriate prescribing guidelines. If guidelines do exist, they are often outdated due to increasing
resistance patterns or they are not followed by clinicians. Many health centers with guidelines base
them on WHO standards for low and middle-income countries, which are not exclusive to
Cambodia or even Southeast Asia [22]. As a result, some physicians vocalize their desire for
updated, evidence-based prescribing guidelines specific to Cambodia [4].
At many pharmacies, the assistant working behind the counter is not licensed. However,
even licensed pharmacists often do not know or follow proper prescribing and dispensing
guidelines for antibiotics. “Pill cocktails” are frequently given loose in clear plastic bags without
labels, where the exact composition and dose are unknown [5]. When medicines are dispensed this
way, patients rarely receive clear instruction on how to take them properly.
Even if localized guidelines for clinicians and pharmacists were developed, the lack of
political will, support, and enforcement surrounding antibiotic resistance makes it difficult to hold
individuals accountable. To be effective, updated guidelines must be part of a larger policy that
includes consequences for distributing antibiotics improperly. Additionally, physicians, nurses,
and pharmacists must all understand the basics of antibiotics, including how they work and when
they are needed. There must be many training opportunities where healthcare workers and
pharmacists can learn more about proper prescribing and dispensing practices. Above all, they
must be aware that following guidelines is not optional and that ignoring them is dangerous.

Poor Clinical Infection Control

Fourth, clinical infection control is a major concern, particularly in public hospitals.
Conditions can be dirty and family members are expected to come to the hospital with the patient,
cleaning the room without proper disinfectant or sterilization supplies. Family members also
provide food and perform basic tasks related to the patient’s hygiene. Physicians realize this
environment is favorable for the spread of disease, so they often give antibiotics to patients as
prophylaxis, or a preventative, against hospital-acquired infections [4].
Improving basic sanitation in hospitals would reduce risk, and physicians may feel less
inclined to give antibiotics as prevention. In a hospital setting, there is already high use of
antibiotics and a large presence of bacteria. Introducing more antibiotics than necessary allows
greater opportunity for resistant bacteria to emerge, or for drug-resistant bacteria to overcome
susceptibility to other drugs. With greater interaction between antibiotics and bacteria, the higher
the likelihood resistance will develop.

Current Interventions: What is Being Done to Prevent Further

Resistance?
For World Health Day 2011, WHO launched a six-part policy package to fight antibiotic
resistance. This strategic framework provides a basic outline of areas countries should build or

10
strengthen to create a program that would slow antibiotic resistance. Summarized, the six points
are:
1. Commit to a national “master plan” with funding, accountability, and community
engagement
2. Strengthen surveillance (monitoring) of disease and laboratory ability to identify disease
3. Ensure continuous access to high-quality medicines
4. Regulate and promote proper medicine use in human patients and agriculture
5. Enhance infection and disease prevention and control
6. Encourage research and development of new tools such as medicines, treatments, and
diagnostics [24]

WHO also began the Global Antimicrobial Resistance Surveillance System (GLASS) in 2015,
meant to improve knowledge of global resistance rates among the eight key organisms. However,
as of 2017, Cambodia had not reported any data, and only eight hospitals nationwide were enrolled
[7]. While improved surveillance is necessary to combat antibiotic resistance on a global scale,
this program only accounts for a small amount of data. Additionally, because this system is so
large, it cannot fully consider the vast differences that exist between nations or regions in resistance
patterns. A comprehensive, national surveillance system in Cambodia would provide data to create
evidence-based interventions and more targeted approaches to antibiotic resistance.
In 2014, the Ministry of Health published the National Policy to Combat Antimicrobial
Resistance. Its framework outlined the same steps promoted by WHO. However, as Minister of
Health Professor Eng Huot stated, implementation will require large amounts of funding and
unwavering political will [25]. Some items specific to Cambodia outlined in the National Policy
include the creation of an AMR working group, selection of an AMR reference laboratory for
surveillance purposes, improving access to full courses of antibiotics by policies such as tax
exemptions, regulating the advertisement of antibiotics, updating clinical guidelines, and regularly
informing clinicians of antibiotic susceptibility rates [25].
In addition to government-focused health institutions such as the Ministry of Health and WHO,
other stakeholders are using their influence to fight antibiotic resistance. For example, The Idea
Consultancy, a group that functions as a marketing company and is involved in corporate social
responsibility, has created an implementation-stage program called Health Awareness Campaign
Kampuchea (HACK). The goal of HACK is to provide accessible, actionable information to the
public and to incorporate its messaging into all of The Idea’s programming. For instance, The Idea
hosts Slaprea, Cambodia’s biggest food festival, and uses the event as an opportunity to educate
people about hand hygiene and food safety. At the festival, they teach proper handwashing
technique and provide education about food safety through learning activities such as games, fun
quizzes, and handwashing stations. HACK aims to increase the public’s knowledge through
campaigns built around awareness and individual empowerment rather than fear and avoidance
[26].
A scientific-based entity working to increase knowledge about antibiotic resistance is Insitut
Pasteur du Cambodge. Their clinical microbiology lab tests samples from hospitals and individual
clients for resistant bacteria and informs patients’ doctors of their resistance. Institut Pasteur du
Cambodge stores this data for their surveillance purposes, helping to quantify the number of
patients with resistant infections and to monitor the kinds of bacteria they are infected with [27].
The data is also used to prepare publications that help increase awareness about antibiotic

11
resistance in Cambodia. By doing so, the goal is to aid in preventing future transmission of resistant
bacteria.
Institut Pasteur du Cambodge also meets monthly with partners such as WHO and Calmette
Hospital to discuss antimicrobial resistance and whether any new patterns have been observed
[27]. Professional collaborations such as this one are a start to increasing awareness and dialogue
about antibiotic resistance. More coalitions similar to this need to be formed within the country
among different groups, including doctors, labs, and the Ministry of Health.
A large gap in current interventions is the lack of educational campaigns. The low level of
public knowledge is one of the greatest barriers to reducing antibiotic consumption and resistance
of bacteria. This is in part due to the absence of public messaging campaigns. If people do not
know about resistance or proper antibiotic use, they cannot be expected to change their health
behaviors. There needs to be a strategy that communicates this issue to the general population and
informs them of its increasing threat to the country. One way to do this is via messaging from the
Ministry of Health spread via various media including social media, television, and radio [27]. The
rising consumption of electronic media by Cambodians would allow the information to quickly
reach a large proportion of the population.

Conclusions
Antibiotic resistance is a large and growing threat to the health of Cambodians. It is an
issue that is invisible to the eyes, but one that is becoming more visible in clinical practice and
society. Resistance cannot be stopped, but the process can be slowed. Many different groups of
people including doctors, nurses, pharmacists, health policy makers, and the general public each
have a role to play in reducing the impact that resistant bacteria have on the population. Raising
awareness and education among all of these groups is essential.
While some programs, laws, and regulations do currently exist, they are not enough.
Antibiotics are still easily dispensed by pharmacies and health centers, and patients are still
requesting and taking these drugs improperly. Shifting beliefs, knowledge, and attitudes about
antibiotics will be very difficult, but it will save thousands of lives. Already, people in Cambodia
are facing bacterial infections that are either very difficult or impossible to treat. In a world that
has been revolutionized by the development of antibiotics, it is a grim thought that soon, these life-
saving drugs may become ineffective.
However, the worst-case situation can still be avoided. Everyone, no matter their title or
role, can learn more about antibiotic resistance. People can be encouraged to go to their doctor
before visiting the pharmacy for medicine. When prescribing or dispensing antibiotics, doctors
should educate their patients on antibiotic resistance and the importance of taking the medicine
properly. At the pharmacy, patients should speak to their pharmacist. They should ask which
medicine they are being given and how this medicine should be taken. Pharmacists should also
have knowledge on when giving antibiotics is appropriate.
While social, economic, and political barriers to proper antibiotic use cannot be lifted
quickly, Cambodians in all aspects of society need to feel empowered in the fight against antibiotic
resistance.

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 References
1. National Institute of Allergy and Infectious Diseases. Causes of Antimicrobial (Drug)
Resistance. 2011 [cited 2019 Aug 1]. Available from:
https://www.niaid.nih.gov/research/antimicrobial-resistance-causes
2. Bionumbers. Normal Doubling Time in Human Intestinal Tract. n.d. [cited 2019 Aug 1].
Available from:
https://bionumbers.hms.harvard.edu/bionumber.aspx?id=102096&ver=7&trm=doubling+
time&org=
3. Bionumbers. Doubling Times in Different Media. n.d. [cited 2019 Aug 1]. Available
from: https://bionumbers.hms.harvard.edu/bionumber.aspx?s=n&v=0&id=110058
4. Om, C., Daily, F., Vlighe, E., McLaughlin, J.C., & McLaws, M.L. “If it’s broad
spectrum, it can shoot better”: Inappropriate antibiotic prescribing in Cambodia.
Antimicrob Resist In. 2016 [cited 2019 Jul 29]; 5(58). doi: 10.1186/s13756-016-0159-7.
5. Om, C., Daily, F., Vlieghe, E., McLaughlin, J.C., & McLaws, M.L. Pervasive antibiotic
misuse in the Cambodian community: Antibiotic-seeking behavior with unrestricted
access. Antimicrob Resist In. 2017 [cited 2017 Jul 20];6(30). doi: 10.1186/s13756-017-
0187-y.
6. Ritchie, H. How Do We Reduce Antibiotic Resistance from Livestock? 2017 Nov 16
[cited 2019 Aug 13]. Available from: https://ourworldindata.org/antibiotic-resistance-
from-livestock
7. World Health Organization. GLASS Report Early Implementation 2017-2018. Geneva:
World Health Organization; 2018 [cited 2019 Aug 2]. Available from:
https://www.who.int/glass/resources/publications/early-implementation-report-2017-
2018/en/
8. Vlieghe, E., Sary, S., Lim, K., et al. First national workshop on antibiotic resistance in
Cambodia: Phnom Penh, Cambodia, 16-18 November 2011. J Glob Antimicrob Re. 2013
Jul 28 [cited 2019 Jul 15]; 31-34. doi: 10.1016/j.jgar.2013.01.007.
9. O’Neil, J.; The Review on Antimicrobial Resistance. Antimicrobial Resistance: Tackling
a Crisis for the Health and Wealth of Nations. 2014 [cited 2019 Aug 7]. Available from:
https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-
%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nati
ons_1.pdf
10. Nadimpalli, M., Vuthy, Y., de Lauzanne, A., et al. Meat and fish as sources of extended-
spectrum beta-lactamase-producing Escherichia coli, Cambodia. Emerg Infect Dis. 2019
Jan [cited 2019 Aug 15];25(1):126-131. doi: 10.3201/eid2501.180534.
11. Kuo, C.Y., Su, L.H., Perera, J., et al. Antimicrobial susceptibility of Shigella isolates in
eight Asian countries, 2001-2004. J Microbiol Immunol Infect. 2008 [cited 2019 Aug
5];41:107-111. Available from:
https://pdfs.semanticscholar.org/b000/cf5ed582db1fde5966ff113a797721df801d.pdf
12. Isenbarger, D.W., Hoge, C.W., Srijan, A., et al. Comparative antibiotic resistance of
diarrheal pathogens from Vietnam and Thailand, 1996-1999. Emerg Infect Dis. 2002 Feb
[cited 2019 Aug 5];8(2):175-180. doi: 10.3201/eid0802.010145.
13. Quagliarello, A.B., Parry, C.M., Hien, T.T., & Farrar, J. Factors associated with carriage
of Penicillin-resistant Streptococcus pneumoniae among Vietnamese children: A rural-
urban divide. J Health Popul Nutr. 2003 Dec [cited 2019 Aug 6];21(4):316-324.
Available from: https://www.jstor.org/stable/23499339

13
 14. Institut Pasteur. Food Contamination in Cambodia Contributing to the Burden of
Antibiotic Resistance. 2019 Feb 1 [cited 2019 Aug 15]. Available from:
https://www.pasteur.fr/en/institut-pasteur/institut-pasteur-throughout-world/news/food-
contamination-cambodia-contributing-burden-antibiotic-resistance
15. Meng, C.Y., Smith, B.L., Bodhidatta, L., et al. Etiology of diarrhea in young children and
patterns of antibiotic resistance in Cambodia. Pediatr Infect Dis J. 2011 Apr [cited 2019
Jul 15];30,4:331-35. doi: 10.1097/INF.0b013e3181fb6f82
16. Vlieghe, E.R., Phe, T., De Smet, B., et al. Bloodstream infection among adults in Phnom
Penh, Cambodia: Key pathogens and resistance patterns. PLoS One. 2013 Mar [cited
2019 Aug 5];8(3):e59775. doi: 10.1371/journal.pone.0059775
17. Nadimpalli, M., Fabre, L., Yith, V., et al. CTX-M-55-type ESBL-producing Salmonella
enterica are emerging among retail meats in Phnom Penh. J Antimicrob Chemother. 2018
Oct [cited 2019 Aug 15];74:342-8. doi: 10.1093/jac/dky45.
18. Om, C., Vlieghe, E., McLaughlin, J.C., Daily, F., & McLaws, M.L. Antibiotic
prescribing practices: A national survey of Cambodian physicians. Am J Infect Control.
2016 [cited 2019 Jul 20];44:1144-8. doi: 10.1016/j.ajic.2016.03.062.
19. Amendment of Law on the Management of Pharmaceuticals, No. 17 Ch.L. (December
28, 2007). Available from:
http://moh.gov.kh/content/uploads/Laws_and_Regulations/Law/Law%20on%20Amendm
ent%20of%20Law%20on%20Pharmaceutical%20Management_Eng.pdf
20. Dunlop, N. Feeding the Guilty. In: Dunlop, N. The Lost Executioner: The Story of
Comrade Duch and the Khmer Rouge. London: Bloomsbury Publishing; 2005. Chapter
13.
21. Guillou, A.Y. Medicine in Cambodia during the Pol Pot regime (1975-1979): Foreign
and Cambodian Influences. New York, USA: “East Asian Medicine Under Communism:
A Symposium,” Graduate Center, City University of New York; 2004 [cited 2019 Aug
12]. Available from: https://halshs.archives-ouvertes.fr/halshs-00327711
22. Cambodian physician. Personal communication. 23 Jul 2019.
23. Dasaraju, P.V. & Liu, C. Infections of the Respiratory System. In: Baron, S., editor.
Medical Microbiology 4th Edition. Galveston (TX): University of Texas Medical Branch
at Galveston; 1996. Chapter 93. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK8142/
24. World Health Organization. World Health Day 2011: Policy Briefs. 2011 Apr 7 [cited
2019 Aug 12]. Available from: https://www.who.int/world-health-
day/2011/policybriefs/en/
25. Ministry of Health, Cambodia. National Policy to Combat Antimicrobial Resistance.
2014 Sept [cited 2019 Aug 12]. Available from:
http://extwprlegs1.fao.org/docs/pdf/cam169612.pdf
26. Representative from The Idea Consultancy. Personal communication. 5 Aug 2019
27. Institut Pasteur du Cambodge representative. Personal communication. 20 Aug 2019.

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