Hooked On Antibiotics - livestock industry

The UK livestock industry is drug dependent, and needs urgent help to kick the habit, for the sake of the health of the population as a whole.

In 1953, just 10 years after penicillin became widely available, Iain Macleod, the then minister of Health, told the House of Commons that feeding antibiotics to farm animals to make them grow faster would have `no adverse effect whatever on human beings.'[1]

Government research had, in fact, only looked at the economic and practical aspects of using antibiotics in this way. Questions posed on possible resistance and long-term consequences for animal and human health remained unanswered. The so-called 'penicillin for pigs bill'[2], was enthusiastically backed by MPs.

Ten years on, the revelation that antibiotic resistance could be passed on from one bacterial species to another[3] should have caused Parliament to repeal the legislation. It did not. The Netherthorpe Committee gave its all clear.

Unwittingly, MPs had brought about a major intensification of livestock production. With the routine inclusion of antibiotics in feed or water, animals could be housed more densely; taken out of fields and kept on concrete, while vacated land was brought under the plough. Economics forced farmers to get out, or adopt factory methods. Wealthy new agri-businessmen formed a powerful lobby with the pharmaceutical companies and found a sympathetic ear at the Ministry of Agriculture.

In 1969, the Swann Committee made a genuine attempt to restore some sanity into livestock production, but the combined influence of the interested parties forced it to water down its recommendations. Department of Health officials caved in to industry lobbying and reversed the ban on tylosin for growth promotion in pigs[4] and MAFF quietly allowed growth promoting antibiotics in cattle over three months of age[5] (the limit previously set by Swann). By 1976, use was rising again,[6] and over the following two decades rose so dramatically that the overall use of tetracycline and penicillin, for example, which Swann had succeeded in getting banned for growth promotion, increased by a staggering 1,500 per cent and 600 per cent.[7] This led to an increase in tetracycline resistance in Salmonella typhimurium from five per cent during Swann's day to almost 95 per cent in our own time.

The industry had, however, sensed a public relations problem with growth promoting antibiotics and called them `performance enhancers'. This only brought to mind images of muscle bound athletes on illegal drugs, so it then tried `digestive enhancers'. Finally it supported moves throughout the EU to reclassify all growth promoting antibiotics as `zootechnical feed additives'.

Once scientific evidence of problems for human health finally began to emerge in the 1990s this could not prevent belated regulatory interest and an eventual ban on seven of the eleven listed growth promoters in Annex 1 of the EU Feed Additives Directive. Avoparcin, manufactured by Roche Products Ltd, was one of these and licensed for most farm species. Yet it was little more than the hospital drug of last resort, vancomycin, under another name. Despite vigorous rearguard action by the industry, strongly supported in Britain by the Veterinary Products Committee (VPC), DNA sequencing eventually showed that use of avoparcin in livestock feed was responsible for the emergence of the superbug Vancomycin-Resistant Enterococci (VRE)[8] which causes bacteraemia, especially round catheters in kidney units. As a result avoparcin was banned in the EU in 1997, followed by six similar drugs in 1999.

Since this purge things have gone rather quiet again. Several new committees have been established, but they have been slow to start work and there is a noticeable lack of urgency. An illustration of this is the government's latest figures on the use of farm antibiotics for 1999.[9] With an election due, they conveniently show an overall 21 per cent reduction over the previous year in weight of active ingredient, to 448 tonnes. Commenting on the data, Baroness Hayman said: `These figures confirm that the government is succeeding in getting across its message on the importance of reducing the use of antibiotics on farms.'[10]

The reduction comes partly from falls in the use of tetracycline, penicillin and streptomycin-type drugs, which are down 18 per cent, 13 per cent and 17 per cent respectively. However, pig numbers have declined by 8 per cent and poultry by 3 per cent during that period and MAFF found it `impossible to quantify' the trade in illegal imports of antibiotics.

There has also been a trend towards new, more potent antibiotics, so decreases in the relatively bulky tetracyclines are not such a meaningful indicator. The figures could also be inaccurate as there is no statutory basis for their collection. Use of some types of antibiotics has increased significantly.

The trimethoprim/sulphonomides mixture, being used in some countries in the fight against tuberculosis in HIV sufferers, increased by 3 per cent to 82 tonnes, while the use of the macrolides tylosin and tilmicosin rose by an alarming 21 per cent to 29 tonnes. Annual tylosin sales worldwide reached $200 million in 1995.[11]

In 1997, when presented with evidence that tylosin was implicated in the development of resistance to the closely related erythromycin, the VPC took no action. Erythromycin is commonly used for patients allergic to penicillin and children infected by serious forms of campylobacter food poisoning.[12] Other member states were less complacent and the ban on tylosin for growth promotion was eventually pushed through at an EU level. Erythromycin resistance in the most common strain of campylobacter, C. jejuni, is still relatively low, but high in the less common strain, C. coli.[13] With 87 per cent of all pigs infected with pathogenic campylobacter,[14] reducing macrolide use in pig production should be a real priority for government. However, just as with penicillin and the tetracyclines in the past, vets are now simply prescribing more macrolides generally to make up for the ban on tylosin as a growth promoter.

`According to industry sources the increase might have been due to the high incidence of gastrointestinal problems in pigs following the ban on the growth promoters,'[15] was the government's embarrassed explanation. Tylosin is routinely used to control the diarrhoea piglets suffer when weaned at three weeks of age or less, and for the health problems and wasting syndromes to which this predisposes them.

Yet another cause for concern relates to fluoroquinolones. These are some of the medical profession's most important drugs, yet resistance has been rising in Salmonella and Campylobacter ever since they were first allowed in livestock production in 1993.[16] Ciprofloxacin is the drug of choice for treating serious Salmonella infections and the one to which doctors first turn in case of erythromycin-resistant Campylobacter food poisoning in adults.

However, ciprofloxacin and more than a dozen newer fluoroquinolone antibiotics are cross-resistant to enrofloxacin. Sold as `Baytril', this is added to poultry drinking water to treat various infections. In October last year the US Food and Drug Administration reviewed evidence against fluoroquinolones and called for an outright ban.[17] In the UK, the VPC equally reviewed the evidence, but true to form, only called for further research.[18] The industry has adopted a voluntary code of practice in an attempt to stave off a ban, but a House of Lords' committee recently commented, 'use of these potent drugs has hardly changed.'[19]

But there are important considerations, which the 1999 figures do not take into account. For example, attempts to ban avilamycin, one of the four antibiotics still permitted for growth promotion within the EU, have been recently dropped. What this means is that UK sales of this growth promoting antibiotic are likely to rise. Meanwhile unpublished research by the Orion Corporation has shown that the adding avilamycin to poultry feed increases colonisation of salmonella in chickens.[20]

Yet another unwelcome trend relates to the use of lincomycin. Being cross-resistant with the medical drug clindamycin it was banned as a growth promoter during the 1970s. However, its routine prophylactic use in pig production is being `pushed' by its manufacturers Pharmacia and Upjohn, for the control, among other things, of Campylobacter. However, lincomycin induces resistance in bacteria in exactly the same way as tylosin and has also been implicated in the development of erythromycin resistance in Campylobacter.

While reducing the overall use of antibiotics is important, the main threat comes from the way in which they are used. Today 80 per cent of all antibiotics are given in food, and a further 10 per cent are added to drinking water. In intensive farming systems drugs are either used in a routine preventative way or to treat both ill and well alike. This creates the ideal conditions for the development, perpetuation and spread of antibiotic resistant infections which can then transfer to us on food or by direct contact.

The UK's livestock system is drug dependent. The only durable way this can be changed is through a fundamental overhaul of the systems in which farm animals are kept. Until this is recognised and changed, antibiotic resistance in foodborne infections will continue to pose a problem for doctors treating life-threatening conditions.

REFERENCES

[1] Hansard 13 May 1953, col. 1327

[2] The Therapeutic Substances (Prevention of Misuse) Bill, 1953.

[3] Watanabe, T, 1963. `Infective heredity of multiple drug resistance in bacteria', Bacteriological Review 27:87-115

[4] Mackinnon. J.D. 1981. `The Use of Tylosin in Fedd and Therapy - A Review. Ten Years on from Swann'. Proceedings of a Symposium. Association of Veterinarians in Industry; p.53.

[5] Browning. A. Written Parliamentary Questions 1172,17 March 1997.

[6] Linton, A.H., 1977. `Antibiotic Resistance; the present situation reviewed'. Veterinary Record 100:54-60

[7] Harvey, J. and Mason, L., 1998. `The Use and Misuse of Antibiotics in UK Agriculture Part 1 Current Usage'. The Soil Association, Bristol

[8] Wegener, H.C., Aarestrup, EM., Jensen, L.B., Hammerum, A.M., Bager, F., 1999. `Use of anti-microbial growth promoters in food animals and Enterococcus faecium resistance to therapeutic antimicrobial drugs in Europe', Emerging Infectious Diseases, v 5, pp. 329-35

[9] Sales of Antimicrobial Products used as Veterinary Medicines or growth promoters in the UK in 1999. Veterinary Medicines Directorate website: www.vmd.gov.uk

[10] MAFF, 2001. `Farmers cut back on use of antibiotics'. Press Release 56/01.19 February.

[11] Colgrave, T, 1995. `The Feed Additives Market' p.44. PJB Publications Ltd.

[12] Moore, J.E., Madden, R.H., Kerr, J.R., Wilson, T.S. and Murphy, P.G. 1996. Erythromycin-resistant thermophilic Campylobacter species isolated from pigs', Veterinary Record 138:306-7

[13] Thwaites, RT and Frost, J A, 1999. Drug resistance in Campylobacter jejuni, C. coil and C.lari isolated from humans in north-west Engalnd and Wales, 1997

[14] Newall. D.G. 2000. `Campylobacter in cattle, sheep and pigs, monitoring and control.' Zoonotic infections in livestock and the risk to public health. Conference 7 Dec. FSA, MAFF, DH, Scottish Executive.

[15] Op. cit. 7

[16] House of Lords, 1998a. Resistance to Antibiotics and Other Antimicrobial Agents, p 61. Evidence submitted to the House of Lords Select Committee on Science and Technology; London, The Stationery Office

[17] Food and Drug Administration 2000. Enrofloxacin for Poultry; Opportunity for Hearing, Department of Health and Human Services

[18] VPC Summary Minutes January 2001

[19] Select Committee on Science and Technology, 2001. Resistance to Antibiotics -- Third Report. The Stationery Office. London

[20] Renny, D.J., 1999. Personal communication

Richard Young farms a 390-acre organic farm in Worcestershire. He is policy adviser to the Soil Association and co-ordinates their campaign against the overuse of antibiotics on farms.

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