Community strategy against antimicrobial resistance
The Community strategy to combat antimicrobial resistance consists of fifteen actions in four key areas: surveillance, prevention, research and product development, and international co-operation (Table 1). Here, the eleven points of action and the Council Recommendation are described that are directly related to human medicine. Community related activities are presented that received funding under the 1996-2002 Community action programme on public health (hereinafter referred to as PHP) and through the Fifth Framework Programme (hereinafter referred to as FP5) for Research and Technological Development (1998-2002)(9).

Surveillance
Action 1 concerns the development of networks dedicated to surveillance.
The Council Recommendation calls on Member States to establish or strengthen sustainable antimicrobial resistance and antimicrobial use surveillance systems. Table 2 provides an overview of antimicrobial resistance related projects funded under the PHP. The large European Antimicrobial Resistance Surveillance System (EARSS) is a network of national surveillance systems that currently comprises about 700 laboratories from 28 countries (10). The main function of EARSS is to monitor variations in resistance of indicator pathogens of major public health relevance and assist with targeting interventions and assessing effectiveness of national intervention programmes. Several other surveillance systems also monitor susceptibility of pathogens. For instance, the 'Enter-net' network performs surveillance of Salmonella and verotoxin-producing E. coli (VTEC) infections, including the susceptibility to antimicrobials, whilst 'EuroTB' performs surveillance of tuberculosis including (multi) drug resistant TB. Susceptibility of meningococci, gonococci and syphilis is also being monitored.

Action 2 calls for improvement in the collection of data on consumption of antimicrobial agents in all sectors. Such data exist in many Member States but they are scattered, heterogeneous, and in many instances not easily accessible. The Council Recommendation asks that Member States co-operate with the European Commission to develop indicators to monitor prescribing practices.
The Commission is funding, through the PHP, the European Surveillance of Antimicrobial Consumption in humans (ESAC) project that started in November 2001 with first results of the retrospective data collection presented at the 13th ECCMID conference in Glasgow (11). Through this network, some 30 countries deliver comprehensive national data on cost and volume of antimicrobial consumption in ambulatory and hospital care. Prospective and standardised data collection started in 2003 and indicators to evaluate the appropriateness of antimicrobial use are being developed.

Also starting in 2003, the Antimicrobial Resistance in the Mediterranean (ARMed) project, supported by FP5, aims to extend the implementation of the defined methodologies of EARSS and ESAC into the Mediterranean region, involving Malta, Cyprus, Turkey, Egypt, Tunisia, Morocco and Jordan.
To guide intervention, it is critical to understand the relation between antimicrobial resistance and use. A recent study using EARSS data showed that in the EU, antimicrobial resistance of S. pneumoniae to penicillin is correlated with use of beta-lactam antibiotics and macrolides at country level (12). To further study and monitor the link between antimicrobial resistance data and antimicrobial use, EARSS and ESAC are linking their respective datasets.

Prevention
Action 3 of the Community strategy aims to increase the importance of antimicrobial resistance information for the market authorisation process. Regulators have expressed concerns that different indications, doses, dose regimens (duration of treatment) and different pharmacodynamic information exist for similar products already licensed in the EU. National competent authorities in consultation with the European Agency for the Evaluation of Medicinal products (EMEA) are currently considering the issue of divergent product information and Member States are requested, again by the Council Recommendation, to initiate activities to evaluate and update and harmonise the summary of product characteristics (SPC) where necessary. The EMEA has published a discussion paper on antimicrobial resistance outlining its activities and points out the need to find ways to promote new effective antibiotics (13). Criteria for market authorisation of new antibacterial medicinal products are outlined in three EU guideline documents (14, 15, 16).

Action 4 sets out to support educational campaigns to avoid overuse and misuse of antimicrobial agents.
The Council Recommendation encourages Member States to promote education and training of health professionals on the problem of antimicrobial resistance. They should also promote training on hygiene and infection control standards and immunisation programmes in order to reduce the spread of microorganisms. The general public should be informed on the importance of prudent antimicrobial use through raised awareness of the problem of resistance, proper prescription, good patient adherence, the value of hygiene, and the impact of vaccination.
The Commission is taking this forward in part by funding (under the PHP) a television documentary on the battle against resistant bacteria to be used as an educational tool to promote appropriate antimicrobial use. Also, the FP5 supported European Resistance Intervention Study (EURIS), is evaluating different approaches to reduce the prevalence of resistant pneumococci among children in European day care centres. These approaches include education of doctors, day care staff, parents and children, optimised dosing, improved hygiene, notification of resistant strains and isolation of carriers.
Finally, the Antibiotic Resistance Prevention And Control (ARPAC) project, aims at identifying hospital policies and prescription patterns associated with lower resistance rates to evaluate and harmonise strategies for prevention and control.

Action 5 reinforces the principle that antibacterial substances should be available in human and veterinary medicine by prescription only. Antimicrobial agents for systemic use in human medicine are by law prescription-only medicines in all Member States, but enforcement of this regulation varies. The PHP funded project 'Self-medication with Antibiotics and Resistance levels in Europe' (SAR) aims to quantify the consumption of antibiotics sold over the counter (without prescription) and of leftover (prescribed) antibiotics hoarded at home.

Action 6 concerns prevention of infections, and in particular immunisation.
The pneumococcal disease in Europe (PNC-Euro) project, funded by FP5, focuses on the epidemiology of S. pneumoniae in a variety of European countries prior to the introduction of new conjugate vaccines and aims to design cost effective prevention strategies against pneumococcal infection.
Containment of antimicrobial resistance is intrinsically linked to infection control practices. Hospitals in Europe Link for Infection Control and Surveillance (HELICS) is a Commission funded project (PHP) to monitor hospital acquired infections, to develop protocols for databases on surgical and intensive care unit infections, and to set up evidence based infection control standards and recommendations.
The Council Recommendation appealed to the Member States to exercise good practice in marketing antimicrobial agents. Member States should implement preventive measures, ensuring proper implementation of hygiene and infection control standards and encourage national immunisation programmes.
Actions 7 to 10 refer to preventive action in the fields of animal growth promoters, food, and environment and, although indirectly very relevant to public health, do not fall within the scope of this paper.

Research and product development
Actions related to antimicrobial resistance were initiated already under the Fourth Framework Programme for Research and Technological Development (1994 to1998), but efforts have been greatly reinforced during FP5. Currently about 80 projects related to antimicrobial resistance are funded at a total contribution of over € 100 million. This project portfolio addresses anti-bacterial, anti-fungal, anti-viral and anti-protozoan resistance through various approaches, covering research into basic mechanisms of emergence and transmission of resistance, development of new drugs and diagnostic tests and epidemiological and public health research (a comprehensive overview of all these projects is available at: http://www.cordis.lu/lifescihealth/major/drugs.htm)

Action 11 of the Community strategy promotes the development of new antimicrobial agents. About one third of the antimicrobial resistance project portfolio of FP5 is devoted to the discovery of new anti-infectives, either through identification of novel molecular targets for the development of new classes of antimicrobials or through exploitation of antibiotic producing organisms.

Action 12 of the Community strategy encourages the development of alternative treatments and vaccines. Current FP5 research includes the development of resistance inhibitors, such as inhibitors of bacterial conjugation and bacterial adhesion. Lactic acid bacteria, already widely used as probiotics for human consumption, are now subject to a rigorous biosafety evaluation study. Vaccine development is a major priority in FP5 and several research projects are currently on going with special emphasis on tuberculosis, malaria, HIV/AIDS, and hepatitis C virus. Also influenza, respiratory syncytial virus, shigellosis and Neisseria meningitidis serogroup B are being addressed and efforts devoted to the development of novel vaccine delivery systems and formula. In addition, a unique effort has been launched in Europe to provide an infrastructure for clinical trials of vaccines. This European and Developing Countries Clinical Trials Partnership (EDCTP) has been set up by a joint collaborative initiative among Member States and developing countries with the Commission as supporting partner. The main goal is to support phase II and III clinical trials of promising new clinical interventions against HIV/AIDS, malaria and tuberculosis in, with and for developing countries.

Action 13 supports the development of rapid and reliable diagnostic and susceptibility tests. Currently funded FP5 projects include the development of sensors for multi-drug resistant strains of tuberculosis, a DNA chip based diagnostic test for P. aeruginosa, nucleic acid based amplification methods for the detection of respiratory pathogens in community acquired pneumonia and a network for automated bacterial strain fingerprinting.

International cooperation
Action 14 encourages the development of partnership at international level, in particular via existing international organisations. The Commission and the World Health Organisation (WHO) have signed a Memorandum of Understanding reconfirming their common interest in health. Antimicrobial resistance is among the agreed priorities and close cooperation with WHO has been ensured for all antimicrobial resistance related networks. The Commission is developing a programme with WHO on strengthening pharmaceutical policies, including the rational use of drugs and particularly supporting national programmes to contain antimicrobial resistance through the expansion of projects that link surveillance data to rational prescribing programmes.

Action 15 attributes special attention to applicant and developing countries. The participation of non-EU Member States is foreseen and most candidate countries already participate in antimicrobial resistance surveillance networks. The FP5 research portfolio on antimicrobial resistance includes seven projects that are specifically focused on international issues, covering broad geographical areas.

Discussion
As has been presented here for human medicine, there is a wide range of activities being undertaken at Community level and in Member States. Community funded projects were initiated and through a legal provision (7), recommendations for action were made. Whilst in other areas some Community acts already existed (17, 18), for public health it was necessary to add a separate legal provision in the form of a Council Recommendation.

Effective implementation requires several key features, including a clear action plan, delegation of authority and power to act, resources and sound mechanisms to assess the effectiveness of interventions and thus allow feedback of results to influence future strategies. One of the key conclusions of the Council Recommendation is that Member States should put in place an 'intersectoral mechanism' for implementing relevant measures and for effective coordination with other Member States and the Commission. No specific recommendations are made as to the nature of this mechanism, but one might assume that in this body local, regional and national health authorities, the legislator, professionals of the different disciplines concerned and consumers would be represented. This national mechanism should coordinate reporting structures at local and hospital level, prioritise the action needed, and charge the health authorities responsible with taking action. The Commission has created a working group of representatives of the different national intersectoral mechanisms to assist in evaluating the implementation of the Council Recommendation. Member States are to report to the Commission on the implementation of the Council Recommendation within two years of its adoption. The Commission intends to follow up on these reports to assess whether the outlined Community strategy is successful or may need re-adjustments.

Disease surveillance networks currently face problems with comparing susceptibility data because of differences in methodology and interpretation. The Council recommends that the Member States build upon existing national and international systems for collecting data and using, wherever possible, internationally recognised classification systems and comparable methods. It also asks the Commission to propose where appropriate, common methodology, case definitions, and type of data to be collected and consequently to support initiatives to standardise susceptibility testing in Europe so that comparable results and interpretations are produced.

In 2002, a new programme of Community action in the field of public health (2003-2008) was adopted (19). This programme provides an annual public health work plan and a funding mechanism for projects addressing priorities such as antimicrobial resistance.
Over recent years emphasis has been given to surveillance initiatives, whereas the focus of future public health work plans may need to be broadened. Activities that develop principles and guidelines for good practice on the prudent use of antimicrobial agents are needed as well as educational activities and intervention programmes to combat antimicrobial resistance.

The Sixth Framework Programme (FP6) for Research and Technological Development (2002-2006) is supported by a set of new instruments designed to ensure more effective research in Europe (20). These instruments are 'Networks of Excellence' which aim to structure, integrate and coordinate research resources and activities around a given topic and 'Integrated Projects', which bring together expertise to address ambitious research objectives. Research on antimicrobial resistance is one of the priority areas also in FP6. The new instruments are a tool to channel microbial and human genomic research towards applications such as new molecular drug targets, alternative therapeutic and preventive strategies, new diagnostic and susceptibility tests, epidemiological approaches and improved knowledge of molecular mechanisms behind resistance. Furthermore, measures to provide scientific support to antimicrobial resistance in the context of public health (like intervention strategies and tools for behavioural changes) are high on the FP6 agenda under policy oriented research (21, 22).

In conclusion, in past years the problem of antimicrobial resistance was addressed through an increasing number of individual measures. Through the Community strategy, the Commission has outlined a more comprehensive and pro-active approach to contain antimicrobial resistance, working closely in partnership at international level, in particular with the WHO. In addition to legislative measures the Commission considers antimicrobial resistance as a key priority for its public health and research programmes.