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WHO | Antimicrobial resistance …
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WHO | Antimicrobial resistance http://www.who.int/mediacentre/factsheets/fs194/en/index.html
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Health topics Fact sheet N°194
Revised January 2002
Publications
Data and statistics Antimicrobial resistance
Programmes and
Since their discovery during the 20th century, antimicrobial agents (antibiotics and related medicinal
projects
drugs) have substantially reduced the threat posed by infectious diseases. The use of these "wonder
Media centre drugs", combined with improvements in sanitation, housing, and nutrition, and the advent of widespread
immunization programmes, has led to a dramatic drop in deaths from diseases that were previously
News widespread, untreatable, and frequently fatal. Over the years, antimicrobials have saved the lives and
eased the suffering of millions of people. By helping to bring many serious infectious diseases under
Events control, these drugs have also contributed to the major gains in life expectancy experienced during the
Fact sheets latter part of the last century.
Multimedia These gains are now seriously jeopardized by another recent development: the emergence and spread of
microbes that are resistant to cheap and effective first-choice, or "first-line" drugs. The bacterial
Contacts infections which contribute most to human disease are also those in which emerging and microbial
resistance is most evident: diarrhoeal diseases, respiratory tract infections, meningitis, sexually
transmitted infections, and hospital-acquired infections. Some important examples include
penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant enterococci, methicillin-resistant
Staphylococcus aureus, multi-resistant salmonellae, and multi-resistant Mycobacterium tuberculosis. The
development of resistance to drugs commonly used to treat malaria is of particular concern, as is the
emerging resistance to anti-HIV drugs.
CONSEQUENCES
The consequences are severe. Infections caused by resistant microbes fail to respond to treatment,
resulting in prolonged illness and greater risk of death. Treatment failures also lead to longer periods of
infectivity, which increase the numbers of infected people moving in the community and thus expose the
general population to the risk of contracting a resistant strain of infection.
When infections become resistant to first-line antimicrobials, treatment has to be switched to second- or
third-line drugs, which are nearly always much more expensive and sometimes more toxic as well, e.g.
the drugs needed to treat multidrug-resistant forms of tuberculosis are over 100 times more expensive
than the first-line drugs used to treat non-resistant forms. In many countries, the high cost of such
replacement drugs is prohibitive, with the result that some diseases can no longer be treated in areas
where resistance to first-line drugs is widespread. Most alarming of all are diseases where resistance is
developing for virtually all currently available drugs, thus raising the spectre of a post-antibiotic era. Even
if the pharmaceutical industry were to step up efforts to develop new replacement drugs immediately,
current trends suggest that some diseases will have no effective therapies within the next ten years.
CAUSES
Microbes (the collective term for bacteria, fungi, parasites, and viruses) cause infectious diseases, and
antimicrobial agents, such as penicillin, streptomycin, and more than 150 others, have been developed to
combat the spread and severity of many of these diseases. Resistance to antimicrobials is a natural
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microbes which adapt and survive carry genes for resistance, which can be passed on.
Bacteria are particularly efficient at enhancing the effects of resistance, not only because of their ability to
multiply very rapidly but also because they can transfer their resistance genes, which are passed on when
the bacteria replicate. In the medical setting, such resistant microbes will not be killed by an antimicrobial
agent during a standard course of treatment. Resistant bacteria can also pass on their resistance genes
to other related bacteria through "conjugation", whereby plasmids carrying the genes jump from one
organism to another. Resistance to a single drug can thus spread rapidly through a bacterial population.
When anti-microbials are used incorrectly - for too short a time, at too low a dose, at inadequate
potency; or for the wrong disease - the likelihood that bacteria and other microbes will adapt and
replicate rather than be killed is greatly enhanced.
Much evidence supports the view that the total consumption of antimicrobials is the critical factor in
selecting resistance. Paradoxically, underuse through lack of access, inadequate dosing, poor adherence,
and substandard anti-microbials may play as important a role as overuse. For these reasons, improving
use is a priority if the emergence and spread of resistance are to be controlled.
UNPRECEDENTED TRENDS
In the past, medicine and science were able to stay ahead of this natural phenomenon through the
discovery of potent new classes of antimicrobials, a process that flourished from 1930-1970 and has since
slowed to a virtual standstill, partly because of misplaced confidence that infectious diseases had been
conquered, at least in the industrialized world. In just the past few decades, the development of resistant
microbes has been greatly accelerated by several concurrent trends. These have worked to increase the
number of infections and thus expand both the need for antimicrobials and the opportunities for their
misuse. Such trends include:
urbanization with its associated overcrowding and poor sanitation, which greatly facilitate the
spread of such diseases as typhoid, tuberculosis, respiratory infections, and pneumonia;
pollution, environmental degradation, and changing weather patterns, which can affect the
incidence and distribution of infectious diseases, especially those, such as malaria, that are spread
by insects and other vectors;
demographic changes, which have resulted in a growing proportion of elderly people needing
hospital-based interventions and thus at risk of exposure to highly resistant pathogens found in
hospital settings;
the AIDS epidemic, which has greatly enlarged the population of immunocompromised patients at
risk of numerous infections, many of which were previously rare;
the resurgence of old foes, such as malaria and tuberculosis, which are now responsible for many
millions of infections each year;
the enormous growth of global trade and travel which have increased the speed and facility with
which both infectious diseases and resistant microorganisms can spread between continents.
As the number of infections and the corresponding use of antimicrobials have increased, so has the
prevalence of resistance. In addition, the enhanced food requirements of an expanding world population
have led to the widespread routine use of antimicrobials as growth promoters or preventive agents in
food-producing animals and poultry flocks. Such practices have likewise contributed to the rise in
resistant microbes, which can be transmitted from animals to man.
FACTORS THAT ENCOURAGE THE SPREAD OF RESISTANCE
The emergence and spread of antimicrobial resistance are complex problems driven by numerous
interconnected factors, many of which are linked to the misuse of antimicrobials and thus amenable to
2 of 5 change. In turn, antimicrobial use is influenced by an interplay of the knowledge, expectations, and 12/13/2007 10:21 AM
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Patient-related factors are major drivers of inappropriate antimicrobial use. For example, many patients
believe that new and expensive medications are more efficacious than older agents. In addition to
causing unnecessary health care expenditure, this perception encourages the selection of resistance to
these newer agents as well as to older agents in their class.
Self-medication with antimicrobials is another major factor contributing to resistance. Self-medicated
antimicrobials may be unnecessary, are often inadequately dosed, or may not contain adequate amounts
of active drug, especially if they are counterfeit drugs. In many developing countries, antimicrobials are
purchased in single doses and taken only until the patient feels better, which may occur before the
pathogen has been eliminated. Inappropriate demand can also be stimulated by marketing practices.
Direct-to-consumer advertising allows pharmaceutical manufacturers to market medicines directly to the
public via television, radio, print media, and the Internet. In particular, advertising on the Internet is
gaining market penetration, yet it is difficult to control with legislation due to poor enforceability.
Prescribers' perceptions regarding patient expectations and demands substantially influence prescribing
practice. Physicians can be pressured by patient expectations to prescribe antimicrobials even in the
absence of appropriate indications. In some cultural settings, antimicrobials given by injection are
considered more efficacious than oral formulations. Such perceptions tend to be associated with the
over-prescribing of broad-spectrum injectable agents when a narrow-spectrum oral agent would be more
appropriate. Prescribing just to be on the safe side" increases when there is diagnostic uncertainty, lack
of prescriber knowledge regarding optimal diagnostic approaches, lack of opportunity for patient
follow-up, or fear of possible litigation. In many countries, antimicrobials can be easily obtained in
pharmacies and markets without a prescription.
Patient compliance with recommended treatment is another major problem. Patients forget to take
medication, interrupt their treatment when they begin to feel better, or may be unable to afford a full
course, thereby creating an ideal environment for microbes to adapt rather than be killed. In some
countries, low quality antibiotics (poorly formulated or manufactured, counterfeited or expired) are still
sold and used for self-medication or prophylaxis.
Hospitals are a critical component of the antimicrobial resistance problem worldwide. The combination of
highly susceptible patients, intensive and prolonged antimicrobial use, and cross-infection has resulted in
nosocomial infections with highly resistant bacterial pathogens. Resistant hospital-acquired infections are
expensive to control and extremely difficult to eradicate. Failure to implement simple infection control
practices, such as handwashing and changing gloves before and after contact with patients, is a common
cause of infection spread in hospitals throughout the world. Hospitals are also the eventual site of
treatment for many patients with severe infections due to resistant pathogens acquired in the
community. In the wake of the AIDS epidemic, the prevalence of such infections can be expected to
increase.
Veterinary prescription of antimicrobials also contributes to the problem of resistance. In North America
and Europe, an estimated 50% in tonnage of all antimicrobial production is used in food-producing
animals and poultry. The largest quantities are used as regular supplements for prophylaxis or growth
promotion, thus exposing a large number of animals, irrespective of their health status, to frequently
subtherapeutic concentrations of antimicrobials. Such widespread use of antimicrobials for disease control
and growth promotion in animals has been paralleled by an increase in resistance in those bacteria (such
as Salmonella and Campylobacter) that can spread from animals, often through food, to cause infections
in humans.
THE NEED FOR A GLOBAL RESPONSE
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problem that must be addressed in all countries. No single nation, however effective it is at containing
resistance within its borders, can protect itself from the importation of resistant pathogens through travel
and trade. Poor prescribing practices in any country now threaten to undermine the potency of vital
antimicrobials everywhere.
The strategy recommends interventions that can be used to slow the emergence and reduce the spread
of resistance in a diverse range of settings. The interventions are organized according to groups of people
whose practices and behaviours contribute to resistance and where changes are judged likely to have a
significant impact at both national and international levels. These include consumers, prescribers and
dispensers, veterinarians, and managers of hospitals and diagnostic laboratories as well as national
governments, the pharmaceutical industry, professional societies, and international agencies. Global
principles for the containment of antimicrobial resistance in food-producing animals were issued by WHO
in June 2000.
As much of the responsibility for containing resistance rests with national governments, the strategy
gives particular attention to interventions involving the introduction of legislation and policies governing
the development, licensing, distribution, and sale of antimicrobial agents. The strategy is sufficiently
flexible to be applied in poor and wealthy nations alike. The process for selecting the necessary
interventions to limit emerging antimicrobial resistance can be based on the diseases most prevalent in a
given country. In advocating widespread adoption of this strategy, WHO aims to encourage the urgent
actions needed to reverse or at least curtail trends which have major economic as well as health
implications. Moreover, in view of the global nature of the antimicrobial resistance problem, the efforts of
any nation to implement the WHO Global Strategy are likely to be felt worldwide.
The strategy builds on a number of WHO activities aimed at both monitoring the global emergence and
spread of antimicrobial resistance and extending direct support to countries. WHO helps countries
establish laboratory-based networks for the surveillance of resistance. Specific activities include staff
training, support in methods for the quality assurance of laboratory tests, and provision of laboratory
reagents. In addition, WHO distributes a computer software program, WHONET. Microbiologists,
clinicians, and infection control workers may use this software to improve the systematic monitoring of
drug resistance in their hospitals and communities and to share their data in a common format among
national networks.
Since 1977, WHO has produced Model Lists of Essential Drugs in order to help governments select the
most effective and appropriate drugs in line with priority needs. The lists, which are regularly revised,
also contribute to the rational purchasing and use of drugs. Studies have demonstrated that in those
areas in which an essential drugs programme is in operation, significantly more essential drugs are
available, significantly fewer injections and antimicrobials are utilized, and drug stocks last about three
times longer than in regions without such a programme. At present over 120 countries have implemented
an essential drugs list. With the first global strategy for containment of antimicrobial resistance now
available, WHO is also in a position to advise health policy-makers and managers on the specific
interventions needed to safeguard the effectiveness of vital drugs and thus ensure that their life-saving
capacity remains available to future generations.
For more information contact:
WHO Media centre
Telephone: +41 22 791 2222
E-mail: mediainquiries@who.int
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