BRITISH VETERINARY ASSOCIATION

REPORT OF THE ANTIMICROBIALS WORKING GROUP

Following acceptance by Council of the initial Antimicrobials Working Group report IN jULY 1997, further evidence relating to antimicrobial use in animals has been collected and assessed. This has been reviewed against the current concerns with food safety, in the UK and internationally, and the suggested role of livestock as disseminators of antimicrobial resistant bacteria perceived as dangerous to human health.

A BVA policy is proposed together with some required supporting actions to protect both the welfare of animals under veterinary care as well as the role of the veterinary profession in society.

The working group comprised Dr A.H. Andrews, Dr K. Lawrence, Professor Q. McKellar, P.F. McMullin, Dr A.J. Mudd, Professor W.J. Reilly, R.M. Stevenson and Bruce V. Jones(Chairman).

In the preparation of this report oral evidence and advice was taken from Dr Tony Little(Weybridge Laboratories), Dr Chris Bostock (IAH Compton), Professor John Bourne (past Director IAH), Dr M. Rutter and Mr S. Dean (VMD), Dr G. Rae (BMA), Dr G. Scott (UCH), Mr David Miller (Novartis), Mr David Schofield (Hoechst-Roussel) plus representatives from BCVA, BSAVA, BVPA, and SVS.

CONTENTS Paragraphs
Introduction 1-9
Synopsis of Discussions 10-33
Conclusions 34-35
BVA Policy 36-44
BVA Agenda for action 45
BVA General Guidelines on the use of antimicrobials Annex A

INTRODUCTION

1. Following presentation of the Antimicrobials Working Group report to, and acceptance by,BVA Council in July 1997, the AWG was reconvened at the end of the year with the brief to:

2. The group was enlarged to expand the expertise base and a series of meetings has been held to refine the conclusions expressed in the initial report. Important additional efforts have been made to hold discussions with representatives of BVA divisions and in obtaining additional expert evidence on issues related to the study.

3. A key part of the proposed strategy is the production of guidelines, both general and species-related, for antimicrobial use. These are being written in association with the relevant species divisions and other interested parties but are not yet complete.

4. The guidelines are important as a means of demonstrating that the veterinary profession recognises that s the use of antimicrobials may lead to antibacterial resistance, as an animal and human health hazard, and has taken practical steps to demonstrate its responsible approach.

5.This report has been prepared against a background of continuing concern about the use of antimicrobials in man and animals accompanied by significant media comment on the subject: most of this has been critical of the use of antimicrobials in livestock (in particular related to the in-feed growth promotant use). The issue of growth promotant use is a major cause for concern, and is discussed in this report.

6. Use of antimicrobials may lead to resistance patterns that could endanger human or animal health. This has to be recognised as a natural consequence of antimicrobial use and therefore raises the difficult problem of getting "logic" into the discussion: antimicrobials control disease, but have a consequence. The group would like to see a full benefit:risk analysis for all antimicrobial uses. . It can be noted that two such studies are now in progress, one in Europe and one in the USA: the data should be available before the end of 1998.

7. In the Autumn of 1997 the World Health Organisation held a meetin in Berlin entitled "The Medical Impact of the Use of Antimicrobials in Food Animals". The meeting was important and much of what was said there is consistent with the results of the working groups first report. Two sections of the published text of the Recommendations from the Report are copied here as they raise important consequences for the future use of antimicrobials in animals:

'Use of growth promoters

The recommendation made by the previous WHO advisory group (1994) is
reinforced:

The use of any antimicrobial agent for growth promotion in animals
should be terminated if it is:

Risk assessment

No antimicrobial should be administered to a food animal unless it has
been evaluated and authorised by competent national authorities. This
evaluation should include a:

If such emergence is detected, appropriate action should be taken, which
may include the withdrawal of the antimicrobial in question'


8. As the AWG was completing this current report the House of Lords Select Committee on Science and Technology report, Resistance to Antibiotics and other Antimicrobial Agents was published, followed by the House of Commons Agriculture Select Committee report on food safety. The conclusions and recommendations of the former are particularly commended for their broad coverage of the total antimicrobial use environment.

9. In July 1998 the Standing Medical Advisory Committee is due to report on the use of antibiotics in humans and later in the year the Advisory Committee on the Microbiological Safety in Food is also due to report on its assessment of the risks to humans of drug resistance across the whole food chain.

SYNOPSIS OF DISCUSSIONS

10. Evidence was taken both from invited guests and from expert members of the group. The specific discussions had three main themes: required research, clinical usage of antimicrobials and alternative disease control strategies.

Required Research

11. The group recommended previously that "a priority should be the establishment of epidemiological surveys as a means of quantifying the problems and defining the risks" posed by the widespread use of antimicrobials in livestock as possibly creating a human health risk. Such a study is now underway in several EU member States.

12 Associated with this the group recommended studies on, "the pathogenesis and epidemiology of both zoonotic and non-zoonotic disease, which could lead to recommendations for disease control which may then minimise antimicrobial use."

13. There is no question that the need for this research (a need that was originally cited in the Report of the Swann Committee, 1969) has to be a continuing demand by the BVA. Without such basic knowledge little or no progress can be made in gaining a full understanding of the problem.

14. The group recognises that expeert knowledge will be required to design such studies and they will be costly to implement. There is a fundamental need for this work to be carried out. Additionally there is also a need for research to look at antimicrobial administration strategies, to determine how antimicrobials can be used to reduce the development of resistance and to reduce the overall amount of antimicrobial use.

15. The current restrictions on animal health research must be vigorously challenged to ensure that resources will be forthcoming from public funding. There needs to be a recognition of the underfunding of animal health research. The proposed Food Standards Agency must take an interest in this and co-ordinate funding from and with MAFF and other independent sources such as the Wellcome Trust. The FSA provides an opportunity for a co-ordinated (MAFF:DOH) approach to the subject, in the interests of public health.

Clinical Usage of Antimicrobials

16. There is no significant evidence to demonstrate that there is misuse of antimicrobials by veterinarians, however due to the exigencies of practice some usage is inevitable before results of antibacterial sensitivity testing are available. Therefore as a part of good clinical practice, guidelines for the use of such products should be available.

17. The group has produced a first general guideline which is a statement of the principles of antimicrobial use. It is intended that this will be supplemented with specific guidelines for each of the major species.

18. It is important that these advisory notes are not seen as limitations to the clinicians judgement, but as a checklist for consideration before using these substances. These guidelines are discussed and agreed with the relevant BVA species Divisions to ensure that they can be of maximum value. Guidelines have been drafted for antimicrobial use in cattle, pigs, poultry and sheep and discussions are in process for companion animal use.

19 These guidelines are not only essential to provide advice to the profession, but are also valuable as a means of demonstrating the responsible approach taken by practising veterinary surgeons.

20. Any guidance issued on the use of antimicrobials must correlate with that given in the BVA Code of Practice in Medicines: all professional guidelines must harmonize both in use of words as well as general principles.

Alternative Disease Control Strategies

21. The group met with the Directors of the three centrally funded research Institutes and also representatives of the pharmaceutical industry and concluded that the outlook for, what could be termed replacement products is not encouraging.

22. The Government is providing inadequate funding for the study of many significant or developing disease problems. Particular note must be made the negligible of funding of research into pig health related problems. Other areas where watching briefs or active studies should be in process are woefully undersourced.

23 Certain problem areas however are being addressed by the three Institutes, in particular the food-borne diseases of Salmonella and Campylobacter (Weybridge, Compton), and a significant vaccine effort for certain ruminant diseases (Moredun). But much basic vaccine development work needs to be done by the public sector, which currently does not have the funding. As a consequence of this the numbers of qualified research staff who could undertake such studies are dwindling.

24 The pharmaceutical industry naturally follows market-driven forces and is keen to commercially develop vaccines which may be evolved in the public sector. There is also a significant research involvement by biologicals manufacturing businesses in researching new vaccines, but these are done against a global needsand and not necessarily a UK need. Additionally industry sources have a serious funding problem. Global regulatory authorities make increasing demands which inhibit new product investment, in particular in the so-called cutting edge technologies.

25. The development and use of vaccines has to be a major alternative strategy to control bacterial and mycoplasmal disease. There are few other approaches perceived which are going to offer the same capability of disease control as the currently available antimicrobials. This point has also formed a part of the recommendations in both the House of Lords and House of Commons Committee reports. Also of relevance are the current activities leading to an international harmonization of vaccine production and regulation.

26. Other approaches do not appear at this time to offer a replacement to existing antimicrobial use: competitive exclusion has a limited place in poultry salmonella control, but immunomodulation and immunostimulation products and probiotics, enzymes and other feed inclusions either do not live up to expectations or are more aimed at improving feed efficiency rather than controlling disease.

27. For therapeutic use there are no immediate foreseen replacement products. For growth promotant or digestive enhancement uses there are a number of candidate replacements. However the evidence that these can produce the same range of effects as currently approved products is still lacking; there may also be issues with respect to
safety, quality and efficacy.

28. An immediate strategy for disease control, in effect means a return to basic principles of vaccine use, disease eradication programmes, attention to good husbandry practices and rigorous hygiene maintenance. The general implementation of biosecurity measures to control and prevent ingress of pathogens is necessary. Long-term, but beyond forecastable limits, there may be genetic modification and selection for resistance to disease and improved productivity factors.

Growth promotant use of antimicrobials

29. The House of Commons Agriculture select committee report recommended that the use of antimicrobials as growth promotants be stopped, whereas the House of Lords, on the basis of a more extensive review recommended a more pragmatic approach.

30. A precipitate ban on this use would probably raise serious consequences for both the health and welfare of pigs and poultry (as has been demonstrated with the withdrawal of avoparcin on a concurrent rise of poultry necrotic enteritis). The group therefore recommends that the products now in use, subject to scientific assessment, be re-classified to bring them into line with other antibiotics. Such a possibility was built into the original feed additive Directive 70/524/EEC which stated that whereas medicinal substances, such as coccidiostats should, during a first stage, be regarded in relation to feeding stuffs as additives, these should be examined further if a directive on medicinal
feeding stuffs is drawn up. The same comment is relevant for antibiotics and growth promoters. Now that a medicinal products directive is in place we recommend that such products be transferred and only be available under veterinary control. Such a move would allow for a critical review and reassessment, as well as giving the producer and the veterinarian time to consider and regulate the change in production practices.

The Food Standards Agency

31. When established the FSA could be a potent force to affect both veterinary product and growth promotant use. It is important that the veterinary profession should have representation at the commission level and be able to exert its
influence on FSA actions.

32. Healthy animals, sanitary slaughter and the handling of raw livestock produce are the key areas of concern; these areas are where the profession is both active now and where it can continue to provide advice and expertise in the interests of public health.

The Swedish approach

33. The ban on growth promoting antibiotics introduced in Sweden should be regarded as an experiment which now needs to be looked at closely. Firm evidence is required which can describe the results for both human health and animal health and welfare.

CONCLUSIONS

34. The British Veterinary Associationhas examined both the background to, and the current concerns in relation to the use of antimicrobials (antibiotics) in animals. The study was undertaken following the EU decision to ban the use of certain antibiotics and against the background of consumer anxiety in relation to food safety in the UK.

35. Following from the review the BVA concludes that:-

BVA POLICY

36. A clear, direct approach is required. The current environment regarding the use of antimicrobials in animals and their role in transmission of antimicrobial resistant organisms to man needs careful scientific evaluation rather than the emotional negative approach frequently taken by the media and consumer groups.

37. There is without question a significant population of antimicrobial resistant bacteria now present in both human and animal environments. All studies indicate that this is not a simple issue and that there is probably no quick or easy way to resolve the problem.

38. Antimicrobials are just as essential for animal heath and welfare as they are for human health. Animal use also has broader social impacts outside of the health issue, as altering the current status quo would impact animal welfare, food costs and related issues such as food safety.

39. It is suggested that an initial precept should be to recognise that:Antimicrobial use in animals is part of a complex embracing livestock health, animal welfare, human health, food safety, farm economics, food costs and companion animal care. If there is a problem then it must be tackled by examining the total environment and not just one facet.

40. One core issue is the growth promotant use of antimicrobials, it has to be recognised that this is now a major public concern, well highlighted by the reports and recommendations from the WHO, House of Lords and House of Commons Committees. The BVA agrees in principle that the practice of using antimicrobials as growth promotants be stopped if careful assessment shows an unacceptable risk. In the interest of both health and welfare of the animals concerned, in particular for pigs and poultry, BVA coucils caution against precipitate action. Following scientific assessment it should be possible to retain the use of some of the currently available products, but licensed and used in
the same way as other antimicrobials.

41. Consideration should also be given to other issues:-

42. The role of the veterinarian can be simply stated:

43. These three interlocking capabilities make the veterinary contribution the essential input to the livestock farming economy and companion animal care. Any policy statement must implicitly build on this basic position.

44. The BVA recommends that,

BVA AGENDA FOR ACTION


45. In order to gi ve weight to the policy decisions, the following strategic and tactical approaches have been agreed. The BVA will:-

Strategy

Tactics

 

BRITISH VETERINARY ASSOCIATION

GENERAL GUIDELINES ON THE USE OF ANTIMICROBIALS

Introduction

1. The use of antimicrobial agents provides an effective method for the control and treatment of infectious or contagious diseases caused by bacteria and certain other micro-organisms. Their application in veterinary practice since the 1950's has assisted in ensuring the health of livestock and companion animals. Antimicrobial use has also enabled the production of meat and milk products which are unlikely to present disease problems for the consumer or those concerned with their production. Antimicrobial use is also justifiable on welfare grounds ("freedom" to receive treatment of disease is incorporated in the Welfare Codes).

2. It must be remembered at all times that widespread use of antimicrobials is not a substitute for efficient management or good husbandry practice.

Principles of Antimicrobial Use

3. The appropriate selection of antimicrobials in practice is a critical decision and should be based on:

Routine Considerations

4. Antimicrobial agents should only be used when it is known or suspected that an infectious agent is present which will be susceptible to such therapy.

5. When antimicrobial agents are used, every effort should be made to determine the origin of the problem and to ascertain the most effective treatment.

6 . While therapy may need to be initiated before results of diagnostic or sensitivity tests are known, it will need to be reassessed as test results become available. In such circumstances decisions, before the results are known, as to the choice of antimicrobial will need to be made,

7. Infectious disease should be treated with the antimicrobial found, on appropriate testing, to be most efficacious and also based on the previous history of effective antimicrobial use on the premises.

8. Careful calculation of dose is always important, but in particular if an extra-label use of a product is being considered. In such cases caution needs to be exercised regarding meat and milk withholding periods.

9. The efficacy of all disease treatments should be monitored and, if part of the treatment regime was undertaken by the livestock or pet owner, a check should be made to ensure that they have understood fully the instructions on dosage and duration of any antimicrobial use. Quantities of antimicrobials left with the animal owner should correctly reflect the needs, to avoid an oversupply.

10. Antimicrobial usage should always be part of, and not a replacement for, an integrated disease control programme. Such a programme is likely to involve hygiene and disinfection procedures, biosecurity measures, management alterations, changes in stocking rates, vaccination etc.

11. Continued antimicrobial use in such control programmes should be regularly assessed as to effectiveness and whether their use can be reduced or stopped.

12. Protocols should be agreed between the veterinary surgeon and client as to when veterinary involvement is required in on-going disease conditions. These protocols must be regularly and frequently reviewed and updated.

13. Protocols should be agreed and documented for treatment of all endemic conditions on the farm or other livestock rearing or production premises. These protocols must be regularly reviewed and updated.

Dosage Strategy Recommendations

14. In order to minimise the likelihood of broad antimicrobial resistance developing it is recommended that where an appropriate narrow spectrum agent is made available it should be selected in preference to a broad spectrum agent which will exert a greater selection pressure on commensal bacteria.

15. It is recommended that optimal therapeutic dosage strategies be used and that all efforts be made to avoid administration of sub-therapeutic dosages, which can lead to a lack of efficacy (in some specific cases such as fluoroquinolones and erythromycin use of this practice has been shown to induce resistance). Dosage recommendations as laid down in the relevant Data Sheet should always be followed.

16. Should there be recurrence of disease following successful treatment (and control) of an outbreak, it will need to be investigated thoroughly to ascertain why this has occurred and the most suitable therapy to be used.

17. Use of antimicrobials for the prevention of disease can only be justified where it can be shown that a particular disease is present on the premises, or is likely to become so, and that strategic antimicrobial use will prevent clinical outbreaks of that disease.

18. Antimicrobials need to be used with care to maintain their efficacy. If possible look for alternative methods of disease control (vaccination) to reduce antimicrobial use.

Regulatory Concerns

19. Any use of antimicrobials outside normal Data Sheet recommendations (in accordance
with the "cascade") should be carefully justified and documented.

20. Note must be made, and documented, of any adverse reactions which may be observed or a decline in efficacy of a previously effective antimicrobial.

19. All antimicrobials in use must be used and stored correctly in the manner outlined in the BVA Code of Practice on Medicines. In accordance with statutory requirements full records must be kept of all products used.

20. Consideration must always be given to the health of the person administering the products. Any necessary warnings should be issued.

Note: these guidelines are intended to act as an adjunct to clinical judgement. It may not be possible for every consideration to be observed in every case, but they should always form part of an automatic check list when deciding an antimicrobial use regime.

17 September 1998