............. Prudent Use of Antimicrobials : a Poultry Specialist's View

Paul McMullin MVB DPMP MRCVS

BRITISH VETERINARY POULTRY ASSOCIATION

Summary:
As in other areas of medicine, antimicrobials have revolutionised the practice of poultry medicine over the past 50 years. However they now form only one important facet of the complex of health-promotion measures used. Prudence in their use requires effective input from producers, veterinarians, and governments. The integrated structure of much of the poultry industry favours the dissemination of information which would encourage prudent use. Radical changes in the regulation of antimicrobial use are not required and could prove counter-productive by generating a broad range of unintended consequences.

Introduction:
All medicines should be used prudently, regardless of type or species in which they are used. Prudence should aim to maximise benefits while minimising any adverse effects. Antimicrobials have, in addition to the possible adverse effects associated with any medicine, the potential to select for microbial resistance in target organisms and other sensitive organisms. Prudence in antimicrobial usage in farm animals requires actions by farmers, veterinarians and governments.

What is different about Poultry Medicine?
Poultry farming for commercial food production is invariably based on flocks rather than on individuals. Flocks may range from groups of 500 birds or less. up to 30,000 or more. In these circumstances decisions to medicate must nearly always be based on the population, the flock, rather than the individual. While this may be thought of as a disadvantage there are many compensating advantages. Much production is based on so-called 'integrated systems' which usually give the prescriber easy access to health-related information - health status of parent flocks and hatcheries for instance. Specific pathogen eradication programmes and all-in/all-out production cycles are much more commonly practised than in most types of veterinary medicine. Generation intervals are short, allowing rapid genetic progress for both production and disease-related traits. Perhaps most importantly of all, large flock sizes mean that medication is expensive - this encourages routine sensitivity testing prior to medication.

Poultry production is based on a pyramid such as is illustrated in figure 1. At the apex of the pyramid is a very small population of elite breeding birds. Successive generations both within the primary breeding company and at the level of commercial farms means that 1 male selected by the primary breeder could theoretically contribute genes to up to 20 million broiler chickens. This can result in rapid dissemination of improvements in disease resistance.

Many of the classical infectious diseases which affect poultry have been solved by eradication programmes or vaccines. These greatly reduce the need for antimicrobial medication. The remaining disease problems tend to be complicated. Frequently they present as 'complexes' in which multiple environmental factors interact with management and various sorts of pathogens. Most commonly viral pathogens reduce host resistance, either by a direct immuno-suppressive effect or by damage to mucosae, and hence permit tissue invasion by 'normal' bacteria. Here the emphasis is on managing the problem by the identification and progressive reduction of risk factors.

Producer Prudence
Poultry farmers can do much to reduce their need for therapeutic and prophylactic antimicrobial medication by careful attention to basic principles of good management. Among the important issues to be considered are:

High health status stock Production planning and system organisation
Site and house biosecurity Cleaning and disinfecting houses and equipment
Competitive exclusion Control of insects, rodents and exposure to wild birds
Feed hygiene Drinking water hygiene
Litter Nutrition
Immunisation Dead bird disposal
Environment stockmanship
Veterinary health plan programming========== Programme monitoring/audit

The actions to be undertaken need to be adapted to the requirements of each production system, company and farm, and will constantly evolve in response to changes in the animals, the farms, disease status, the environment etc. The extent to which these individual topics can influence the need for antimicrobial will also vary from farm to farm. In general it is necessary to carefully co-ordinate activities under different headings in order to achieve the desired effect. Of particular importance is the establishment of good 'biosecurity' principles to avoid disease transmission between successive flocks and to prevent infections reaching flocks from the general environment. It must, however, be recognised that the 'thickness of the biosecurity shield' will tend to reduce as we move down through the levels of the production pyramid. Many measures applicable to elite breeding stock simply will not be feasible for final-generation stock because of the large number of birds and farms involved.

Veterinarian Prudence
It could be argued that the most prudent use of antimicrobials is that which is not required! The specialist veterinarian is well placed to advise producers on the complex process of planning and executing the various activities discussed in the previous section. However, diseases will occur in spite of the best efforts of all involved. The British Veterinary Poultry Association has recently published (6) guidelines for its members with respect to antimicrobial medication. These guidelines are, to a large degree, simply a reflection of what has been normal practice for a number of years. The full text is available on the Internet but they may be summarised:

Therapeutic antimicrobial products should..
1. not be used as an alternative to good management, vaccination, or site hygiene.
2. should only be prescribed for animals under care of attending veterinarian
3. not be used long-term in absence of disease
4. be used in accordance with sensitivity of causal organisms
5. be used in prophylactic medication only in accordance with agreed policy of practice
6. be used in such a way as not to adversely affect the documented preventative medicines programmes
7. be used in a dosage regimen to maximise efficacy while minimising resistance.
8. Usage monitoring schemes should not hinder prevention of suffering and should take into account potency of compounds used. The simplest approach is to record the number of Kgs. of animal treated/day as a proportion of the total Kgs. of animal at risk

Demonstration of therapeutic prudence requires good documentation of medicine usage. This will include advisory work relating to on-farm recording systems. Specialist poultry practices will commonly hold a broad range of animal health-related information on which they can base treatment decisions. In our practice we have separate computerised systems dealing with health programming, farm visits and necropsy submissions, serological testing and microbiological testing. In addition we have simple computerised systems to document all medicines issued. A sample (fictitious) prescription is illustrated in figure 2 below. Note that a 'Human Food Residue Avoidance ' notice is included which shows the recommended withdrawal period for meat and, if appropriate, eggs.

Figure 2: Fictitious example of a medicine prescription for poultry

SPECIALIST VETERINARY SERVICES Telephone 01XXX XXXXX Fax:01XXX xxxxx
Veterinary Laboratory, Back Lane, Hemingborough, Anyshire
 
  PRESCRIPTION Ref: RH.96.0108  
       
To: Mr J. Smith cc.Woodside Farm  
  Big Chickens Ltd    
  The Hatchery    
  Upper Broadland    
  Littleton    
  Anyshire AN23 7XY    
       
Site: Woodside Species:Broiler Chicken House(s): 3  
Supplied: Vetremox - 23 x 75 g. pot(s) from store:D    
       
For Animal Treatment Only      
This prescription documents the supply of medicine for birds under our care

Vetremox Product License: 11003/4000 Legal Category POM
Dosage Rate: 20mg/kg amoxycillin, use one 75 g. pot per 3750 kg per day.
Route and Course of treatment: Drinking water for 3 days. The requirement of 23x75 g. pot(s) of Vetremox was calculated on the basis of 3 days treatment of 23000 birds weighing 1.2 kg each. Use approximately 7.7 x 75 g. pot(s) per day.

 
IMPORTANT: Human Food Residue Avoidance Information.
The treated birds may only be slaughtered for human consumption after 24 hours have elapsed after the end of the period of treatment.
 

Governmental Prudence
Governments and their agencies must also play a part in encouraging prudence in the use of antimicrobials. Given the long lead times for new products to be developed and approved it is important that they implement regulatory systems which are stable and which encourage product development. Approval process should be based on the traditional criteria of safety, quality and efficacy but a special effort should be made to facilitate the licensing of products which have the potential for reducing dependence on antimicrobials. Once the systems are in place, political interference in the details of product approval should be minimised. It is, of course, recognised that genuine errors may occur in the regulatory process and new information may come to light which justify a change in indication, dosage range, or even product withdrawal. It is however, important, that the relative risks of maintaining and withdrawing the product are properly evaluated. Any action should be proportionate to the identified risk.

Feed Additive Antibiotics (Dir. 70/524) These compounds are not used under veterinary prescription, though their use (species, dose) has been carefully controlled for many years. Producers can only be expected to show prudence in the use of these compounds by using them in accordance with their official approvals. For those of us outside the regulatory system it would appear that if imprudence there be in this area, it lies within the actions of governments and regulatory authorities. For many years these products have been approved on a basic understanding which was restated as the only formal recommendation on the subject by the WHO meeting on antimicrobial resistance held in Berlin in 1997:

"The use of any antimicrobial growth promotion in animals should be terminated if it is: used in human medicine; or known to select for cross-resistance to antimicrobials used in human medicine"(1)

However, this approach has been 'mutated' over the past year to include all products which themselves, or whose related products, might possibly someday be used in human medicine. This in effect amounts to a "back-door" blanket ban on all such use. The so-called "precautionary principle" has been used as the justification, given that current EU legislation does not allow for a blanket ban. Since these products have been in use for 20-40 years it is highly questionable whether any human health benefit will be achieved by a "retrospective precaution" such as this. The application of a precaution which is not, itself, zero-risk, should only occur after a careful analysis of the risks of the various options available. The application of a blanket ban on these products based on limited experience in a few countries, which are not typical of the rest of Europe, could have a number of unintended consequences.

Swedish producers themselves acknowledge that they would not have been able to do without these products had they not previously instituted radical changes in their production systems to attempt to eradicate Salmonella infections (3). To force the rest of Europe rapidly down this route is likely to place European producers at a substantial disadvantage in competition with foreign producers not similarly burdened. This will lead to further reduced profitability of European agriculture with its inevitable effects on the ability to make the investments required to improve food safety and animal welfare. Increased imports from third countries will tend to reduce the European consumers influence on, and control of, issues such as animal welfare, food hygiene , residues. Because these products do not leave residues it will be difficult to enforce any ban on imports even if WTO rules allowed it. Concerns have also been expressed by veterinarians about indirect effects of product suspensions on the environment, animal welfare, animal disease and the need to use therapeutic medication (4,5,7). The issuing of "Guidelines on application of precautionary principle" issued by the EU Commission Consumer Affairs DG XXIV in October 1998 is to be welcomed (2). The final approved guidelines which will be used by both DGVI and DGXXIV are urgently needed. We await with interest, evidence of their application to the review of digestive enhancing antibiotics. It is widely accepted that antibiotics should be used prudently with a view to maximising their benefit and minimising risk to man. Suspensions/bans are acceptable where there is reasonable scientific evidence. However the balance of risk must be evaluated and be clearly favourable before a ban is introduced.

The RUMA Alliance
Vested interests on both sides of the "use of antimicrobials debate" have embarked on an intensive campaign to woo legislators and the public to their point of view over the past year. Some of these campaigns have concentrated more on building on uneducated prejudices and worries, rather than on presenting a balanced case. In the UK an organisation has come together to attempt to address the issues in a balanced fashion. The RUMA (Responsible Use of Medicines in Agriculture) Alliance, is formed by representatives of the various segments of agriculture, feed manufacture, pharmaceutical industry, veterinarians, food retailers and consumers. It has commissioned species sub-groups to produce papers to fulfil the following objectives:

1. To review the use of antimicrobials in agriculture and to produce responsible use guidance for farmers.

2. To establish and communicate practical strategies by which use of antimicrobials might be reduced.

3. Ultimately to enable poultry producers to discontinue routine antimicrobial use without adversely affecting either the welfare of their animals or the viability of their business.

It is expected that the first papers arising from this process will be published shortly.

Conclusions
Poultry medicine is population based. Disease prevention is based on a multi-faceted approach to health promotion. However antimicrobials are required to deal with the occasions on which this approach fails. Effective prudence in antimicrobial usage requires input from producers, veterinarians, and governments, working in harmony and in the knowledge of what is feasible. Radical changes in the way products are approved may seem attractive but the unintended consequences need to be avoided!

References
1. Anon (1997) The Medical Impact of the use of Antimicrobials in Food Animals. Report of a WHO Meeting, Berlin 13-17 October 1997

2. Belveze, H. (1998) Guidelines on the application of the precautionary principle.European Commission DG XXIV Consumer Policy and Consumer Health Protection 17th October 1998

3. Lundstrom, L (1999) Managing without Growth promotors. South West Broiler Conference, Cannington, Somerset February 10th 1999

4. Sainsbury, D.W.B. (1999) EU Ban on four antibiotic feed additives Veterinary Record 144(3)80

5. Taylor, D.J.(1999) EU Ban on four antibiotic growth promoters Veterinary Record 144(5)126

6. Thorp, B. McMullin, P.F. (1998) Antimicrobials Guidelines and "Mass Medication" Veterinary Record 143 (7):203

(The BVPA guidelines are available on the Internet at http://www.bvpa.freeserve.co.uk/microbia.htm and also on this site BVPA Antimicrobials Guidelines)

7. Thorp, B., Cargill, P. (1999) Ban of digestive enhancers. Veterinary Record 144(1)27-28