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Misuse of drugs and development of their resistance




  • Chemotherapy is essential in intensive poultry production all over the world. It has played a significant role in helping to meet the ever growing demands for animal protein. Antibiotics have been used for therapy, prophylaxis and for growth promotion in poultry. However, choosing between the available drugs and using them to the best advantage is not always straightforward and the rational use of drugs is particularly complex for poultry veterinarian.

    Chemotherapy is essential in intensive poultry production all over the world. It has played a significant role in helping to meet the ever growing demands for animal protein. Antibiotics have been used for therapy, prophylaxis and for growth promotion in poultry. However, choosing between the available drugs and using them to the best advantage is not always straightforward and the rational use of drugs is particularly complex for poultry veterinarian.

    A vet should come up with an effective flock health programme which combines management, hygiene, quarantine and chemotherapy in the most rational and profitable way. A chemotherapeutic programme should be efficacious, safe, practical and legal and ethical. Most importantly, the vet must not panic or allow himself to be rushed into poorly planned, ineffective, unwarranted or unethical medication programmes.

    In our poultry industry, in spite of heavy reliance on medication, poultry health is deteriorating; there are new diseases, high drug dependency and susceptibility to epidemics.

    Medicate or not – a critical decision ?

    Medication is justified in bacterial outbreaks. However, it is essential that a diagnosis, even if only tentative, is made before embarking on medication. Important questions such as whether a treatment is required and with what drug, hinge on the diagnosis. Without a reasonably accurate diagnosis, chemotherapy becomes a trial and error or hit and miss affair.

    Medication is not justified when it will be ineffective such as uncomplicated viral infections, uncomplicated management induced problems, disease caused by environmental factors, nutritional diseases and toxic diseases. Ineffective medication will reduce the credibility of the veterinarian or the drug.

    Furthermore, medication my create a false sense of security, or detract from the real cause of the problem and how it should be corrected. Medication is unwarranted if the only reason for using it is to provide non-specific cover over a stress period, be seen to be doing something, bring piece of mind (in the absence of any real disease risk), satisfy the argument that “it won’t do any harm but it just might do some good”, use up drug stocks. Sometimes a drug is used as the scapegoat for poor flock performance.

    Medication can sometimes be counterproductive. Examples are:

    • It may delay desirable exposure and immunity to coccidiosis.
    • Medication of mycoplasmosis during rearing may simply delay the inevitable exposure until a less desirable time, such as point of lay.
    • Prolonged use of antibacterial can upset the normal flora of the digestive tract and lead to secondary fungal infections.
    • Medication may hinder or delay the detection of infection with Myco. gallisepticum or salmonella.
    • Medication may encourage the development of microbial resistance to the drug, especially if sub therapeutic levels are administered repeatedly or for a prolonged period.
    • Many antibiotics including chloramphenicol, chlortetracycline, gentamicin, oxytetracycline and tylosin are immunosuppressive and their use will prolong uncomplicated viral diseases.
    • Medication is not justified if it is illegal or unethical.

    Selection Of A Drug

    The selection of the most effective drug should be based on a combination of theoretical knowledge, laboratory sensitivity testing, historical records, and practical experience. There is no point in using a drug it won’t work, no matter what its other advantages may be. Even in case of a broad spectrum of activity, the principal activity of most drugs is directed against a fairly narrow range of infectious organisms. Some diseases have a drug of first choice and a guide must be considered.

    In theory, bactericidal is preferable to bacteriostatic activity, particularly in severely ill and immunosuppressed patients. In practice, it makes little difference, as a functional immune system is essential to the resolution of all infections irregardless of the mode of action of the drug used to treat it.

    Multiple drug therapy is a very poor substitute for accurate diagnosis and selection of the most efficacious treatment. Complicated infections may require the use of two drugs at the same time. Some drug combinations are synergistic, increasing both the efficacy and spectrum of activity.

    Given the large number of birds in intensive systems, when a small proportion of the birds become ill, mass medication with therapeutic antibiotics is practiced because treating only the infected birds is considered impractical.

    Dose Rate And Frequency Of Medication

    Ideally, the dose rate of each drug should be based on the minimum inhibitory concentration (MIC) which is required, attained and maintained in infected tissues. Unfortunately little work is done on drug absorption, tissue distribution, metabolism and excretion of drugs in the chicken. Also, the dose rates should be adjusted to allow for spillage or wastage.

    Dose rates should be calculated based on body weight rather than on concentration in water or feed as this gives accurate and consistent dosage. Flock dosage based on water and feed consumption will fluctuate from day to day and from flock to flock, potentially resulting in under- or over-dosage and a variable and unpredictable clinical response. For greatest efficacy, treatment of disease outbreaks should always commence at maximum dose rates. Remember that doses used in excess of those recommended will not be any more effective and may be toxic. Chickens have been accidentally paralyzed by overdosing ionophores. For long term prevention, use the minimum effective dose rate. Remember that doses below the recommended will be ineffective. When controlled challenge and immunity are desired, such as with coccidiosis, a suboptimal dose rate may be employed.

    In theory, the MIC of a drug should be maintained or exceeded in tissues throughout the course of treatment. In practice, it is not critical. Continuous medication is more desirable with bacteriostatic drugs. On the other hand, bactericidal drugs are probably as or more effective when given in two divided doses daily.

    Onset And Duration Of Medication

    Normally treatment of a disease outbreak should commence within 24 hours. The sooner medication is commenced the more effective it will be. Sometimes, treatment is best delayed in order to allow the whole flock to become exposed and immune e.g., early treatment of mild coccidiosis or coryza in replacement breeders or pullets may result in uneven flock immunity and subsequent relapses. Prophylactic medication should commence just before the anticipated disease challenge.

    With acute disease outbreaks, medication should continue until mortality stops and clinical signs are no longer present in the flock. Usually this takes at least 3 days. Usually, an acute disease outbreak is under control within 5-7 days. However, if a response is not apparent within 3-5 days, then the diagnosis and treatment regime should be carefully reassessed.

    After an initial period of treatment at maximum dose rates, and once the outbreak has subsided, it may be necessary with some diseases to continue medication at lower levels for a few weeks to allow controlled exposure and immunity to develop throughout the flock. However, remember prolonged exposure to low levels of drug is more likely to encourage acquired resistance.

    Chronic flock infections such as Mycoplasma or Haemophilus, often respond poorly to medication, so an initial period of treatment may be followed up with intermittent medication at treatment dose rates, or more prolonged medication at control dose rates.

    Route Of Administration

    In general, the most effective route depends on the site of infection. Parenteral medication is the most effective route of treating systemic diseases. IM injection is recommended for long-acting drugs. Oral medication is the most effective route for alimentary infections. Remember some drugs are not absorbed from the digestive tract and will be ineffective against systemic infections if given by this route. DW medication is usually more effective in disease treatment than in feed medication. Remember sick birds continue drinking longer than eating. Enteric absorption of many drugs is delayed in the presence of food. Topical medication is the most effective way of treating external parasites.

    Drug Sensitivity And Resitance

    All infectious organisms have an inherent pattern of sensitivity and resistance to specific drugs. Resistance to certain drugs may also be acquired. This can occur through mutation and selection and cross resistance. Multiple drug resistance may be to a number of unrelated antibiotics. R-plasmids (transferable drug resistance) may be transferred between individual bacteria within a strain, between strains or species, and between genera, e.g., E.coli and salmonella.

    Antibiotics are selecting an ever widening range of resistant bacteria and this is being potentiated by gene transfer. We must expect the incidence and types of resistant bacteria to continue to increase if the overall rate of antibiotic usage continues.

    Antibiotic resistant E. coli are particularly prevalent in the gut flora of poultry. Antibiotic resistant E. coli persist long after the antibiotic has been withdrawn since many of these strains are good colonisers of the gut. There is no evidence that E. coli of animal origin cause disease episodes in man. Their importance lies in the fact that they constitute a highly versatile pool of R plasmids which may be transferred ultimately to important pathogens.

    Safety
    Safety is an important prerequisite for any flock health programme. There is no point in using a drug if it will cause more problems than it solves. Safety referes to both poultry and people.

    Drug toxicity to poultry may occur due to inherent features of the drug, overdosage, prolonged usage and interaction with other drugs or chemicals. Lack of safety in poultry may manifest as:

    1. Clinical signs or mortality caused directly by the drug.

    2. Reduced growth rate, feed conversion efficiency, egg production, fertility or hatchability.

    3. Reduced feed or water consumption.

    4. Secondary or super-infections.

    Drug toxicity to people may occur due to consumption of drug residues in poultry meat and eggs. This may result in an immediate clinical reaction (allergy to penicillins and sulophonamides), gradual development of a fatal aplastic anaemia (in people sensitive to chloramphenicol), acquisition of an allergy or sensitivity to the drug or acquired resistance by human bacteria. Furazolidone, and chloramphenicol are potentially carcinogenic.

    Antibiotic-resistant bacteria in food pose a substantially greater risk to human health than antibiotic residues. Consumption of drug resistant bacteria on poultry meat can cause food poisoning in humans. Poultry enteric bacteria may transfer their resistance plasmids to human pathogens. Multiple-drug resistance is increasing at an alarming rate.

    The possible adverse effects on people can be avoided by:
     
    1. Using antibiotics correctly and only when necessary.
    2. Avoiding prolonged use of subtherapeutic doses which encourage bacterial resistance.
    3. Adhering to withdrawal/product withholding periods before poultry are processed or eggs are sold.
    4. Not using chloramphenicol.

    5. Avoid contact with drugs when they are handled.

    6. Minimising salmonella infection in poultry flocks and salmonella contamination of poultry carcasses and products.

    7. Cooking poultry thoroughly and handling it hygienically.

    Cost :

    Cost has a large bearing on the practicality of chemotherapy. Medication cost has 3 main components: drug cost, administration cost and cost of adverse effects. Sometimes it may be cheaper to live with a minor or refractory disease than to attempt to control it through medication. Cost may be expressed as an amount per kg, per egg or as a proportion of the total flock value.

    There is a high expenditure on veterinary drugs in modern poultry production in Pakistan.

    Recommendations 

    1. The establishment by government of a surveillance system for antimicrobial resistance.
    2. The use of antibiotics for growth promotion should be banned immediately.
    3. Fluroquinolones, and 3rd generation cephalosporins, should no longer be permitted for mass medication. This is to prevent the further development of resistant food poisoning strains.

    4. Poor prescribing by vets should lead to retraining and excessive prescribing should result in legal action.

    5. The Government should help establish a School of Preventative Veterinary Medicine. It should research, collate and disseminate reliable information to farmers, vets and others.
    6. Veterinary and agricultural colleges should place greater emphasis on the teaching of drug-free preventative medicine.

    7. Practical and technical help should be given free of charge to producers to encourage them to alter production methods in order to reduce dependency on antibiotics. 
    8. The Concept of Positive Health: we need to shift away from pathogen-targeted fire-fighting towards proactive, health-targeted policies and practices. Organic farming is a holistic system for achieving positive animal health with proven positive effects.
    a. Short-term biosecurity or treatment measures.

    b. The long-term goal of positive animal health.


    By : Ahmed Din Anjum

    Professor, Department of Veterinary Pathology, University of Agriculture, Faisalabad

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