European Surveillance of Antibiotic Resistance (ESAR)

A Study of the European Society of Biomodulation and Chemotherapy

Aims of the study

Surveillance of antimicrobial resistance is essential for good healthcare resource utilisation. It helps to ensure the best use of antimicrobials and infection control practices, optimum clinical outcomes and help in new anti-infective strategies. A study is proposed to set up a European wide programme of surveillance on incidence and mechanisms of resistance using sentinel laboratories and standardised methodology. Organisms to be studied are included in the lists of Alert and Target organisms. The benefits of a successful surveillance system are improved nation-wide co-operation, better prescribing and reduced levels of resistance. The main objectives are:

  1. To establish a representative network of sentinel diagnostic laboratories across Europe which will enable antibiotic resistance monitoring according to standardised methods.
  2. To identify new resistance mechanisms at an early stage and prevent their dissemination.
  3. Early detection and prevention of outbreaks.

The proposed scheme is comprehensive and will enable baseline data to be established for relevant clinical pathogens. Anticipated events such as vancomycin resistance in Staphylococcus aureus or penicillin resistance in Corynebacterium diptheriae and Streptococcus pyogenes can be spotted early. New but established crisis such as vancomycin resistant Enterococci and multi-resistant Mycobacterium tuberculosis can be monitored.

Less dramatic, but no less important, problems such as 4-fluoroquinolone resistance in Enterobacteriaceae and methicillin resistant S. aureus (MRSA) can be quantified and overall trends of organism susceptibilities to a wide range of clinically important antimicrobials can be established.

As well as collecting data in a standard way the project will allow identification and estimation of problems and their solutions. Timely feedback of results and analysis to clinicians, microbiologists and epidemiologists will allow influence on future resistance problems by advising on and evaluating programmes of antibiotic use and infection control. This is crucial to the success of the project. Thus a system of data collection, analysis, hypotheses, investigation and feedback will be in place to test new ways of reducing the rapidly escalating and viscous circle of antibiotic prescribing/antibiotic resistance.

Significance of proposed research co-operation

This will be the first co-ordinated approach to antimicrobial resistance surveillance between the EC and former Eastern Block countries. The proposed methodology and quality control will ensure good quality data and by generating this locally it will form the basis for individual national surveillance projects which ultimately will be able to contribute to this European initiative. The proposed methodology while being simple enough to be set up de-novo in the proposed laboratories, remains robust and sensitive and is well placed to detect subtle, yet ultimately important, shifts in resistance and sensitivity over the years as well as the rapid emergence of epidemic resistant organisms. While detection of the latter is important and can be used to take outbreak control precautions, the former is also crucially important in the development of resistance in many organisms. If we are aware of these changes we can take appropriate action such as changing antibiotic use to delay or reverse these trends. Therefore, it is crucial to develop proper surveillance in order to control development and spread of this resistance.

The use of the Internet and the facilities of ESBiC will ensure good analysis and dissemination of results ensuring the best chance that the results will be used to curtail the development and spread of resistance.

Many laboratories in central/eastern Europe are able to use the latest molecular techniques for determining methods of resistance for the first time. Consequently, new mechanisms may be discovered which will help in our understanding of the overall resistance problem and might be useful in the design of new antimicrobials.

Finally, while the link between antibiotic use and resistance is well established, many details remain to be established, particularly about prevention and reversal once it has occurred. The data collected within this project will be a good basis for the generation of hypothesis on the cause/effect relationship of antibiotic use/resistance and the testing of these hypothesis.

Scientific and technical description

All the partners, including the two co-ordinators will be responsible for generating and communicating their own local data. The antibiotic disc sensitivity testing methodology which will be used complies with the standards of the National Committee for Clinical Laboratory Standards (NCCLS 1993) and utilises adequate controls. Zone sizes will be measured objectively using a Mast or Biomic automated radius zone reader. The NCCLS method has been chosen because it is the best standardised disc sensitivity testing method. A disc method is preferred for long term surveillance as it allows both measurement of MICs (by regression-line analysis) and detection of more subtle changes in MIC levels than can be picked up by broth or agar dilution testing. It is also relatively simple and cheap to perform.

ESBiC will use the results of the programme to:

  1. Monitor trends in antibiotic resistance patterns using data derived both from the project and from existing databases.
  2. Develop a proposal for and, subject to funding, implement an ongoing system of antibiotic resistance monitoring in Europe across a wider range of organisms in collaboration with Medical Microbiology/Infectious Diseases colleagues.
  3. Develop the most appropriate means of disseminating results from the monitoring programme.

The two main methods of reporting to ESBiC will be:

  1. Monthly compilation of Alert organisms. These are considered crucial in the frontline battle against resistance. Outbreaks will be documented.
  2. A system of Target Organism Surveillance where detailed quarterly data will be assimilated on a preselected range of organisms to an agreed antimicrobial battery. Single isolates per patient and exclusion of multiple strains from any one outbreak will ensure distinct isolates.

Computer software for antimicrobial resistance surveillance will be developed and delivered by ESBiC Data Center Munich and ESBiC will analyse the data and prepare it for presentation and publication. Meetings of the key participants will be used to develop strategies to modify the detected patterns of resistance development.

A minimum data set will be collected for each Alert organism including data on level of care, travel, underlying diseases, specimen type, clinical trial (may be more susceptible) or screening specimen, detected before/after treatment, nosocomial outbreak or community acquired. A smaller data set will be collected with regard to Target organism.

A monthly system of quality control will be set up with supply of test organisms of unknown sensitivity. Genotypic characterisation and mechanisms of resistance will be assessed in a small selection of isolates.

Organisation and management

Delivery, setting up and initial QC of the testing system will be achieved in the first 3 months.

First reports of Alert organism prevalence and analysis of hospital/community demographics and denominator organism numbers will be available at 4 months and of Target organisms at 6 months (analysis later to be extended to yearly blocks).

First meeting of investigators at 6 months (prior to this if necessary). Construction of first hypothesis. Production of first report (to be produced 6 monthly).

Production of interim report and first ESBiC meeting at 1 year. Testing of first hypothesis. Liaison with other groups as and when appropriate.

Genotyping and investigation of resistance mechanisms as and when appropriate.

Expected results

The potential benefits will be heightened awareness of resistance, a better understanding of the existing burden of resistance and its variations, the development of an effective reporting system and audit capabilities, understanding of risk factors and ultimately, delay in development and spread of resistance.

The information on antibiotic sensitivity patterns obtained from this study will find direct application in the implementation of rational antibiotic therapy. Dissemination of data from this project through ESBiC and Internet will minimise inappropriate prescribing, which will result in:

A resume of data dissemination includes:

  1. Monthly availability of good quality data on Internet.
  2. Regular publication/analysis through annual ESBiC meetings and bimonthly publication.
  3. Collaborative meetings will be held with other interested parties.

It will help countries to set up their own national surveillance systems. In addition, the scheme will allow early detection and characterisation of local outbreaks on antibiotic-resistant strains which will in turn allow appropriate and timely intervention as well as elucidation of new mechanisms of resistance.

Finally it will allow a greater understanding of the causes of resistance and ways to control it through the development and testing of hypothesis by implementation of strategic control plans.

Data Entry

The ESBiC Data Center, Munich, has developed a computer programme for data entry to comply with the needs of documentation and presentation of the results.


ESBiC Datacenter Munich, 1999