Proposal for a Council Recommendation on the prudent use of antimicrobial agents in human medicine
Date: 2001-06-20
Institutions: European Commission
Subjects: disease prevention, epidemiology, health control, infectious disease, information network, international cooperation, microorganism, public health, scientific research

COMMISSION OF THE EUROPEAN COMMUNITIES

Brussels, 20.06.2001
COM(2001) 333 final

VOLUME II

Proposal for a

COUNCIL RECOMMENDATION

on the prudent use of antimicrobial agents in human medicine

(presented by the Commission)

EXPLANATORY MEMORANDUM

The use of antimicrobial agents has greatly contributed to improvements in health. Such
“antimicrobial agents” (which for
this Recommendation encompass
the purposes of
substances produced either synthetically or naturally by bacteria, fungae or plants, used to kill
the growth of micro-organisms,
or inhibit
including bacteria, viruses and fungae, and
parasites,
in particular protozoa, exhibiting the phenomenon of resistance) have been
introduced for decades to treat communicable diseases and prevent infections. However, in
addition to their benefits, their use has also resulted in certain selected micro-organisms
previously sensitive to these agents to develop resistance so-called “antimicrobial resistance”.
Antimicrobial resistance leads to prolonged suffering of the individual and enhanced costs for
health care and society. It has developed into a wide spread public health problem,
particularly for antibacterial agents (the term antibiotic is used in a generic way in common
parlance to cover substances that kill or inhibit micro-organisms but is not specific enough for
the purposes of this Recommendation).

The purpose of this proposal is to recommend a number of specific measures aimed at
containing the spread of antimicrobial resistance by prudent use of antimicrobial agents in
humans within the Community. Of major concern is the overuse and inappropriate use of
antibiotics, especially in children with respiratory infections. Studies in Iceland, Finland and
Sweden have shown the impact of intervention measures which reduced consumption of
certain antibiotics, and consequently reduced the rate at which pathogens acquire resistance.

In 1998 a European Union Conference on “The Microbial Threat” resulted in “The
Copenhagen Recommendations”1, calling for action to preserve the effectiveness of
antimicrobial agents by restricting their use to treatment and prevention of infectious diseases.
Similar conclusions were drawn by the EC Economic and Social Committee2, the WHO 51st
World Health Assembly3, and further supported by national evaluations of the situation such
as the report of the Standing Medical Advisory Committee (SMAC) report in the United
Kingdom4.

The Committees for Proprietary Medicinal Products (CPMP5) and Veterinary Products
(CVMP6) of the European Agency for the Evaluation of Medicinal Products (EMEA)
identified areas where regulatory actions are relevant for antimicrobial resistance.

On 24 September 1998 the European Parliament and Council adopted Decision 2119/98/EC
setting up a Community Network for the Epidemiological Surveillance and Control of
Communicable Diseases7. Antimicrobial treatment is one of the major tools employed in the
control of communicable diseases. On the basis of that Decision the Commission in its
Decision 2000/96/EC of 22 December 1999 on the communicable diseases to be

1

2

3

4

5

6

7

Report from the Invitational European Union Conference on “The Microbial Threat” hosted by the
Danish Government in Copenhagen, Denmark, 9-10 September 1998
Economic and Social Committee opinion on the “Resistance to antibiotics as a threat to public health”,
OJ C 407, 28.12.1998, p. 7
World Health Organisation: Emerging and other Communicable Diseases: Antimicrobial Resistance,
May 1998
“The Path of Least Resistance”, Standing Medical Advisory Committee Sub-group on Antimicrobial
Resistance, Department of Health, United Kingdom, 1998
see table
see table
OJ L 268, 3.10.1998, p. 1

2

progressively covered by the Community Network under Decision 2119/98/EC8 listed
antimicrobial resistance as a priority health issue to be addressed by this Community
Network.

Since then the Commission has developed a comprehensive strategy to tackle antimicrobial
resistance in areas such as human and veterinary medicine, animal production and plant
protection. This initiative fulfils requests made by the Scientific Steering Committee of the
Commission in its opinion of May 1999, the Council in its Resolution of June19999 and the
Council Conclusions of December 199910. This strategy is outlined in the recent Commission
Communication11.

As a follow up to the Council Resolution of June 1999 and the Council Conclusions of
this Recommendation proposes a number of specific measures to be
December 1999,
implemented by the Member States to contain the spread of antimicrobial resistance by
prudent use of antimicrobial agents in human medicine:

• Collection and analysis of data on antimicrobial resistant micro-organisms and on
consumption of antimicrobial agents available to prescribers, pharmacies,
industry, health insurance providers etc. to detect potential links for intervention
measures;

• Enforcing the principle that antibacterial agents

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 principles for evaluation of applications for marketing authorisation;

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

• Enhancing knowledge on the problem by specialised education programmes for

health professionals;

• Raising awareness of the problem of antimicrobial resistance by informing the

general public;

• Encouraging research on the development of antimicrobial resistance and the
to enable efficient early treatment of

rapid diagnostics

development of
communicable diseases;

• Identify or establish, for these purposes, national organisations with effective co-
ordination between the Member States and the Commission to achieve
Community results.

8

9

10

11

OJ L 28, 3.2.2000, p. 50
Council Resolution on Antibiotic Resistance “A Strategy Against the Microbial Threat” (OJ C 195,
13.7.1999, p.1)
Council Conclusions on Future Actions in the Framework of the Strategy against Antimicrobial
Resistance, DG B II 13920/99
Commission Communication …

3

The Commission will establish an advisory group through the Community network on the
epidemiological surveillance and control of communicable diseases (Dec. 2119/98/EC) to
support Member States’ efforts and ensure a co-ordinated Community approach in addressing
this action plan. The Commission will also ensure close co-operation with EEA/EFTA
countries, applicant countries and international organisations such as WHO to increase
synergy and avoid duplication of effort in the fight for a prudent use of antimicrobial agents.

The enclosed table lists epidemiological surveillance networks concerned with antimicrobial
resistance and their recommendations on the containment of antimicrobial resistance in
Member States, the Commission, the European Agency for the Evaluation of Medicinal
Products (EMEA), the U.S. and the WHO.

4

Epidemiological surveillance networks on antimicrobial resistance and reports with
recommendations to contain antimicrobial resistance

Table

Denmark

Finland

France

Ireland

The
Netherlands

Sweden

UK

agents

antimicrobial

(DANMAP): Consumption of

Danish Integrated Antimicrobial Resistance Monitoring and Research
and
Programme
occurrence of antimicrobial resistance in bacteria from food animals, food
and humans in Denmark, July 1999. http://www.svs.dk
A national committee was nominated consisting of members from the
Ministry of Health and Ministry of Agriculture to enhance development of
national policy. In the human health care, the Finnish Study Group for
Antimicrobial Resistance (FiRe) network collects on antibiotic resistance in
annually.
report
Finland.
www.mmm.fi/publications/
Proposals for a national action plan to control antibiotics resistance in France
("Propositions pour un plan national d'actions pour
la maîtrise de la
résistance aux antibiotiques”: InVS, Janvier 1999, Engl. Version July 1999)
A draft strategy document has been drawn up and the Ministry of Health will
consider the final report during 2000. http://www.ndsc.ie/ A Strategy for
control of Antimicrobial Resistance in Ireland (SARI)

published

FINRES

The

is

Party

Dutch Working
(WIP):
In 1981 the WIP was found to stimulate infection prevention in the
Netherlands. Professionals from four Dutch societies are participating in this
working party:

Prevention

Infection

on

The Infectious Diseases Society of the Netherlands and Flanders
The Dutch Society of Medical Microbiology
The Dutch Society of Microbiology
The Society for Hygiene and Infection Prevention in Health Care

The aim is to develop and publish up-to-date, scientifically based guidelines
for infection prevention in hospitals, nursing homes,
institutions for the
mentally handicapped, dental care and home care.
An expert group on the national
level was formed : Swedish Strategic
Program for the Rational Use of Antimicrobial Agents and Surveillance of
Resistance (STRAMA). 1994. http://www.strama.org/eng.html
A ”National plan against antibiotic resistance” has been proposed for the
government by the National Board of Health and Welfare in collaboration
with 17 government boards, institutions and other interested parties. 2000.
http://www.sos.se (In Swedish)
UK Department of Health. Standing Medical Advisory Committee, Sub-
Group on Antimicrobial Resistance. Main Report: The path of
least
resistance, London, UK. Dept. of Health September 1998.
http://www.doh.gov.uk/smacsyn.htm
Resistance
UK
http://www.doh.gov.uk/arbstrat.htm

Antimicrobial

Strategy

Action

Plan:

and

5

EMEA

1. Discussion Paper on Antimicrobial Resistance (EMEA 9880/99.Rev 1).

http://www.eudra.org/humandocs/humans/general.htm

2. EMEA/CVMP/818/99 A Risk Management Strategic Plan for controlling

Antimicrobial Resistance through the Authorisation of Veterinary
Medicines: Recommendations consequent to the Report and Qualitative
Risk Assessment of the CVMP of July 1999

European
Commission

Scientific Steering Committee: Opinion of the Scientific Steering Committee
on Antimicrobial Resistance. http://europa.eu.int/comm/dg24/index.html
Network for the epidemiological surveillance and control of communicable
diseases in the Community (Council Decision 2119/98/EC). One of the
resistance
priorities to be covered by that network is antimicrobial
(Commission Decision 2000/96/EC). Technical backbone is the Health
Surveillance System on Communicable Diseases within the European Public
Health Information Network (HSSCD-EUPHIN), comprising two areas of
information: A restricted one for exchange of information between public
health authorities and specific surveillance structures, and a website on
information for the general public: http://hsscd.euphin.org It links to home
pages of the following specific networks supported by the European
Commission and dealing with antimicrobial resistance:
1. European Antimicrobial Resistance Surveillance System (EARSS), a
laboratory based network of national surveillance systems which aims to
aggregate comparable and reliable data on resistant pathogens for public
health purposes, having started on staphylococcus
and
streptococcus pneumoniae in 1998. http://www.earss.rivm.nl

aureus

2. Enter-Net, established in 1994 for the surveillance of salmonella and
verotoxin-producing E.coli (VTEC) infections, is also concerned with
the
pathogens:
surveillance
http://www2.phls.co.uk

resistance

antibiotic

enteric

of

in

3. EuroTB, a specific network for the Surveillance of Tuberculosis in
Europe to provide epidemiological information on tuberculosis (TB) for
improving TB control, has included surveillance on drug resistance a key
component of tuberculosis surveillance since 1999:
http://www.ceses.org/eurotb.htm

Draft public health action plan to combat antimicrobial resistance, part I:
Domestic issues. http://www.cdc.gov/drugresistance/actionplan/
Containing Antimicrobial Resistance: Review of the Literature and Report of
a WHO Workshop on the Development of a Global Strategy for the
Containment of Antimicrobial Resistance. Geneva, Switzerland, 4-5
February 1999. http://www.who.int/emc-documents

USA

WHO

6

Proposal for a

COUNCIL RECOMMENDATION

on the prudent use of antimicrobial agents in human medicine

(Text with EEA relevance)

THE COUNCIL OF THE EUROPEAN UNION,

Having regard to the Treaty establishing the European Community, and in particular Article
152(4) thereof,

Having regard to the proposal from the Commission12,

Having regard to the opinion of the European Parliament13,

Whereas:

(1)

(2)

(3)

12

13

14

15

infections. For

the purposes of

The use of antimicrobial agents has greatly contributed to improvements in health.
Such “antimicrobial agents” have been introduced for decades to treat communicable
diseases and prevent
this Recommendation,
antimicrobial agent means 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 of parasites,
in particular protozoa,
exhibiting the phenomenon of resistance. However, their use has also resulted in
certain selected microbes previously sensitive to these agents developing resistance,
so-called “antimicrobial resistance”. This leads to increased danger, to prolonged
suffering of the individual, and to enhanced costs for health care and society.
Therefore concerted action is necessary at Community level to contain this problem
by encouraging the prudent use of antimicrobial agents in human medicine and better
hygiene and infection control;

The Council of the European Union on 8 June 1999 adopted a Resolution on
the microbial threat"14. The Resolution
antibiotic resistance "A strategy against
highlights that antimicrobial resistance increases morbidity and mortality due to
communicable diseases leading not only to a diminution of quality of life but also to
additional health and medical care costs, and that actions need to be taken at
Community level;

The own-initiative opinion of
the Economic and Social Committee on the
“Resistance to antibiotics as a threat to public health”15 identified possible initiatives
and actions that should be taken at Member States’ and Community level to address
the problem of antimicrobial resistance;

OJ …
OJ …
OJ C 195, 13.7.1999, p. 1
OJ C 407, 28.12.98, p. 7

7

(4)

(5)

(6)

(7)

(8)

(9)

(10)

(11)

(12)

(13)

There is an association between growing consumption of antimicrobial agents and an
increase in the prevalence of micro-organisms resistant to those agents, which can
not be overcome by the lengthy process of continuously developing new
antimicrobial compounds;

To develop strategies for prevention of infections and containment of resistant
pathogens, accurate surveillance systems generating valid, reliable and comparable
data on incidence, prevalence and modes of spread must be established throughout
the Community;

Surveillance on prescription and consumption of antimicrobial agents should form an
essential component for an overall surveillance strategy to address the problem of
antimicrobial resistance;

An important step to avoid or even reverse further increases in resistant micro-
organisms would be to reduce unnecessary and inappropriate use of antimicrobial
agents. General principles and methods for the prudent use of these agents in humans
must be identified, and defined and implemented;

Improved strategies for hygiene and infection control in hospitals and the community
will help to avoid the spread of resistant micro-organisms and will be an important
step to reduce the quantities of antimicrobial agents used;

To bring about the necessary changes in prescribers’ and patients’ behaviour, health
professionals and the general public need to be informed on the problem of
antimicrobial resistance and associated factors by

• Improved product information (Summary of Product Characteristics (SPC) and

Patient Information Leaflet (PIL),

• Awareness-raising by adequate information and training during professional

education and in-post training,

• Information campaigns to the general public and specifically to the patient;

Support of research will be essential for tackling the problem of modes of spread of
antimicrobial resistance;

There is also a relationship between the occurrence of antimicrobial resistant
pathogens in humans and their occurrence in animals and the environment. This
Recommendation does not preclude further initiatives in other areas;

Measures taken by the Member States in this area, and the way they have taken into
account
this Recommendation, should be the object of reports at national and
Community level;

In accordance with the principle of subsidiarity, any new measure taken in an area
which does not fall within the exclusive competence of the Community, such as
protection of the public against
to
antimicrobial agents, may be taken up by the Community only if, by reason of the
scale or effects of the proposed action,
the objectives proposed can be better
achieved by the Community than by Member States; antimicrobial resistance, as with

the increase of infectious agents resistant

8

communicable diseases cannot be confined to a geographical region or Member State
therefore any necessary action requires concerted action at Community level.

HEREBY RECOMMENDS THAT MEMBER STATES:

I.

set up specific strategies targeted towards the prudent use of anti-microbial agents in
the aim of containing the increase of pathogens resistant to these agents. These
strategies should be based on the best available scientific data and advice, and should
comprise measures in relation to surveillance, education, information, prevention and
control, and research. To implement these strategies Member States should establish
or designate, according to national use and practice, a multi-disciplinary and cross-
sectoral national organisation representing health authorities
levels,
surveillance and research institutions, relevant professionals and consumers. This
organisation will be responsible for developing information exchange and co-
operation between organisations representing veterinary medicine, animal production
and plant protection. Its nature and composition should be communicated to the
Commission and the other Member States within the framework of Decision
2119/98/EC within six months of the adoption of this Recommendation.

all

at

This national organisation should:

1.

Establish or strengthen surveillance systems on antimicrobial resistance and the
consumption of antimicrobial agents in order to

(1)

(2)

gather reliable, comparable data by means of a laboratory based system
of the susceptibility of pathogens to antimicrobial agents. The data
should be amenable to time trend analysis and early warnings and to
monitor spread of resistance at national, regional and community level;

collect data on prescription and consumption of antimicrobial agents on
national, regional, hospital and community level, involving prescribers,
pharmacists and other parties collecting such data, in order to be able to
potentially link prescription and consumption of antimicrobial agents to
the development of pathogens resistant to those agents.

These surveillance systems should be maintainable with clear regulation of data
access and ownership. They should comply with the data protection regulations and
guarantee the confidentiality and security of data. These systems should build upon
existing national and international surveillance systems, using, wherever possible,
internationally recognised classification systems and comparable methods

2.

Enforce control and preventative measures on the prudent use of antimicrobial
agents by

(1)

developing evidence-based principles and guidelines on good practice for
the management of communicable diseases, to maintain the effectiveness
of antimicrobial agents. These practices should include
(cid:1)

Restriction of antibacterial agents to prescription-only use, and
promoting and monitoring of optimal prescription practices;

9

(cid:1)

(cid:1)

(cid:1)

Setting rules for the use of other antimicrobial agents that are not
subject to requirements for prescription-only use and an assessment
of the need for changes;

Establishment of clinical and microbiological criteria for rapid on-
the-spot diagnosis of infections, and

Optimising choice of drug, dosage and duration for the treatment
and prevention of infections.

(2)

Implementing hygiene and infection control standards in Institutions
(hospitals, child care facilities, nursing homes etc.) and in the
prevention of
community,
communicable diseases and the need for antimicrobial agents;

assessing

in the

impact

their

and

(3) Encouraging national

immunisation programmes

to progressively

eliminate vaccine preventable diseases,

3.

Promote education and training of health professionals on the problem of
antimicrobial resistance by

(1)

(2)

(3)

teaching principles and guidelines on the appropriate use of antimicrobial
agents by incorporation into undergraduate and postgraduate training and
and in regular continuous training for physicians, dentists, pharmacists
and nurses and others in the medical profession, using effective good
practice methods with continuous feedback;

stressing training on hygiene and infection control
eventually reduce the need for antimicrobial agents;

standards

to

training on immunisation programmes and their role in preventing
infections, thereby reducing outbreaks of diseases and thus the demand
for antimicrobial agents.

4.

Inform the general public of the importance of prudent use of antimicrobial
agents by

(1)

(2)

raising awareness of
resistance and
encouraging realistic public expectations for prescribing of antimicrobial
agents;

the problem of antimicrobial

launching national, regional and local campaigns on the importance of
interventions to reduce the unnecessary use of antimicrobial agents, and
the principles and guidelines on good practice to motivate patients'
adherence;

(3)

highlighting the impact of basic hygiene and vaccination programmes on
reducing the need for antimicrobial agents.

5.

Inform and communicate with other Member States and the Commission,
surveillance and control of
through the Network on epidemiological
communicable diseases, on national
research initiatives relating to the
containment of antimicrobial resistance, with emphasis on

10

-

-

-

-

-

the mechanisms of emergence and spread of antimicrobial resistance
among humans and from animals to man;

the quality of diagnostic tools and the development of rapid and reliable
diagnostic and susceptibility testing;

developing new modalities for prevention and treatment of infections;

developing alternatives to antimicrobial agents to contain the spread of
infections, and

developing new surveillance methods to contain antimicrobial resistance;

6.

within one year of the adoption of this Recommendation, provide a strategy
plan for the development and implementation of these actions. The plan should
be progressively put in place over a period of time not exceeding four years
from the adoption of this Recommendation;

co-operate with the Commission in the development of indicators for monitoring
prescribing practices of antimicrobial agents on the basis of the evidence-based
principles and guidelines on good practice for the management of communicable
diseases within two years of the adoption of this Recommendation, and evaluate
these indicators once developed with regard to potential improvements of prescribing
practices and feedback to prescribers;

establish and implement control systems on good practice of marketing of
antimicrobial agents to ensure compliance with the evidence-based principles and
guidelines on good practice for the management of communicable diseases within
two years of the adoption of this Recommendation;

initiate with other Member States and the Commission activities aimed at
harmonising and updating the product information (SPC) for antibacterial medicinal
products particularly related to indications, dose and dose regimen and prevalence of
acquired resistance;

inform the Commission within one year of the adoption of this Recommendation,
and annually subsequently, of how the provisions of this Recommendation have been
implemented.

II.

III.

IV.

V.

HEREBY INVITES THE COMMISSION:

1.

2.

to facilitate mutual information, consultation, co-operation, and action through the
the
procedures and mechanisms available
epidemiological surveillance and control of communicable diseases
(Decision
2119/98/EC) in the field covered by this Recommendation;

in the Community Network for

to establish texts on principles and guidelines of best practice on the prudent use of
antimicrobial agents in human medicine having regard to national policies and
activities of the European Agency for the Evaluation of Medicinal Products (EMEA)
focussing on requirements for market authorisation and on the quality and content of
the Summary of Product Characteristics (SPC), which lays the basis for all
promotional activities of an antimicrobial agent;

11

3.

4.

5.

6.

to propose, where appropriate, common methodology, case definitions and nature and
type of data to be collected for the surveillance on pathogens resistant to antimicrobial
agents and the use of these agents;

to develop under the auspices of the above mentioned Community Network an
information system linking prescribers, pharmacists, other interested parties and the
public to the respective surveillance systems on pathogens resistant to antimicrobial
agents and the volumes of those agents used at national, regional, hospital and
community level for timely feed back regarding the development of antimicrobial
resistance;

to keep matters covered by this Recommendation under review, with a view to its
revision and updating, and submit an annual report to the Council on the basis of
Member States’ annual reports;

to strengthen participation of applicant countries within the framework of the Network
on epidemiological surveillance and control of communicable diseases in the
Community, to ensure that the problems of antimicrobial resistance are properly taken
into account by these States.

Done at Brussels,

For the Council
The President

12