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Antimicrobial resistance
13 October 2020
Key facts
Antimicrobial resistance (AMR) is a global health and development threat. It requires urgent
multisectoral action in order to achieve the Sustainable Development Goals (SDGs).
WHO has declared that AMR is one of the top 10 global public health threats facing humanity.
Misuse and overuse of antimicrobials are the main drivers in the development of drug-resistant
pathogens.
Lack of clean water and sanitation and inadequate infection prevention and control promotes the
spread of microbes, some of which can be resistant to antimicrobial treatment.
The cost of AMR to the economy is significant. In addition to death and disability, prolonged illness
results in longer hospital stays, the need for more expensive medicines and financial challenges for
those impacted.
Without effective antimicrobials, the success of modern medicine in treating infections, including
during major surgery and cancer chemotherapy, would be at increased risk.
What are antimicrobials?
Antimicrobials – including antibiotics, antivirals, antifungals and antiparasitics – are medicines used
to prevent and treat infections in humans, animals and plants.
What is antimicrobial resistance?
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Antimicrobial Resistance (AMR) occurs when bacteria, viruses, fungi and parasites change over
time and no longer respond to medicines making infections harder to treat and increasing the risk of
disease spread, severe illness and death.
As a result of drug resistance, antibiotics and other antimicrobial medicines become ineffective
and infections become increasingly difficult or impossible to treat.
Why is antimicrobial resistance a global
concern?
The emergence and spread of drug-resistant pathogens that have acquired new resistance
mechanisms, leading to antimicrobial resistance, continues to threaten our ability to treat common
infections. Especially alarming is the rapid global spread of multi- and pan-resistant bacteria (also
known as “superbugs”) that cause infections that are not treatable with existing antimicrobial
medicines such as antibiotics.
The clinical pipeline of new antimicrobials is dry. In 2019 WHO identified 32 antibiotics in clinical
development that address the WHO list of priority pathogens, of which only six were classified as
innovative. Furthermore, a lack of access to quality antimicrobials remains a major issue. Antibiotic
shortages are affecting countries of all levels of development and especially in health- care systems.
Antibiotics are becoming increasingly ineffective as drug-resistance spreads globally leading to more
difficult to treat infections and death. New antibacterials are urgently needed – for example, to treat
carbapenem-resistant gram-negative bacterial infections as identified in the WHO priority pathogen
list. However, if people do not change the way antibiotics are used now, these new antibiotics will
suffer the same fate as the current ones and become ineffective.
The cost of AMR to national economies and their health systems is significant as it affects
productivity of patients or their caretakers through prolonged hospital stays and the need for more
expensive and intensive care.
Without effective tools for the prevention and adequate treatment of drug-resistant infections and
improved access to existing and new quality-assured antimicrobials, the number of people for whom
treatment is failing or who die of infections will increase. Medical procedures, such as surgery,
including caesarean sections or hip replacements, cancer chemotherapy, and organ transplantation,
will become more risky.
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What accelerates the emergence and spread
of antimicrobial resistance?
AMR occurs naturally over time, usually through genetic changes. Antimicrobial resistant organisms
are found in people, animals, food, plants and the environment (in water, soil and air). They can
spread from person to person or between people and animals, including from food of animal origin.
The main drivers of antimicrobial resistance include the misuse and overuse of antimicrobials; lack
of access to clean water, sanitation and hygiene (WASH) for both humans and animals; poor
infection and disease prevention and control in health-care facilities and farms; poor access to
quality, affordable medicines, vaccines and diagnostics; lack of awareness and knowledge; and lack
of enforcement of legislation.
Present situation
Drug resistance in bacteria
For common bacterial infections, including urinary tract infections, sepsis, sexually transmitted
infections, and some forms of diarrhoea, high rates of resistance against antibiotics frequently used
to treat these infections have been observed world-wide, indicating that we are running out of
effective antibiotics. For example, the rate of resistance to ciprofloxacin, an antibiotic commonly
used to treat urinary tract infections, varied from 8.4% to 92.9% for Escherichia coliand from 4.1% to
79.4% for Klebsiella pneumoniae in countries reporting to the Global Antimicrobial Resistance and
Use Surveillance System (GLASS).
Klebsiella pneumoniae are common intestinal bacteria that can cause life-threatening infections.
Resistance in K. pneumoniae to last resort treatment (carbapenem antibiotics) has spread to all
regions of the world. K. pneumoniae is a major cause of hospital-acquired infections such as
pneumonia, bloodstream infections, and infections in newborns and intensive-care unit patients. In
some countries, carbapenem antibiotics do not work in more than half of the patients treated for K.
pneumoniae infections due to resistance.
Resistance to fluoroquinolone antibiotics in E. coli, used for the treatment of urinary tract infections,
is widespread.
There are countries in many parts of the world where this treatment is now ineffective in more than
half of patients.
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Colistin is the only last resort treatment for life-threatening infections caused by carbapenem
resistant Enterobacteriaceae (i.e. E.coli, Klebsiella, etc). Bacteria resistant to colistin have also been
detected in several countries and regions, causing infections for which there is no effective antibiotic
treatment at present.
The bacteria Staphlylococcus aureus are part of our skin flora and arealso a common cause of
infections both in the community and in health-care facilities. People with methicillin-
resistant Staphylococcus aureus (MRSA) infections are 64% more likely to die than people with
drug-sensitive infections.
In 2019, a new AMR indicator was included in the SDG monitoring framework. This indicator
monitors the frequency of bloodstream infections due to two specific drug resistant
pathogens: methicillin-resistant Staphylococcus aureus (MRSA); and E. coli resistant to third
generation cephalosporins (3GC). In 2019, 25 countries, territories and areas provided data to
GLASS on blood-stream infections due to MRSA and 49 countries provided data on bloodstream
infections due to E.coli. While the data are still not nationally representative, the median rate
observed for methicillin-resistant S. aureus was 12.11% (IQR 6.4–26.4) and that for E. coli resistant
to third generation cephalosporins was 36.0% (IQR 15.2–63.0).
Widespread resistance in highly variable strains of N. gonorrhoeae has compromised the
management and control of gonorrhoea. Resistance has rapidly emerged to sulphonamides,
penicillins, tetracyclines, macrolides, fluoroquinolones, and early generation cephalosporins.
Currently, in most countries, the injectable extended-spectrum cephalosporin (ESC) ceftriaxone is
the only remaining empiric monotherapy for gonorrhoea.
Drug resistance in mycobacterium tuberculosis
Antibiotic resistant Mycobacterium tuberculosis strains are threatening progress in containing the
global tuberculosis epidemic. WHO estimates that, in 2018, there were about half a million new
cases of rifampicin-resistant TB (RR-TB) identified globally, of which the vast majority have multi-
drug resistant TB (MDR-TB), a form of tuberculosis that is resistant to the two most powerful anti-TB
drugs. Only one-third of the approximately half a million people who developed MDR/RR-TB in 2018
were detected and reported. MDR-TB requires treatment courses that are longer, less effective and
far more expensive than those for non-resistant TB. Less than 60% of those treated for MDR/RR-TB
are successfully cured.
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In 2018, an estimated 3.4% of new TB cases and 18% of previously treated cases had MDR-TB/
RR-TB and the emergence of resistance to new ‘last resort’ TB drugs to treat drug resistant TB
poses a major threat.
Drug resistance in viruses
Antiviral drug resistance is an increasing concern in immunocompromised patient populations,
where ongoing viral replication and prolonged drug exposure lead to the selection of resistant
strains. Resistance has developed to most antivirals including antiretroviral (ARV) drugs.
All antiretroviral (ARV) drugs, including newer classes, are at risk of becoming partly or fully inactive
because of the emergence of drug-resistant HIV (HIVDR). People receiving antiretroviral therapy
can acquire HIVDR, and people can also be infected with HIV that is already drug resistant. Levels
of pretreatment HIVDR (PDR) to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) among
adults initiating first-line therapy exceeded 10% in the majority of the monitored countries in Africa,
Asia and Latin America. The prevalence of PDR among infants is alarmingly high. In sub-Saharan
Africa, over 50% of the infants newly diagnosed with HIV carry a virus that is resistant to
NNRTI. Informed by these findings, latest WHO ARV guidelines now recommend the adoption of a
new drug, dolutegravir, as the preferred first-line treatment for adults and children. The use of this
drug is particularly urgent in averting the negative effects of resistance to NNRTIs.
Increasing levels of resistance have important economic implications since second- and third-line
regimens are much more expensive than first-line drugs. WHO’s HIV drug resistance programme is
monitoring the transmission and emergence of resistance to older and newer HIV drugs around the
globe.
Drug resistance in malaria parasites
The emergence of drug-resistant parasites poses one of the greatest threats to malaria control and
results in increased malaria morbidity and mortality. Artemisinin-based combination therapies (ACTs)
are the recommended first-line treatment for uncomplicated P. falciparum malaria and are used by
most malaria endemic countries. ACTs are a combination of an artemisinin component and a partner
drug. In the WHO Western Pacific Region and in the WHO South-East Asia Region, partial
resistance to artemisinin and resistance to a number of the ACT partner drugs has been confirmed
in Cambodia, Lao People’s Democratic Republic, Myanmar, Thailand, and Viet Nam through studies
conducted between 2001 and 2019. This makes selecting the right treatment more challenging and
requires close monitoring.
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In the WHO Eastern Mediterranean Region, P. falciparum resistance to sulfadoxine-pyrimethamine
led to artesunate-sulfadoxine-pyrimethamine failures in some countries, necessitating a change to
another ACT.
In Africa, evidence has recently been published showing emergence of mutations linked to partial
artemisinin resistance in Rwanda. So far, ACTs that have been tested remain highly efficacious.
However, further spread of resistance to artemisinin and ACT partner drugs could pose a major
public health challenge and jeopardize important gains in malaria control.
Drug resistance in fungi
The prevalence of drug-resistant fungal infections is increasing and exasperating the already difficult
treatment situation. Many fungal infections have existing treatability issues such as toxicity
especially for patients with other underlying infections (e.g. HIV). Drug-resistant Candida auris, one
of the most common invasive fungal infections, is already widespread with increasing resistance
reported to fluconazole, amphotericin B and voriconazole as well as emerging caspofungin
resistance.
This is leading to more difficult to treat fungal infections, treatment failures, longer hospital stays and
much more expensive treatment options. WHO is undertaking a comprehensive review of fungal
infections globally and will publish a list of fungal pathogens of public health importance, along with
an analysis of the antifungal development pipeline.
Need for coordinated action
AMR is a complex problem that requires a united multisectoral approach. The One Health approach
brings together multiple sectors and stakeholders engaged in human, terrestrial and aquatic animal
and plant health, food and feed production and the environment to communicate and work together
in the design and implementation of programmes, policies, legislation and research to attain better
public health outcomes.
Greater innovation and investment is required in operational research, and in research and
development of new antimicrobial medicines, vaccines, and diagnostic tools especially
those targeting the critical gram-negative bacteria such as carbapenem-resistant
Enterobacteriaceae and Acinetobacter baumannii. The launch of the Antimicrobial Resistance Multi
Partner Trust Fund (AMR MPTF), the Global Antibiotic Research & Development Partnership
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(GARDP), AMR Action Fund and other funds and initiatives could fill a major funding gap. Various
governments are piloting reimbursement models including Sweden, Germany, the USA and the
United Kingdom. More initiatives are needed to find lasting solutions.
Global Action Plan on Antimicrobial Resistance (GAP)
Globally, countries committed to the framework set out in the Global Action Plan1 (GAP) 2015 on
AMR during the 2015 World Health Assembly and committed to the development and
implementation of multisectoral national action plans. It was subsequently endorsed by the
Governing Bodies of the Food and Agriculture Organization of the United Nations (FAO) and the
World Organisation for Animal Health (OIE). To ensure global progress, countries need to ensure
costing and implementation of national action plans across sectors to ensure sustainable progress.
Prior to the endorsement of the GAP in 2015, global efforts to contain AMR included the WHO global
strategy for containment of Antimicrobial Resistance developed in 2001 which provides a framework
of interventions to slow the emergence and reduce the spread of AMR.
Tripartite Joint Secretariat on Antimicrobial Resistance
The political declaration at the UN High Level Meeting on AMR, commited to by Heads of State at
the United Nations General Assembly in New York in September 2016, confirmed a strong focus on
a broad, coordinated approach that engages all including the human, animal, plant and
environmental health sectors. WHO is working closely with FAO and OIE in a ‘One Health’ approach
to promote best practices to reduce the levels of AMR and slow its development.
The Interagency Coordination Group (IACG) on AMR was convened by the Secretary-General of the
United Nations after the UN High-Level Meeting on Antimicrobial Resistance in 2016. The IACG
brought together partners across the UN, international organizations and individuals with expertise
across human, animal and plant health, as well as the food, animal feed, trade, development and
environment sectors, to formulate a plan for the fight against antimicrobial resistance. The
Interagency Coordination Group on AMR submitted its report “No time to wait: Securing the future
from drug-resistant infections” to the UN Secretary-General in April 2019. Its recommendations are
now being implemented.
A tripartite joint secretariat (FAO, OIE and WHO) has been established and is hosted by WHO to
drive multi-stakeholder engagement in AMR. The key governance structures agreed include the One
Health Global Leaders Group on AMR, the Independendent Panel on Evidence for Action against
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AMR and the Multi-Stakeholder Partnership Platform. These structures are in the process of being
established.
World Antimicrobial Awareness Week (WAAW)
WAAW was previously called the World Antibiotic Awareness Week. From 2020, it will be called the
World Antimicrobial Awareness Week. This will reflect the broadened scope of WAAW to include all
antimicrobials including antibiotics, antifungals, antiparasitics and antivirals. Held annually since
2015, WAAW is a global campaign that aims to raise awareness of antimicrobial resistance
worldwide and encourage best practices among the general public, health workers and policy
makers to slow the development and spread of drug-resistant infections. The Tripartite Executive
Committee decided to set all future WAAW dates as 18 to 24 November, starting with WAAW 2020.
The overarching slogan used for the last 5 years was “Antibiotics: Handle with Care.” This has
been changed to “Antimicrobials: Handle with Care” in 2020.
The Global Antimicrobial Resistance and Use Surveillance
System (GLASS)
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015
to continue filling knowledge gaps and to inform strategies at all levels. GLASS has been conceived
to progressively incorporate data from surveillance of AMR in humans, surveillance of the use of
antimicrobial medicines, AMR in the food chain and in the environment. GLASS provides a
standardized approach to the collection, analysis, interpretation and sharing of data by countries,
territories and areas, and monitors the status of existing and new national surveillance systems, with
emphasis on representativeness and quality of data collection. Some WHO regions have
established surveillance networks that provide technical support to countries and facilitate
enrollment into GLASS.
Global Research and Development priority setting for AMR
In 2017, to guide research and development into new antimicrobials, diagnostics and vaccines,
WHO developed the WHO priority pathogens list. It will be updated in 2022. On an annual basis,
WHO reviews the pre-clinical and clinical antibacterial pipelines to see how the pipeline is
progressing with respect to the WHO priority pathogens list. A critical gap remains in research and
development, in particular for antibacterial targeting of the gram-negative carbapenem resistant
bacteria.
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Global Antibiotic Research and Development Partnership
(GARDP)
A joint initiative of WHO and the Drugs for Neglected Diseases Initiative (DNDi), GARDP
encourages research and development through public-private partnerships. By 2025, the partnership
aims to develop and deliver five new treatments that target drug-resistant bacteria identified by WHO
as posing the greatest threat.
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Q&A: What is antimicrobial resistance?
World Antimicrobial Awareness Week
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