INTRODUCTION

Veterinarians treating food fish with antimicrobial drugs have four primary responsibilities:

• To optimize stock production for those who own and care for food fish through effective disease prevention;
• To diagnose and then treat or control disease in their patients through the safe and effective use of therapeutants;
• To ensure that fish harvested for food meet established safety standards; and,
• To ensure that antimicrobial drug administration does not adversely impact the environment receiving production facility effluent

Consumers expect that veterinarians have prudently and judiciously used all therapeutants, particularly antimicrobial drugs. There is particular concern that veterinarians manage antimicrobial drug use to minimize the emergence or development of antimicrobial resistance.

Veterinarians in food fish practice are acutely aware of these responsibilities to producers and consumers. Conservation of available antimicrobial drugs requires that veterinarians select and use these products appropriately. Compliance with the judicious use principles in this document will provide assurance to food fish consumers and groups advocating food safety that farm grown fish products are produced using sound practices. The potential impact of antimicrobial drug use on pathogen susceptibility to these drugs will continue to be discussed. However, veterinarians can minimize these concerns through prudent and judicious antimicrobial use.

There are very few antimicrobial drugs approved for use in food fish treatment at this time. Therefore, the food fish veterinarian already places disease management emphasis on sound biosecurity, nutrition, disease surveillance, and production management programs. Additionally, veterinarians work closely with other fish health management specialists in the development and implementation of fish disease control programs.

Production of safe and wholesome aquaculture products for human consumption is a primary goal of veterinarians caring for food fish. To reach that goal, practitioners should emphasize disease prevention, particularly through promotion of a healthy fish immune system through vaccination, stress reduction and careful nutritional management. Proper and timely management practices reduce the incidence of disease and therefore reduce the need for antimicrobial treatment. Despite appropriate management measures, antimicrobial drugs will remain a necessary tool to manage infectious diseases in aquaculture.

To reemphasize the points made earlier, prudent and judicious use of antimicrobial drugs is necessary to:

- Restore fish population health;
- Protect the economic livelihood of food fish producers;
- Ensure the continued production of foods of animal origin; and,
- Minimize the shedding of zoonotic bacteria into the environment and potentially the food chain.

The following are specific recommendations for the prudent and judicious use of antimicrobials in food fish aquaculture.

JUDICIOUS ANTIMICROBIAL USE PRINCIPLES

The food fish veterinarian should:

• Accept responsibility for helping clients design management, immunization, production unit and nutritional programs that will reduce the incidence of disease and the need for antimicrobial treatment.

Development and implementation of appropriate disease prophylaxis through effective vaccination is likely to reduce the incidence of disease and subsequent need for antimicrobial treatment. Insuring high quality nutrition for both broodstock and rapidly growing production fish is of paramount importance and will provide health benefits throughout the production cycle. When there is an increased disease incidence, efforts to identify and correct immunosuppressive factors should be implemented. Optimal nutrition can lead to a reduction in morbidity and mortality with a consequent decrease in the need for antimicrobial treatment. Water source quality should be evaluated for use in fish production operations, including an assessment of the potential disease transmission risk from feral populations and the related need for biosecurity measures to protect production populations. This will help to prevent the introduction of additional pathogenic microorganisms that could cause diseases requiring antimicrobial treatment. Veterinarians should work closely with other fish health experts employed at the facility in the design and implementation of fish health management programs.

• Use antimicrobial drugs only within the confines of a valid veterinarian-client-patient relationship, including both the dispensing and issuing of prescriptions. Extra-label usage should be consistent with regulatory agency laws, regulations and policies.

The veterinarian must
- Be either the person responsible for diagnosis of disease conditions on a fish production operation or working directly with a fish health professional on the production operation; - Be available for questions or concerns following treatment with antimicrobial drugs; and, - Accept responsibility for health care of the fish on that operation.

Under these circumstances, the veterinarian will be able to make a recommendation on appropriate antimicrobial drug treatment and minimize the development of antimicrobial resistance. Veterinarians prescribing, dispensing or administering antimicrobials to fish should utilize the services of unbiased and reputable sources (e.g. Food Animal Residue Avoidance Databank) to provide scientifically sound withdrawal times for producers.

• Properly select and use antimicrobial drugs. Veterinarians should participate in continuing education programs that include therapeutics and emergence and/or development of antimicrobial resistance.

Human food safety concerns are discussed at numerous regional, state and national meetings every year. At least some portion of required continuing education hours should be received on the topic of antimicrobial susceptibility of animal and potential zoonotic pathogens. Material accessible from reliable sources such as the FDA/CVM, FARAD and AVMA home pages, and from the many available additional sources of professional information, should be incorporated into treatment considerations and recommendations. Many aspects of fish health management, including nutrition and immunology, are topics of active research. Veterinarians should stay current in their knowledge of this research in order to develop effective disease control programs.

• Have strong clinical evidence of the identity of the disease etiology, based upon history, clinical signs, necropsy, laboratory data, or past experience before recommending antimicrobial drug treatment.

Records and observations on individual operations or within population subgroups, such as ponds, tanks, pens and raceways within a veterinarian's area of practice may be very helpful in developing antimicrobial drug treatment recommendations. Historical diagnostic material obtained from post mortem and moribund fish examinations may also be helpful. Diagnostic data reports are a useful barometer of changes in pathogen sensitivity patterns, although susceptibility profiles may be skewed (perhaps due to prior therapy). The status of the originating hatchery should be considered when establishing a diagnosis in disease outbreaks and when selecting a treatment protocol. Proven biosecurity measures should be implemented when fish are introduced to a production facility to reduce the need for antimicrobial therapy.

• Treat food fish with antimicrobial drugs according to the product label recommendations (including indication, dosage, duration, fish species and environmental conditions).

The product label recommendations are established through sound scientific data. Veterinarians should follow these recommendations (e.g. "top-coating" or "top-dressing" of feed is not among the currently approved formulation methods). Furthermore, the goal of therapy should be to reduce fish mortality and minimize disease recurrence. Veterinarians should strive for the lowest dosage and appropriate duration of treatment that achieves these goals. Veterinarians should rely on previous medical records and valid published information to support clinical judgments on the proper time to discontinue therapy.

The antimicrobial drug label may require specific waste handling, or may limit the concentration allowed in production facility effluent. The veterinarian should assure that the drug containing waste or effluent is handled according to the product label directions. The veterinarian should also assure that the production facility complies with appropriate federal and state laws and regulations (e.g. National Pollutant Discharge Elimination System permits) applicable to drug use and discharge before authorizing drug administration.

• Choose an antimicrobial drug and treatment regimen based on available laboratory and label (including package insert) information, additional data in the literature and consideration of the pharmacokinetics, spectrum and pharmacodynamics of the drug.

When this information is combined with the clinical and laboratory information previously mentioned, prudent and judicious antimicrobial use decisions are possible. The label dose, route, frequency and duration should be followed except where extra-label use is necessary and falls within government laws, regulations and policies. Familiarity with extra-label use requirements is essential given the limited availability of approved antimicrobial drugs for food fish use.

• Use antimicrobial drugs with a specific clinical outcome(s) in mind, including a specific target for population morbidity and/or mortality rate reduction.

Specific outcome criteria prevent unnecessarily long therapy and indicate when the current therapy is ineffective.

• Determine production population pathogen susceptibility at the first indication of increasing morbidity or mortality and monitor the therapeutic response to detect changes in microbial susceptibility and to evaluate antimicrobial selections.
• Routine necropsy examination of fish populations should be periodically performed, including antimicrobial susceptibility testing, to update historical information for developing treatment and control protocols.
• Use products that have the narrowest spectrum of activity and known efficacy in vivo against the pathogen causing the disease problem.

In clinical situations, the boundary between a narrow and broad spectrum of activity may be difficult to determine. Narrow- and broad-spectrum levels of activity will vary depending upon both the bacteria affected by the antimicrobial and the treatment regimen chosen. In spite of the difficulty in confining antimicrobial use to a narrow spectrum of activity, resistance to antimicrobials should be minimized by selecting an antimicrobial with a narrow spectrum of activity whenever possible. The food fish veterinarian presently has access to a very limited armamentarium of long-approved antimicrobial drugs. However, this situation may change as new products are developed and approved. The veterinarian needs to be attuned to the potential for change.

• Choose antimicrobial drugs of lesser importance in human medicine, if these receive future food fish use approval, and not choose an antimicrobial for which emergence of resistance is expected to be in an advanced stage.

Drugs that are of lesser importance in human medicine should be chosen before considering extralabel use of a newer generation animal antimicrobial drug (should this be permitted under future regulations). This is of particular concern if the extralabel drug is in the same class as a human antimicrobial drug that may be the primary or sole treatment for a human infection.

New antimicrobials should be reserved for cases that can be predicted to be refractory to other therapies and should be used according to label directions or extralabel drug use regulations.

• Use, whenever possible, an antimicrobial drug labeled to treat the condition diagnosed.

The veterinarian should work with producers to ensure that appropriate diagnostic procedures are in place to evaluate disease causation and initiate appropriate antimicrobial therapy when indicated.

• Not use combination antimicrobial drug therapy unless there is information to show that this decreases or suppresses target organism resistance development.

There are no scientific data available to indicate that combination antibacterial therapy is beneficial with the few products labeled for use in food fish.

• Not compound antimicrobial drug formulations.
• Not use antimicrobial drugs to treat cases with a poor chance of recovery.

Chronic, non-responsive cases, such as fish that fail to grow and/or fish that exhibit early maturation, should be removed or isolated from the population. This will reduce interfish aggression and remove individuals who are more susceptible to disease.

• Not use antimicrobial drugs prophylactically.

No antimicrobial drugs are approved for disease prevention in food fish. Veterinarians should actively discourage any consideration of this action.

• Ensure proper on-farm drug use and protect antimicrobial drug integrity through proper handling, storage and observation of the expiration date.
• Prescribe, dispense or write a Veterinary Feed Directive for drug quantities appropriate to the production-unit size and expected need using the approved formulation.

The amount of a particular antimicrobial drug prescribed or written in a veterinary feed directive should be consistent with previous and expected disease incidence and treatment requirements. If the antimicrobial drug is not dispensed by the veterinarian, then good communication between the veterinarian, animal producer, feed mill and/or pharmaceutical distributor is essential. This communication needs to be coupled with the appropriate prescription or veterinary feed directive and correct medicated feed labeling to ensure proper drug usage. At a future date when prescription or veterinary feed directive aquaculture antimicrobial drugs are approved, then the prescribing veterinarian should seek to review or receive copies of invoices of scripted drug purchases to ensure that appropriate quantities are being purchased for use.

• Work with producers and/or facility fish health management personnel to ensure that farm personnel receive adequate training on the use of antimicrobial drugs including indications, diagnosis, dosages, withdrawal times, route of administration, storage, handling, and accurate record keeping.

The veterinarian should ensure that labels are adequate to instruct farm personnel on the correct use of antimicrobial drugs.

• Work closely with all other fish health experts involved in fish population health management at the fish production facility.

Veterinarians are encouraged to work with producers to develop written standard operating procedures for initiating disease diagnostic activities and implementing treatment. Those protocols should include specific instructions for procedures to follow when administering antimicrobials at fish production facilities.

Source: Scientific Activities Division, Aquatic Veterinary Medicine Committee and Food Safety Advisory Committee