Introduction

The availability of over-the-counter and prescription antimicrobials, and the benefits they provide to animal health, welfare and production efficiency, has seen them become an integral component of swine production systems. But do we take them for granted? In your operation, how often are you using antimicrobial compounds, either by injection, in feed, or in water? How aware are you of the legality of your actions in using these drugs, and are you aware of any adverse consequences of antimicrobial use? Below I have listed some things I see as good, bad and ugly regarding antimicrobial use in swine production.

There is little point in reminding producers of the beneficial aspects of antimicrobial use, so the rest of this discussion will focus on the things we prefer not to hear. For several decades now, some members of the medical fraternity and industry critics have opposed the widescale use of antimicrobials in food animal production, particulary for purposes other than disease therapy. These groups do have arguments to support their positions.

Residues

This refers to levels of antimicrobial (or other) compounds detected in slaughtered pigs, that are above allowable levels. Antimicrobial residues in slaughtered pigs have been a problem for the swine industry in the past - the prevalence of violations in sulfonamide tests was 7% in 1984, but declined to 0.61% in 1991, and have remained around this level. This has been a marked improvement but is still far from perfect, given that we are talking of only 1 of many available antimicrobials. Antimicrobial residues are solely the result of the actions of producers and veterinarians - unlike some foodborne diseases, where actions of processors, retailers and consumers markedly affect product safety. The Pork Quality Assurance (PQA) program of the NPPC is a successful program and now covers over 40% of national production. Hopefully, given the efforts of the NPPC to promote this educational program, you all are aware of PQA and have benefited from it. Recently, as part of its quality assurance program, a major packer in the Mid-west announced that it will only slaughter pigs from herds certified under PQA. As packer and consumer scrutiny of pork increases, the consequences of careless or improper use of antimicrobials are likely to get greater, for both the individual and the industry. Product image maybe the major casualty, particularly in export markets, and an image problem regarding pork safety or quality is not what the industry needs at the moment.

Antimicrobial resistance

Antimicrobials revolutionized the treatment of bacterial diseases of humans and animals. Many of these substances were based on naturally occurring compounds produced by living organisms. However, it did not take long for the specter of bacterial resistance to emerge and we've come to learn that bacteria are truly formidable adversaries. Resistance to antimicrobial compounds exists in nature, without medical or veterinary use of antimicrobials. Exposure to antimicrobials selects for bacteria that bear these resistance traits.

Human infections with antibiotic resistant bacteria are a major medical problem. It is estimated that resistant bacteria generate $4-5 billion annually in medical costs in the USA. Multiple resistance (bacteria resistant to more than one compound) is on the increase, and we are only now learning how efficiently bacteria can transfer resistance. For example, a strain of Salmonella called Salmonella typhimurium DT104, has increased rapidly in both human and food animal populations in Europe over the last 10 years. This strain of Salmonella is resistant to 5 antibiotics (ampicillin, chloramphenicol, tetracycline, streptomycin, sulphonamides). Resistance to all 5 antimicrobials is encoded in one piece of DNA which can be transferred as a 'package'. Exposure to any of these compounds can lead to selection for resistance to all 5. DT104 has been isolated from at least 33 states in the USA, and from a wide range of animals, including swine, and can be transferred from animal to human populations by foodborne infections (and probably directly).

Few people would argue that use of antimicrobials does not lead to selection of resistant strains of bacteria in animal populations. How important this is to the rising problem of resistant human infections represents a 30 year debate that is ongoing. However, recent events related to this question indicate that likely future restriction of antimicrobial use in food animals, particularly the use of 'subtherapeutic' (legally meaning treatment for more than 2 weeks at less than 200g/ton) and 'growth promotant' antimicrobials in feed.

Examples of these developments are:

• A World Health Organization meeting in October 1997 recommended that the subtherapeutic use of antimicrobials in food animals should be terminated.
• The Center for Disease Control and Prevention endorsed WHO recommendations that
  1. The use of any growth promoter should be terminated if it is used in human therapeutics
  2. The use of any growth promoter should be terminated if it selects for cross-resistance to antimicrobials used in human medicine
  3. It is essential to have a systematic approach towards replacing growth promoters with non-antimicrobial alternatives
• A report from the National Research Council in 1998 stated that there is evidence linking the use of antibiotics in food animals, the development of resistance, and the spread of pathogens to humans. This report also calls for investigation into alternatives to antibiotic use for maintaining animal health and productivity
• Denmark (the major pork exporter) banned virginiamycin and avoparcin (not available in the USA) in food animals in Denmark, based on risk of cross-resistance to drugs used in humans. Banning of all subtherapeutic uses in planned.
• Veterinary groups in Europe are supporting termination of subtherapeutic use of antimicrobials in food animals

What are our responsibilities?

The is an existing legal framework governing the use of antimicrobials in swine. If and when these rules will change is difficult to predict, but the direction of any change is certain - towards greater restrictions. Meanwhile, it is most important that producers and Veterinarians pay attention to how they are using antimicrobials in food animals. The responsibility of producers and veterinarians is to avoid improper or illegal use of these compounds by knowing the rules. Equally, we must not be careless in our use or indifferent to the rules. Our industry is under the microscope on this and other issues - we do not need our own behaviors to be our enemy. The following list provides a refresher on some key points related to proper and legal drug use on the farm:

Drug Labeling Terms

Label: A display of written, printed, or graphic matter attached to the immediate container of the article (drug).

Over-the-counter drug (OTC): A drug that can be purchased and used by a producer without supervision of a veterinarian. The label of an OTC drug must bear adequate directions for use by the producer and be written to be understood by the producer. When used by a producer in the absence of a veterinarian's order, an OTC drug must be used to comply with the labeling.

Veterinary prescription drug (Rx): A drug for which adequate directions for layman use cannot be written because of toxicity, or possible harmful effects, and as such, requires the supervision and knowledge of a veterinarian to ensure its safe and effective use. All veterinary prescription drugs are required to bear the statement: "CAUTION: Federal Law restricts this drug to use by or on the order of a licensed veterinarian."

Extra-label use: The use of a drug (OTC and/or ) in a manner other than that listed on its label constitutes extra-label use. This can occur, for example, when a product is used at a different dosage, by a different route of administration, for a different species of animals, or an unlabeled disease condition. Extra-label use by a producer is illegal. Extra-label use criteria:

1. A careful medical diagnosis is made by an attending veterinarian within the context of a valid veterinarian-client-patient relationship.
2. A determination is made that (a) there is no marketed drug specifically labeled to treat the condition diagnosed, or (b) drug therapy at the dosage recommended by the labeling has been found clinically ineffective in the animals to be treated.
3. Procedures are instituted to assure that identity of the treated animals is carefully maintained.
4. A significantly extended time period is assigned for drug withdrawal prior to marketing meat, milk; steps are taken to assure that the assigned time frames are met, and no illegal residues occur.

Veterinarian-Client Patient Relationship (VCPR): "An appropriate veterinarian-client-patient relationship will exist when:

1. The veterinarian has assumed the responsibility for making medical judgments regarding the health of the animal(s) and the need for medical treatment, and the client (owner or caretaker) has agreed to follow the instructions of the veterinarian; and when
2. There is sufficient knowledge of the animal(s) by the veterinarian to initiate at least a general or preliminary diagnosis of the medical condition of the animal(s). This means that the veterinarian has recently seen and is personally acquainted with the keeping and care of the animal(s) by virtue of an examination of the animal(s), and/or by medically appropriate and timely visits to the premises where the animal(s) are kept; and when
3. The practicing veterinarian is readily available for follow-up in case of adverse reactions or failure of the regimen of therapy."

In compliance with the preceding guidelines, both Over-The-Counter (OTC) and Prescription (Rx) drugs may be used on an extra-labeled basis, as long as the new label contains the following information:

1. Veterinarian's name and address.
2. Client's name.
3. Date.
4. Animal's ID.
5. Drug name.
6. Dosage and route of administration.
7. Withdrawal times for meat and milk even if zero.
8. Storage temperature and category (i.e., age and physiologic status: lactating or dry cow).
9. Expiration date.
10. Name of manufacturer.
11. Active ingredient.

Supervision

1. Drug use should be supervised by one specific person on the premises, and that person must interact with all personnel involved in use of the drug.

2. Misunderstanding and poor communication are major reasons for poor management of drugs and/or animals that have received treatment. The following recommendations are encouraged:
   1. Store each drug to comply with safety, temperature, and label guidelines.
   2. Keep an inventory of all drug purchases.
   3. Record usage of each dose of every drug.
   4. Identify all treated animals.
   5. Follow all withdrawal directions.
   6. Know where to seek help to conduct residue tests.

3. A properly labeled drug for food animals sometimes can produce residues beyond the withholding period, particularly when:

• Excessive dosages are administered relative to animal weight (high doses may be required, on occasion, to save an animal's life, but administration should be supervised by a veterinarian and that drug must be on a prescription label).
• Abnormal drug administration routes are used (i.e., injecting a drug in muscle instead of subcutaneously).
• Combinations of drugs are used for treatment.
• Drugs approved for one animal species are used in another.
• The animal is critically ill causing normal drug clearance time to increase.

4. The large number and variety of drugs mandate maintenance and use of good records, in addition to better management and identification of treated animals. Many of these must be used in an extra-label manner as FDA approval of the drug does not allow other usage.

Producers must accept a few basic requirements for ensuring legal and prudent antimicrobial use in swine prodution. These are:

1. Appropriate veterinary oversight and diagnosis
2. Proper labeling
3. Record keeping for all agricultural products
4. READ THE LABELS and follow the instructions

The reputation of the industry is under fire, and all producers must use antimicrobial products in a compliance with existing regulations.