Communication from the Commission on a Community Strategy against antimicrobial resistance
Date: 2001-06-20
Institutions: European Commission
Subjects: disease prevention, epidemiology, health control, infectious disease, international cooperation, microorganism, public health, scientific research, transmission network

COMMISSION OF THE EUROPEAN COMMUNITIES

Brussels, 20.06.2001
COM(2001) 333 final

VOLUME I

COMMUNICATION FROM THE COMMISSION

ON A COMMUNITY STRATEGY AGAINST ANTIMICROBIAL RESISTANCE

EXECUTIVE SUMMARY

The emergence and spread of antimicrobial resistance has become a major public health
problem, within the Community and world-wide. Overuse and misuse of substances to kill or
inhibit the growth of micro-organisms (including bacteria, viruses and fungae), and certain
parasites (for example protozoa) have favoured the growth of resistant organisms. This so-
called “antimicrobial resistance” can spread to other microbial populations. Infections by
resistant organisms endanger the human population, animals and plants, including those not
previously in contact with antimicrobial agents.

For the purposes of this Communication, the term “antimicrobial agent” encompasses a
substance produced either synthetically or naturally by bacteria, fungae or plants, used to kill
or inhibit the growth of micro-organisms, including bacteria, viruses and fungae, and parasites
exhibiting the phenomenon of resistance (in particular protozoa). Antibiotics are substances
with antibacterial effects.

Recent scientific opinions pointed out that prompt action is needed in the following areas:
prudent use of antimicrobial agents, prevention of diseases, development of new products and
methods of treatment and monitoring the situation.

Antimicrobial resistance is already addressed by the Community through various individual
measures. The need is clear for an overall approach to this question, based on the provisions
of Article 152 of the Treaty establishing the European Community which provides that a high
level of health protection shall be ensured in the definition and implementation of all
Community policies and activities.

On this basis, the Commission proposes to put in place a Community strategy on four key
areas of action:

(1)

(2)

(3)

(4)

Surveillance: Monitoring the evolution and the effects of interventions through the
establishment/strengthening of accurate surveillance systems on antimicrobial
resistance in the human and veterinary sector and the consumption of antimicrobial
agents.

Prevention of communicable diseases, and infection control to reduce the needs for
antimicrobial agents. This includes the prudent use of antimicrobial agents which
information for authorised antibacterial
entails the need for
medicinal products and the promotion of educational and behavioural actions towards
the professionals and the general public.

improved product

Research and product development: New modalities for prevention and treatment of
infections and continued support of research for new drugs and alternatives.

International co-operation: Antimicrobial resistance does not respect frontiers. An
effective strategy requires close co-operation and consultation between the
Commission, the Member States and other involved parties, especially at international
level.

The attached proposal for a Council Recommendation on the prudent use of antimicrobial
agents plays an important part
in the Community's multi-disciplinary and multi-faceted
approach.

2

COMMUNICATION FROM THE COMMISSION

ON A COMMUNITY STRATEGY AGAINST ANTIMICROBIAL RESISTANCE

(Text with EEA relevance)

3

TABLE OF CONTENTS

EXECUTIVE SUMMARY .................................................................................................... 2

Introduction ........................................................................................................................... 5

1.

Surveillance, Monitoring And Data Collection ......................................................... 7

1.1.

Surveillance Networks on antimicrobial resistance ................................................... 7

1.1.1. Human medicine ...................................................................................................... 7

1.1.2. Veterinary medicine ................................................................................................. 8

1.2.

Monitoring of antimicrobial consumption............................................................... 10

1.2.1. Humans .................................................................................................................. 10

1.2.2. Animals.................................................................................................................. 10

1.2.3.

Plant Protection ...................................................................................................... 10

1.3.

Safety evaluation of antimicrobial agents used in plant protection .......................... 10

2.

Towards An Improved System Of Prevention and Control...................................... 11

2.1.

Market authorisation and user information on antimicrobial agents......................... 11

2.1.1. Human medicine .................................................................................................... 11

2.1.2. Veterinary medicine ............................................................................................... 11

2.2.

Prudent use of antimicrobial agents ........................................................................ 12

2.2.1. Human medicine: Commission proposal for a Council Recommendation ............... 12

2.2.2. Veterinary medicine ............................................................................................... 13

2.3.

Additives................................................................................................................ 13

2.3.1.

In food ................................................................................................................... 13

2.3.2.

Phasing out and replacement of antimicrobial agents as growth promoters in animal
feed ........................................................................................................................ 14

2.4.

Antimicrobial resistance as markers of Genetically Modified Organisms (GMOs).. 14

3.

4.

Preparing For The Future........................................................................................ 15

International co-operation....................................................................................... 16

Conclusion........................................................................................................................... 18

4

INTRODUCTION

Background

The discovery, development and availability of substances which kill or inhibit the growth of
micro-organisms (bacteria, viruses and fungae), and parasites (for example protozoa) have
over the last century revolutionised the treatment of infectious diseases, leading to a dramatic
reduction in morbidity and mortality. Such “antimicrobial agents” (which for the purposes of
this Communication include substances produced either synthetically or naturally by bacteria,
fungae or plants, used to kill or inhibit the growth of micro-organisms, including bacteria,
viruses and fungae, and parasites exhibiting the phenomenon of resistance, in particular
protozoa, have greatly contributed to improvements in the health of the population.
Antibiotics are substances with antibacterial effects.

However, disease-causing organisms have a remarkable ability to adapt themselves, notably
to acquire and transmit antimicrobial resistance. Moreover, the excessive and uncontrolled
use of antimicrobial agents favours the growth of resistant organisms and thus jeopardises the
conquests of previous decades. Even though antimicrobial resistance from natural sources
is
existed even before antimicrobial agents were introduced into medical
generally accepted that there is an association between the quantities used and the increase in
resistant organisms.

treatment,

it

Despite ongoing research to find new groups of drugs to combat resistant organisms, it is
uncertain if and when such drugs will be available. Therefore, antimicrobial agents must be
used prudently in order to limit the further emergence and spread of resistant germs. Product
development and product information must hold an important place within the strategy and
the success of the actions to address antimicrobial resistance will need full support and
contributions from the pharmaceutical industry as well as actions from governments.

the problem of antimicrobial resistance has been recognised and
At Community level,
addressed for several years. This document gives a global overview of the situation and sets
out a Community strategy against antimicrobial resistance, including enhanced actions to
address the problem which at international, Community and national level is seen as a
growing and serious threat to health. In this context the various Recommendations of the
Council, the Copenhagen Recommendations on antimicrobial resistance1 endorsed by Council
as well as the work of international organisations, in particular WHO and OIE, are significant.

The fight against emergence and spread of antimicrobial resistance is thus a public health
priority.

Article 152 of the Treaty establishing the European Community provides the legal basis for
action in the public health field. It stipulates that a high level of health protection shall be
ensured in the definition and implementation of all Community policies and activities. The
obligation thus lies with all Community institutions and with Member States.

The issue of antimicrobial resistance forms an inherent part of the Community's health
strategy and comprises actions in all the relevant sectors: public health, veterinary and

1

Report from the Invitational European Union Conference on “The Microbial Threat” hosted by the
Danish Government in Copenhagen, Denmark, 9-10 September 1998.

5

phytosanitary sectors. Under the Community Network for the Epidemiological Surveillance
of Communicable Diseases, surveillance of antimicrobial resistance is one of the priorities.
Many initiatives and measures have been taken within the veterinary and phytosanitary
sectors. As regards human medicine, a Commission proposal for a Council Recommendation
on the prudent use of antimicrobial agents is attached to this communication. This represents
another step in the Community's multi-disciplinary and multi-faceted approach to tackling
antimicrobial resistance.

A Science Based Approach

The Community strategy on antimicrobial resistance is multidisciplinary and based on
scientific advice.

On 28 May 1999, the Scientific Steering Committee (SSC) of the European Commission
delivered an opinion on antimicrobial resistance2. The SSC's evaluation stated that prompt
action was needed to reduce the overall use of antimicrobial agents in a balanced way in all
areas: human medicine, veterinary medicine, animal production and plant protection. The
strategies most
likely to be effective in the control and containment of antimicrobial
resistance will be those that can be introduced speedily without undue costs in all Member
States, and which can be monitored and enforced across the EU. The SSC pointed to the
possible need to introduce effective legislation and regulation to support the achievement of
its proposals. The important areas of action identified concern the prudent use of
antimicrobial agents, prevention,
the development of new methods for prevention and
treatment, and monitoring the effects of interventions.

A Comprehensive Action Plan to Combat Antimicrobial Resistance

The Commission has on this basis identified four key areas of action which form the major
elements of the Community strategy to contain antimicrobial resistance:

(1)

(2)

(3)

(4)

Surveillance: Monitoring the evolution and the effects of interventions through the
establishment/strengthening of accurate surveillance systems on antimicrobial
resistance in the human and veterinary sector and the consumption of antimicrobial
agents.

Prevention of communicable diseases, and infection control to reduce the needs for
antimicrobial agents. This includes the prudent use of antimicrobial agents which
entails the need for
information for authorised antibacterial
medicinal products and the promotion of educational and behavioural actions towards
the professionals and the general public.

improved product

Research and product development: New modalities for prevention and treatment of
infections and continued support of research for new drugs and alternatives.

International co-operation: Antimicrobial resistance does not respect frontiers. An
effective strategy requires close co-operation and consultation between the
Commission, the Member States and other involved parties, especially at international
level.

2

http://europa.eu.int/comm/food/fs/sc/ssc/out50_en.html

6

1.

SURVEILLANCE, MONITORING AND DATA COLLECTION

1.1.

Surveillance Networks on antimicrobial resistance

1.1.1. Human medicine

In January 1999, a Community Network for the Epidemiological Surveillance and Control of
Communicable Diseases3 was set up. Antimicrobial resistance is one of its priorities. The two
main pillars of the Community Network for the Epidemiological Surveillance and Control of
the Communicable Diseases are an early warning and response system on public health
threats, and an epidemiological surveillance system on communicable diseases.

information on trends,

Surveillance of communicable diseases, especially monitoring of outbreaks and the timely
exchange of relevant
is essential for intervention strategies on
prevention and infection control. Quick co-ordinated action by the public health authorities of
Member States is essential for the containment of morbidity and mortality which could
emerge from rapidly spreading infections that do not respect borders. This can have an
important impact on the reduction of antimicrobial treatment.

The progressive development of this Community network over the next five years will be an
important step towards co-ordinated efforts among Member States, EEA/EFTA members and
candidate countries regarding prevention of infections and containing resistant organisms.

Specific networks within the Community network framework are:

• EARSS – European Antimicrobial Resistance Surveillance System4

Comparison of resistance in the different Member States is biased by differences in the
antimicrobial agents tested, the samples chosen for testing, the susceptibility test systems used
and breakpoints adopted. To obtain more comparable and reliable data, the Commission has
supported the Antimicrobial European Resistance Surveillance System (EARSS), an
international network of national surveillance systems which, since 1998, aims to aggregate
comparable and reliable antimicrobial resistance data for public health purposes in Europe
The network is growing. At present 23 countries have agreed to participate in EARSS: the 15
EU Member States, Iceland, Norway, Hungary, Czech Republic, Bulgaria, Slovenia, Malta,
Israel. In addition, Estonia, Poland, Slovakia, Romania, and Russia have expressed an interest
in participation. Of the participating countries 18 have delivered data thus far. The estimated
average coverage of the population of participating countries is 53% and ranges from 14% to
90%.

As far as future perspectives are concerned, the collection of routinely generated data could
speed up the process of bringing more pathogens under surveillance. Progress has been made
on software-tools to process and analyse resistance data. The next step will be to make this
data widely accessible through the Health Surveillance System for Communicable Diseases
within the European Public Health Information Network.

3

4

Decision 98/2119/EC, OJ L 268, 3 October 1998
http://www.earss.rivm.nl

7

• Enter-Net – International Surveillance Network for the Enteric Infections Salmonella

and VTEC 01575

Enter-net was established in 1994 for the surveillance of salmonella and verotoxin-producing
it has been an essential part of the
Escherichia coli (VTEC) infections. Since 2000,
Community network for epidemiological surveillance and control of communicable diseases.
A major objective is rapid recognition of outbreaks of disease. Enter-net has contributed
directly to the recognition of several international outbreaks and has enabled the subsequent
investigations to be accelerated due to the efficient communication and collaboration within
the network. It is also concerned with the surveillance of antibiotic resistance in enteric
pathogens.

• Euro-TB6

The general objective of the Euro-TB programme for the Surveillance of Tuberculosis in
Europe is to provide epidemiological information on tuberculosis (TB) to be used to improve
TB control. Drug resistance is a key component of tuberculosis surveillance. Prevalence,
particularly of multi-drug resistance (MDR), is important for public health as MDR-TB
represents a major epidemic risk, particularly to immuno-suppressed individuals such as HIV-
infected persons and those in institutions such as hospitals and care centers. Monitoring drug
resistance is an important means to facilitate targeted control measures to reduce occurrence.
The Euro-TB programme co-ordinated the elaboration of
recommendations on the
standardisation of antituberculosis drug resistance surveillance in Europe.

• Nosocomial infections

Nosocomial infections are infections occurring in a patient in a hospital which were neither
present nor incubating prior to admittance but were acquired during hospitalisation. They also
may occur in hospital personnel.

In 2000, a pilot project was started to develop a European Network on nosocomial infections.
The main goals include the creation of databases on surgical and intensive care unit
infections, the development of consensus for prevalence surveys, on validation of methods for
the setting-up of evidence-based standards and recommendations and creation of the
conditions for extended consensus surveys, training and fellowships.

1.1.2.

Veterinary medicine

• Monitoring and control of zoonoses7

Community legislation on measures against zoonoses8, at present under review, seeks to
establish a reliable reporting system on the incidence of zoonoses in animals and humans.
Currently the specific control measures provided by this Directive cover only the occurrence
of two invasive Salmonella serotypes in poultry breeding flocks, frequently the origin of
human salmonellosis from consumption of eggs. Two Community Reference Laboratories
have been established to co-ordinate and harmonise the work of national laboratories and to

5

6

7

8

http://www2.phls.co.uk
http://www.ceses.org/eurotb.htm
Any disease and/or infection, which is naturally transmissible directly or indirectly from animals to
humans
Council Directive 92/117/EEC, OJ L 62, 15 March 1993

8

collect data on zoonoses including some information of antimicrobial resistance in zoonotic
bacteria.

Member States have submitted yearly reports since 1995 on the occurrence of certain
zoonotic organisms. However, the collection of resistance data linked to this reporting is not
yet harmonised, and the methods used for testing resistance differ between Member States.

In addition to these horizontal provisions, requirements on the control of certain zoonoses
(e.g. tuberculosis, brucellosis) at farm level have been laid down in various directives
regarding animal health conditions. Specific measures on the control of zoonotic agents in
processing and distribution of foodstuffs of animal origin are contained in the corresponding
hygiene directives.

The Commission has clearly identified food safety as one of its top priorities. The White
Paper on Food Safety9 sets out the plans for a proactive new food policy following the “farm
to fork” principle by in particular modernising legislation to form a coherent and transparent
set of rules in order to produce safer food from healthier animals. This policy needs to take
account of the prevalence of zoonotic agents in the Member States and to give guarantees for
the improvement of the safety of consumers by introducing pathogen reduction programmes
to be implemented by the Member States.

In the framework of the review of the zoonoses legislation, the Commission is considering the
possibility to introduce a requirement to monitor antimicrobial resistance in certain zoonotic
in certain animal populations. A
micro-organisms,
proposal for new legislation to improve monitoring and reporting of systems for diseases
transmissible from animals to man is foreseen to be submitted in 2001.

like salmonella and campylobacter,

• Monitoring antimicrobial resistance

In addition to initiatives concerning zoonotic agents, monitoring antibiotic resistance in
bacteria of animal origin is a concerted action10 in the Community. This action aims to
harmonise the antibiotic resistance monitoring in Europe and to develop research projects
aiming at better understanding the mechanisms of emergence and spread of resistance within
a species, and from animal to man and environment.

The Commission introduced the requirement to monitor resistance in animal bacteria of feed
additive antibiotics and substances related to them in Commission Directive11 suspending the
use of avoparcin as a feedingstuff additive in January 1997. This obligation was reconfirmed
in the Council Regulation12 of December 1998 suspending the use of four other antibiotics
used as growth promoters in feedingstuffs as a condition to re-examine the issue.

The Commission has also supported an industry-led surveillance programme on resistance to
antibiotics used as feed additives in bacteria isolated from pigs and broilers in the
slaughterhouses in six European countries. A report will be provided in the near future.

9

10

11

12

http://europa.eu.int/comm/dgs/health_consumer/library/pub/pub06_en.pdf
FAIR5-CT97-3654
Directive 97/6/EC, OJ L 35, 5 February 1997
Regulation 2821/98, OJ L 351, 29 December 1998

9

However, it should be ensured that surveillance systems are established which provide the
the
collation of resistance data from all relevant bacteria in animals and foodstuffs at
Community level.

1.2.

Monitoring of antimicrobial consumption

1.2.1. Humans

Sound data on the consumption of antimicrobial agents is needed for the development of
intervention strategies. Such data already exist in many Member States but they are scattered,
heterogeneous, and in many instance not easily accessible. This data needs to be accessed,
collected and analysed to enable the development of a Community-wide surveillance system
on the use of antimicrobial agents and procedures for intervention measures. The attached
Commission proposal for a Council Recommendation on the prudent use of antimicrobial
agents in human medicine addresses this problem.

1.2.2.

Animals

• Veterinary medicines

Only a few Member States currently monitor the consumption of antimicrobial agents as
veterinary medicinal products. This kind of consumption data is nevertheless essential for the
assessment of the risk from the transfer to humans of resistant micro-organisms in animals.
Further action at Community level should be considered on this aspect.

• Feed additives

Following the Copenhagen Recommendations, a system has been established to collect data
on the supply and consumption of antimicrobial agents as additives in feeding stuffs, both as
veterinary medicinal products and growth promoters. On the basis of guidelines for the
collection of the relevant information agreed in the Standing Committee for Animal Nutrition,
the monitoring started in January 2000. The first results should be available by mid 2001.

1.2.3.

Plant Protection

The use of antibiotics in plant protection is monitored in all Member States, where such uses
are available. Total prohibition of antibiotics are effective in Sweden, Finland, Italy, Portugal,
Ireland, Luxembourg, Denmark, France, United Kingdom and Germany. The Standing
Committee for Plant Health already in 1999 has established a procedure to collect data from
those member States which still allow the use in emergency situations and keeps the survey
available.

1.3.

Safety evaluation of antimicrobial agents used in plant protection

Community legislation on plant protection products13 provides the legal basis also for the
evaluation of antibiotics used in plant protection. All data requirements and decision-making
criteria laid down in the Directive apply in principle also for antibiotics used. However, in
view of the prohibition of such uses in a majority of the Member States and the minor
amounts used and restrictions imposed in others, the Commission has set other priorities for
the ongoing review programme under the Directive. Antibiotics currently in use in the

13

Directive 91/414/EEC, OJ L 230, 19 August 1991

10

Community will be reviewed under the third stage of the review programme, which will begin
in 2002.

Fungicides are authorised in all Member States and the active substances are being reviewed
in the ongoing programmes under Directive 91/414/EEC.

2.

TOWARDS AN IMPROVED SYSTEM OF PREVENTION AND CONTROL

2.1.

Market authorisation and user information on antimicrobial agents

2.1.1. Human medicine

The European Agency for the Evaluation of Medicinal Products (EMEA) is involved in
activities which focus on requirement for market authorisation and on the quality and content
of the Summary of Product Characteristics (SPC) which, in particular, lays the basis for all
promotional activities of an antimicrobial agent.

The EMEA has published a discussion paper on antimicrobial resistance14 outlining its
activities and pointing out the need to find ways to promote new effective antibiotics so as not
to prematurely exhaust their potential clinical benefits.

Criteria for market authorisation of new antibacterial medicinal products are outlined in three
EU guideline documents that became operational in 1997 and 2000 (14-16)15. In particular,
information on acquired resistance for relevant bacteria/antibiotic combinations has to be
regularly updated by the marketing authorisation holders. A better rational for giving dose
recommendations for antibiotics has also been addressed in one guideline. It may be assumed
that better dose recommendations will contribute to optimal treatment of infections and a
reduction in unnecessary and inappropriate use of antibiotics.

Concerns have been expressed by regulators in different European authorities that different
indications, doses, dose regimens (duration of treatment) and different pharmacodynamic
information exist for the same and similar products already licensed in the EU. National
competent authorities in consultation with EMEA are currently considering the issue of
divergent product information.

2.1.2.

Veterinary medicine

The authorisation of veterinary medicinal products should ensure that recommended dosages
and treatment regimes are optimum to minimise the development of resistance. Moreover,
susceptibility patterns of populations of target bacteria may need to be monitored after the
authorisation.

The Committee for Veterinary Medicinal Products (CVMP) of the EMEA pointed out in its
Report on Antimicrobial Resistance and Qualitative Risk Assessment that the vast majority of
antibiotics used in veterinary medicine are related to, or identical to, human medicinal
products and can select for cross-resistance or co-resistance. It also identified a lack of data
and of harmonisation which prevent a coherent and scientific approach at European level.
Furthermore, a Risk Management Strategic Plan has been developed setting out proposals on

14

15

EMEA document 9880/99: http://www.eudra.org/humandocs/humans/general.htm
EMEA documents CPMP/EWP/558/95, CPMP/EWP/520/96, CPMP/EWP/2655/99

11

the containment of antimicrobial resistance and the following major areas of CVMP activity
are currently underway:

a)

b)

c)

d)

Critical evaluation of the data related to minimum inhibitory concentrations (MICs)
and of the current relevance of using MIC and kinetic data in the setting of dosage
levels.

Development of guidelines to satisfy the requirements for the resistance section in a
regulatory dossier for antimicrobial agents, with particular emphasis on a description
of the testing aimed at establishing the likelihood of resistance development to novel
antimicrobial agents, i.e pre-authorisation sensitivity testing guidelines.

Consolidation and standardisation of phrases and formats used in the Summary of
Product Characteristics to define clearly and consistently throughout the European
Union posology/treatment regimes, target organisms and diseases in accordance with
prudent use principles.

Development of definitive guidelines for antimicrobial prophylaxis, combination
therapies, in-feed and water mass medication, given that resistance is driven by the
volume of active use and the route of administration.

2.2.

Prudent use of antimicrobial agents

2.2.1. Human medicine: Commission proposal for a Council Recommendation

The Commission has developed a proposal for a Council Recommendation on the prudent use
of antimicrobial agents in humans, attached to this communication.

The main elements of this proposal are the following:

• Collection and analysis of data on antimicrobial resistant pathogens and on consumption

of antimicrobial agents to identify potential links for intervention measures;

• Enforcing the principle that antibacterial substances should be available by prescription
only, and evaluating whether this rule should be applied to all antimicrobial agents as a
precaution;

• Developing guidelines and principles on the prudent use of antimicrobial agents,

including systems for evaluation;

• Improving prevention of infections to reduce the needs for antimicrobial agents by
reinforcing immunisation programmes and developing infection control standards in
hospitals and the community;

• Raising awareness of the problem of antimicrobial resistance by information to the

general public;

• Enhancing knowledge on the problem by education programmes

for health

professionals;

• Encouraging research on the development of antimicrobial resistance and the development

of rapid diagnostics to enable efficient early treatment of communicable diseases;

12

• Nominating,

for

these purposes, a multi-disciplinary and cross-sectoral national

organisation to ensure mutual information and co-ordination of efforts.

2.2.2.

Veterinary medicine

An important element in ensuring the prudent use of antimicrobial agents in veterinary
medicine is the monitoring of residues in food. Community legislation16 requires monitoring
of certain substances (including antimicrobial agents) or residues in live animals and animal
products. Levels of sampling are governed by Council Directive 96/23/EC, and maximum
residue limits are fixed according to scientific advice, under Regulation (EEC) 2377/90.
Member States and Third Countries (for the products they export to the EU) provide the
Commission with yearly results of the monitoring according to their residue plans which have
to be approved by the Commission. Compliance with EC requirements is moreover regularly
checked on site by the Commission Food and Veterinary Office.

Currently, samples with positive findings on residues represent less than 1% of the total.
However, within these positives, antibiotics represent approximately 70%. Although current
legislation,
through Directives 81/851/EEC and 81/852/EEC, establishes harmonised
requirements for marketing authorisations in the European Union, and Regulation (EEC)
2377/90 ensures a harmonised procedure for the authorisation of analytical methods, the
significant number of substances on the market authorised over the years, identifies the need
that national competent authorities in connection with the EMEA further consider the issue of
divergent product information.

There have been several public and private actions taken in the Member States and at the
international and European level to produce guidelines on the prudent use of antimicrobial
agents as veterinary medicines. For example the Federation of Veterinarians of Europe (FVE)
has prepared a guide on prudent use of antibiotics in veterinary medicine and in addition to
that some Member States have their own national guidelines. Also the World Organisation for
Animal Health (OIE) and the Codex Alimentarius are currently working with issues related to
prudent use of antimicrobial agents in animals, the OIE having just published principles on
prudent use. In order to harmonise these actions at
it should be
considered whether comparable measures to those proposed in the Recommendation on the
prudent use in humans are necessary in the veterinary field. In particular, emphasis should be
given to the prevention of infectious diseases in animals, as it is an effective way to decrease
the quantities of antimicrobial agents used. In addition it is vital to encourage the Member
States to strengthen their controls on illegal distribution and use of antimicrobial agents in
agriculture thus diminishing the possibilities for imprudent use of the substances.

the Community level

2.3.

Additives

2.3.1.

In food

The use of food additives is harmonised in the European Union. Community legislation on
food additives17 lays down the principles for approving food additives and their uses in
foodstuffs. Two antimicrobial agents, Nisin (E 234) and Natamycin (E 235), are authorised
for preservation of certain foods. The Commission will review the safety and need for the use
of these substances.

16

17

Council Directive 96/23/EC, OJ L 125, 23 April 1996.
Council Directive 89/107/EEC, OJ L 40, 11 February 1989

13

2.3.2.

Phasing out and replacement of antimicrobial agents as growth promoters in animal
feed

The Commission has paid increasing attention to the need to restrict antibiotic use to serious
human and animal health problems. Indeed the number of antibiotics authorised as growth
promoters in animal nutrition has been constantly decreasing. Following the bans on
avoparcin in January 1997, ardacin in January 1998, and in December 1998 of a further four
antibiotics (bacitracin zinc, virginiamycin, tylosin phosphate and spiramycin), there are only
four substances still authorised as growth-promoting agents. These substances do not belong
to classes used in human and/or veterinary medicine. Following a review of further evidence,
the Scientific Steering Committee has recently concluded that the evidence justifying the
original ban of these substances remains valid.

However, as set out in the White Paper on Food Safety, the Commission will pursue the
prohibition or phasing-out of antibiotics used as growth promoters in the EU as part of its
broad strategy to control and contain antibiotic resistance.

In the meantime, it is necessary to carry out studies on the most critical sectors (in particular
for piglets and broiler production) to minimise possible economic losses or the increase in use
of antibiotics for treatment under veterinary prescription. The studies should estimate the gap
between the current situation and the husbandry standards which will be required following
the abolition of antimicrobial growth promoters.

The Commission supports the view that the phasing out would also be easier to pursue if other
classes of growth promoting additives were made available. In this respect nineteen micro-
organisms have been authorised so far and others are very near to being authorised. An
application to authorise an organic acid as a growth promoter is under examination and
Member States have received several other requests for authorisations for other types of
products which have a positive effect on animal production.

A proposal to phase out the four remaining antimicrobial feedingstuff additives by January
2006 is in preparation and is expected to be adopted by the Commission in the near future.

2.4.

Antimicrobial resistance as markers of Genetically Modified Organisms
(GMOs)

The SSC has recommended to remove antibiotic resistance marker genes from plant cells
before commercialisation whenever this is feasible. Whilst this is possible in the case of more
recent constructs, it would prove difficult or impossible for older products. In the latter case,
the clinical importance of the respective antibiotic and gene promoter, a regulatory DNA
sequence that functions to activate expression of genes, has to be taken into account before
authorisation.

Community legislation on the deliberate release of genetically modified organisms has been
revised recently and the new Directive 2001/18/EC came into force on 17 April 200118.
Member States shall implement this Directive into national legislation by 17 October 2002.
Directive 2001/18/EC provides that Member States and the Commission shall ensure that
GMOs which contain genes expressing resistance to antibiotics in use for medical or
veterinary treatment are taken into particular consideration when carrying out an
environmental risk assessment, with a view to identifying and phasing out antibiotic

18

OJ L 106, 17 April 2001

14

resistance markers in GMOs which may have adverse effects on human health and the
environment.

3.

PREPARING FOR THE FUTURE

Research targeted at antimicrobial resistance has long played a part in Community research.
In the Fourth Framework Programme for Research and Technological Development (1994-
1998)19 and in the current Fifth Framework Programme (1998-2002)20, several projects
contribute directly or indirectly to the different pillars of a medium to long-term approach to
antimicrobial resistance. Most of the relevant research topics are covered by the key action 2
“Control of Infectious Diseases” of the Quality of Life Programme, where ongoing research
projects address the following issues:

• Vaccines against

tuberculosis, malaria, HIV and other major diseases ultimately to

contribute to reduced morbidity and thereby the need for antimicrobial treatment.

• Development of new classes of antimicrobial agents against multi-drug resistant strains
of serious pathogens (e.g. Mycobacterium tuberculosis) and other new treatment strategies,
such as conjugation inhibitors or efflux pump inhibitors.

• Development of rapid and reliable diagnostic and susceptibility tests as an essential

prerequisite for the prudent prescription of antibiotics.

• Identification of new strategies to reduce the spread of infections in day-care centres.

• Improved understanding of the molecular mechanisms behind the development, spread and

reversibility of antibiotic drug resistance.

• Evaluation and harmonisation of strategies for prevention and control of antibiotic resistant

pathogens in European hospitals.

Other key actions in the Quality of Life Programme address issues which complement the
above outlined priorities. Key action 1 ‘Food, Nutrition and Health’ focuses on transfer
mechanisms of antibiotic resistance between animal, microbial and human reservoirs via food
ingestion; development and validation of rapid and/or cost-effective detection tests of
antibiotics; as well as pro- and pre-biotics combinations as alternatives to today’s antibiotics.
Key action 3 ‘The Cell Factory’ focuses on design and development of new antimicrobial
agents as well as near-patient diagnostic tests and key action 4 ‘Environment and Health’ on
environmental factors influencing transmission. Key action 5 ‘Sustainable agriculture,
fisheries and forestry, and integrated development of rural areas including mountain areas’
aims at new strategies for reducing antibiotic use in animal husbandry.

The Commission's Joint Research Center is involved in the development of analytical
methods and reference materials to be used for detection of antibiotic residues in various
foods and feeds.

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20

OJ L 126, 18 May 1994
OJ L 26, 1 February 1999

15

The Commission has presented its proposal for the next framework programme (2002-
2006)21, hightlighting the fight against resistance to drugs as a priority.

4.

INTERNATIONAL CO-OPERATION

Tremendous expansion in global trade and travel has increased the speed of spread of disease
and of antimicrobial resistance between countries and continents. Antimicrobial resistance
does not respect borders and concerns the entire world; it cannot be tackled successfully by a
single country or even by a group of countries. Concerted international action is therefore a
key element in the approach to this problem.

Intensive co-operation is already in place with many non-EU countries. In the context of the
future enlargement of the Union, a special emphasis has been placed on co-operation with the
candidate countries, who already take part in several health programmes and are included in
most of the European surveillance networks.

Developing countries cannot be left aside, and assistance is provided to them throughout all
the fields of the fight against antimicrobial resistance: surveillance networks, data gathering,
research and licensing procedures of new drugs and vaccines, disease prevention, education of
prescribers. Of note is the EC Development Policy22. Support is also provided to fight against
counterfeit drugs which, in addition to the economic losses they cause to the pharmaceutical
sector, have a great influence on the spread of antimicrobial resistance (inappropriate dosage
and duration of treatment, reduced efficiency).

This international co-operation requires the involvement of national governments and
agencies, non-governmental organisations, professional societies and international agencies. It
needs to generate a synergy and avoid conflicting messages. Data and information on
experience should be shared between all parties to maximise the success of all strategies.
There is also great progress to be made in the harmonisation of data gathering, in order to be
able to exploit them at the international level.

In that context, the Commission has put in place several important links:

– The World Health Organisation (WHO) and the European Commission recently
reconfirmed their common interests in health and health related fields with the signing of a
Memorandum of Understanding. Linking communicable disease and health monitoring
networks and the development of methodologies and standards
addressing
antimicrobial resistance threats are agreed priorities for future co-operation. The WHO has
participated in developing the attached proposal for a Council Recommendation on the
prudent use of antimicrobial agents in humans. The Commission contributes to WHO
activities on establishing a global strategy for the containment of antimicrobial resistance.

for

– The Codex Alimentarius is also concerned by antimicrobial resistance, in particular as
regards maximum residue limits in food. Steps are being taken for the European
Community to become a member as such of the Codex Alimentarius together with the
Member States and will promote and encourage a concerted and harmonised approach.

21

22

OJ …
COM(2000) 585 final and COM(2001) 96 final

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– The Office International des Epizooties (OIE - the international organisation for animal
health) has clearly established antimicrobial resistance as one of its priorities for coming
years and has conducted a world-wide consultation on its recommendations relating to
control of antibiotic resistance.

– An EU/US Task Force on communicable diseases was created in 1995 as part of the
Joint EU-US Action Plan to implement the New Transatlantic Agenda. Work related to
combating antimicrobial resistance is a EU/US Task Force priority, with a specific
working group on the subject.

– In June 2000 the Heads of Governments and States of the Member States of the European
Union adopted the Northern Dimension Action Plan and invited the European
Commission to take a leading role in its implementation. Within its objectives on public
health, the surveillance and control of communicable diseases are described as priorities,
including actions on antimicrobial resistance.

– The Baltic Sea States Task Force on Communicable Diseases Control in its last
meeting at
the end of 2000 in Copenhagen issued recommendations on antibiotic
resistance: prescription only drugs, collection and exchange of data, improvement of
diagnostic, surveillance networks and early warning systems, training of staff.

– The first Euro-Med Conference of Health Ministers in Montpellier on 3 December 1999
agreed that the European Community Network for the Epidemiological Surveillance and
Control of Communicable Diseases is an important element in strengthening co-operation
in public health.

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CONCLUSION

The following list details the priority actions in the four identified key areas of the
the specific
Community strategy against antimicrobial
Recommendation on the prudent use of antimicrobial agents.

resistance, which complement

Surveillance

Action 1:Develop co-ordinated and coherent surveillance networks at the European level.
Encourage the participation of non-EU countries and the links between already
established surveillance networks in human and veterinary medicines

Action 2:Put in place and improve the collection of data on consumption of antimicrobial

agents in all sectors.

Prevention

Action 3:Increase the importance of antimicrobial resistance information for the market
authorisation process in human medicine, veterinary medicine and agriculture.

Action 4:Support, at Community level, educational campaigns directed at professionals
(clinicians, veterinarians, farmers) and the general public to avoid overuse and
misuse of antimicrobial agents.

Action 5:Fully apply the principle that antibacterial substances are available in human and
veterinary medicine by prescription only and distributed in a controlled way in
agriculture, and evaluate whether the prescription-only rule should be applied to all
antimicrobial agents as a precaution.

Action 6:Reinforce and promote prevention programmes of

infections in human and

veterinary medicine, in particular immunisation programmes.

Action 7:Reinforce the residue monitoring system in food as regards methods of analysis,

sanctions and reporting system.

Action 8:Phase out and replace antimicrobial agents used as growth promoters in feed.

Action 9:Review the use of the two authorised antimicrobial agents in food.

Action 10: ensure that GMOs which contain genes expressing resistance to antibiotics in use
for medical or veterinary treatment are taken into particular consideration when
carrying out an environmental risk assessment, with a view to identifying and
phasing out antibiotic resistance markers in GMOs which may have adverse effects
on human health and the environment.

Research and product development

Action 11:Encourage the development of new antimicrobial agents.

Action 12:Encourage the development of alternative treatments and vaccines.

Action 13:Support the development of rapid and reliable diagnostic and susceptibility tests.

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International co-operation

Action 14:Encourage strongly the development of co-operation, co-ordination and partnership
at international level in particular via the existing international organisations.

Action 15:Pay special attention to candidate and developing countries by helping them putting

in place the appropriate structures.

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