Fact Sheet N°
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
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
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
Antimicrobial use in food animals
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
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
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.
Scale of antimicrobial use outside human medicine
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
Factors contributing to overuse of antimicrobials in
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
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
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
www.who.int/inf-fs/en/fact255.html and www.who.int/inf-fs/en/fact139.html
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
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
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
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:
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
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.
Journalists can contact the WHO Spokesperson's Office, Geneva, at
Telephone (+41 22) 791 2599; Facsimile (+41 22) 791 4858 or E-mail: firstname.lastname@example.org
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