Antibiotics report

The Use and Misuse ofAntibiotics in UK Agriculture Part 1: Current Usage by John Harvey and Liz Mason with a preface by Peter Luff MP £15.00 (Soil Association members, £10.00) 40-56 Victoria Street T 0117 929 0661
F 0117 925 2504
Published Dec 1998 Preface by Peter Luff MP The Soil Association's recommendations Introduction and analysis by Richard Young, Soil Association Campaigns and Policy Coordinator Historical Perspective by Richard Young PART 1 – Data on Antibiotic Usage The Difficulty of Obtaining Data Antibiotic Use Figures PART 2 – Issues in the Agricultural Use of Antibiotics Controversial Usage Irresponsible Usage Overseas Use and the Question of Imports Loopholes in Regulation PART 3 – Antibiotic Use According to Livestock Class 3.1.1 Beef Production 3.1.2 The Dairy Herd 3.3.1 Pig ‘Vices' 3.3.2 Residues in Pigmeat 3.4.1 Broiler Production 3.4.2 Residues in Eggs The Use and Misuse of Antibiotics in UK Agriculture by Peter Luff, MP for Mid Worcestershire and Chairman of the Commons Agriculture Committee Perhaps we are too free in our use of antibiotics when treating human ailments.
But antibiotic use in livestock production is also of concern, both to farmers andconsumers.
Clearly farmers must be able to treat animals if they become ill. Consumers alsoneed to be sure that the use of antibiotics on farms does not pose a threat tohuman health. The distinction between the use of antibiotics for growth promotion and therapyhas seemed a simple one, but in fact the issue is more complex since some growthpromoting antibiotics afford a degree of disease protection. At a time when there isgrowing public pressure for tighter controls on the use of antibiotics in livestockproduction it is in everyone's interest that there should be a fuller understandingof the ways in which they are used and why. This Soil Association report is a welcome attempt to provide that hard evidence. More needs to be done to monitor the development and spread of antibioticresistance in farm animals. We also need to gather statistics on antibiotic use sothat we can establish whether changing trends in their use are reflected in the typeand spread of resistance. This report publishes estimates from NOAH (the National Office of AnimalHealth Ltd) and UKASTA (the United Kingdom Agricultural Supply TradeAssociation) on the total volume of antibiotics used in the UK and compares thesewith their use in human medicine. Interestingly it also compares use today withthat thirty years ago, by reprinting data from the report of the Swann Committee. Many would argue that this information should be collected centrally on anannual basis. I hope this report will both stimulate and inform the debates on thisimportant issue. The Use and Misuse of Antibiotics in UK Agriculture This report is part of the Soil Association's continuing campaign against the exces-sive use of antibiotics in agriculture. It aims to provide an overview of the scale andnature of antibiotic usage on UK farms in order to inform the debate on the extentto which this may be contributing to the problem of drug-resistant disease in thehuman population. It exposes a number of failures in the regulatory system andthrough the publication of the first detailed statistics for thirty years on the ton-nage of antibiotics used on farms, highlights the extent to which antibiotics use inintensive livestock production has continued to rise despite all previous attempts tocurtail it.
Key findings of the report are:
• Tetracycline use has increased by 1500% in 30 years, when it was supposed to • Penicillin type drug use has increased by 600% over the same period • Comparing industry estimates with published figures from the DOH suggest that about 1225 tonnes of antibiotics are used annually in the UK in thefollowing proportions: Farm animals 37%, Pets and horses 25%, Medical use38% • Inclusion of the ionophores, a major class of in-feed antibiotics, which the industry leaves out of its tables on a technicality, would give a considerablyhigher percentage figure for farm use • The Ministry of Agriculture Fisheries and Food does not collect data on antibiotic use on farms, despite this being a recommendation of severalindependent committees • As many as 10,000 farmers in the UK may be illegally top dressing livestock feed with antibiotics • There is a major disagreement between the British Veterinary Association and the pharmaceutical industry over the advertising of Prescription OnlyMedicines direct to farmers • Virtually all growing pigs and broiler chickens receive antibiotics in their feed throughout their lives up to and including the day of slaughter • Most intensively reared cattle are fed antibiotics routinely in replacement milk powders, compounded feed and feed blocks • Banning individual antibiotics will not stop the problem continuing to get worse. A complete change in the way in which animals are reared is required The Use and Misuse of Antibiotics in UK Agriculture THE SOIL ASSOCIATION'S RECOMMENDATIONS The Soil Association is calling for:
• A ban on all non-medical use of antibiotics in agriculture • The prophylactic use of therapeutic antibiotics to be restricted to cases of genuine need and only made available as part of a planned diseasereduction programme involving changes in housing, feeding andmanagement practice • Coordination of all government departments, agencies and other bodies with a statutory involvement in the regulation of antibiotic use on farmsto be undertaken by the proposed Food Standards Agency • Responsibility for the safety evaluation of veterinary medicines to pass to the proposed Food Standards Agency, as suggested in the Green Paper • The establishment by government of a surveillance system for antimicrobial resistance, comparable with that for antimicrobial residues • The central, annual collection of data on the use of antimicrobial agents on farms, in order to monitor trends in usage • Livestock products imported into the European Union to be subject to routine surveillance for bacteria carrying antibiotic resistance andsubject to the same controls in relation to permitted antibiotics as thoseproduced within the EU.
• A ban on the advertising of antibiotics directly to farmers.
The Soil Association further recommends that:
• Veterinary surgeons should charge directly for advice and recoup a smaller proportion of their income from the sale of drugs.
• Veterinary and agricultural colleges should place greater emphasis on the teaching of drug-free preventative medicine The Use and Misuse of Antibiotics in UK Agriculture INTRODUCTION AND ANALYSIS by Richard Young, Soil Association Policy and Campaigns Coordinator Franz Fischler, the EU Agriculture and Rural Affairs Commissioner, has recentlyproposed a ban on four of the eight antibiotics currently licensed for growth pro-motion in farm animals throughout the EU. Because Britain permits the use ofolaquindox, one growth promoting antibiotic not used elsewhere in Europe, such aban would leave five antibiotics licensed for use in the UK without a veterinary pre-scription.
The move to introduce a ban on virginiamycin, tylosin phosphate, spiramycin andzinc bacitracin follows concern that their routine use may be a significant factor inthe increasing incidence of drug-resistant disease in the human population. At firstglance it may appear that the implementation of such a ban would resolve theproblem in one easy step. However, while the Soil Association wants to see a ban onthese antibiotics, it believes this is essentially a political gesture. Closer analysisreveals that banning a handful of drugs is an easier route for politicians than tack-ling the root cause of a problem, which is likely to continue getting worse despitethe proposed ban, unless a more structured approach is adopted.
Concern about the way in which antibiotics are used on farms has been voiced bymicrobiologists for several decades, but action has only been precipitated recentlyby increasing, though as yet scientifically inconclusive evidence, that this legalised‘misuse' of antibiotics on intensive livestock farms is directly linked to the rise ofuntreatable infections in people. Bringing this to a head at the present time is theaccession of Sweden and Finland to the European Union. These two countriesalready had bans in place on some or all growth promoting antibiotics before theyapplied to join the EU. In the interest of free trade within the community theywere given only a limited period in which either to allow their use, or to persuadeother member states that an EU-wide ban was appropriate. In the case of Swedenthat period of grace is due to run out at the end of the year.
In the UK we are currently awaiting a report, now expected in January 1999, fromthe Advisory Committee on the Microbiological Safety of Food (ACMSF), whichhas had a working party investigating the spread of resistance through the foodchain for the last two years. We are also expecting a reply from government to therecommendations made last April by the House of Lords Science and Technologysub-committee. In Europe growth promoting antibiotics are being considered oneby one by the Scientific Committee for Animal Nutrition, the Standing Committeeon Animal Feedingstuffs and a Multi-disciplinary Working Party under DG24.
This report was commissioned by the Soil Association to establish the extent ofantibiotic use on UK farms, something we believe the government should be doingon an annual basis. We feel this task is important for two reasons. Firstly, withoutdetailed information on antibiotic use it is difficult to establish precisely the extent The Use and Misuse of Antibiotics in UK Agriculture to which the use of antibiotics on farms is contributing to the problem of antibioticresistance. Secondly, we believe that the banning of individual antibiotics will not,on its own, be sufficient to resolve the problem of antibiotic resistant bacteria pass-ing from farm animals to people. While production systems remain unchangedfarmers will simply move to those growth promoting antibiotics still licensed andthe evidence suggests that, in many situations, veterinary surgeons will also findthemselves with little alternative but to prescribe increased quantities of therapeu-tic antibiotics, both for disease prevention and for treatment. This is because all thegrowth promoting antibiotics also afford some degree of disease control. Until nowthe industry has kept very quiet about this, since openly to admit the therapeuticvalue of growth promoting antibiotics would be to expose the lie behind the wholeindustry and blow wide open the delicate compromise which has allowed their useto continue for the last thirty years.
British and, to a large extent, EU legislation on the farm use of antibiotics is stillheavily based on the recommendations of the Swann Committee in 1969. It is quiteclear from the Swann report that the committee wanted to ban all non-medical useof antibiotics. However, in the end the committee bowed to industry pressure andaccepted that those antibiotics which have little or no application as therapeuticagents in man or animals could be used for growth promotionpurposes. It is on this basis that the growth promoting antibiotics have been licensed. Nowthat bans are becoming a real possibility the industry is referring to these therapeu-tic properties in a desperate attempt to win a stay of execution.
A clear example of this is given by Paul McMullin, the Head of the British PoultryVeterinary Association in a letter printed in the Veterinary Times in September 1997.
We have already seen a substantial increase in mortality attributed tonecrotic enteritis, and cholangiohepatitis, since the, still temporary,suspension of … avoparcin. The inevitable consequence of a ban onsuch products would be the increased use of therapeuticantimicrobials. In other words, not only are many of the growth promoting antibiotics causingcross-resistance with important related therapeutic drugs, but the therapeutic prop-erties of these drugs are also providing a prophylactic effect, even at the low dosesat which they are used.
The Soil Association therefore believes that the British government and theEuropean Union must recognise that a more detailed agronomic approach is need-ed which will bring about changes in the way in which farm animals are kept, inorder to reduce the primary need for medication. Bans on individual productsshould then be scheduled sufficiently far in advance to give the industry time to The Use and Misuse of Antibiotics in UK Agriculture make the necessary alterations to production methods. For this to be achieved we need first to have a clearer understanding of how andwhy such large quantities of antibiotics are currently being used; we then need aministerial acknowledgement of the real scale of the task before us. This report, byfreelance agricultural journalists John Harvey and Liz Mason, aims to provide someof that information. It is our hope that it will help to move the debate from a sim-ple review of the safety of individual drugs to a review of the safety of modern live-stock production methods which make such dependence on antibiotics inevitable.
The report provides, for what we believe could be the first time in 30 years,detailed estimates of the total quantities of antibiotics used annually on UK farms.
It also looks at the use of antibiotics for each farm animal species. The report alsoexamines a range of regulatory issues and exposes the fact that: • 10,000 farms may be top dressing animal feed with antibiotics illegally, • there is a major rift between the pharmaceutical manufacturers and British Veterinary Association over the advertising of antibiotics tofarmers. At the request of the National Office of Animal Health Ltd (NOAH) and theUnited Kingdom Agricultural Supply Trade Association (UKASTA) who kindly pro-vided some of the statistics published in this report, we have printed data compar-ing medical use with agricultural use. The information on farm use is far fromcomplete. Critically, it has not been possible to provide data for all antibiotics or tobreak down the antibiotic growth promoters by type. Nevertheless, even in thisincomplete form it is possible to note some significant details. On the basis of theinformation we have been able to obtain, total antibiotics use is about 1,225 tonnesannually. Of this, it is estimated that 38% is used in human medicine, 25% for petsand horses, and 37% in farm animals. However it is important to point out that thefigures relating to farm animals notably exclude the ionophores. These are proba-bly the most widely used antibiotic class of all, included as coccidiostats in therations of virtually all poultry destined for the table, and used in most cattle andsome pig feed specifically for growth promotion. While we have been unable toobtain data on the quantities of ionophores used, indications are that their inclu-sion in the tables could double the total quantities listed as growth promoters. TheSoil Association will show in a future report that the ionophores too pose seriouspotential health problems for the human population and also to some animalspecies.
Comparing medical and farm use of antibiotics, however, tells us only a limitedamount. In addition we have therefore also reprinted some data for farm antibioticuse from 1966 so that an historical comparison can also be made. Many of the cur-rently used growth promoting antibiotics and a small number of the therapeuticones were either not available or not widely used in 1966. As a result it is not possi-ble to make direct comparisons for all classes of antibiotics over this 30 year period.
The Use and Misuse of Antibiotics in UK Agriculture However it is striking that the use of the penicillins and of the tetracyclines, the twoclasses of antibiotics which the Swann Committee banned for growth promotion onthe grounds of the ‘considerable evidence to show that their use as feed antibioticshas led to the emergence of bacterial strains with widespread resistance to them',have seen massive increases in use. Tetracycline use has in fact increased by 1500%over the last 30 years, and that of penicillin type drugs by 600% . The mechanisms by which such use encourages the development of resistant bacte-ria are now well documented and understood, and it may be no coincidence thatthe incidence of multi-drug resistant salmonella resistant to tetracycline, hasincreased from about 15% in the early 1970s to over 80% today. However the theo-retical possibility must also exist that such massive use of broad spectrum drugs likethe tetracyclines, active as they are against the Gram negative food poisoning bacte-ria, may also have created, in ways perhaps not yet fully understood, a selectionpressure for the development of entirely new food poisoning strains such as E. Coli0157 and Salmonella Typhimurium DT104. It is ironic that not only did the Swann recommendations usher in a new range ofgrowth promoting antibiotics, only now threatened with a partial ban, but it alsocompletely failed to restrict the use of penicillin and tetracycline as it set out to do.
It is in all our interests to ensure that we do not make the same mistake again.
Evidence in this report provides a testimony to the extent that farm animal produc-tion has become addicted to the routine use of antibiotics. We all know that suchaddictions cannot be cured simply by attempting to restrict the supply of drugs.
Alongside the bans we must create a new climate for the production of inherentlyhealthy animals from farm systems in which the animals are kept in more naturaland less stressful conditions and routinely treated with respect rather than withantibiotics. This will require a concerted effort from MAFF, veterinary surgeons,agricultural advisers and farmers. Veterinary and agricultural colleges too will haveto begin teaching the practices of sound farming methods and drug-free preventa-tive medicine. Most of the information is already available, it has simply been over-looked in the years when drugs have been cheap, plentiful and poorly regulated.
Above all it will need support from consumers willing to pay a little more for meatover the counter and a little less for it through their taxes. It will also need confi-dence that such changes can be made. The Soil Association believes and hopes thatthe experience gained by organic farmers over the last few decades can help toprovide such confidence and a number of inspirational models for more humane,safe and enlightened animal production in the future.
The Use and Misuse of Antibiotics in UK Agriculture HISTORICAL PERSPECTIVE A fuller understanding of how antibiotics came to be so widely used in agricultureis only possible by considering a brief history of their use.
In 1953, the British government passed the Therapeutic Substances (Prevention ofMisuse) Bill. The name is somewhat misleading. The Bill extended the controlsalready in existence on the therapeutic use of penicillin, streptomycin and chlorte-tracycline to a range of new antibiotics coming on to the market at that time.
However, just ten years after penicillin had first become widely available to savelives in a way never before possible, this bill made it legal for farmers and feedcompounders to include penicillin and chlortetracycline (marketed as aure-omycin) in the feed of pigs and poultry without veterinary prescription for the pur-pose of growth promotion.
The Bill had an easy passage through Parliament. Just one MP, Colonel Gomme-Duncan, spoke out strongly against it: ‘May I ask whether we have all gone mad,'he said, ‘to give penicillin to pigs to fatten them? Why not give them good food, asGod meant them to have?' MPs were told that adding these two antibiotics to pigand poultry food would make animals grow faster and thereby increase the supplyof cheap meat. With the food shortages of the war and post-war period still strongin the nation's mind it was an irresistible idea. A few MPs asked polite questionsabout possible residues and resistance, but received reassurances from Sir ThomasDugdale, Minister of Agriculture, and Iain Macleod, Minister for Health, who said‘I am assured by the Medical Research Council […] that there will be no adverseeffect whatever upon human beings'.
Three years of trials by the Agricultural Research Council had shown that about75% of pigs and poultry given antibiotics on a daily basis showed increased growthrates and, more significantly since Britain imported large volumes of grain andother livestock feed, increased efficiency in converting food into meat. The greatesteffect was found with aureomycin, but this was only manufactured in the USA.
British drug companies were producing penicillin and, although paying royalties tothe Americans who had managed to obtain international patents despite the pio-neering development in Britain, it was still thought better for British industry andthe balance of payments to promote penicillin alongside aureomycin.
By 1953 penicillin resistance in some bacteria had been frequently observed, how-ever it was believed that this arose solely through mutation and the selective pres-sure of antibiotic use. However, in 1959 a Japanese scientist, T. S. Watanabe, discov-ered that antibiotic resistance could be infectious - that is that it could be trans-ferred from one bacteria to another inside the alimentary system of human or ani-mal. Suddenly there was a realisation that the continuous feeding of low doses ofantibiotics to animals could after all pose a threat to human health. The govern-ment set up the Netherthorpe Committee in 1960 to examine the issue, but gave it The Use and Misuse of Antibiotics in UK Agriculture only limited terms of reference. In 1968 after serious outbreaks of multi-drug resis-tant salmonella food poisoning which were linked to the use of antibiotics in live-stock production, government established the Swann Committee to examine thepractice of feeding antibiotics to animals in relation to the issue of infectious drugresistance. What was perhaps not counted on in 1953 was that the routine administration ofantibiotics to farm animals for growth promotion also had a suppressing effect onthe diseases to which animals are vulnerable. Animals in an antibiotic-induced stateof artificial ‘health' could be kept at a much higher density and savings made onspace, labour and cost. As a result the use of antibiotics ostensibly only for growthpromotion made possible the super-intensification of farm animals and also creat-ed a powerful lobby to resist any changes.
With insufficient hard evidence that the routine use of all antibiotics in livestockproduction really did pose a threat to human health the Swann Committee wasforced into a compromise. Penicillin and the tetracyclines would be banned forunrestricted use as growth promoters, but vets would be allowed to prescribe themboth prophylactically and therapeutically. Only antibiotics which would ‘not impairthe efficacy of a prescribed therapeutic antibiotic or antibiotics through the devel-opment of resistant strains of organisms' would be allowed as growth promoters.
This gave a green light for the development of antibiotics just for growth promo-tion but total antibiotic use did fall immediately post-Swann. By 1977, however, itwas rising again on an annual basis, leading long-standing critics of governmentpolicy on antibiotics such as Professor Alan Linton, a member of the VeterinaryProducts Committee, to set out a detailed paper on ‘Why Swann Has Failed'.
Linton found that not only were we introducing a new range of growth promotingantibiotics, but the prophylactic use of therapeutic drugs was continuing toincrease.
With increased intensification and specialisation being driven by agricultural policyand lucrative EEC capital grants, often conditional on increased intensification,there was an ever-increasing demand for the drugs that would make such stress andovercrowding possible. A few vets stood out against this, but simply saw their clientstake their custom elsewhere. The vets of super-intensification tended to separatesomewhat from the rest of the veterinary profession. Some were employed full-timeby the large companies which came to dominate pig and poultry production. Allwere in the position where their monopoly 50% mark up on drugs provided thebulk of their income.
Watered down though the Swann Committee recommendations were, they werevigorously opposed by the industry which claimed, for example, that they wouldadd threepence to a pound of bacon. The government was forced into a series ofsubtle back steps, much of it never fully reported. The Department of Health gavein to industry pressure and allowed tylosin to be used for both therapy and growth The Use and Misuse of Antibiotics in UK Agriculture promotion. Then in 1976 the use of growth promoting antibiotics was extendedadult and breeding cattle, again totally against the Swann recommendations. By1981 the Veterinary Products Committee (with little microbiological expertise, butstrong industry representation) was falling out with a sub-committee of microbiolo-gists set up to advise it. Exasperated, the sub-committee approached ministersdirect for permission to review the safety of the very antibiotics under scrutiny andproposed for a ban today. Ministers refused to discuss the issue and simply sackedthe sub-committee. From that time until the establishment of a Working Group under the ACMSFthere has not been an expert committee of microbiologists reviewing the safety ofantibiotics in relation to the development of antibiotic resistance. Antibiotic use inagriculture has continued to increase and has broadened to include the wide-spread prophylactic use of important therapeutic drugs such as the fluro-quinolones.
The Soil Association therefore awaits the ACMSF's report with interest.
The Use and Misuse of Antibiotics in UK Agriculture PART ONE – Data on antibiotic usage 1.1 The difficulty of obtaining data
Precise data on antibiotic use in animal and poultry husbandry in the UK is verydifficult to obtain. This seems extraordinary in the context of the current debateabout resistance and whether or not antibiotics should be more rigidly controlled.
Even the Ministry of Agriculture has no data on annual use and the VeterinaryMedicines Directorate (VMD), which licences antibiotics, is trying to improve theaccuracy of the little information it has. The VMD has issued a tender for a surveyto produce detailed information on antibiotic use in different animal species.
At the moment, there is no statutory requirement for the VMD to collect the data,and it is ironic that a detailed table of human antibiotic use in general practicesand hospitals in the UK has just been published (SMAC, 1998). Ever since thereport of the Swann Committee on the use of antibiotics in animal husbandry andveterinary medicine was published in 1969, eminent committees have been askingfor statistics on annual use. In October last year, for example, a Ministry ofAgriculture workshop in Birmingham reported that Consumption figures for different countries in the European Unionwere presented and related to the overall presence of resistant bacteria.
For the UK, this data was exceptionally difficult to obtain
(MAFF, 1998).
More recently, the same message came from a meeting organised by the DanishMinistries of Health and Agriculture in Copenhagen in September. Part of its rec-ommendation states Evaluation of the benefits and risks of antimicrobials depends oncollecting detailed information about their consumption by animalsand humans and their use in aquaculture and horticulture. Datashould also be collected on antimicrobial agents used to treat animals(by species) and for growth promotion (Ministry of Health, 1998).
In its tone, this is similar to a comment from the British Veterinary Association'santimicrobials working group: Use of antimicrobials may lead to resistance patterns which couldendanger human or animal health. […] The group would like to seea full benefit-risk analysis for all antimicrobial uses. Two such studiesare in progress in Europe and the USA, and the data should beavailable before the end of 1998 (BVA, 1998).
Last year, the World Health Organisation organised a meeting in Berlin called ‘TheMedical Impact of the Use of Antimicrobials in Food Animals'. Under the heading‘risk assessment', the meeting concluded: ‘No antimicrobial should be adminis- The Use and Misuse of Antibiotics in UK Agriculture tered to a food animal unless it has been evaluated and authorised by competentnational authorities. This evaluation should include a thorough risk assessmentwhich includes the development of resistance that may impact public health; andpost-market monitoring programmes to detect emergence of resistance of publichealth significance' (WHO, 1997).
In another context, the working group of the Advisory Committee for theMicrobiological Safety of Food (ACMSF) has also had a struggle to obtain data, asone of its members, Dr Norman Simmonds, explained to a House of Lords enquiryinto antimicrobial resistance.
We had great difficulty finding out how much antibiotics are given toanimals. I think that figures from NOAH [National Office ofAnimal Health Ltd, representing the drug companies], which arebased on cost clearly do not tell you very much, and a lot ofinformation is regarded as commercially sensitive. There is no centralregister of use. The records on farms are not that good even where theyare meant to be good, and even on the best farms they are not perfect(House of Lords, 1998, Evidence).
These statements show the importance of collecting usage data, and they are likelyto be reflected in the report of the ACMSF on antibiotic resistance expected earlynext year. At about the same time, the Government will reply to the report by theHouse of Lords Select Committee on Science and Technology, entitled ‘Resistanceto Antibiotics'.
In response to the House of Commons agriculture select committee food safetyreport (House of Commons, I, 1998), which called for a ban on the use of antibi-otics as growth promoters, the Government said it would act on the advice of itsscientific committees, including the ACMSF and the Veterinary ProductsCommittee (VPC). It reiterated the VPC's policy on the use of antibiotics as veteri-nary medicines: ‘New antibiotics should not necessarily be precluded from thera-peutic use in animals but their prophylactic use should be discouraged.' The VPCitself organised an open meeting on resistance in June, and is planning to offeradvice to the health and agriculture ministers on the best ways of ensuring ‘respon-sible use' of antibiotics by veterinary practices. The phrase ‘responsible use' crops up quite often, and is obviously seen by thefarming industry as a way of preventing unilateral bans on specific antibiotics intro-duced by some EU member states. A National Farmers Union report on antibioticsis called ‘Responsible Use of a Precious Resource' (NFU, 1998), and the NFU isnow co-operating with other industry organisations to produce another report on‘responsible use' to coincide with the release of the ACMSF report.
The Use and Misuse of Antibiotics in UK Agriculture 1.2 Antibiotic use figures
In September, the British Medical Journal tried to establish usage. Mac Johnston,senior lecturer in veterinary public health at the Royal Veterinary College, said thatin penicillin equivalents ‘the veterinary use of antibiotics is just under 500,000 forall species compared with just over 760,000 for all medical use' (Johnston, 1998).
Mr Johnston said a total of 1900 drugs is licensed for use in animals in the UK.
Their market value in 1997 was £379 million, with 40% of sales for pets.
Antimicrobial agents for farm and pet animals totalled about £80 million: of this,antibiotic growth promoters for foodstuffs were valued at £12 million. NOAH claims the figures show that the market for animal medicines in the UK issmall compared to the £6.6 billion spent in the UK on human medicines (about 30times the farm animal expenditure). But when questioned by the House of LordsSelect Committee on Science and Technology Roger Cook, NOAH director, con-ceded that a comparison between animal and human use on the basis of cost wasnot very realistic as a measurement of the amount of antibiotics used. Mr Cook toldthe Lords committee that NOAH had ‘been trying to get information on the vol-umes of antibiotic usage in human medicine so we could present a proper compar-ative picture. Unfortunately it seems that nobody, not even the Department ofHealth, has those statistics'.
However, statistics have since been published in a report produced by theDepartment of Health's Standing Medical Advisory Committee (SMAC). NOAHagreed to provide comparative figures on animal usage for this report. The UnitedKingdom Agricultural Supply Trade Association (UKASTA) also provided figureson the annual use of antibiotics through veterinary use and in livestock feed. Thisis the first time these figures have been released or published in this form.
ANTIBIOTICS active against bacteria and a few viruses. Originally fermented from natural
microorganisms, they are now often produced synthetcally.
ANTIBACTERIALS active against bacteria. Includes all antibiotics and chemically synthesised drugs, such
as sulphonamides.
ANTIMICROBIALS Includes all antibacterials and some other drugs active against other microorganisms
such as fungi and protozoa.
The Use and Misuse of Antibiotics in UK Agriculture TABLE 1 UK human and animal use of antibiotics (kg active ingredient)
1966 Swann Report 1996 NOAH survey1 Cephalosporins,B-Lactams inc. Penicillins Fluoroquinolones inc. Nalidixic acid Clindamycin Lincomycin 1 The 1996 NOAH survey involved all NOAH members supplying antibiotics products for farm and pet/horse use in the UK.
2 The 1996 DoH figures were taken from the DoH publication "Prescription Cost Analysis - England 1996". These figures exclude
Wales, Scotland, Northern Ireland and hospitals (and private medicine).
3 These 1997/8 figures are from the report from the Standing Medicines Advisory Committee (SMAC) of the DoH entitled "The path
of least resistance" published in September 1998 and covering the year to January/February 1998. The source of the data is given as
"IMS Health, Maxims Database" year ended January/February 1998.
The Use and Misuse of Antibiotics in UK Agriculture TABLE 2 Estimated annual usage of antibiotics in humans and animals in the EU in 1997
(tonnes active ingredient at 100% purity)
Animal (therapeutic and prophylactic use) Animal (growth promoters) 1 Currently FEDESA are doing an EU wide survey of antibiotic usage. As yet no detailed results are available, but this table gives the
‘broad' result published at a meeting in Copenhagen in September.
2 Although this table appears to show that the usage of antibiotics by weight is slightly lower for farm animals than for human
medical purposes, it is important to note that the ionophores, licensed for growth promotion and the control of coccidiosis, were not
included in either the veterinary or the growth promoting categories. Since these are probably the most widely used in-feed antibi-
otics of all, their inclusion would have a significant effect on the figures.
TABLE 3 Quantity of active medicine incorporated into commercial compound feeds in the UK
in 1996 (tonnes)
Total output of commercial compound feeds Total output of feed with VWD1 (@ average 150 mg active medicine/kg feed) Total active medicine incorporated under VWD1 Total output of feed with PML2 (@ average 20 mg/kg feed) Total active PML medicine used SOURCE United Kingdom Agricultural Supply Trade Association Ltd (UKASTA).
1 Veterinary written directions (VWDs) refers to the situation in 1996. The VWDs have now been replaced by medicated foodstuffs
prescriptions (MFS) which are now required to incorporate ‘Presciption Only Medicines' (POMs) into feed.
2 The ‘Pharmacy and Merchants' List' (PML) (available without prescription) boxes would cover growth promoters.
The Use and Misuse of Antibiotics in UK Agriculture TABLE 4 Tonnages of pig and poultry feed in 1995
(thousand tonnes) Broiler grower Broiler finisher Turkey starter Turkey grower Turkey finisher Chicken starter Chicken grower Layers for egg production The Use and Misuse of Antibiotics in UK Agriculture TRENDS IN USE
NOAH says an increasing amount of antibiotics are being administered in water,although there are no figures on this. There are three reasons for adding antibi-otics to water rather than feed on pig and poultry farms in particular: • farmers can be much more precise about when treatment stops and starts by switching off a tap in the pig or poultry house • animals or birds which are very sick are more likely to drink than eat, and water is an efficient way of treating them. ‘If you have 3000chickens, this is much better than chasing them around with a syringe',said NOAH's director, Roger Cook • management of feed mills is made easier because there is less likelihood Jim Reed, director-general of UKASTA, said that with reasonably healthy animals orbirds, you can be pretty sure of the amount of antibiotic they will receive from ameasured dose in feed. ‘If you put the antibiotic in water, much the same applies.
But there can be some conditions of livestock which cause them to drink excessive-ly. If you apply it to them in any other form (than feed) which is all ad lib, you willhave even less control.' After vaccines, feed was the most measured way to adminis-ter medicines, followed by water, Mr Reed said. Figures are only of limited value without putting them into the context of the cur-rent debate about antibiotics. This is dealt with in the following section.
The terminology with regard to medicinal feed additives can be confusing. European Union legislationwhich came into force in May 1998 has replaced ‘Veterinary Written Direction' (VWD) with ‘MedicatedFeedingstuffs' prescription, and ‘Prescription Only Medicines' (POMs) are now known as ‘MedicatedFeedingstuffs'. Antibiotic and chemical growth promoters and other antibiotics and medicinal additiveswhich were known as ‘Pharmacy and Merchants' List' (PML) products are now called ‘Zootechnical FoodAdditives'.
The Use and Misuse of Antibiotics in UK Agriculture PART 2 – Issues in the agricultural use of antibiotics 2.1 Controversial usage
Anitbiotics are used in farm animals for three reasons: to promote growth, to treatdisease (therapeutic use) and to prevent disease (prophylactic use).
Following the Swann Committee report (House of Commons, 1969), legislation wasintroduced under the Medicines Act to divide antimicrobials into non prescriptionmedicines (called Pharmacy and Merchants' List products or PMLs, for growth pro-motion and coccidiosis control) and prescription only (or POM products for dis-ease control). Antibiotics used in human medicine, including penicillin, oxytetracy-cline and chlortetracycline were banned as growth promoters. However, no restric-tions were made on the use of such antibiotics for prophylaxis or therapy in animalhusbandry or veterinary medicine.
In 1992 the Expert Group on Animal Feedingstuffs (the Lamming Committee) rec-ommended that: Not only should antibiotics giving cross-resistance to those used inhuman medicine not be used as growth promoters but theirprophylactic use in animals should be reconsidered (MAFF, 1992). In response the Government said it would seek advice from the Veterinary ProductsCommittee (VPC) and the Committee on the Safety of Medicines. The VPC recom-mended in 1992 that new antibiotics should not necessarily be precluded fromtherapeutic use in animals but that their prophylactic use should be discouraged.
In other words it was to do nothing about the prophylactic or growth promotinguse of older, previously licensed antibiotics.
In November 1993, the VPC approved the use of enrofloxacin, a fluoroquinolone,in animals in the UK, despite evidence from the Netherlands demonstrating thatthe use of this antibiotic in poultry resulted in an upsurge of ciprofloxacin resistantcampylobacter in poultry and humans. Enrofloxacin is used in broiler chickens inthe first week of life to reduce vaccination damage, or in the third or fourth weekto reduce respiratory difficulties caused by E. coli. Ciprofloxacin is the fluoro-quinolone probably most used in humans in the UK (House of Lords, 1998,Evidence, p219-220). Fluoroquinolones are not used as growth promoters, but according to a WorldHealth Organisation press release this June they are currently used for treating ani-mal disease in many countries and, in some regions, they are also used for diseaseprevention. However, according to WHO, ‘the data available so far on their usageare scarce and are often the proprietary information of the drugs' manufacturers'.
Some scientists say fluoroquinolones, which are only licensed to treat disease, are The Use and Misuse of Antibiotics in UK Agriculture being used for ‘mass medication'. They are used in vaccine programmes and invery young animals, so although they are not used for growth promotion, masstreatment is causing concern (House of Lords, 1998, Evidence, p230).
Other antibiotics related to antibiotics used in man have been used, or continue tobe used, as growth promoters or for widespread prophylaxis. The following aresome of the most widespread: avoparcin: a member of the group of antibiotics called glycopeptides which also
include vancomycin and teicoplanin. Vancomycin and teicoplanin are used in
human medicine. (House of Lords, 1998, Evidence, p218-219). The use of
avoparcin as a feed additive was suspended by the EU Commission from April 1,
1997 - only the UK voted against the ban. Between 1975 and 1996, avoparcin
was used in feed for broiler chickens, turkeys, pigs, beef and dairy cattle, calves,
sheep and goats. Depending on the livestock species, 4-50 milligrams per kg was
added to animal feed.
virginiamycin: used as a growth promoter in chickens, turkeys, pigs and cattle.
Also used to prevent coccidioisis in chickens and turkeys, and in pigs to treat
and control swine dysentery. Virginiamycin is a streptogramin antibiotic.
Quinupristin/dalfopristin, another streptogramin mixture, has recently com-
pleted phase three clinical trials in the United States and Europe, and it was
hoped that it would be suitable for the treatment of patients with GRE (gly-
copeptide-resistant enterococci) infections. But now there are doubts because
virginiamycin use in animals may have already resulted in quinupristin/dalfo-
pristin resistance. (House of Lords, 1998, Evidence, p.219).
tylosin phosphate: the most popular growth promoting antibiotic in pig produc-
tion. A member of the macrolide group of antibiotics and closely related to ery-
thromycin, the drug of first choice for patients allergic to penicillin. Tylosin is
also licensed as a therapeutic antibiotic. In 1969 the Swann Committee recom-
mended that Tylosin should not be allowed for growth promotion, but the
Department of Health eventually caved in to intense industry lobbying
(McKinnon 1980). Tylosin has already been linked, along with virginiamycin, to
the appearance of erythromycin-resistant campylobacter in humans.
zinc bacitracin: a polypeptide widely used in pig and poultry production. It has
so far not shown cross-resistance to therapeutic antibiotics. It is not used system-
atically since it is capable of causing kidney damage, but is used in a number of
topical preparations.
avilamycin: after not being used for a number of years avilamycin was relaunched
by Elanco in April 1998 to exploit the market opportunity which arose from the
ban on avoparcin. It is now widely used in poultry production. Although there is
no evidence to show that avilamycin use compromises the effectiveness of any
human drug used at present, it is known that bacteria resistant to it confer cross
The Use and Misuse of Antibiotics in UK Agriculture resistance to a new and related antibiotic, Ziracin, currently being developed inthe hope of treating vancomycin-resistant enterococcal infections in humans.
TABLE 5 Growth promoting antibiotics licensed for use in the UK
Elanco Animal Health Pigs, broiler chickens, turkeys Pigs, cattle, domestic fowls, turkeys, rabbits (all growth) Romensin G100, Elancoban Elanco Animal Health Cattle except lactating dairy cows (growth), broiler andlayer chickens (prophylactic) Enterodox 100 BMP Pigs up to four months of age Sacox 120, Kokcisan 120 G, Broiler chickens (prophylactic) Elanco Animal Health Pigs, growth, prophylactic and Tylan G20, Tylasul G50 and Smithkline Beecham Chicken, pigs, cattle (all Albac 150 granulated, Growth promotion in pigs, (mixture of cyclic Albac 100 lactodispersible poultry calves and lambs SOURCE Soil Association.
2.2 Irresponsible usage
Many in the farming industry know that veterinary pharmacies in Ireland are cur-rently sending UK farmers antibiotics through the post. This is acutely embarrass-ing because it undermines the industry's efforts to portray the use of antibiotics asresponsible. Veterinary practices in England have discovered invoices from theirfarmer clients for Irish products sent through the post. The Veterinary MedicinesDirectorate says that since February 1 this year, farmers importing from Ireland arelikely to have committed an offence. This is because since that date any productimported for administration to a farmer's own animals must be labelled for the UKmarket and carry the market authorisation number. So anything brought in with-out the label is illegal.
‘Our main concern is that there could be a trade in products which are not POM The Use and Misuse of Antibiotics in UK Agriculture medicines in Ireland but which are POMs in England', said a VMD spokesman.
Farmers could then administer an antibiotic without veterinary supervision which isan offence under the 1968 Medicines Act. Roger Cook, director of NOAH, which represents companies making antibiotics,explains that some products (for example, dry-cow intramammaries) are the Irishequivalent of our PML products. In Ireland, farmers wouldn't need a prescriptionor have to be supervised by a vet to use these antibiotics. Irish VAT rules are differ-ent from England, which makes the imported antibiotics cheaper. ‘Because theyare being sold through the post by unscrupulous wholesalers, they are not incur-ring overheads such as veterinary advice' said Mr Cook. The VMD is co-operatingwith the Irish authorities to try to stop the trade.
The agricultural trade press advertises antibiotics every week. Both NOAH and theVMD say this is allowed under the Medicines Act, but the British VeterinaryAssociation (BVA) is more equivocal. In its latest code of practice on medicines theassociation says: POM medicines should not be advertised or displayed to the public.
Some commonly used medicines such as flea preparations are POM.
Therefore, this restriction on advertising could limit education andprovision of information to clients. The Royal College of VeterinarySurgeons has indicated that it is acceptable for members to displayposters advertising POM medicines within the veterinary practicebecause this would constitute advertising to clients and not thegeneral public (BVA, 1998).
A VMD spokesman interpreted the advice as trying to persuade vets to treat ani-mals on the basis of their own diagnosis and to discourage veterinary practicesfrom ‘promoting one product over another'. NOAH seemed surprised by this advice, and Roger Cook said he would discuss thestatement with the BVA. NOAH itself has a code of practice ‘for the promotion ofanimal medicines' which is printed at the front of its Compendium of Data Sheets forVeterinary Products (NOAH, 1998). This says ‘promotions shall be fair and shall notinclude exaggerated claims or inappropriately encourage the use of particular vet-erinary medicinal products'. A clause in the code covering journal and posteradvertisements says such advertisements should contain the following information:the brand name of the product; the approved or other non-proprietary names ofthe active ingredients; a form of words which indicates clearly that further informa-tion is available on request; the company name and address; and, when promotinga POM medicine to the business or lay user, a form of words which indicates clearlythat advice should be sought from a vet.
The Use and Misuse of Antibiotics in UK Agriculture In its current guide to professional conduct, the RCVS states: All advertising must be legal, decent and truthful. It must be fair,responsible and always in the interests of the animal actually orpotentially under the care of the veterinarian. It must not endangerthe good name and reputation of the profession (RCVS, 1996). In spite of all this careful wording, there is a difference of opinion between theBVA and NOAH about advertising POMs.
Chrissy Nicholls, head of veterinary services at the BVA, said: ‘It is still our beliefthat advertising POMs in the farming press in particular should not happenbecause the veterinarian is pressurised to use a particular product - even if it is notone that he might wish to use'. Ms Nicholls added that there had been a cut-backin advertising POMs in the weekly veterinary press in favour of the weekly farmingpress because the manufacturers knew their advertisements had an impact on farm-ers. Bob Stevenson, a former BVA president, said his ‘gut feeling' was that POMsshould be promoted and carefully detailed to the veterinarian but not the farmer.
‘I think advertising in a journal such as Farmers Weekly is inappropriate because itputs a lot of pressure on the farmer to approach his vet - and he doesn't under-stand why the vet might then say this product is not right for you.' Mr Stevensonadded there was a danger that young vets trying to make their reputation would beleaned on by farmers saying that they would go somewhere else unless the productwas made available. ‘A very overt push of a potent POM without a very large slice ofresponsibility is totally unacceptable in my view', he added.
2.4 Overseas use and the question of imports
There seems little point in restricting antibiotic use in the UK if over-use in othercountries encourages the build-up of bacteria resistant to antibiotics. Poultryimported from other EU countries for example may carry fluoroquinolone resis-tant campylobacter (House of Lords, 1998, Evidence, p220). This raises the issue ofmonitoring, including monitoring for antibiotic residues and monitoring of live-stock and/or meat imports to see if they contain antibiotic-resistant bacteria. In evi-dence to the House of Commons agriculture select committee on food safety, thePublic Health Laboratory Service (PHLS) said the following amounts of food wereimported into the UK between January and October 1996 from non-EU countries(House of Commons, II, 1998): (figures in tonnes) feeding stuff for animals (excluding unmilled cereals).2,897,957
fish (not marine animals), crustaceans, and molluscs .339,953
live animals .717
meat and meat preparations .239,629
The Use and Misuse of Antibiotics in UK Agriculture Countries which export meat and other animal products into the UK are supposedto deposit their own residue surveillance plans with the European Commission.
The Commission then has the right to carry out inspections in third countries. Inaddition, under the relevant veterinary checks directive, member states can inspectup to a 1% sample of what is being imported. The VMD is not currently doing anyimport monitoring. A VMD spokesman said: ‘We are currently talking to ourEuropean colleagues about whether we can give them any help on the residuesprogramme'.
The Copenhagen meeting organised by the Danish Ministries of Health andAgriculture said European surveillance of resistance should be started. This should‘collect data on trends in resistance in bacteria of human and animal origin'. DrDavid Livermore, head of the Public Health Laboratory Service's antibiotic refer-ence unit, said this kind of surveillance had not started yet, but ‘it's moving furtherup the agenda, particularly with publication of the ACMSF working group report'.
Concern over antibiotic resistance has prompted EU animal health companies toset up a surveillance programme covering six EU countries, the UK, Spain,Sweden, Denmark, France and Holland. Strains of the bacterium Enterococcus faeci-um will be taken from pigs and poultry and tested for their sensitivity or resistanceto antibiotics. Final results are expected early in the year 2000, according toNOAH, in their submission to the Advisory Committee on the MicrobiologicalSafety of Food Working Group. On the animal feed side, Jim Reed, director-general of the United KingdomAgricultural Supply Trade Association (UKASTA), which represents companieswhich mix antibiotics into livestock and poultry feed, said there were no medicatedfeeds coming into the UK from non-EU countries. ‘There may be some trade inspecialist products such as vitamins and minerals, but trade in medicated feedacross the English Channel scarcely happens at all.' However, the Royal Pharmaceutical Society of Great Britain (RPSGB) says activeingredients for antibiotics and growth promoters are manufactured in Holland,Sweden and Norway and imported into the UK. POMs are also imported and dis-tributed through agents. Figures on this are confidential. The RPSGB says medicat-ed feed is also imported: for example Denkavit, a subsidiary of Dalgety, has a ware-house in Poole for importing milk replacers. This makes up a ‘substantial propor-tion' of what is used in the UK, and is manufactured within the European Union.
The Use and Misuse of Antibiotics in UK Agriculture 2.5 Loopholes in regulation
In May this year new controls on additives and medicines in animal feeds wereannounced by the Ministry of Agriculture. These new controls, including theFeedingstuffs (Zootechnical Products) Regulations 1998 and the MedicatedFeedingstuffs Regulations 1998, were introduced to fully implement an EUDirective. Before the new regulations the Medicines Act 1968 regulated all animalmedicines, including growth promoters and other feed additives such as coc-cidiostats. But under European law growth promoters and coccidiostats are notconsidered to be medicines but zootechnical feed additives. Announcing the new rules Junior Farm Minister, Jeff Rooker said: These measures form an important part of the safeguards on theproduction and use of animal feedingstuffs. At all stages of the foodchain it is essential that there are proper controls in place. But even such ‘proper controls' can be avoided. The Medicated Feedingstuffs Regulations apply to anyone incorporating a prescrip-tion only medicine (POM) into animal feed, including feed compounders andfarmers who mix their own feed, the so-called home mixers. All feed compoundersand on-farm mixers are required to be registered with the Royal PharmaceuticalSociety of Great Britain (RPSGB) or the Department of Agriculture in NorthernIreland. But the BVA code of practice on medicines, published this year, states thatthe Medicated Feedingstuffs Regulations do not apply to farmers ‘top-dressing'feed or medicating via the drinking water.
‘Top-dressing' is literally sprinking product on feed, for example in a trough. Tenyears ago, 17,000 home mixers, mostly farmers, asked for application forms to beregistered so that they could be inspected under the old regulations by the RPSGB.
But only 7000 forms were returned. The RPSGB says today that it cannot know howmany of those remaining 10,000 units are still ‘top dressing' with growth promotersand may have exploited the loophole which allowed ‘top-dressers' to escape regis-tration. The loophole arose because home mixers could claim that ‘top dressing'was not incorporating. It is also interesting that the RPSGB expects just 3000 onfarm mixers to be registered under the new regulations - 4,000 less than returnedtheir forms ten years ago. An RSPGB spokesman said that even the latest regula-tions were imperfect, and that the society would rely on court cases to test the newregime.
The Use and Misuse of Antibiotics in UK Agriculture SECTION 3 – Antibiotic use according to livestock class 3.1 Cattle
Antimicrobial therapy in dairy and beef units begins with the calf. Antibiotics areused for the treatment of infection in the young calf. In older calves, they play anessential role in the control of calf pneumonia (NFU, 1998). Neonatal diarrhoea(in newborn calves) is still regarded as the most important disease of young calvesin both dairy and beef herds, and mortality varies widely from 0-80%. Neonatal E. coli infections may be treated with antimicrobials, usually administered orally asboluses or by injection. Occasionally water medication will be given, but this isexceptional. Diarrhoea may occur later in the calf's life (MAFF, 1998).
Medicated milk replacers may also be used to treat calves. The main prescriptiononly medicines (POMs) included in cattle feed are prescribed mainly for youngcalves and include chlortetracyclines and oxytetracyclines (House of Lords, 1998,Evidence, p.531). An example of an antibiotic additive containing chlortetracy-cline, and marketed for use to treat respiratory infections, is Aurofac 200 MilkReplacer Additive. This is a soluble powder added to dried milk or milk replacerpowder and incorporated at the time of manufacture or on the farm. It can also beadded to liquid milk or to a small quantity of liquid as a drench. Treatment is recc-ommended for five to seven days or until signs of disease are no longer apparent(NOAH, 1998). The NFU says that antibiotics (for example, virginiamycin) have been used effec-tively and safely in calves, and whilst not used widely they can prove to be valuableaids to cattle farming (NFU, 1998). But scientists are concerned that the prophylac-tic use of medicated calf feed has contributed to the rise of multi-resistant strains ofsalmonellae in cattle. A report for the Ministry of Agriculture cites a continuousoutbreak of S. typhimurium DT 204C amongst calves, adult cattle and farm staff inthe UK. ‘The multi-resistance of this organism was considered to be a problemresulting from the use of chlortetracycline and furozolidone in calf feed as prospec-tive prophylactic medication' (MAFF, 1998, p.66). The antibiotic resistant S. typhimurium DT 204 organisms are spread from farm to farm by animal move-ment and historically by calf movement, particularly through dealers.
3.1.1 Beef production
Calves destined to be reared for beef may be given an antimicrobial feed additiveto promote growth when they begin to ruminate. Now that avoparcin is no longeravailable, monensin is the main antimicrobial growth promoter used in beef andgrowing cattle receiving supplementary feed (MAFF, 1998). The main PML addi-tives for cattle feed are monensin and virginamycin (House of Lords, 1998,Evidence, p531).
The Use and Misuse of Antibiotics in UK Agriculture Monensin sodium is an ionophore and not included in data obtained from NOAHfor this report. It is marketed for use in cattle under the trade name Romensin. Itis described by the manufacturers as suitable for use for improved feed conversionefficiency and/or weight gain in cattle, except in lactating dairy cows. It may bemixed into complete feed for housed cattle at a rate of 100g-400g/tonne to provide10-40mg monensin/kg (10-40ppm) of finished feed. In supplementary feeds, themaximum dose in the daily ration must not exceed 140mg monensin/day for ananimal of 100kg liveweight. Romensin can also be incorporated into feed blocks toprovide a maximum of 230mg monensin/head/day for animals over 250kgliveweight. Cattle from commencement of rumination to 250kg liveweight shouldreceive no more than 125mg monensin/head/day (NOAH, 1998). Romensin hasno withdrawal period which means animals given feed containing this additive canbe slaughtered immediately for human consumption.
3.1.2 The dairy herd
Dairy cows are routinely given antibiotics to treat and prevent mastitis. Mastitis,which is an infection of the cow's udder, is a common disease in dairy cows. It canbe subclinical, where cows show no obvious symptoms, or clinical which causespainful swellings in one or more quarters of the udder. Mastitis is commonly treat-ed with antibiotics administered as intramammaries directly into the cow's teat.
The NFU says antibiotic treatment is essential for mastitis (NFU, 1998, p.22). Butsome experts disagree. ‘Where there are visible clots in the milk but cows are notill, standard practice is to use antibiotics, but this may not be the best option - stud-ies show that some of these cows would show a visible cure just as quickly withoutantibiotic treatment' says Helen Biggadike, researcher at ADAS Bridgets Farm, in arecent Farmers Weekly article.
There are various types of mastitis-causing organisms including staphylococci.
Staphylococci are currently the third most commonly isolated organism from milksamples by the Veterinary Investigation Centres. Antibiotics used to treatStaphylococcus aureus mastitis include: penicillin, nafcillin, cloxacillin, ampicillin,cefquinone, cephalexin, cefoperazone, cefuroxime, cephatrile sodium, cephaloni-um, streptomycin, neomycin, erythromycin, tylosin, spiramycin, and novobiocin.
These may be given alone or in combination where appropriate (penicillin andstreptomycin, for example). Figures for S. aureus in the UK suggest that around60% of strains are penicillin resistant (MAFF, 1998, p63). Streptococcus uberis is the second most commonly isolated bacterium from milk andis particularly associated with straw bedding. The same range of antimicrobials isused as for staphylococci (see above). But penicillins are the drug of first choice,often mixed with streptomycin. These are significantly cheaper than many othertreatments. Streptococcus agaclactiae in the UK is sensitive to penicillin and only occa-sional isolates resistant to it have been described in the UK. Other streptococci are The Use and Misuse of Antibiotics in UK Agriculture present in bovine mastitis (S. dysgalactiae and S. uberis) and are much more fre-quently resistant to antimicrobials (MAFF, 1998, p64). Mastitis infection can be monitored in herds through cell counts in milk and farm-ers are financially penalised by dairy companies for high cell counts. Big penaltiesare also imposed for milk contaminated by antibiotic residues and milk from treat-ed animals must be withheld from sale for the required withdrawal period.
Consequently it makes sense to prevent infection. Good hygiene is vital and farm-ers are also advised to use so-called dry cow therapy (or long acting antibiotic drycow intramammaries) during the cow's dry period. This form of preparation hasthe dual role of treatment and prevention and has been well recognised for its ben-efits to cattle for about 40 years, The dry period is ideal because it occurs whenthere is no removal of the antibiotic or economic loss from the disposal of milkwith antibiotic residues.
All 120 dairy cows which make up to the herd at Greenmount College, NorthernIreland are given ‘routine mastitis treatment appropriate for the length of the dryperiod'. The need to prevent summer mastitis, so called because disease peaks inlate July/early August, through use is also stressed in the college's dairy manage-ment notes. ‘The emphasis must be on prevention, including dry cow tubes used toprevent access of mastitis causing bacteria, use of insecticides and dry cow antibiot-ic tubes to discourage flies actually landing and resting on hind quarters/uddersevery fortnight.' The prevailing consensus is that summer mastitis has to be pre-vented because in almost every case following infection the quarter will be lost andinevitably will cause the cow or heifer to be culled (NOAH evidence to ACMSFworking party). Other common uses of antibiotics in the dairy herd are to treat infection after calv-ing and to treat lameness. Results of surveys show lameness is widespread in UKdairy herds affecting about 25% of cows. Bad feeding of high yielding dairy cowscan make them prone to lameness which can be incurable. Badly designed housingparticularly cubicles and rough concrete floors can also cause lameness. The NFUsays antibiotic treatment is essential (NFU, 1998).
3.2 Sheep
Of all farm animals sheep receive the least antimicrobial treatment. The NFU say atypical less favoured area unit of 1000 ewes and 50 suckler cows will use about 2-4100cc bottles of a long acting penicillin-type antibiotic in the whole year acrosssheep and cows (NFU, 1998). Sheep vets including Richard Rowland, secretary of the Sheep Veterinary Society,Eifion Evans, vice-president of the British Veterinary Association, and JamesHindson, say antibiotics are not used as growth promoters in sheep husbandry, andmonensin (which was used to treat coccidiosis and toxoplasmosis) is no longer The Use and Misuse of Antibiotics in UK Agriculture used. They agree that if a farmer helps with lambing by putting his hand into theewe, he will often give a shot of penicillin to prevent the spread of infection inindoor flocks. Some experts advise farmers to keep antibiotics on hand duringlambing. Greenmount College management notes recommend including an antibi-otic injection and antibiotic drench in the first aid cupboard at lambing. This is themost difficult time for sheep farmers as 75% of ewe deaths and 70% of lamb deathsoccur at or near lambing.
Sheep are often housed during the last part of their pregnancy. In some cases, thiscontinues for a few months and can lead to a build-up of E. coli and other environ-mental contaminants causing problems post-lambing in newly-born lambs. Wherethe build-up of E. Coli leads to scouring in newly-born lambs, oral antibiotics areused. Because there are numerous strains of E. coli, laboratory analysis of lamb fae-cal samples will determine the most appropriate antibiotics for a particular strain.
In their first year of lambing, ewes have two injections of a combined clostridialand pasteurellosis vaccine. In each subsequent year, there will be one vaccine. Butoutbreaks of pasteurella and pneumonia can occur despite vaccination: whereacute clinical cases occur, intravenous injections of crystalline penicillin can beeffective in big outbreaks across farms. Where there are a lot of cases, the vet mayhave to re-vaccinate. The stress of gathering ewes for this operation may cause yetmore pasteurella, so the vet may use a long-acting formulation of penicillin to pre-vent the pasteurella spreading even further.
For enzootic abortion in ewes, a range of different vaccines is available. But if afarmer has not had this condition before and is hit by an abortion storm, he isadvised to use a long-acting preparation of oxytetracycline to keep chlamydia bacte-ria under control.
With foot rot, vets used to rely on a foot bath and foot paring. They now recognisethe beneficial effect in virulent outbreaks of foot rot of an initial injection of peni-cillin or oxytetracycline.
Eifion Evans, whose practice has eight vets covering hill and lowland flocks inNorth Wales, said vets have seen more listeria in sheep in the last few years. Thereis no vaccine against listeria, and any decision on the use of antibiotics woulddepend on the degree of infection, how long it has been present and which routeit has taken to the brain. Mr Evans has used very high doses of oxytetracycline. Butto emphasise the unpredictability of listeria, Mr Evans said he knew of one flock of2,500 ewes with five cases of listeria where four recovered; in another flock of 200ewes, there were 20 cases of listeria, and all but three of these cases died.
According to the NFU report the main reasons for antibiotic treatment in sheepare: pneumonia (respiratory problems), some foot rots (foul), mastitis, followingassisted births, bites and inflamed wounds (dogs, snakes), joint ill, watery mouthand E. coli (scour).
The Use and Misuse of Antibiotics in UK Agriculture Pigs reared in indoor, intensive systems will receive antibiotic treatment throughouttheir life until slaughter - usually at under 6 months old. The amount appears todepend on the health status of the herd. In high health pig herds antibiotic usemay be restricted to injections and growth promoter use. However, in most conven-tional herds water and feed medication is also practised. Important periods of useare in the farrowing house, and in the weaner and growing phases. Growth pro-moters are widely used during the early stages of growth. In a survey of pig farms in 1995, farms were found which used only penicillin andstreptomycin and, perhaps, tetracycline for wounds. These were high health herdsand were free of most of the diseases requiring treatment. Other herds were infect-ed with a range of diseases had been prescribed up to ten antimicrobials (MAFF,1998, p67). The NFU say prophylactic antibiotics are given mostly in feed, sometimes in thewater when pigs are judged by the veterinary surgeon to be likely to suffer from anoutbreak of disease (NFU, 1998, p24). It appears from the evidence that pigs inintensive conventional systems are likely to suffer from an outbreak of disease atmost stages in their life. In most conventional herds antibiotic treatment starts soon after birth. Piglets willreceive treatment for enteritis and for respiratory disease. In a typical herd there isuse of neomycin, apramycin, amoxyclav, ampicillin, enrofloxacin or trimethroprimsulphonamide in the diarrhoeic piglets for E. coli enteritis (MAFF, 1998).
At weaning (usually 3 weeks) all piglets are gathered, mixed and then reared to fin-ishing weights. From weaning pigs will receive feed medicated with a growth pro-moter. Virginiamycin, tylosin, salinimycin, avilamycin or bacitracin zinc are com-monly used. Copper at 175 ppm will be present in all rations. Weaners usually develop post weaning diarrhoea caused by E. coli which occurs onday 3 post weaning. At weaning pigs will receive medication to treat the post wean-ing E. coli diarrhoea and any oedema (swelling) disease which may be present. In50% of herds the feed is medicated with zinc oxide at 3000 ppm to prevent thisand is usually given for two weeks in the feed (MAFF, 1998). This point has also been made by NOAH in their submission to the ACMSF work-ing group. In most instances on farm, say NOAH, preventative medicine should beintegrated with management changes such as disinfection and on-farm movementcontrols. In oral evidence to the House of Lords select committee, Peter Watson,NOAH chairman of technical affairs and registration and development managerwith drug company Bayer, said it was known that ‘two days after you wean the pigsthey will develop diarrhoea, and some will become very ill. You include a therapeu-tic drug over that period to prevent that happening and that is what we understand The Use and Misuse of Antibiotics in UK Agriculture as prophylaxis' (House of Lords, 1998, Evidence, p.208). Post-weaning diarrhoea is quickly followed by a range of other diseases. GlassersDisease (Haemophilus parasuis) occurs at 4 weeks, pleuropneumonia at 6-8 weeks,proliferative enteropathy from 6 weeks and spirochaetal diarrhoea and colitis atany time from 6 weeks onwards (MAFF 1998). So, from two weeks after weaningpig feed may contain antibiotics to treat these diseases. This feed usually contains atetracycline and is often a combination of chlortetracycline, sulphadimidine andpenicillin (MAFF, 1998). The MAFF review adds ‘it is important to realise thatalthough each pig may receive a treatment course of a week at most, medication onthe farm is continuous, as new pigs enter that age group every week'. At 8 weeks the pigs are termed growers and moved to another house. Here theywill develop enzootic pneumonia, streptococcal meningitis (Streptococcus suis) and,possibly, swine dysentery. Respiratory disease may cause problems until slaughter(MAFF, 1998).
The main use of antimicrobials against streptococci in farm animals is for the treat-ment and control of S. suis infection in pigs. Most isolates of S. suis are extremelysensitive to penicillin but resistance has been identified. Treatment is by using peni-cillin in feed or water. Recently, amoxycillin or amoxyclav have taken over this role(MAFF, 1998). Mycloplasma treatment is particularly frequent in the pig (M. hyopneumoniae) and isthe reason for the use of significant amounts of antimicrobial (MAFF, 1998).
Mycoplasma is an infective agent distinct from bacteria as well as viruses. The prod-ucts used include: tetracyclines, tylosin, tilmicosmin erythromycin in the udder, tia-mulin, lincomycin and enrofloxacin. Resistance has been identified to all thesemicrobials with the exception of enrofloxacin. (MAFF, 1998). From the grower accommodation, pigs will be moved to the finisher accommoda-tion at about 60kg until slaughter at 95-105kg. Antibiotic treatment may be given tosows for metritis, mastitis and for specific diseases such as erysipelas or leptospirosis(MAFF, 1998). 3.3.1 Pig ‘vices'
As well as disease challenges, pigs in confined, intensive systems face injury fromeach other as a result of so-called ‘vices', including tailbiting, and ear and flankchewing. An important factor in the development of such ‘vices' is greasy pig dis-ease or exudative epidermitis. A skin infection or wet eczema begins on the tip ofthe tail or ears, often started by a combination of feed contaminating the skin andsplitting of the skin caused by trauma. Staphylococcus hyicus then invades and causesinfection. The pig is attracted to the lesion and eventually this leads to vice. TheGreenmount College management notes state that ‘this situation is particularlyapparent when pigs are first weaned into flat decks or nurseries or when they are The Use and Misuse of Antibiotics in UK Agriculture moved into second stage accommodation particularly if mixing takes place. Otherdiseases such as pneumonia can result in disadvantaged pigs being traumatised byothers'.
Treatment involves determining the antibiotic sensitivity of the Staphylococcus hyicusif this is part of the problem and medicating feed for 7-10 days, injecting trauma-tised pigs with long-acting antibiotics, management control and prevention. Thenotes add ‘if Staphylococcus hyicus infection is part of the problem, there will usuallybe a very good response to in-feed medication with tetracyclines'.
3.3.2 Residues in pigmeat
Not surprisingly the widespread use of antibiotics in pigs has resulted in residueproblems. In 1995 representatives of UKASTA, together with officials from theVMD, Central Veterinary Laboratory and State Veterinary Service were involved ininvestigations into the source of sulphonamide residues in pig meat. This hap-pened after a large pig slaughterhouse had some consignments of pigmeat export-ed to the Far East rejected. UKASTA told the Lords select committee, The conclusions of the investigations indicated that the sulphonamideresidue problem could be due to a combination of factors includingdeficiencies in the safe handling and usage of veterinary medicinesand medicated feedstuffs on farm; increased use of sulphonamidemedicated feedstuffs due to the increased level of respiratory diseaseoccurring in intensively reared pigs; low level cross-contamination infeedingstuffs; and cross-contamination between medicated and non-medicated pigs on farm, during transport and in a lairage at theabattoir (House of Lords, 1998, Evidence, p530).
The authors of MAFF's review of antimicrobial resistance say that the main prob-lems with pig farms are ‘the amount of antimicrobial used, the use of tylosin in thefarm which results in the presence of Campylobacter coli resistant to tylosin at slaugh-ter and the contribution made to the antimicrobial resistance pool by gut flora'.
3.4 Use in poultry
The poultry industry is split into two parts: the broiler industry, which producesbirds slaughtered at 6-7 weeks old for the table, and the egg-producing sectorwhere layers are reared and placed in percheries, laying barns or battery cages at16-18 weeks for one egg laying cycle and then killed (MAFF 1998).
3.4.1 Broiler production
Broilers are placed on the floors of their houses which have been cleaned and dis- The Use and Misuse of Antibiotics in UK Agriculture infected since the previous batch. According to MAFF, they may be given a probiot-ic and will receive antimicrobial growth promoters (virginamycin, zinc bacitracin,bambermycin, and formerly avoparcin) and coccidiostats which may include mon-ensin and salinomycin in their heat-treated diet (MAFF 1998). According to UKAS-TA, the main POM medicines incorporated into feed for poultry are penicillins,chortetracyclins and sulphonamides, while the main PML feed additives, whichinclude growth promoting antibiotics and a range of antibacterial coccidiostats,are: virginamycin, zinc bacitracin, lasalocid, nicarbazin, monensin, salinomycin,narasin, clopidol, methylbenzoquate, dimetridazole, and nifursol (House of Lords,1998, Evidence, p531).
The NFU says that antibiotics such as virginiamycin and avilamycin help birdsachieve maximum benefit from their food. ‘It is important for the health and wel-fare of broilers that birds are as even as possible in size and weight. Such uniformi-ty is vital to give equal opportunity of access to food and drink' says the NFUantimicrobial working party report. ‘They also help to prevent diarrhoea andnecrotic enteritis which occurs in poultry whether kept for meat or eggs, whetherin houses or on free range. The only birds that do not suffer from this conditionare those kept in cages because they are separated from their own faeces'. The NFU and the British Poultry Meat Federation (BPMF) say that as well as assist-ing welfare, growth enhancers reduce the amount of waste excreted and allowmore land to be available for food production. But for some scientists reducing theamount of poultry litter produced is not a justifiable reason for antibiotic use.
‘Antibiotics are a fantastic gift. To waste them just to get smaller amounts of animalfaeces seems to me to be a mistake', Dr Norman Simmons told the House of Lords.
The BPMF says the only antibiotics authorised as digestive enhancers are ones thatare not used or related to those used in human medicine. That may the case at themoment but as previously mentioned virginiamycin is a member of the strep-togramin group of antibiotics and there are fears that quinupristin/dalfopristin,another streptogramin mixture developed for use in humans may not be effectivebecause virginiamycin use in animals may have already resulted in human resis-tance (House of Lords, 1998, Evidence, p219).
What's in a name? Growth promoting antibiotics are often referred to by the industry as Performance Enhancers or DigestiveEnhancers. Under European law they have now been reclassified as Zootechnical Feed Additves.
According to the British Poultry Meat Federation they are not appetite stimulants. ‘They do not make thebird grow any bigger than it otherwise would, so it is misleading to refer to them as growth promoters.
Digestive enhancers reduce the amount of feed nutrients used by the bird to maintain its intestinal flora,freeing more nutrients for absorption, thereby improving the efficiency of feed conversion.' (House ofLords, 1998, Evidence, p.338) The Use and Misuse of Antibiotics in UK Agriculture Treatment is required for any outbreak of necrotic enteritis, Colisepticaemia sal-monellosis causing mortality, outbreak of mycoplasma infection or outbreak ofnecrotic dermatitis (Staphylococcus aureus). The antimicrobials used for salmonellaand E. coli may include enrofloxacin and, now that necrotic enteritis is no longersupressed by avoparcin, amoxycillin/amoxyclav is commonly fed to birds to treat it.
Colisepticaemia is one of the most serious and intractable disease problems of thegrowing birds and the antimicrobials used in its treatment are similar to those usedfor salmonella (MAFF, 1998). The poultry industry says prophylactic medication is only used in specific cases ofpredicted disease infection. Rather than wait for the birds to become clinically ill(and possibly unable to eat or drink properly) before being treated, they are med-icated at the time when the infection is predicted to occur (House of Lords, 1998,Evidence, p387). However, the NFU Antimicrobial Working Party says that Routine prophylactic use of antibiotics is not considered good practice,but there are occasions when prevention is better than cure. In a shedthere may only be at any one time a small proportion of birds that areactually ill, but mass medication is necessary to protect the rest, sothis is essentially a mix of prevention and therapy (NFU, 1998).
But given the large number of birds, even on relatively small holdings, mass oralmedication is the only practical method of treating birds in most cases.
Therapeutic treatment is applied when birds in a flock are either clinically illand/or dying as a result of a bacterial infection. It is standard practice to identifythe bacteria involved and carry out an antibiotic sensitivity test on them prior to orconcurrently with any treatment (House of Lords, 1998, Evidence, p387).
Examples of water soluble therapeutic antibiotics are amoxycillin for mycoplasmaand bacterial infections. Neomycin may be given in water or in feed.
In 1993 the fluoroquinolone enrofloxacin was licensed for use in broilers in theUK. The MAFF review of antibiotic resistance also mentions ‘the practice of inject-ing eggs with enrofloxacin prior to hatching'. The licensing of enrofloxacin hascaused controversy due to the emergence of antibiotic resistant bacteria and somescientists are concerned over ‘mass medication'. This has promoted drug manufac-turers to respond stressing the controls on use.
It is Bayer Animal Health's policy to market fluoroquinolones fortherapeutic use in animals only if a number of requirements havebeen fulfilled. Specifically, drugs are to be given on prescription onlyand administered under the supervision of a veterinary surgeon. Adiagnosis should be based, wherever possible, on bacterial culture andsensitivity testing. Extra-label1 and prophylactic use are not promoted;advertising is only to veterinary surgeons (Watson et al, 1998).
1. The extra-label use of veterinary drugs refers to their use for purposes and animals for which they are not licensed at the veterinarysurgeon's own discretion.
The Use and Misuse of Antibiotics in UK Agriculture Nonetheless, scientists from the PHLS have pointed out that since 1994 the inci-dence of isolates of multi drug-resistant Salmonella typhimurium DT104 from humanswhich are resistant to ciprofloxacin, a powerful and much used fluoroquinoloneused in man, ‘has increased exponentially', with 14% of isolates resistant to thisantimicrobial in 1996 (Threlfall et al, 1997).
3.4.2 Residues in eggs
Chicken and eggs are not subject to statutory residue surveillance requirements,but antimicrobial and antibiotic residues have been found in substantial propor-tions of the egg samples which are analysed each year on a non-statutory basis. The figures are divided into statistics concerning free-range and ‘other' eggs. In1997, residues of the antibiotic coccidiostat nicarbazin were found in 6.8% of thesamples of each type of egg tested, compared to 10.7% overall in the previous year.
Residues of lasalocid, another antibiotic coccidiostat, were present in 2.3% of free-range and 1.4% of other eggs in 1997.
It has been recognised that contamination with these drugs seems at least partlyattributable to deficiencies in the manufacturing process. In 1995, when attentionfocused on the isolation of lasalocid residues in eggs, the fine powdery nature ofthe product was blamed for holdups in the mill and therefore contamination offeed destined for laying hens. After the introduction of a new, more granular ver-sion, it became noticeable that residues dropped. More recently there has beenconcern for the same reason over nicarbazin residues. The VMD has said thatwhilst the concentrations being found are not considered a health risk to con-sumers, the substance is not licensed for use in laying hens. ‘Discussions are beingheld between the egg industry, UKASTA and the VMD on these findings', UKASTAtold the House of Lords. Dimetridazole and ronidazole (DMZ/RNZ) are antimicrobials not licensed for usein laying birds and which should therefore not be present in eggs at all. Theirresidues are present in the form of a common metabolite, and are listed in a singlecombined figure. DMZ/RNZ residues were found in 5.9% of free range and 4.8%of other eggs tested in 1997 (from samples of 219 and 207 eggs respectively). Theproportions in 1996 were 8.8% and 13% (VMD, 1998). These antimicrobials arelisted by MAFF as ‘antimicrobials used in agriculture which may affect the antimi-crobial resistance status of food borne pathogens or contribute to the antimicrobialresistance pool in man' (MAFF, 1998).
In the case of nicarbazin and lasalocid residues, the VMD report says that ‘toxico-logical advice has stated that these concentrations did not pose a risk to humanhealth'. For DMZ/RMZ residues, no comparable assurance was made. No mentionis made at all of possible resistance issues.
The Use and Misuse of Antibiotics in UK Agriculture 3.5 Use in fish
Data on the use in fish are contradictory. The SMAC report from the Departmentof Health seems satisfied that use in salmon farming is falling. In the late 1980s, thesalmon farming industry ‘used considerable amounts of tetracyclines and, later, ofquinolones'. In Norway, says the report, this usage peaked at 47 tonnes of antibac-terial agents in 1987, but decreased to 1.5 tonnes by 1994 ‘reflecting increased reg-ulation, vaccination and the segregation of farmed fish by age'.
However, a report published in 1993 by the International Council for theExploration of the Sea was not nearly so complacent.
The main [antibacterial] compounds licensed for [fish farming]include oxytetracycline, oxolonic acid and tribrissen […] Most of theantibiotics used are persistent in the environment and spread from thefarms to surrounding areas where accumulation in sediments mayoccur. Residues of oxolonic acid have been found in wild fish,shellfish and crustaceans in close proximity to fish farms, and theconcentrations may far exceed levels accepted for human consumption[which were then 0.01mg/kg in Norway]. Little is known of theeffects of these antibiotics, which can also reach wild fish and caninduce the development of resistant bacteria (North Sea Task Force, 1993).
Those sentiments are still relevant in 1998: ‘Oxytetracycline is used [in fish farm-ing], although it is recognised as unsuitable: salmon absorb only seven% of theadministered dose and carp 1%, so most of the drug is wasted for its intended pur-pose and escapes into the environment' (Dr. Alan Long, private communication,1998).
The Ministry of Agriculture review points out that freshwater and seawatersalmonoid farms are important sources of fish in the UK. Major bacterial diseasesof these fish include rainbow trout fry syndrome, bacterial kidney disease, entericredmouth and furunculosis which cause significant losses. Vaccination has reduced the need for treatment in furunculosis and the risk ofantimicrobial resistance spreading from fish is now lower than for some years.
As far as imports are concerned, antimicrobial use is largely uncontrolled in Indiaand the Far East which are sources of freshwater prawns and other cultured shell-fish and farmed fish. The waste from poultry and pig units are used to feed fishand the fish are treated with a wide variety of antimicrobials. Imports of catfishfrom the United States may carry similar levels of antimicrobial resistant bacteria(MAFF, 1998). The Use and Misuse of Antibiotics in UK Agriculture The information on antibiotic usage on UK farms detailed in this report raises The extent to which this use is contributing to the development of drug-resistant disease in the human population. Changes needed in legislation and strategies that should be developed to reduce the threat posed to human health. These will be the subject of future reports in this series by the Soil Association.
The Use and Misuse of Antibiotics in UK Agriculture BVA, 1998 I, BVA Code of Practice on Medicines; MacKinnon, J.D., 1981, ‘The Use of Tylosin in feed and London, British Veterinary Association Publications therapy - a review' in Ten Years on from Swann,Proceedings of a symposium organised by the Association BVA, 1998 II, Report of the Antimicrobials Working of Veterinarians in Industry; London, AVI Group; London, British Veterinary Association Publications Ministry of Health, 1998, The Copenhagen House of Commons, 1969, Report of the Joint Committee Recommendation. Report of the European Union on the use of Antibiotics in Animal Husbandry and Conference, ‘The Microbial Threat', 9-10 September Veterinary Medicine; London, Her Majesty's Stationery 1998, Copenhagen; Copenhagen, Ministry of Health and Ministry of Food, Agriculture and Fisheries House of Commons, 1998, I. Food Safety, Fourth report Mounsey, A.D., 1998, Handbook of Feed Additives, 1998- of the House of Commons Agriculture Committee, vol. I, 99; Bakewell, HGM Publications Report and proceedings of the committee; London, TheStationery Office NOAH, 1998, Compendium of Data Sheets for VeterinaryProducts, 1998-99; Enfield, National Office of Animal House of Commons, 1998, II. Food Safety, Fourth report of the House of Commons Agriculture Committee, vol. II,Minutes of evidence and appendices; London, The NFU, 1998, Antimicrobials, ‘Responsible Use of a Stationery Office Precious Resource', Report of the Antimicrobials WorkingGroup; London, National Farmers Union House of Lords, 1998, Evidence. Resistance to Antibioticsand Other Antimicrobial Agents. Evidence submitted to North Sea Task Force, 1993, North Sea Quality Status the House of Lords Select Committee on Science and Report; London, Oslo and Paris Commissions, Technology; London, The Stationery Office International Council for the Exploration of the Sea House of Lords, 1998, Report. Resistance to antibiotics RCVS, 1996, Guide to Professional Conduct 1996; and other antimicrobial agents. Report of the House of London, Royal College of Veterinary Surgeons Lords Select Committee on Science and Technology;London, The Stationery Office SMAC, 1998, The Path of Least Resistance, Report of theStanding Medical Advisory Committee; London, The Johnston, M. 1998, ‘Use of antimicrobial drugs in veteri- Stationery Office, 1998 nary practice' in BMJ, vol. 317, 5 September 1998,pp665-7; London, BMJ Publishing Watson et al, 1998, ‘Fluoroquinolone susceptibility of S.
typhimurium DT104', Letter from P.M. Watson, G.D.Bell, MAFF, 1992, Report of the Expert Group on Animal M.M. Webster and R.A. Fitzgerald, The Veterinary Record, Feedingstuffs; London, Ministry of Agriculture, Fisheries April 4, p374; London, British Veterinary Association WHO, 1997, The Medical Impact of the Use of MAFF, 1998, A Review of Antimicrobial Resistance in the Antimicrobials in Food Animals, Report of a WHO meet- Food Chain; London, Ministry of Agriculture, Fisheries and ing, Berlin, Germany, 13-17 October 1997; Geneva, World Health Organisation The Use and Misuse of Antibiotics in UK Agriculture This report is part of the Soil Association's continuing campaign against the excessive use of antibiotics in livestock production. Its publication has been made possible thanks to the generous The Matthew Eyton Charitable Trust The William A. Cadbury Charitable Trust The Mary Webb Trust The Spear Charitable Trust The Rufford Foundation The Summerfield Charitable Trust The Polden-Puckham Charitable Foundation 40-56 Victoria Street T 0117 929 0661
F 0117 925 2504


The natural stress-protection molecule Table of contents 1. Introduction 2. Characteristics and origin 3. Mode of action 4. Effectiveness and efficacy 4.1.1 Protection of lipid membranes 4.1.2 Decrease of inflammation process caused by external pollutants Ectoine for dermatology 4.2.1 Protection against UV

Cme: asthma bronchiale - gina 2014 (update 2015): was ist neu, was ist wichtig?"

Schriftliche zertifizierte Fortbildung „Asthma bronchiale – GINA 2014 (Update 2015): Was ist neu, was ist wichtig?" Prof. Dr. med. Stephan SorichterKlinik für Pneumologie im St. Josefskrankenhaus VNR: 276062016042800008Gültigkeitsdauer: 15.02.2016 – 15.08.2016 ist [1]. Diese Entscheidung des internationalen Ex-pertengremiums wird allerdings derzeit sehr kritisch