resistance in men
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E-DRUG: Use of antimicrobials in fish, animals and plants and
resistance in men
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[interesting factsheet of WHO; for a better layout, see the original
at
http://www.who.int/inf-fs/en/fact268.html
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WB]
Fact Sheet N� 268
January 2002
USE OF ANTIMICROBIALS OUTSIDE HUMAN MEDICINE
AND RESULTANT ANTIMICROBIAL RESISTANCE IN HUMANS
Antimicrobials are natural or synthetic drugs which inhibit or kill
bacteria. This capability makes them unique for the control of deadly
infectious diseases caused by a large variety of pathogenic bacteria.
Today, more than 15 different classes of antimicrobials are known.
They differ in chemical structure and mechanism of action. Specific
antimicrobials are necessary for the treatment of specific pathogens.
Following their 20th century triumph in human medicine, antimicrobials
have also been used increasingly for the treatment of bacterial
disease in animals, fish and plants. In addition, they became an
important element of intense animal husbandry because of their
observed growth-enhancing effect, when added in sub-therapeutic doses
to animal feed. Antimicrobials are also used in industry, e.g. to
eliminate bacterial growth on the inside of oil pipelines.
The antimicrobial resistance problem
The widespread use of antimicrobials outside human medicine is of
serious concern given the alarming emergence in humans of bacteria,
which have acquired, through this use, resistance to antimicrobials.
Most of the rising antimicrobial resistance problem in human medicine
is due to the overuse and misuse of antimicrobials by doctors, other
health personnel and patients.
However, some of the newly-emerging resistant bacteria in animals are
transmitted to humans; mainly via meat and other food of animal origin
or through direct contact with farm animals. The best-known examples
are the foodborne pathogenic bacteria Salmonella and Campylobacter and
the commensal (harmless in healthy persons and animals) bacteria
Enterococcus. Research has shown that resistance of these bacteria to
classic treatment in humans is often a consequence of the use of
certain antimicrobials in agriculture.
Further study is required to investigate other possible ways of
transmission of antimicrobial resistant bacteria to humans. For
example, the impact on human health of the widespread distribution of
non-metabolized antimicrobials through manure and other effluents from
farm animals into the environment is still unknown.
Antimicrobial use in food animals
In addition to being administered to sick food animals individually to
treat them, antimicrobials are used for mass treatment against
infectious diseases or continuously in feed at very low doses (parts
per million) for growth promotion, particularly in pig and poultry
production. Use of antimicrobials for these purposes has become an
important part of intense animal husbandry.
Some growth promoters belong to groups of antimicrobials (e.g.
glycopeptides and streptogramins) which are essential drugs in human
medicine for the treatment of serious, potentially life-threatening,
bacterial diseases, such as Staphylococcus or Enterococcus infections.
Scale of antimicrobial use outside human medicine
The amount of antimicrobials used in food animals is not known
precisely. National statistics on the amount and pattern of use of
antimicrobials in human medicine or elsewhere exist in only a few
countries.
It is estimated that about half of the total amount of antimicrobials
produced globally is used in food animals.
In Europe, all classes of antimicrobials licensed for disease therapy
in humans are also registered for use in animals, a situation
comparable with other regions in the world where comprehensive
registration data are much more difficult to obtain.
A recent review in Europe has shown that an average amount of 100
milligrams of antimicrobials is used in animals for the production of
one kilogram of meat for human consumption.
The increase in meat production in many developing countries is mainly
due to intensified farming, which is often coupled with increased
antimicrobial usage for both disease therapy and growth promotion.
Factors contributing to overuse of antimicrobials in food animals
Education on antimicrobial resistance and prudent antimicrobial use is
lacking amongst dispensers and prescribers of antimicrobials. In many
countries, antimicrobials are dispensed by inadequately-trained
individuals. One study reported that more than 90% of all veterinary
drugs used in animals in the United States of America (USA) in 1987
were administered without professional veterinary consultation. In
addition, inappropriate doses and combinations of drugs are frequently
used in animals. Furthermore, administering antimicrobials to animal
flocks and herds in their feed causes problems of inaccurate dosing
and inevitable treatment of all animals irrespective of health status.
Empiric treatment (based on clinical investigations, rather than
isolation and typing of the causative pathogen) predominates because
of the widespread lack of diagnostic services (particularly in
developing countries). In many countries, submission of clinical
specimens and samples from sick animals is uncommon due to costs
involved, time restrictions and the limited number of laboratories.
In many countries, including several developed countries,
antimicrobials are available over-the-counter and may be purchased
without prescription.
Inefficient regulatory mechanisms or poor enforcement of regulations,
with lack of quality assurance and marketing of substandard drugs, are
important contributory factors. Discrepancies between regulatory
requirements and prescribing/dispensing realities are often wider in
veterinary medicine than in human medicine.
Antimicrobial growth promoters are not considered as drugs and are
licensed, if at all, as feed additives.
As in human medicine, pharmaceutical industry marketing of
antimicrobials influences prescribing behaviour and use patterns of
veterinarians and farmers. Unlike in human medicine, there are
currently few countries with industry codes or government rules that
oversee advertising practices for antimicrobials for non-human use.
There is a significant increase in intensive animal production,
particularly in countries with economies in transition, where the
above-mentioned general factors are present: improper prescription and
dispensing, lack of licensing and enforcement, poor drug quality,
veterinary education and food safety, etc.
Examples of the consequences of the overuse of antimicrobials in food
animals
Studies in several countries, including the United Kingdom (UK) and
USA, have demonstrated the association between the use of
antimicrobials in food animals and antimicrobial resistance. Shortly
after the licensing and use of Fluoroquinolone, a powerful new class
of antimicrobials, in poultry, fluoroquinolone-resistant Salmonella
and Campylobacter isolations from animals, and shortly afterward such
isolations from humans, became more common. Community and family
outbreaks, as well as individual cases, of salmonellosis and
campylobacteriosis resistant to treatment with fluoroquinolones have
since been reported from several countries. The US Food and Drug
Administration (FDA) believes that each year the health of at least
5000 Americans is affected by use of these drugs in chickens. (WHO
Fact Sheets on Campylobacter and Multi-drug Resistant Salmonella
Typhimurium can be found at the following URLs:
www.who.int/inf-fs/en/fact255.html and
www.who.int/inf-fs/en/fact139.html respectively);
With the emergence of vancomycin-resistant strains of Enterococcus
bacteria in many hospitals around the world, the question arose if the
use of vancomycin in agriculture could have compounded the worsening
problem. Indeed, vancomycin-resistant enterococci were isolated in
animals, food and non-treated volunteers in countries where vancomycin
is also used as a growth promoter in animals;
Because of the health threat from vancomycin-resistant enterococci,
Denmark banned use of vancomycin as an animal growth promoter in 1995
and all European countries followed suit in 1997. After the ban,
prevalence of resistant Enterococcus in animals and food, particularly
in poultry meat, fell sharply.
Antimicrobial use in aquaculture
Various antimicrobials are licensed and used in fish and shrimp
production, particularly in Asia. Unfortunately, little information is
available on the type and amount of antimicrobials used in
aquaculture, making assessment of emerging public health risks more
difficult;
There is an urgent need to review the current usage patterns of
antimicrobials in aquaculture to identify looming hazards in food
safety and infectious disease control in humans. (This also applies to
other uses of antimicrobials, including for plant protection and in
industry);
Because of lessons learned from antimicrobial use in species living on
land, some countries have been looking for non-antimicrobial
alternatives for some time. Norway, for instance, has been able to
diminish antimicrobial use in aquaculture by more than 90% in a very
short period of time after changing certain production practices and
increasing use of vaccines.
Containment of antimicrobial resistance
1. The World Health Organization (WHO) is developing a Global Strategy
for the Containment of Antimicrobial Resistance. This strategy targets
all areas where antimicrobials are used in the community, hospitals
and agriculture.
2. As part of this strategy, WHO, jointly with other organizations
such as the United Nations Food and Agriculture Organization (FAO) and
the Office International des Epizooties (OIE), developed global
principles (recommendations) for antimicrobial use in agriculture. The
overall aim of this activity is to minimize the potential negative
public health impact of the use of antimicrobial agents in animals
used for human food, whilst at the same time providing for their safe
and effective use in veterinary medicine. The global principles may be
consulted on the Internet at the following address:
http://www.who.int/emc/diseases/zoo/who_global_principles.html
3. Few countries have active surveillance for antimicrobial resistance
in bacteria from food animals and food of animal origin. Existing
programmes rarely involve all relevant zoonotic and commensal
microorganisms and do not test for all the antimicrobials that may be
relevant from a public health perspective. Furthermore, methods used
are not sufficiently standardized to enable comparison of data between
different surveillance programmes focused on animals or humans.
Consequently, there is an absence of adequate data to evaluate the
consequences of antimicrobial use in animals and to monitor the effect
of different interventions applied to reduce antimicrobial resistance
in bacteria from animals.
4. Through a concerted effort with partners from national agencies and
research institutions, WHO is enhancing foodborne disease surveillance
and antimicrobial resistance testing of foodborne bacteria. The
laboratory strengthening focuses on salmonellosis and antimicrobial
resistance surveillance in foodborne Salmonella and includes the
following activities:
Development of the Global Salm-Surv (http://www.who.int/salmsurv), a
web-based, up to date databank on national and regional laboratories;
Establishment of a network of electronically-linked national and
regional reference laboratories. Currently, more than 260 scientists,
microbiologists, epidemiologists and others from 109 institutions in
101 countries are participating;
Conducting external quality assurance programmes. By the end of 2000,
80 national reference laboratories will have completed evaluation of
their Salmonella typing and antimicrobial susceptibility testing;
Establishment of international centres of excellence for surveillance
and containment of antimicrobial resistance resulting from
antimicrobial use in agriculture.
5. Containment of antimicrobial resistance will require national and
local efforts to reduce use of antimicrobials. Through legislation,
some countries have recently taken steps to reduce the problem of
antimicrobial resistance in food animals. The European Union banned
all antimicrobial animal growth promoters which are also used in human
medicine in 1997. Already in 1986, Sweden banned the use of all animal
growth promoters, even those which are not used in human medicine.
Denmark voluntarily suspended the use of all animal growth promoters
in 1999 and Switzerland did the same in 2000. Studies in Denmark have
shown that voluntary suspension resulted in an overall reduction of
antimicrobial use in Danish livestock of more than 60% with no
significant economic impact or negative change in animal health status
and food safety.
6. WHO encourages countries to use all opportunities to reduce, to the
extent possible, the use of antimicrobials outside human medicine.
This will minimize the risk of the emergence of antimicrobial
resistance in bacteria, which can be transmitted to humans from
animals or the environment. The overall aim is to ensure that
infectious disease in humans can be controlled more efficiently.
Further information Journalists can contact the WHO Spokesperson's
Office, Geneva, at Telephone (+41 22) 791 2599; Facsimile (+41 22) 791
4858 or E-mail: inf@who.int All WHO Press Releases, Fact Sheets
(including N� 255 on Campylobacter and N� 139 on Multi-drug Resistant
Salmonella Typhimurium) and Features can be obtained on Internet on
the WHO home page http://www.who.int
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