Advisory Committee on the Microbiological Safety of Food

 

MICROBIAL ANTIBIOTIC RESISTANCE in Relation to Food Safety

SYNOPSIS

Advises the Government on the Microbiological Safety of Food

London: The Stationery Office

   
  Report on Microbial Antibiotic Resistance in Relation to Food Safety

SYNOPSIS

Introduction

  During. the course of 1995 the Advisory Committee on the Microbiological Safety of Food (ACMSF) took stock of the position in relation to antibiotic resistance in enteric bacteria infecting animals and man with a view to deciding whether the Committee nee ded to involve itself further in assessing the situation, given the work already being undertaken in this area by other bodies and agencies. The Committee's consideration of th e issue took place against the background of concern about a rising incidence of certain antibiotic-resistant enteric pathogens in humans and animals. Exploratory consultations with other committees and bodies having interests and responsibilities in the subject encouraged the ACMSF to embark upon an in depth review of the role of good in transferring microbial antibiotic resistance.
  A Working Group with the following terms of reference was set up for this purpose.

TERMS OF REFERENCE

To assess the risks to humans from antibiotic resistant microorganisms entering the food chain and to consider the need for any action to protect public health

Membership of the Working Group, details of which are given in the Annex, included individuals with experience spanning medical and veterinary science, microbiology, public health, the food industry, farming and consumer issues. The Group had particular expertise in relation to microbial antibiotic resistance. The Group held its first meeting on 30 August 1996.

The Report produced by the Working Group and endorsed by the full Committee represents the outcome of a comprehensive study of what is an extremely complex subject. By way of preparation, the Group carried out an in depth evaluation of relevant scient ific literature and also undertook wide ranging consultations with interested parties including the pharmaceutical industry, farming bodies, the veterinary and medical professions, consumer groups, food companies and other experts. Consultation embraced both written submissions by interested parties and detailed oral presentations by key stakeholders. The Working Group was also assisted by a special literature review and associated international workshop, both sponsored by the Ministry of Agriculture, F isheries and Food. A fact finding visit was made by a Working Group delegation to Sweden to examine the outcome there of the ban on antibiotic growth promoters in 1986.

Given the complexity of the subject and the depth in which the ACMSF has covered i t, the Report is necessarily a large document. It is therefore prefaced with an extended Overview and Summary section which distils the conclusions and recommendations and includes a broad strategy for reducing the use of antibiotics in the rearing of food animals.

   

SUMMARY AND OVERVIEW

8. There is a fundamental question which superimposes itself on our consideration of the issue of microbial antibiotic resistance in relation to food safety. It is whether the administration of antibiotics to animals results in the selection of resistant bacteria which may be transferred to humans in food and cause human infections which are difficult to treat.

9. This question has been the subject of heated debate for more than 40 years, but never more so than now. Much of modern medicine depends upon the control of infection with antibiotics and, if this were to become largely ineffective, it would have calamitous consequences.

10. The deepening anxiety over antibiotic resistance which is evident today is a result not only of a recognition of the seriousness of its consequences but also the apparently inexorable growth in the number of resistant bacteria. This anxiety has been enhanced by the realisation that the discovery of "new" antibiotics which can replace those that have become ineffective is now, at least, extremely rare.

11. When a bacterial population is exposed to an antibiotic, the few relatively resistant organisms have a selective advantage over those fully sensitive organisms whose growth is inhibited, and the greater and more frequent the exposure, the greater the selective pressure. Moreover, some resistant bacteria are capable of transmitting genetic elements to sensitive bacteria, rendering the recipient organisms resistant to antibiotics they have never encountered. It is highly probable that the greatest stimulant to the production of resistant bacteria in humans is the use of antibiotics in human medicine and, for this reason, doctors are now being exhorted to use antibiotics only when they are of proven value. In the United Kingdom, it is no longer acceptable for doctors to prescribe antibiotics for viral infections, or other conditions for which they are ineffective, in the unfounded hope that they might do some good.

12. If the administration of antibiotics to food animals results in an acceleration in the rate at which antibiotic resistance is emerging in humans, there is clearly a case for restricting the use of antibiotics in animals, particularly as the resistant bacteria would be capable of causing not only gastroenteric infections but other serious illnesses. Some people, albeit now a minority of those who have considered the problem, believe that the case has not been made for such a restriction, but many others believe that it shows conclusively that giving antibiotics to animals results in the emergence of some resistance bacteria which infect humans. Furthermore, the potential for resistant bacteria from animals to transfer genetic elements which confer resistance to bacteria pathogenic to humans exacerbates the problem. However, the extent to which antibiotics given to animals contributes to the overall problem of bacterial antibiotic resistance in humans is uncertain and the evidence and information needed to resolve the uncertainty is lacking.

13. For more than a year we have tried, unsuccessfully, to discover the amounts of antibiotics used in animals in the UK, the numbers and species of animals to which they were given, and the purpose of administration. We recognise that much of this information is commercially sensitive/or difficult to assemble. We nevertheless believe that a robust system to gather this information should be put in place as soon as possible.

14. Studies on the emergence of bacterial resistance in animals given antibiotics are few, and little research has been done into the transmission of resistant bacteria in food to humans. Without more and better research and surveillance studies, the extent to which giving antibiotics to animals results in antibiotic resistance in bacteria in humans will remain largely unresolved. We have made a number of recommendations in respect of these problems.

15. In spite of the difficulties, we believe that sufficient evidence exists to support the recommendations we have made which, if implemented, will result in a reduction in the use of some antibiotics in animals, particularly where effective alternatives exist or where they are being used as a substitute for hygienic animal husbandry. Moreover, such a reduction will not only benefit humans. It will carry the added bonus of prolonging the effective life of those antibiotics used in animal therapy. As far as the use of antibiotics for animal growth promotion is concerned, our recommendations are based largely on the principles set down by the SWANN Committee in 1969. We believe that these are as valid today as they were when they were first made.

16. Many of the recommendations we have made will require discussions and action at a European Union or wider international level, and not merely for legalistic reasons. Bacteria, whether or not they are resistant to antibiotics, do not recognise international frontiers and there is enormous international trade in food. There may therefore be little point in banning the use of an antibiotic in the UK whilst importing food, with its accompanying bacteria, from other countries in which no such ban exists. Such action might have little effect on antibiotic resistance and, at the same time, place British agriculture at a competitive disadvantage. This does not mean that nothing can be done. We found clear evidence of an international determination to take steps to reduce the rate at which antibiotic resistance is emerging, and some steps can and should be taken in the UK now so that future generations can enjoy the maximum benefits of effective antibiotic therapy.


Antimicrobials, antibiotics and resistance


17. Our Report addresses the question of microbial antibiotic resistance in relation to food safety. It might, at the outset, be helpful to define what we mean by the terms antimicrobial agent, antibiotic and antibiotic resistance :-

an antimicrobial agent is a compound which, at low concentrations, exerts an action against microorganisms and exhibits selective toxicity towards them . The term antimicrobial includes any substance of natural, synthetic or semi-synthetic origin which is used to kill the growth of microorganisms (bacteria, fungi, protoza and viruses). Antimicrobials include antibiotics, disinfectants, preservatives and other substances (eg. copper, zinc);

an antibiotic is a substance - produced by, or derived from, a microorganism - which selectively destroys, or inhibits the growth of, other microorganisms. Because compounds such as sulphonamides and quinolones are synthesised chemically, they are not strictly antibiotics. However, in practice the term "antibiotics" often encompasses such agents and this broader view has been adopted in the terminology used in this Report,
antibiotic resistance is the ability of a microorganism to withstand an antibiotic.

Use of antibiotics in animals

18. There has been widespread use of antibiotics in human and animal medicine, and in animal husbandry, over the past 60 years. This has led to the emergence of antibiotic resistance in some bacterial species. Historically many of the antibiotics which are important in human clinical use have, because of their efficacy, also been used in veterinary medicine. In addition, the veterinary use of antibiotics has not been confined to therapy of clinical cases but has also embraced treatment of clinically normal but infected animals, prophylaxis and growth promotion. To avoid confusion, it should be noted that, for the purposes of our Report, we have ascribed the following meanings to these terms:-

therapy the treatment of disorders or disease;

prophylaxis : the administration of antibiotics in advance of symptomatic disease;

metaphylaxis the use of antibiotics for the prevention of disease or the control of its spread. In the context of farmed livestock, when an animal which is kept, as part of a group, in close proximity to others contracts an infection, there is a high probability that others in the group will also be infected, whether or not they are exhibiting symptoms at the time. The administration of antibiotics to all animals in contact within the group, to treat a symptomatic disease in some and to prevent disease in others, is what we regard as metaphylaxis;

growth-promoters antimicrobials used in low concentrations to stimulate an animals growth, resulting in increased daily liveweight gain and feed conversion efficiency. The mode of action of growth promoters is thought to be associated with their effect on the composition and distribution of the intestinal microflora.

19. Concern has been expressed both nationally and internationally about the long-term use of antibiotics in animals. The question of whether the use of antibiotics in animals serves to compromise the treatment of infectious disease in humans has been addressed by a number of committees, bodies and organisations world-wide. In the UK, the topic has been addressed in various reports, notably those of the Netherthorpe Committee in 1962, the Swann Committee in 1969, and the Lamming Committee in 1992. An underlying and recurrent theme from these reports, which are examined in greater detail in Annex A of our Report, has been the potential threat of establishing resistant microorganisms in food animal populations and the consequent need to restrict the use of antibiotics in animal husbandry.

20 More recently, the World Health Organisation (WHO) held a meeting in 1997 on the use of antimicrobials in feed animals. The principal aims were to obtain an international consensus on priority medical problems arising from the use of antimicrobials in livestock production; and recommend steps to advance the development of guidelines for the control and containment of the emergence of medically-relevant antimicrobial resistance in food animals. We have noted the strength of the conclusions and recommendations which emerged from the meeting, notably that:-

the use of any antimicrobial agent for growth promotion in animals should be terminated if it is used for human therapeutics or known to select for cross-resistance to antimicrobials used in human medicine;

national authorities should define threshold levels of resistance in bacteria and circumstances where mitigation procedures should be instigated and, if such procedures are unsuccessful, when approval should be withdrawn; and

no antimicrobial should be administered to a food animal unless it has been evaluated and authorised by the competent national authorities. Evaluation should include a thorough risk assessment (including the development of resistance which may impact on public health); a post-marketing monitoring programme to detect the emergence of resistance of public health significance; and, if such emergence is detected, appropriate action should be taken which may include the withdrawal of the antimicrobial in question.

21. The WHO held a further meeting in June 1998 at which the problems associated with the use of quinolones in food animals and the potential impact on human health were addressed. The meeting called, amongst other things, for research to be conducted in connection with quinolone resistance.

22. The House of Lords' 1998 "Report on Resistance to Antibiotics and other Antimicrobial Agents" called for the voluntary phasing out of the use of virginiamycin for growth promotion and a Code of Prescribing Practice for veterinarians. A House of Commons Report on "Food Safety" in 1998 went further, calling for a ban on the use of antibiotics in farming as growth promoters, and tighter restrictions on their use for sub-therapeutic or prophylactic purposes.

23. Consumer groups have also been actively involved in consideration of the issue and two in particular (the Consumers in Europe group, and the National Consumer Council) drew the ACMSF Working Group's attention to their various concerns.


Developments in a food safety context

24. The issues considered by the ACMSF in a food safety context include:-

the high prevalence of multiply-resistant strains of Salmonella typhimurium definitive phage type (DT) 104 and evidence of food-associated infection;

concern of campylobacters developing resistance as a consequence of quinolone usage in farming;

the therapeutic and prophylactic use in animals of antibiotics of importance in treatment of human infections;

EU consideration of the case for banning the use as growth promoters of a number of antibiotics

the different approach to the veterinary (as compared with the human clinical) use of antibiotics whereby drugs are administered to large groups of animals or poultry at the first appearance of disease, on the premise that this is the most effective means of preventing the spread of disease within the group;

the important part played by antibiotics in the development of modern aquaculture.

the possibility that imported foods might be more likely to contain' antibiotic-resistant organisms than domestically-produced food as a consequence of the freer availability of antibiotics to agricultural producers in other countries; and

the use of antibiotic markers in genetically-modified food organisms.

25. On this last point, this is an issue which has been kept under close scrutiny by the Advisory Committee on Novel Foods and Processes (ACNFP). For this reason, the ACMSF has not itself considered the matter in any detail. We support the ACNFP's approach to assessing the safety of antibiotic resistance markers in food genetically modified organisms and its policy of encouraging the use of alternative marker systems wherever possible.


Antibiotics in human medicine

26 Whilst we have concentrated in our Report on the question of microbial antibiotic resistance in relation to food safety, we do recognise the argument that human exposure to resistant bacteria through food chain pathways is part of a much larger issue of resistance and that the contribution of antibiotics used in animal husbandry may be small compared with the contribution made by the use of these drugs in community and general practice. Data are not easy to obtain on the amount of antibiotics used in animal populations or of the numbers of animals treated and it would add enormously to the transparency of the situation if there was structured monitoring of the drugs used, the purposes for which they were used and the quantities concerned. However, even if we accept as a working hypothesis that antibiotic usage is greater in human than in veterinary medicine, this is not and cannot be sufficient reason for ignoring the contribution to resistance arising from farm use and transmission via food. Put another way, evidence of the abuse of antibiotics in humans would not of itself excuse any abuse in veterinary medicine. The aim should be to work towards responsible use in both areas. We welcome the initiatives taken by the medical profession, as described in the recent report of the Standing Medical Advisory Committee. We support the recommendations and look to the veterinary profession and the farming industry to adopt a similar philosophy.

Evidence of resistance

27. It is clear that scientific evidence exists that bacteria can acquire resistance through a number of well recognised mechanisms (eg. selection of chromosomal resistance or acquisition of transferable DNA by transformation or conjugation). The more that bacteria are exposed to antibiotics, the better developed their defence mechanisms become and the more adept they become at developing resistance. Given the wealth of available evidence, the Committee firmly believes that, when antibiotics are used in food animals, selection pressures are likely to result in the emergence of resistant strains of bacteria. Moreover, it is clear that some of the resistant strains seen in food animals are capable of infecting humans. The ability of microorganisms to transfer resistance adds to the concerns about multiple-resistant strains like S. typhimurium DT 1O4 entering the food chain.

28. The Committee is conscious of the claim by some parties that there is no compelling evidence of the existence of widespread microbial antibiotic resistance in food animal populations. This reflects the paucity of surveillance and research specifically focusing on problems of resistance. We have confirmed through talking to the pharmaceutical companies themselves that their policy has been to concentrate resources on demonstrating the sensitivity of the majority of pathogenic bacteria to antibiotics. The implication of the appearance of local pockets of resistance needs to be raised to a much higher level of debate. The pharmaceutical companies must monitor where resistance arises and report to the licensing authorities on specific instances and trends. Such information should then be the basis for action by the licensing authorities to rescind product licences where the use of antibiotics in animals is seen to compromise the treatment of human disease.

29. We believe, despite some views to the contrary, that resistant bacteria in food animals have arisen as a consequence of the use of antibiotics in the farm environment and current husbandry practice. We are convinced that this is often the origin of at least some of the same resistant bacteria like Salmonella and Campylobacter which appear both in farm animals and humans. We are also satisfied that some resistant bacteria will find their way to man through food chain exposure pathways, although the importance of direct animal exposure is not overlooked.

30. These views are underpinned by a MAFF-sponsored review between August 1997 and February 1998. The literature on antimicrobial resistance in bacteria associated with foodborne infections was reviewed by a network comprising four teams at the University of Birmingham Medical School, the University of Glasgow Veterinary School, the University of Liverpool Medical School, and the Royal Veterinary College Department of Farm Animal and Equine Medicine and Surgery.
The expertise of the four groups, and advisers from the University of Glasgow Veterinary School and the Scottish Centre for Infection and Environmental Health, was used to evaluate the literature, identify gaps in knowledge and to present the results in the light of their experience. The review was followed by a workshop held in Birmingham in October 1997 involving the investigators, representatives of the sponsors, and invited experts in the field of antimicrobial resistance from the United Kingdom, Europe and the United States of America. A report of the review and workshop was subsequently produced as a technical guide for MAFF and also to help inform the ACMSF's consideration of the question of microbial antibiotic resistance in relation to food safety.

31. Of particular concern are the quinolones (and the fluorinated quinolones - the fluoroquinolones - developed from these original agents). These are the synthetic antibiotics whose mode of action is to inhibit DNA gyrase and topoisomerase IV in susceptible bacteria. The fluoroquinolones, eg. ciprofloxacin, are invaluable agents for the treatment in humans of Gram-negative and Gram-positive infections,, including those caused by methicillin-resistant Staphylococcus aureus (ciprofloxacin, usually in combination with rifampicin - although mutational resistance may emerge as a result of the therapeutic use of these agents), and of enteric fevers caused by Salmonella typhi and Salmonella paratyphi A, B and C. It was hoped, when the quinolones were first introduced, that their mode of action would make the development of resistance in bacteria, including the campylobacters, almost impossible. Unfortunately, this prediction proved to be over-optimistic and we are now increasingly seeing quinolone-resistant campylobacters. Campylobacters are, of course, the most commonly recognised foodborne pathogens in the UK and poultry meat is an important reservoir for Campylobacter jejuni and Campylobacter coli. There is significant usage of the quinolone enrofloxacin in poultry production and there is a belief that the emergence of quinolone-resistant campylobacters reflects the use of the drugs in veterinary medicine

Growth promoters

32. We specifically considered the use of antibiotic substances as growth promoters in food animals and their relevance to the problem of antibiotic resistance. In the past, growth promoters have been generally regarded as of no (or little) direct use in human clinical medicine. However, they are able to give rise to antibiotic resistance, in some cases in a way which could impact on the use of related substances in human medicine.
It should also be kept in mind that clinical applications of related substances might be developed at some future date. The Committee fully supports the recommendations of the SWANN Committee. To comply with SWANN, antibiotics which are used for the treatment of infections in humans and animals should not be used as growth promoters. Having considered the matter very carefully, we concluded that it would be prudent to phase out the use as growth promoters of spiramycin, tylosin phosphate and virginiamycin which might give rise to resistance to clinical antibiotics. We felt additionally that those remaining for use as growth promoters - avilamycin, bambermycin, bacitracin zinc, monensin sodium and salinomycin - should be more closely controlled, with regular reviews of possible implications in human medicine. We note that olaquindox, copper and zinc are also used for growth promotion and it is for consideration whether they select for antibiotic resistance. Finally, we concluded that no new products for use as growth promoters should be developed which utilise substances which have possible applications in human clinical treatment.

33. The growth promoter category of antibiotics is controlled under EC Directive 70/524/EEC and any action to suspend the use of specific agents requires Government action at EU level. With developments in the EU in mind, and conscious that the Government was likely to have to take a view on the question of growth promoters before we had had an opportunity to finalise our Report, the Chairman wrote to Jeffrey Rooker MP, Minister of State at MAFF, on 8 July 1998 setting out the Working Group's views and recommendations (Annex H of our Report). These have since been endorsed by the full ACMSE The EU Agriculture Council decided on 14 December 1998 that the use of bacitracin zinc, spiramycin, tylosin phosphate and virginiamycin should be suspended from 1 January 1999 (but with provision for the introduction of the suspension to be delayed for 6 months).



Good farming practice

34. Vital in tackling the problem of microbial antibiotic resistance will be the preparedness of the livestock industry to accept that the adoption of good farming practice can significantly reduce the need to use antibiotics. We detect, and welcome recent signs that the farming and veterinary communities are increasingly coming to accept the principle that antibiotics should not be used to compensate for poor farming practice and weak standards of management. The Swedish example shows that it is possible through the adoption of good farming practice to reduce significantly reliance on antibiotics for both therapy and prophylaxis. We look to the leaders of industry to take these matters forward. We believe the will to do this exists. It is worthy of note that, during the comparatively short time scale of the Working Group's deliberations, there has been a key redefinition of the position of important representative bodies like the British Veterinary Association (BVA), the National Farmers' Union (NFU) and the British Poultry Meat Federation (BPMF) to embrace recognition that the status quo cannot reasonably be maintained. We should like to see this momentum sustained. To facilitate the evolutionary process, we would wish to see a multidisciplinary liaison group, along the lines proposed by the BPMF, being set up to monitor developments in bacterial resistance to antibiotics, with a view to identifying action which could be taken on a coordinated basis to address any emerging trends. We welcome the setting up of the Responsible Use of Medicines in Agriculture (RUMA) Alliance whose stated aim is to establish guidelines to help the livestock industry reduce its reliance on antibiotic substances


Aquaculture

35. We note the way in which, as the aquaculture industry has developed over time, increasing use has been made of vaccination, with a corresponding fall in the use of antibiotic treatments. We applaud these developments and look to the industry to sustain this approach as it develops new species like sea bass and sea bream.


Companion animals

36. Although the main thrust of our Report is directed towards the food chain pathways through which people may be exposed to resistant microorganisms, we acknowledge the contribution of companion animals (cats, dogs, etc) to the pool of resistance. There is bound to be a continuous exchange of organisms between humans and companion animals, given the routinely close contact between the two groups, and there is thus a potential for a significant transfer of resistant organisms too. By the same token, the use of antibiotics in ornamental fish poses a potential risk through direct contact exposure.


Sewage sludge, farm effluents and abattoir waste

37. We have some concerns about the potential role played by the disposal of sewage sludge, farm effluents and abattoir waste to pasture and other agricultural land in spreading resistant bacteria more widely in livestock and human populations. There are very large volumes of waste materials involved and the implications of these disposal routes merit further attention.


Conclusions

38. Overall, the aim must be to reduce the exposure of farm animal bacterial populations to antibiotics. In Chapter 13 of our Report we map out a strategy for attaining this objective and for achieving benefits both immediately and in the medium to long-term. We see the key elements in such a strategy as :-

constraining the use of growth promoters;

paying much greater attention to the question of resistance in the approval procedures for veterinary medicines and in post-marketing surveillance;

stimulation of the farming industry, its suppliers and the veterinary professions to develop strategies for reducing the use of antibiotics for therapy, prophylaxis etc over time and confronting the difficulties caused by the veterinary use of fiuoroquinolones;

introducing tighter controls on medicated animal feedingstuffs; and

improving our understanding of resistance in bacteria isolated from food animals and foodstuffs, of human infections associated with antibiotic-resistant foodborne pathogens, and of the ways in which the food chain contributes to human infections with antibiotic resistant microorganisms.


39. Such a strategy would reduce the chances both of acquisition of resistance by pathogenic microorganisms and of transmissible resistance by other parts of the farm animal microbial flora. We have had clear advice that the danger of antibiotic-resistant microorganisms in the food chain can be reduced through the raising of husbandry standards across the industry, and by the closer focus of veterinarians and farmers on the threat of microbial antibiotic resistance. In parallel with this, there should be a tightening of controls covering the licensing of antibiotics so that the development of bacterial resistance in animals given antibiotics can be monitored, evidence of any cross-resistance to other antibiotics can be detected and consideration can be given to appropriate action to minimise the risks.

40. We note that a number of important bodies, including Select Committees of both Houses of Parliament, the World Health Organisation and others, who have looked most recently at the question of microbial antibiotic resistance have reached broadly similar conclusions to those which we have ourselves reached in our Report. We look to the Government and, when established and where appropriate, the Food Standards Agency, to respond positively to this body of opinion and more specifically to the recommendations which we have made.


The Report

41. Against the background of our various concerns, we believe that there is a need to tackle the problem of microbial antibiotic resistance on a broad front. Specific areas which would benefit from urgent attention in the short to medium term are identified in the various Chapters of our Report.

Chapter 1: Background to the Review

42. Chapter I sets out the background to our concerns over microbial antibiotic resistance and the consequent setting up of a Working Group to consider the matter in some depth. The Chapter includes the terms of reference of the Group and the scope of its work.

Chapter 2: Mechanisms of Antibiotic Resistance

43. Chapter 2 deals with the mechanisms of antibiotic resistance. Resistance may appear as a result of mutation or by the acquisition of resistance genes. Resistance genes may be located in plasmids or chromosomes and, within these, on transposons or within integrons. The frequency of mutation giving rise to antibiotic resistance is normally low under natural conditions but antibiotics create a selection pressure and give a selective advantage to the resistant bacteria. In addition, resistance genes can be transmitted between bacteria by transformation, transduction or conjugation.

44. Resistance can occur to a single antibiotic or to several antibiotics. Resistance to one member of a chemical class of antibiotics may arise and may provide resistance to all members of that group, or be restricted to a particular member, dependent upon the resistance mechanism. Some recently described mechanisms give rise to multiple antibiotic resistance ie. to several antibiotics of different chemical classes. The extent of this type of resistance is not known but it can occur in up to 25% of fluoroquinolone-resistant Escherichia coli and it may be clinically relevant in other bacterial species.

Chapter 3 : Patterns of antibiotic resistance in bacteria isolated from food animals

45. In Chapter 3 we deal with the patterns of antibiotic resistance in bacteria isolated from food animals in the UK and elsewhere, including pathogens and commensals. The data we have seen based on animal isolates of Salmonella spp. suggests that S. typhimurium comprises the major source of resistance within animal salmonellas in the UK. Antibiotic resistance is low in Salmonella enteritidis and high only to certain antibiotics in Salmonella virchow and Salmonella hadar. Evidence from other countries suggests that the problem is not limited to the UK, although we appear to have a higher prevalence of resistance to antibiotics in S. typhimurium from animals than some other European countries (eg. Denmark). Epidemics of multi-resistant DT 29 occurred in the UK in the 1960s, and of DTs 193, 204 and 204c in the 1970s and 1980s, and DT I O4 in the 1990s. Although there were similarities in the initial emergence of several of these through cattle, they differed in the extent of their spread and whether resistance was carried on plasmids (DT204c) or predominantly on the chromosome (DT 104).

46. We are pleased to see the fall in the number of incidents of DTIO4 in food animals, and in isolations from humans (see Chapter 5). It is hoped that, over the next few years, there will be further reductions to at least the levels seen in the 1980s. However, given the pattern of emergence of different phage types over the last three decades, we are concerned that "new" antibiotic-resistant clones of S.typhimurium will continue to emerge, or old ones re-emerge. The UK data suggest that the majority of antibiotic resistance seen in salmonellas is associated with clones of S. typhimurium. Although reasons have been identified for the spread of some of these clones, we still need to have a better understanding of the processes which bring about their emergence and disappearance.

47. We found evidence of differences between Scotland, and England and Wales in resistance of S. typhimurium isolates from food animals. In particular, the frequency of nalidixic acid resistance appeared to be higher in isolates from England and Wales. It not clear whether the differences between the data sets reflect usage of fluoroquinolones or methodological differences in determining resistance. A similar difficulty was found in comparing Northern Ireland data. We also noted that some laboratories only screened for nalidixlc acid resistance, whereas others include enrofloxacin and/or ciprofloxacin. In addition, arbitrarily chosen breakpoint concentrations by different laboratories have made it very difficult to compare data on quinolone resistance. These problems make it difficult to discern whether there are genuine regional differences in the UK which might relate to antibiotic usage. We understand that the VLA are proposing to work towards adopting a standardised disc diffusion method from the British Society for Antimicrobial Chemotherapy. We welcome this move if it leads to greater standardisation and enables comparisons to be made between resistance data from different sources.

48. Compared to Salmonella spp., we found very little published data on antibiotic resistance in isolates of Campylobacter from animals, and we received no data on the situation in Scotland. Although there is evidence of enrofloxacin and macrolide resistance, the data are based on small local surveys rather than national surveillance. This makes it difficult to identify trends over time or whether there are any regional differences, as there appear to be for salmonellas. When the limited UK information is compared to data from other countries, it would appear that the UK is not unique in seeing resistance in isolates of Campylobacter from animals. In terms of quinolone and macrolide resistance, the UK would appear to be no worse than many other countries. However, there is no room for complacency as Campylobacter is frequent in poultry and we have seen evidence of a substantial increase in nalidixic acid resistance in S. typhimurium isolates associated with chickens and turkeys. Because Campylobacter spp. rarely causes disease in food animals, there is currently no national network for speciating, subtyping or testing antibiotic susceptibility of veterinary isolates of these bacteria on a routine basis.

49 Antibiotic resistance in Escherichia coli 0 1 57 appears to be uncommon in isolates from food animals, although we saw no data on isolates from animals in Scotland or Northern Ireland. Although some groups of enterovirulent E. coli are significant pathogens of animals, E.coli 0157 and other -producing serogroups rarely cause disease in animals. As with Campylobacter, there is no dedicated national network for testing antibiotic susceptibility of animal isolates of E. coli 0157, although the PHLS LEP screen animal isolates submitted by CVL.

50. We understand that MAFF is currently planning to start surveillance of foodborne pathogens (Salmonella, Campylobacter, E. coli0157) in cattle, sheep and pigs at slaughter for human consumption. This surveillance, which is expected to start in 1999, will be undertaken at abattoirs and will include screening of isolates for antibiotic resistance.
Whilst welcoming this initiative, there remains a need for longer-term surveillance so that changes can be monitored over time and in different parts of the UK. We have seen from a study by Calvert et al. that there can be marked variations in the geographical distribution of S. typhimurium DTIO4 from cattle and humans in Scotland, and such factors need to be considered when planning surveillance. We received evidence that resistance in foodborne pathogens such as Salmonella and E. coli from poultry slaughtering plants may not be distributed evenly. We were informed that there may be "pockets of resistance" depending on local practices, and clearly these could be missed if surveillance is not planned in an appropriate way. A well structured surveillance system in animals for zoonotic foodborne pathogens would form an important data source for the proposed Food Standards Agency (FSA). Effective monitoring of foodborne pathogens at both the animal and human ends of the food chain will be essential if the FSA is to be successful in tackling foodborne disease and ensuring the microbiological safety of food.

51. Although we received information on E. coli other than E. coli 0157, this was largely based on isolates from sick animals tested for antibiotic resistance by the Veterinary Investigation Centres (VICS) in England and Wales. There is a need to extend monitoring for Salmonella, Campylobacter, E. coli 01 57 and other E. coli to include "healthy animals". It is important that monitoring is carried out for E.coli as a whole, as this organism is a potential marker for tracking resistance through the food chain.

52. We found little data on Clostridium perfringens and other anaerobic bacteria in the UK, although Cl. perfringens causes animal disease as well as food poisoning in humans. We understand that at present there is limited screening of anaerobic bacteria for antibiotic resistance and that there are plans for the Veterinary Laboratories Agency (VLA) to collate this information.

53. There are currently little UK data on the prevalence of enterococci in food animals. We understand that this is likely to be addressed by a current industry-funded survey of poultry and pigs to determine the prevalence of enterococci in animals at slaughter. The countries involved are Denmark, France, Netherlands, Sweden, Finland, Spain and the UK. In the UK, only poultry will be sampled. This survey will also include screening of isolates for MICs of growth promoters.


Chapter 3 recommendations

54. We recommend that Government should initiate studies to identify the key factors that lead to the emergence and disappearance of multiresistant clones of Salmonella typhimurium. (para. 3.134)

55. Government should ensure that isolates of salmonellas from animals in England and Wales, Scotland and Northern Ireland are compared, using appropriate methodologies, to see whether there are any regional differences in antibiotic susceptibilities. (para. 3.135)

56. As indicated in Chapters 4 and 5 of our Report, we emphasise the need for a coordinated approach to surveillance encompassing the whole food chain. The following recommendations specifically address veterinary surveillance but need to be considered in parallel with those in Chapters 4 and 5.

We recommend that the Government considers how the monitoring of pathogens in food animals could be improved, with a view to obtaining data on the prevalence, subtypes and antibiotic resistance of important foodborne pathogens, and publishing this information on a regular basis (para. 3.136);

we recommend to reference laboratories that the relationship between antibiotic resistance and subtype of animal isolates of Campylobacter should be established, to aid further studies aimed at identifying the sources of antibiotic-resistant strains (para, 3.136);

we recommend to Government that those organisations directing or undertaking surveillance of organisms isolated from animals should work together with organisations monitoring resistance in bacteria from food and humans to produce an annual UK report summarising antibiotic resistance in the food chain (para. 3.136);

we recommend that surveys of UK veterinary laboratories be carried out to ascertain current practices with regard to antibiotic resistance testing of microorganisms important in the food chain, with a view to improving comparability between animal, food and human data. (para. 3.136)

57. We recommend to the Veterinary Laboratories Agency (VLA) that consideration be given to including Escherichia coli in any surveillance of antibiotic resistance in "healthy" food animals. (para. 3.137)

58. We recommend that VLA data on resistance in anaerobes are collated and published at the earliest opportunity. (para. 3.138)


Chapter 4 : Patterns of antibiotic resistance in bacteria isolated from foodstuffs

59. In Chapter 4 we look at the occurrence of resistant microorganisms in foodstuffs. The reports we have seen from other countries suggests that the UK is not unique in having antibiotic-resistant microorganisms in the food chain. However, it is not always possible to compare UK data with those from other countries because of differences in the methodology used and the prevalence of different subtypes (eg. Salmonella serotypes). Although there are initiatives by the European Commission (EC), Office International des Eplzooties (OIE) and World Health Organisation (WHO) to address surveillance for antibiotic resistance in clinical isolates, more needs to be done to address surveillance and standardisation of methods for microorganisms in the food chain.



60. A major problem in the analysis of antibiotic susceptibility data was observed in both the UK and international reports and publications. We found a wide variation in the extent of data available for foodstuffs. Because the size of studies, methodology employed, and basis for data collection vary, it is difficult to make comparisons, particularly between countries, and interpretation of the data has had to be made on broad trends in resistance. This is particularly relevant for fluoroquinolones where use of a high disc concentration (eg. 5mcg) can lead to under-reporting of resistance. In addition, there is as yet no standardised methodology for testing susceptibility of Campylobacter strains to any antibiotic.

61. The low level of resistance and, in particular, multiresistance in most isolates of Salmonella enteritidis in the UK is supported by the findings from other countries. Multiresistance as seen in Salmonella typhimurium isolates from food in the UK is of particular concern as this serotype is the second most frequent Salmonella from humans in the UK.

62. We found very little information on campylobacters from foods in the UK, apart from several local studies. These have provided some information on quinolone resistance in campylobacters from raw foods (mostly poultry) and suggest that levels of resistance are no higher, and may well be lower, than in some other European countries. Apart from Campylobacter coli, erythromycin resistance in UK isolates appears to be low.

63. Apart from those collated by the PHLS, there appear to be little if any published data on resistance in Escherichia coli 0 1 57 isolates from foods. Although the role of antibiotics in treatment of human infections is unclear, it is important that resistance in food isolates of this organism, as well as other verocytotoxin-producing Escherichia coli (VTEC), is actively monitored.

64. Limited information was found on antibiotic resistance in food isolates of Clostridium perfringens, Staphyloccocus aureus and enterococci in the UK. No information was found concerning resistance in Bacillus cereus.

65. In terms of antibiotic resistance, the main foodborne pathogens of direct concern are Salmonella (particularly S. typhimurium), Campylobacter and E. coli. The most extensive data we received on antibiotic resistance of food isolates of enteric pathogens in the UK were from the Public Health Laboratory Service Laboratory of Enteric Pathogens (PHLS LEP). Much of this information has been derived from screening isolates submitted to LEP following surveys, outbreak investigations and routine sampling. Information available from elsewhere in the UK was considerably more patchy. Data are available for Salmonella, but even here, there are gaps which make it difficult to discern national or regional trends or detect changes over time. We are particularly concerned about the lack of comprehensive data on antibiotic resistance for Campylobacter, E. coli and other microorganisms isolated from foodstuffs produced in the UK.

66. We also noted a lack of comprehensive data on antibiotic resistance for Campylobacter, E. coli and other microorganisms isolated from foodstuffs imported into the UK. Such information is essential to determine the effectiveness of measures taken at national or international levels.

67. Antibiotic resistance screening is often regarded as an "add on" component to surveys of microorganisms in foods. However, we feel that its importance needs to be given greater prominence during the planning phase of studies so that careful consideration is given to sampling, the use of appropriate testing methodologies and the archiving of isolates for future reference. There is a need to strengthen the information collected in this area and a need for more surveys where screening for antibiotic resistance is a primary objective rather than a secondary one.

68. Most of our information on antibiotic resistance in foods comes from pathogens isolated from raw foods and, to a lesser extent, ready-to-eat foods, particularly where these are associated with outbreaks. Although this information is relevant to consumer exposure to antibiotic-resistant foodborne pathogens, it forms only part of the picture in terms of the antibiotic resistance residing in the microbial flora of foods. There appears to be little information on antibiotic resistance in relation to the other groups of microorganisms in foods (eg. other Enterobactertaceae, lactic acid bacteria, pseudomonads, bacilli etc). Some of these organisms will have intrinsic resistance to certain antibiotics, a proportion will have been exposed directly to antibiotics, and others will have acquired genetic material conferring antibiotic resistance from interactions within the microflora. The microbial flora and the component which is antibiotic-resistant may be modified by food processing procedures (eg. pasteurisation, addition of acidulants and salt, vacuum or modified atmosphere packaging), interactions between the microbial flora, as well as temperature, storage time and food preparation practices prior to consumption.

69. We highlight in Chapter 2 of our Report the widespread potential amongst bacteria for transfer of genetic material conferring antibiotic resistance. With this in mind, we found little information addressing the effect of food processing and preparation on the antibiotic-resistant microflora of foods or the effect of these processes on transfer of resistance between bacteria.

70. We have already highlighted the fact that resistance data on foodborne pathogens isolated from foods may not reflect antibiotic resistance present in the microflora of foods as a whole. We recognise the need for attention to be given to more general indicator organisms, to enable more sensitive monitoring of national and regional trends in resistance over time for particular food commodities. E. coli would appear to fulfil this role for Gram-negative bacteria and Enterococcus faectum is a possible candidate for Gram-positive bacteria. E. coli is an indicator of human or animal faecal contamination and is more frequent in foodstuffs than Salmonella or Campylobacter. In addition, although most of the gastrointestinalassociated infections in man and animals are associated with enterovirulent strains, the organism is also an important cause of hospital-acquired infections and is the commonest cause of urinary tract infection (UTI) in the community.

Chapter 4 recommendations

71. We recommend enhanced national and international surveillance for antibiotic resistance of microorganisms isolated from foods. Surveys should be conducted where the primary aim is to gather information on antibiotic resistance and , in planning future food microbiological surveys, consideration should be given to the screening of foodborne pathogens and other microorganisms for antibiotic resistance using appropriate methodologies. (para. 4.67)

72. We recommend studies to:-

gather further information on antibiotic resistance in campylobacters in the UK (para. 4.68); and

explore the variability in the isolation of resistant campylobacters from retail poultry observed in several studies. (para. 4.68)

73. We recommend that all microbiological reference laboratories for enteric pathogens in the UK should consider screening these and other microorgansisms isolated from routine food samples for antibiotic resistance and publishing their data on a regular basis. (para. 4.69)

74. As indicated in Chapters 3 and 5 of our Report, we emphasise the need for a co-ordinated approach to surveillance encompassing the whole food chain. The following recommendations specifically address surveillance of food isolates, but need to be considered in parallel with the recommendations in Chapters 3 and 5.

we recommend to reference laboratories that the relationship between antibiotic resistance and subtype of food isolates of - Campylobacter ssp. should be carefully examined to aid further studies aimed at identifying the sources of antibiotic-resistant strains (para. 4.70);

we recommend to Government that those organisations directing or undertaking surveillance of organisms isolated from food should work together with organisations monitoring resistance in bacteria from animals and humans to produce an annual UK report summarising antibiotic resistance in the food chain (para. 4.70);

we recommend that surveys of UK food laboratories be carried out to ascertain current practices with regard to antibiotic resistance testing of microorganisms important in the food chain, with a view to improving comparability between animal, food and human data. (para. 4.70)

75. We recommend to research funding organisations that studies be undertaken to assess the effect of food processing, storage conditions and food preparation on the antibiotic-resistant microflora of foods and the transfer of resistance between food bacteria. (para. 4.7 1)

76. We recommend that, using appropriate methodologies, Escherichia coli isolates from foodstuffs should be screened for antibiotic resistance, to provide a more sensitive indication of differences between food commodities and changes in resistance over time. (para. 4.72)


Chapter 5: Human infections associated with antibiotic resistant foodborne pathogens

77. Chapter 5 considers the human infections associated with antibiotic-resistant bacteria which occur in the food chain, Including trends in both laboratory reports and antibiotic resistance, for the major foodborne pathogens and other relevant microorganisms. Again, the position both within and outside the UK is addressed. Laboratory reports of salmonellas, campylobacters and Escherichia coli 0157 have increased substantially over the last 10 years in the UK. Against this background, there is evidence of an increase in the proportion of isolates exhibiting resistance to single or multiple antibiotics. In salmonellas, multiple antibiotic resistance (ie. to four or more antibiotics) has become more frequent in the epidemiological important serotypes, Salmonella typhimurium, Salmonella hadar and Salmonella virchow and, since 1990, there has been an epidemic of multiresistant S. typhimurium DTIO4 in the UK. Although there was a 26% decline in isolations of S. typhimurium DTIO4 in 1997, related multiresistant phage types DTIO4b, U302, U309, U3 10 and U311 have emerged and will need to be monitored closely. In addition, genotypically-indistinguishable isolates of S.typhimurium DTI2 with the same multiresistance pattern, ACSSUT, have also been identified. The epidemiological changes seen in Salmonella serotypes over a number of years suggests that a better understanding is needed of how and why multiresistant strains emerge and disappear.

78. The data presented in this Chapter have revealed a difference in the prevalence of ciprofloxacin resistance in salmonellas screened by reference laboratories in England and Wales (Public Health Laboratory Service Laboratory of Enteric Pathogens) and Scotland (Scottish Salmonella Reference Laboratory). We understand that these laboratories are now using the same methodology and breakpoint concentrations for defining resistance, and the differences found require further investigation.

79. Although there are fewer data available on Campylobacter, we are particularly concerned about the rise in fluoroquinolone resistance in the UK over the last 10 years. Although reported levels are not as high as in other countries (eg. Spain, Taiwan), this rise is particularly important when set against the background of a continuing rise in the number of laboratory reports of Campylobacter from humans.

Macrolides such as erythromycin are currently the drugs of choice for treating Campylobacter infections and, fortunately, the level of resistance to this antibiotic in the UK is currently low in Campylobacter jejuni and moderate in the less common Campylobacter coli. The emergence of Campylobacter strains exhibiting both fluoroquinolone and macrolide resistance would give particular cause for concern and therefore steps should be taken to reduce or limit the further spread of quinolone and macrolide resistance in these bacteria. As highlighted in our Interim Report on Campylobacter, there is a need for better typing systems for these organisms. Whilst welcoming the various initiatives underway or being considered in this area, we are concerned that there is little information on the relationship between subtypes of Campylobacter and antibiotic resistance, and this needs to be examined. We understand that this is being partly addressed for England and Wales by the PHLS Campylobacter Reference Unit at LEP.

80 Only limited information is available on antibiotic resistance in E. coli 0157. Evidence suggests that there is potential for the further development of resistance in E. coli 0 1 57 and the position requires close monitoring.

81. Comparison of veterinary, food and clinical data is often difficult because of differences in policy and methodology regarding the screening of microorganisms. We were particularly impressed by the DANMAP publications from Denmark linking animal, food and human data on antibiotic resistance with information on antibiotic use in animals and man. Such publications have the advantage of bringing relevant data together in one place thereby making it more accessible to the scientific community. We feel that something similar should be devised for the UK.

82. As highlighted in previous Chapters of our Report, we are not convinced that the methodology being used in veterinary, food and clinical laboratories enables reliable comparisons to be made between data sets both in the UK and internationally. The methodology being used in laboratories should be examined with a view to achieving a consistent approach in assessing resistance of foodborne microorganisms important in the food chain. We recognise that various initiatives in this area are already planned or underway but most only address the problem from either the clinical or veterinary perspective. The European Enter-net initiative, funded by the European Commission, should help in the harmonization of laboratory methods for measuring and recording antibiotic resistance patterns for salmonellas in some laboratories in Europe. However, standardisation and harmonisation needs to go much wider, encompassing all laboratories concerned with organisms which might be important in the food chain.


Chapter 5 recommendations

83. We recommend to funding organisations that research be undertaken to establish why certain Salmonella serotypes (eg. S. hadar, S. typhimurium, S. virchow) develop antibiotic resistance and multiresistance, whereas others (eg. S. enteritidis) have remained largely sensitive. (para. 5.80)

84. We recommend to Government that the basis for regional differences in fluoroquinolone (eg. ciprofloxacin) resistance in salmonellas in the UK should be investigated. (para. 5.81)

85. As indicated in Chapters 3 and 4 of our Report, we emphasise the need for a coordinated approach to surveillance, encompassing the whole food chain. The following recommendations specifically address surveillance of human isolates but need to be considered in parallel with the recommendations in Chapters 3 and 4:-

we recommend to reference laboratories that the relationship between antibiotic resistance and subtype of human isolates of Campylobacter should be carefully examined, to aid further studies aimed at identifying the sources of antibiotic-resistant strains (para. 5.82);

we recommend to Government that those organisations directing or undertaking surveillance of organisms isolated from humans should work together with organisations monitoring resistance in bacteria from animals and food to produce an annual UK report summarising antibiotic resistance in the food chain (para. 5.82);

we recommend that surveys of UK clinical laboratories be carried out to ascertain current practices with regard to antibiotic resistance testing of microorganisms important in the food chain, with a view to improving comparability between animal, food and human data. (para. 5.82)

86. We have seen in Chapter 4 and 5 that foreign travel and imported foods are sources of resistant foodborne pathogens, and that multiresistant bacteria can become world-wide in distribution (eg. S. typhimurium DTIO4). It is important that we have appropriate methodology which will allow such organisms to be monitored for resistance in a consistent and standardised way. We therefore recommend that Government seeks ways of achieving further standardisation of antibiotic resistance testing across Europe and internationally. (para. 5.83)

Chapter 6: Evidence of the food chain contributing to human infections with antibiotic resistant microorganisms

87. In Chapter 6 we consider the evidence of the food chain contributing to human infections with antibiotic-resistant microorganisms. This Chapter also considers other pathways by which antibiotic-resistant microorganisms may infect humans. We have seen in Chapter 3 that the intestinal flora of animals can provide a reservoir of antibiotic-resistant bacteria which can infect or colonise man via the food chain. Such strains are frequently found in food animals, particularly cattle, pigs and poultry, and these or related strains have also been isolated from companion animals, wild animals, birds and the environment.

88. Information from surveillance of Salmonella spp. in animals, food and humans strongly supports the view that antibiotic-resistant strains of these organisms are being transferred from animals to humans, principally via the food chain, but also via direct contact with animals, and with faecally-contaminated environments. It is perhaps no coincidence that evidence supporting food as a pathway is more secure for Salmonella spp. than for other pathogens found in the food chain. The current surveillance system for Salmonella is more extensive, and typing methods more robust, than for other pathogens, making it possible to monitor changes in the animal and human populations. Nevertheless, there is no room for complacency, as there remains a need for a more co-ordinated approach to the surveillance of animals, humans and foodstuffs for salmonellas, as well as fingerprinting methods which enable the source of resistance to be teased out more effectively. Advances in the ability to discriminate between strains of resistant salmonellas such as DTIO4, and to pinpoint the location and mechanism of resistance genes, should eventually enable the origin(s) of human isolates to be defined more precisely. We are encouraged by recent developments in fingerprinting techniques, and the closer links being established between the Public Health Laboratory Service and the Veterinary Laboratories Agency. Sound links in this area are essential, and the proposed Food Standards Agency and appropriate Government Departments will also need to be involved in discussions in this area.

89. The evidence we have seen for the transmission of resistant campylobacters is based on trends observed in quinolone resistance in animal and human populations. We are concerned that Campylobacter is currently the most frequent bacterial pathogen isolated from IID in humans in the UK. At the same time, our information on subtypes and antibiotic resistance is significantly weaker than for Salmonella or Escherichia coli 0157. The trend data we have seen appear to indicate a contribution of veterinary usage of quinolones to resistance in human isolates of Campylobacter. The picture we see with respect to fluoroquinolone resistance in salmonellas also points to a veterinary contribution to this resistance, as illustrated by the trends in the data for DTIO4. Campylobacters and Salmonella typhimurium DTIO4 both occur in poultry, and these pathogens are likely to have been exposed to similar antibiotics. Given the propensity for Campylobacter and certain salmonellas to develop quinolone resistance, it seems reasonable to conclude that veterinary usage of fluoroquinolones will have made a significant contribution to quinolone resistance in isolates of Campylobacter and Salmonella from humans. Given the levels of resistance being seen in some other countries, particularly for Campylobacter, it is important that fluoroquinolones retain efficacy in the treatment of human and animal infections.

90. We are concerned about the increasing prevalence of resistance seen in enterococci, as these organisms could be transmitted to humans via the food chain. These organisms are widespread as components of the normal flora of food animals and humans, and have a propensity to develop multiple resistance to important antibiotics used, or proposed for use, in human therapy.

There is clear evidence that the use of the glycopeptides (avoparcin), macrolides (spiramycin, tylosin) and streptogramins (virginiamycin) in animal husbandry will select for resistance in enterococci, and that resistant strains will be found in the food chain primarily in products of animal origin. The transfer of resistant strains of animal enterococci, and their resistance genes through the food chain to humans, could compromise the treatment in the UK of serious enterococcal and other infections in humans with existing antibiotics (dalfopristin/quinapristin, erythromycin, teicoplanin, vancomycin), and with others that are still under development (everninomycins). Although the full picture of evidence linking resistance in animal, food and human isolates is incomplete, taken as a whole we feel that the information currently available is sufficient to indicate a genuine problem of resistance in this area, and that the contribution from resistance arising in enterococci from food animals is preventable.

91. Based on the limited information currently available, it is difficult to ascertain the relative contribution of different foods within the food chain in the flow of resistance to the human population. For example, enterococcal have been isolated from meat and poultry, although these products are normally cooked prior to consumption. Although enterococci are more heat resistant than many non-spore forming bacteria, they would not be expected to survive cooking. However, experience shows that failure to cook properly, or cross-contamination from raw to cooked foods, means that such organisms can survive and colonise humans. Limited surveillance suggests that numbers of enterococci in foods may be quite low, but we have little information about food consumed in a raw state such as vegetables and fruits, particularly those products which have been fertilised with animal manure or sewage sludge.

92. We found some evidence that fermented foods can contain VRE, and animal products such as certain cheeses, yoghurts and fermented sausages will contain large numbers of lactic acid bacteria (enterococci, lactobacilli, pediococci, which will be consumed. We do not know what contribution organisms in these foods make to resistance in the food chain nor, perhaps more importantly, the potential for exchange of resistance genes with resistant enterococci in animals.


93. The bacterial species which infect those that work in close proximity with animals, such as farmers, veterinary surgeons and slaughterhouse workers, usually present little risk to the human population in general, although there are examples whereby resistance may spread from these groups to the wider population (eg. in the case of streptothricin).

94. The environment is clearly a potential source of antibiotic-resistant organisms which can enter the food chain, or infect/re-infect animals and humans through contact. There is a need for more information through research and surveillance and this is indicated in recommendations in Chapter 12 of our Report.



Chapter 6 recommendations

95. We endorse the recommendation made by the House of Lords Select Committee on Science and Technology, in their report on resistance to antibiotics, that "the veterinary profession must address the problem of over-use of fluoroquinolones" and feel that targeted codes of practice on prescribing should be introduced as soon as possible. (para 6.120)

96. We recommend that the relative contribution of meats, dairy products, raw vegetables and fruits as vehicles for antibiotic-resistant enterococci should be clarified (para 6.121)

97. In addition, we believe that it is extremely important that there should be continual surveillance and assessment of the risks to humans associated with the use of those growth promoters still authorised in the EU. We make appropriate recommendations in Chapter 10 of our Report.


Chapter 7: Approval, prescribing and control measures relating to veterinary medicines

98. Chapter 7 provides background on the conditions governing the approval, prescribing and control of veterinary medicines. There is a comprehensive system of controls on veterinary medicines, based on European Union legislation, in place in the United Kingdom. No antibiotic is authorised for the treatment of food animals until the Veterinary Products Committee has satisfied itself on the questions of safety, quality and efficacy. Included in safety and efficacy is an assessment of the risks of resistance and cross-resistance. In relation to new antibiotics, the VPC operates on the principle that these should not necessarily be precluded from therapeutic use in animals but that their prophylactic use should be discouraged.

99. We note that assessment of the risks of resistance and cross-resistance are included in the examination of safety and efficacy. We should nevertheless like to see the licensing authorities throughout the EU making much greater use of relevant empirical data in the approvals process. By this we mean that, before antibiotic is authorised for veterinary use, including as a growth promoter or in medicated animal feed, there should be testing for microbial antibiotic resistance on the basis of the trialing of the product concerned in target animal species under intended conditions of use. The data generated by these trials should be made publicly available in support of licensing decisions.

100.We do not advocate prohibition of the therapeutic use of antibiotics in animals. But there needs to be a structured approach to the investigation and reporting of the incidence and prevalence of resistance. The emphasis of the pharmaceutical industry's efforts has been the establishment of efficacy of the products they develop and market, and efficacy has not infrequently been assessed in relation to groups of animals which have not been exposed to the antibiotic being investigated. We believe that the regulatory authorities should give a high degree of attention to the question of microbial antibiotic resistance, both in the initial licensing process and subsequently at the 5 year licence review stage.

101 As we have noted elsewhere in our Report, it is virtually impossible at the present time to obtain meaningful data on the amounts of antibiotics used by the veterinary profession in the treatment of food animals and, in addition, administered in the form of medicated feed and growth promoters. The availability of such information would greatly enhance our ability to identify, analyse and respond to problems of resistance in a precise and targeted way and to minimise the potential adverse effects on food safety.

102 We were told on more than one occasion during the preparation of this Report that there is an illegal trade in antibiotics which serves to distort the accuracy of any data on usage. We were presented with no firm evidence on which to judge the extent, if any, of such trade. It is not within the remit of this Committee to pursue the matter but, if there is firm evidence available of the extent of any illegal trade, the data should be published alongside any other usage data which may become available


Chapter 7 recommendations

103 We recommend that the Government, in association with the other Member States of the European Union, should require applicants applying for marketing authorisations for antibiotics for veterinary use to supply data derived from the testing of the antibiotic concerned for microbial resistance in target animal species under intended conditions of use. Such data should be made publicly available in support of licensing decisions. (para. 7.22)

104 We recommend that the Government discusses with the veterinary profession and the pharmaceutical industry ways in which the information gathered as part of post-marketing surveillance, including that on the incidence and prevalence of resistance, could best be made available to the veterinary and medical professions. It is important that the regulatory authorities give a high degree of attention to the question of microbial antibiotic resistance, both in the initial licensing process and subsequently at the 5 year licence review stage. (para. 7.23)

105 We recommend that the Government takes steps to establish the amounts of antibiotics given to food animals. This information should be published at regular intervals by the Veterinary Medicines Directorate and should, at the very least, be so structured as to provide a breakdown by compound, class, medical equivalent (where appropriate) and target species. (para. 7.24)

Chapter 8: The use of antibiotics in farm animals

106. In Chapter 8 we look at practices in relation to the use of antibiotics in farm animals. We are encouraged by a number of guidelines and statements of intent presented to the Working Group by the veterinary profession and the farming industry. We strongly support the following principles which were espoused during the course of the Group's investigations.

107. Antibiotics should never be used as an easy alternative option to good husbandry practice and management, site hygiene or, where it is available, vaccination. All prescribing by veterinarians must be for animals under their care and all antibiotics used for purposes other than growth promotion must be prescription only medicines. Detailed justification should be provided for the use of "cascade" medicines, perhaps as part of the written prescription. If the risks of selecting for resistance are to be minimised, the selection of appropriate antibiotics is essential. The general rule should be that therapy should be based on establishing in advance the sensitivity of the causal organism to the antibiotic treatment proposed. Where antibiotic treatment is essential, careful diagnosis is necessary to enable precisely targeted drugs to be used, thus avoiding the use of broad spectrum products. In all cases, the efficacy of antibiotics used should be closely monitored to ensure continuing sensitivity to the treatments of choice. Consideration should always be given to the question of resistance, particularly when treating large groups of animals over long periods of time.


108. We welcome the suggestion that the development of appropriate dosage strategies should be encouraged. Veterinarians should explore ways of reducing the use of antibiotics in disease control and should assist with studies into alternatives to antibiotics, including vaccination, disease eradication, improved hygiene systems etc. Appropriate codes of practice should be developed and maintained to encourage heightened awareness of the role of veterinary prescribing in relation to antibiotic resistance. Prophylaxis should only be used in clearly defined circumstances and veterinary practices should develop a written policy or protocol covering the circumstances in which it is deemed appropriate. Detailed preventative medicine programmes should be documented for all livestock-based food production enterprises, covering routine medication (including non-prescription medicines such as anticoccidials and growth promoters), competitive exclusion and probiotic treatments and vaccines. Prescribing of antibiotic medication should reflect possible implications for other elements of the programme.

We particularly welcome the British Veterinary Association's expression of its willingness to adopt a leading role in informing and guiding the profession in relation to responsible veterinary prescribing through the promotion of policy, pharmacy courses, the dissemination of information, guidance on the selection and administration of antibiotics and on approaches to the treatment of individual species, and through the publication and promotion of its Code of Practice on Medicines. In view of the fact that veterinarians are a very important vehicle for the supply and administration of veterinary medicinal products, we would welcome their developing a system of self-audit of veterinary practice, with special emphasis on the use of antibiotic substances. We see this as an area where the BVA and other professional representative bodies could take a helpful lead.

109 We also welcome the formation in Summer 1998 of the Responsible Use of Medicines in Agriculture (RUMA) Alliance from amongst the British Pig Association, British Poultry Meat Federation, British Retail Consortium, British Veterinary Association, Meat and Livestock Commission, National Farmers' Union, National Office of Animal Health, United Kingdom Agricultural Supply Trade Association and others. We understand that RUMA's aim is to establish guidelines to help the livestock industry to reduce its reliance on antibiotics and that species-specific Working Groups (covering poultry, pigs, beef and sheep, and the dairy sector) have subsequently been formed to translate the concept of reduced usage into practical proposals and to report back to the main RUMA Board. The central theme of the Groups' terms of reference is to establish and communicate practical strategies by which the use of antibiotics might be reduced. We strongly encourage the RUMA Alliance in its endeavours.

110. The veterinary schools and colleges have a key role to play in ensuring that the, question of microbial antibiotic resistance is given a suitably high profile in undergraduate training. As a first step, existing courses should be reviewed to see whether the issue of resistance is being appropriately covered and, if not, they should be redesigned at the earliest opportunity.

111. We regard high standards of on-farm treatment records as an essential element of any more enlightened approach to the use of antibiotics. We received some evidence that compliance levels were extremely poor. Other information which we saw suggested that performance was appreciably- better, although the data were based on a very low level of inspections (about 1,600 on-farm records inspected annually). Greater effort is needed to ensure that farmers understand their obligations to keep records of veterinary medicines administered to their animals, that regular compliance audits are undertaken by the SVS based on a representative sample of the farm population, and that effective follow up action can be taken where non-compliance is identified.

112. Hazard Analysis Critical Control Point (HACCP) principles are fundamental to improving food safety, and the veterinary profession should bring its skills and influence to bear throughout the food chain in furtherance of these principles.
We would also encourage closer liaison between all parties involved in the production, supply, administration and use of antibiotics in order to monitor developments in microbial antibiotic resistance and to consider practical options for addressing emerging trends.

113. We should like to see all farms or production units receiving regular veterinary visits to audit animal disease profiles and general performance indicators, to accumulate and scrutinise mortality, morbidity and general health data, and to record antibiotic resistance patterns so that antibiotic prescribing can be adjusted accordingly.

114. The State Veterinary Service (SVS) has a statutory role in relation to farms, both in terms of animal disease and welfare. This means that the SVS is ideally placed to take the lead in encouraging changes which the data generated under management plans show to be necessary. We hope they will take this task on board.

115. Given the plethora of farm assurance schemes currently available, it is important that there is consistency to all schemes so that data generated can be meaningfully compared between farms, regions and countries

Chapter 8 recommendations

116. We recommend that the Government coordinates the development of a coherent strategy aimed at reducing the veterinary use of antibiotics. (para. 8.47).

117 More specifically, we recommend Government to take all possible measures to ensure that :-

all antibiotics used for purposes other than growth promotion are prescription only medicines (POM) (para. 8.48);

all prescribing by veterinarians is for animals under their care (para. 8.48); and

detailed written justification is provided by veterinarians using cascade medicines. (para. 8.48)

118. We also recommend that Government brings together the relevant bodies to produce and publish without delay:-

Codes of Practice aimed at reducing the use of antibiotics (para. 8.49);

appropriate dosage strategies (para. 8.49);

detailed preventative medicine programmes for all livestock-based food production enterprises covering routine medication (including the use of anticoccidials and growth promoters), the length of treatment regimes, competitive exclusion and probiotic treatments and vaccines (para. 8.49); and

policies and protocols for the use, storage and disposal of antibiotics (para. 8.49).

119. We recommend that the British Veterinary Association (BVA) and the other relevant professional representative bodies, in cooperation with the veterinary schools and colleges, the farming industry and others, develop appropriate courses to better inform veterinary prescribing and use of antibiotics and to draw attention to the potential dangers of resistance. (para. 8.50)

120. We further recommend that the veterinary schools and colleges review their existing courses to ensure that microbial antibiotic resistance is given a suitably high profile in undergraduate training. (para. 8.5 1)

121. It is a requirement of current residues legislation that specified farm medication records are maintained in a prescribed format and completed within 72 hours of administration. We regard high quality record-keeping as essential and recommend that the Government mounts regular campaigns to remind the livestock industry of its statutory obligations, to improve enforcement, and to greatly enhance current performance levels. (para. 8.52)

122. We also recommend that the Government carries out regular, statistically-robust, compliance surveys and reviews existing arrangements to ensure that effective follow up action can be taken where non-compliance is identified. (para. 8.53)

123. We recommend that the Government encourages the use of HACCP principles as a tool for improving farm practice and as a means of ensuring the responsible use of antibiotics, thus tackling the problem of microbial antibiotic resistance. (para. 8.54)

124. We recommend that Government encourages regular veterinary visits to all livestock farms or production units to audit animal disease profiles and general performance indicators, to accumulate and scrutinise mortality, morbidity and general health data, and to record antibiotic resistance patterns so that antibiotic prescribing can be adjusted accordingly. (para. 8.55)


Chapter 9: recommendations

125. Chapter 9 considers the role of medicated animal feedingstuffs in relation to microbial antibiotic resistance. We have been impressed by the detailed requirements laid down under the United Kingdom Agricultural Supply Trade (UKASTA) Feed Assurance Scheme and the Animal Medicines Training Regulatory Authority (AMTRA) Code of Practice for ensuring that medicated animal feeds intended for food animals are manufactured, stored and distributed in a safe and professional manner. Whilst we do not doubt the dedication of Royal Pharmaceutical Society of Great Britain (RPSGB), Department of Agriculture for Northern Ireland (DANI) and Department of Health and Social Services Northern Ireland (DHSS (NI)) inspectors, we are concerned about the frequency of inspections. We question whether inspecting feed mills once a year on average is sufficient and this statistic leads us to ponder in turn how often on-farm mixers, where the incorporation of medicines may be rather more haphazard, are inspected. We recognise that enforcement is necessarily resource-intensive but it must equally be recognised that regular compliance monitoring is vital to the effectiveness of control arrangements.

126. We were struck by what we regard as some anomalies in the control arrangements. On-farm mixers are exempt from the provisions of medicated feedingstuffs legislation in respect of medication administered through drinking water, as well as through top-dressed feed. The Expert Group on Animal Feedingstuffs which met under the chairmanship of Professor Lamming commented on the unsatisfactory nature of this situation and recommended that on-farm mixers using medicinal additives and intermediate medicated feedingstuffs in any manner should be required to register with the RPSGB or DANI. We support the Lamming view, but are aware that the Government may be constrained by the limitations of EU legislation.

127. We fully support the aims of the UKASTA Feed Assurance Scheme. Manufacturers who fall to comply with these should not be regarded as suitable for registration by the enforcement authorities. In addition, we strongly encourage all those engaged in the manufacture of medicated animal feedingstuffs to apply Hazard Analysis Critical Control Point (HACCP) principles to their operations. This means not only commercial feed compounders and the integrated poultry producers but the on-farm mixers too.

128. We have reservations about the treatment of discarded medicated feed material. The UKASTA Guidelines seek to ensure that discarded material is reduced to a minimum and is handled with circumspection. However, there is a general presumption that much of this material will be reworked into feeds and that this is acceptable provided suitable care is taken. Whilst there may be compelling economic reasons to justify the re-use of this material, the practice gives cause for concern on food safety grounds.

We would therefore prefer to see discards being appropriately disposed of as waste material rather than being re-utilised in batches of feed. We regard this as particularly important in the case of on-farm mixers where controlling the incorporation of veterinary medicinal products into animal feed is likely to be less easily accomplished than in dedicated commercial feed mills.


Chapter 9 recommendations

129. We recommend that the Government:-

requires regular, on-going surveillance of a representative cross-section of commercial feed compounders, integrated poultry producers and on-farm mixers to test compliance with the law and to oversee the guidelines for ensuring that medicated animal feeds intended for food animals are manufactured, stored and distributed in a safe and professional manner (para. 9.23); and

reviews the adequacy of the current frequency of inspections by the enforcement bodies. (para. 9.23)

130. We recommend that on-farm mixers using medicinal additives and intermediate medicated feedingstuffs in any manner should be required to register with the Royal Pharmaceutical Society of Great Britain or the Department of Agriculture for Northern Ireland. (para. 9.24)

130 We recommend that manufacturers who fail to comply with UKASTMS Feed Assurance Scheme should not be regarded as suitable for registration by the enforcement authorities. In addition, we strongly encourage all those engaged in the manufacture of medicated animal feedingstuffs to apply Hazard Analysis Critical Control Point (HACCP) principles to their operations. This means not only commercial feed compounders and the integrated poultry producers but the on-farm mixers too. (para. 9.25)

132. We recommend that the Government reviews the arrangements under which discarded and surplus medicinal additives may be re-used in medicated feed and medicated pre-mixes with a view to phasing out this practice in favour of appropriate disposal as waste material at the earliest opportunity. (para. 9.26)

133. We note from the Food Standards Agency White Paper the Government's commitment to implementing another recommendation of the Lamming Report, calling for the establishment of an independent advisory committee to advise on all matters not covered by existing advisory committees affecting the safety, quality and efficacy of animal feeds. No doubt the Government will consider the extent to which this new committee, when established, can be utilised in connection with the animal feed recommendations contained in this Report.



Chapter 10: The use of antibiotics as growth promoters in food animal production


134. Chapter 10 deals with antibiotic growth promoters. The Committee's consideration of this subject took place against the background of Parallel deliberations in the European Union. Conscious of the pace of EU developments, the likely timetable for the completion of Microbial Antibiotic Resistance, and the consequent need for the Committee to provide Ministers with timely advice in order to assist them in developing the UK's negotiating position, the Working Groups recommendations on growth promoters were made available to Ministers in _July 1998, in advance of the Working Group's draft Report going to the full A CMSF The text of the letter sent by the Chairman is at Annex H of our Report.

135. Antibiotic growth promoters stimulate an animal's growth, mainly by improving daily liveweight gain and feed conversion efficiency. The mode of action of antibiotic growth promoters is thought to be associated with their inhibitory effect on components of the intestinal microflora. Authorisation, use, labelling and distribution of zootechnical additives (which include antibiotics and other growth promoters) are governed by the provisions of Directive 70/524/EEC. Only those additives listed in the annexes to the Directive may be incorporated into animal feeds or pre-mixtures for animal feeds. However, there is no requirement for a feed additive containing a substance listed in Annex I of Directive 70/524/EEC to be specifically licensed. EU controls on zootechnical additives are being strengthened in 1998/99. When the fifth amendment to Directive 70/524/EEC enters effect, a system of product specific approval will apply (ie. approval will be for a product not a substance).

136. Some in-feed growth promoters used in the UK are related to antibiotics used in human medicine. Various reports - Swarm, Lamming, the House of Lords, the House of Commons, WHO - expressed concern about this situation. Sweden has demonstrated that it is possible to overcome disease problems in food animals when the use of growth promoters is stopped, although the Swedish experience suggests that changes need to be made gradually rather than suddenly. The EU suspended the use of avoparcin as a growth promoter in 1997. A surveillance programme for resistant Enterococcus faecium in pigs and poultry has been established and the results will be used in reviewing the suspension.

Chapter 10 recommendations

137. The ACMSF's Working Group gave careful consideration to whether a comprehensive ban on the use of antibiotic growth promoters, as recommended by the Agriculture Select Committee, was either necessary or desirable; and, if not, whether individual growth promoters warranted withdrawal. They concluded that there should be a two-stage approach.

For those growth promoters where there was a medical equivalent antibiotic in current or planned use, the Group concluded that there was sufficient available scientific evidence of microbial antibiotic resistance to Justify a ban. They therefore recommended that the use of spiramycin, tylosin phosphate and virginiamycin as growth promoters should be phased out at the earliest opportunity. We support this view. (para. 10.25)

138. For those antibiotics where there was currently no medical equivalent, or where their medical use was rare - avilamycin, bacitracin zinc, bambermycin, monensin sodium and salinomycin - the Working Group did not feel that there was currently sufficient information to justify calling for an immediate ban. However, they recommended that the use of these substances should be kept under close review, and if any evidence became available of medical equivalents being developed for clinical use, then their use as growth promoters should be phased out. The Group was particularly concerned about possible developments in the use of avilamycin and bacitracin zinc for clinical use. We support these views. (para. 10.26)

139. Finally, the Working Group recommended that no new growth promoters should be developed which utilise substances which have possible applications in human clinical treatment. Again, we support their view. (para. 10.27)

140. It should be stressed that, in supporting the above recommendations, the Committee subscribes wholly to the relevant conclusions of the Swarm Committee. We are conscious that, in calling for the use of spiramycln, tylosin and vlrginiamycin as growth promoters to be phased out, we run counter to the philosophy underlying the recommendations of the Scientific Committee for Animal Nutrition (SCAN) on virginiamycin (and previously on avoparcin). Whilst SCAN acknowledged that there were grounds for concern over emerging patterns of resistance, they concluded that there was currently insufficient evidence of an immediate risk to public health to justify a ban. In contrast, our view is that, if human health is to be fully protected, then our recommendations for action on growth promoters should reflect the precautionary principle.

141. The EU Agriculture Council decided on 14 December 1998 that the use of bacitracin zinc, spiramycin, tylosin phosphate and virginiamycin should be suspended from I January 1999 (but with provision for the introduction of the suspension to be delayed for 6 months), the decision to be reviewed in the light of the results of the surveillance set up following suspension of the use of avoparcin. We are pleased that this decision reflects the precautionary principle.

Chapter 11: Aquaculture


142. Chapter 11 of our Report considers the development of fish farming and the approach of the aquaculture industry to the range of bacterial diseases encountered. As fish farming has developed in the UK and in Europe a range of bacterial diseases has been encountered which caused both major production problems and animal welfare difficulties. These diseases were initially controlled by the use of a limited range of antibiotics. Fish farming is now a sufficiently large and mature industry to have Justified the development of effective vaccines which have largely supplanted the use of antibiotics for the most serious bacterial diseases.

143. For the main fish bacterial diseases, use of antibiotics is now largely confined to emergency use in the event of breakdown of vaccine protection. In addition to the increasing availability of vaccines, fish farming has also developed a range of improved husbandry methods to reduce the impact of disease. Whilst there is evidence that antibiotic resistance can be selected for in normal therapeutic use in aquaculture, the risks of transfer of such resistance to human consumers by any of the possible routes appears to be low.

144. New fish species are under development for farming in the UK and, during the development of these species, bacterial diseases may be expected to occur which will necessitate the use of antibiotics for disease control before vaccines can be developed. If antibiotics were not available in the UK for use with new species, there would be a danger of development transferring to countries with poorer controls on antibiotic use.

145. Use of antibiotics in ornamental fish, particularly in exporting countries, is significant and evidence exists that multiple antibiotic-resistant bacteria may be frequent in such animals. Although ornamental fish are not eaten, they do enter consumer’s homes and there is close contact.

Chapter 11 recommendations

146. In relation to the development of new fish species for aquaculture purposes, we recognise that there may be a need to use antibiotics for bacterial disease control purposes until such time as appropriate vaccines can be developed. We believe, however, that, as with salmon and trout farming, the industry should invest in the development of appropriate vaccines at the earliest opportunity. To encourage this, we recommend that the Government should licence the use of antibiotics in new species being developed for aquaculture for as short a period as is feasible and equitable. (para. 11. 17)

147. We recommend that the Government issues public advice warning of
the potential risk of the transfer of antibiotic-resistant bacteria through direct contact exposure to ornamental fish. (para. 11. 18)

Chapter 12: Research on microbial antibiotic resistance in relation to food safety

148. Chapter 12 considers the question of the research and surveillance needed to improve knowledge of microbial antibiotic resistance. Attention is given to assessment of the situation, improved detection of antibiotic-resistant strains, microbiological risk assessment, improvement, pathogenicity and clinical outcomes, microbial physiology and ecology, and mechanisms of resistance and dissemination of resistance determinants. Our detailed consideration of the very complex issue of microbial antibiotic resistance in relation to food safety has inevitably led us to a wide range of recommendations for research. Funding bodies will clearly wish to consider these in the light of research sensitivities and priorities. There are two areas which we regard as particularly important. First, work is needed on the chain of events which can lead to antibiotic-resistant microorganisms arising from farming practices, being transmitted through food chain pathways, and causing human infection. Second, research is very much needed on possible exposure of general, animal and food microbial flora to resistance, with the accompanying risk of the establishment of a reservoir for the transfer of such resistance to humans.


Chapter 12 recommendations

149. We recommend that research is funded to:-

undertake integrated local surveillance studies to examine the prevalence of antibiotic resistance associated with Campylobacter, Salmonella and commensal bacteria in red meat and poultry throughout slaughter and processing (para. 12.33);

assess the prevalence of antibiotic resistance in wild animals, including birds, and food animals on farms in relation to the usage of antibiotics, particularly a) growth promoters and b) fluoroquinolones. (para. 12.33)

150. We recommend that research is funded to:-

identify risk factors for acquiring an infection with an antibiotic-resistant foodborne pathogen. Such studies need to be conducted both in humans and, where appropriate, animals (para. 12.34);

assess the extent of infections in travellers caused by antibiotic-resistant strains and the contribution these make to the burden of infectious intestinal disease (IID) and antibiotic resistance in the UK (para. 12.34);

assess the importance of imported food and animal feed as a source of antibiotic-resistant bacteria (para. 12.34);

determine the contribution made by microorganisms of human origin to microbial antibiotic resistance in animals and food (para. 12.34);

model current patterns and predict future trends in antibiotic resistance of foodborne pathogens in humans and animals (para. 12.34);

determine the socio-economic costs attributable to antibiotic-resistant foodborne pathogens in humans, above the costs attributable to antibiotic sensitive foodborne pathogens. (para.12.34).


151 We recommend that research is funded to develop methods which will characterise the origins of resistance in foodborne pathogens and commensal microorganisms, so as to improve identification of the sources and routes of transfer of resistant organisms from the farm through food to humans. (para. 12.35)

152. In relation to Microbiological Risk Assessment (MRA) we recommend that research is funded to:-

undertake structured MRA to assess the risk of infectious intestinal (IID) disease from antibiotic-resistant foodborne pathogens and commensal bacteria in food animals, foods and the environment (para. 12.36);

use MRA to quantify the magnitude of the key pathways by which microbial antibiotic resistance can transfer from food animals to humans via the food chain and the environment (para. 12.36);

undertake MRA to assess the links between a) use of growth promoters and, b) fluoroquinolones, in food animals and the development of antibiotic-resistant infections in humans. (para. 2.36)


153. To facilitate a reduction in the usage of antibiotics we recommend that research is funded to :-

underpin effective antibiotic management policies in animals, aimed at optimising administration practices to minimise the risk of development of resistance. This will include investigations of the persistence of antibiotic-resistant bacteria in the gastrointestinal tract of food animals after antibiotic withdrawal (para. 12.37);

further investigate how particular hygiene practices and interventions can bring about a reduction in the need for antibiotics in food animal production, without jeopardising animal welfare (para. 12.37);

evaluate the potential of vaccines, probiotics and competitive exclusion to reduce the usage of antibiotics and the level of resistance in microorganisms in food animals. (para. 12.37)

154. We recommend that research is conducted to:-

determine the relationship between antibiotic resistance and virulence in foodborne pathogens in humans and where appropriate, animals (para. 12.38);

review the clinical picture (duration, severity, treatment and outcome) of cases of IID involving antibiotic-resistant foodborne pathogens, as opposed to cases infected with sensitive isolates, and assess whether there are any longer-term consequences of these infections for the patient. (para. 12.38)

155. We recommend that research is funded to :-

examine antibiotic-resistant pathogens and commensal organisms from animals and humans to determine their survival characteristics in the environment, compared to non-resistant strains (para. 12.39);

examine the effect of antibiotic selection pressure on the survival and persistence of antibiotic-resistant strains, both in vitro and in vivo (para. 12.39);

examine the transfer of resistance determinants between foodborne pathogens and the commensal flora of humans and animals in a) foods and b) the environment. (para. 12.39)


Chapter 13: Conclusions and recommendations


156. For the convenience of the reader, we summarise in Chapter 13 of our Report the conclusions that we have drawn in the course of our investigation of this important topic and the recommendations which we have made.


ANNEX

ADVISORY COMMITTEE ON THE
MICROBIOLOGICAL SAFETY OF FOOD:
WORKING GROUP ON MICROBIAL ANTIBIOTIC
RESISTANCE IN RELATION TO FOOD SAFETY

Terms of reference

To assess the risks to humans from antibiotic-resistant microorgani.sms entering the food chain and to consider the need for any action to protect public health.

Membership

CHAIRMAN

Professor D L Georgala Independent scientific consultant Retired
Director of the Institute of Food Research

VICE CHAIRMAN

Dr G Spriegel Director of Scientific Services, j Sainsbury plc


MEMBERS

Mr JAR Dewhirst Farmer. Member of the East Yorks National Farmers' Union Pigs Committee. Past member of Farm Animal Welfare Council. Vice Chairman of the British Pig Association. UK Chairman of the European Pig Producers'Organisation

Professor C A Hart Department of Medical Microbiology and GenitoUrinary Medicine, Royal Liverpool University Hospital

Professor A M Johnston Professor of Veterinary Public Health, Royal Veterinary College, University of London

Dr LJV Piddock Senior Lecturer, Department of Infection, University of Birmingham

Ms B Saunders Consumer consultant

Dr N A Simmons Emeritus Consultant in Microbiology to the Guy's and St Thomas'Hospital Trust; Honorary Senior Lecturer in Microbiology, St Bartholomew's and the Royal London School of Medicine and Dentistry

Dr DJ Taylor Reader in Veterinary Microbiology, Department of Veterinary Pathology, University of Glasgow Veterinary School

Dr P Wall Chief Executive of the Food Safety Authority of Ireland. Formerly Consultant Epidemiologist, Public Health Laboratory Service Communicable Disease Surveillance Centre

ASSESSORS
Mr PJR Gayford Ministry of Agriculture, Fisheries and Food
Dr L Robinson (a) Department of Health
Dr E M Cooke (b) Department of Health


SECRETARIAT

Administrative Secretary

Mr C R Mylchreest Ministry of Agriculture, Fisheries and Food

Scientific Secretary

Dr P E Cook Department of Health

Administrative Secretariat

Mr P Hayes Department of Health
Mr A Doole (c) Department of Health
(a) Until 26 November 1997
(b) From 12 March 1998
(c) Until 14 August 1998

ADVISORY COMMITTEE ON THE
MICROBIOLOGICAL SAFETY OF FOOD

MEMBERSHIP

CHAIRMAN

Professor D L Georgala Independent scientific consultant. Retired Director of the Institute of Food Research

MEMBERS
Mr D Clarke Operations Manager, Assured British Meat

Dr T Clayton Technical Executive, Marks and Spencer plc

Professor RJ Gilbert Head of Food Safety Policy Development, Public Health Laboratory Service. Visiting Professor at the Royal Veterinary College, University of London

Mrs P Jefford Environmental Health Services Manager, Gravesham Borough Council

Mr D Kilsby Head of Food Microbiology Research, Unilever plc, Colworth Laboratory

Professor A M Johnston Professor of Veterinary Public Health, Royal Veterinary College, University of London

Ms E Lewis Computer consultant. Consumer representative

Dr M J Painter Consultant in Communicable Disease Control, Infection Control and Surveillance Unit, Public Health Laboratory Service (North West)

Professor S R Palmer Chairman of Division, Department of Epidemiology and Public Health, University of Wales College of Medicine

Dr T A Roberts Retired Head of Microbiology, Institute of Food Research

Dr N Simmons Emeritus Consultant in Microbiology to the Guy's and St Thomas' Hospital Trust; Honorary Senior Lecturer in Microbiology, St Bartholomew's and the Royal London School of Medicine and Dentistry

Professor W C S Smith Department of Public Health, University of Aberdeen and Honorary Consultant in Public Health Medicine, Grampian Health Board, Aberdeen

Dr JV Stevens Group Technical Director, Unigate European Food

Mrs B W Thomas Consumer consultant


Dr T D Wyatt Consultant Clinical Scientist, Mater Hospital Trust, Belfast


ASSESSORS

Mr PJ R Gayford Ministry of Agriculture, Fisheries and Food
Dr RJ Harding Ministry of Agriculture, Fisheries and Food
Dr C H McMurray Department of Agriculture for Northern Ireland
Dr A Riley Scottish Office Department of Health
Dr E Mitchell Department of Health and Social Services, Northern Ireland
Dr R Skinner Department of Health
Mr D Worthington Welsh Office

SECRETARIAT
Medical Secretary
Dr J Hilton Department of Health

Administrative Secretary
Mr C R Mylchreest Ministry of Agriculture, Fisheries and Food

Minutes Secretary
Mr P Hayes Department of Health



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