Judicious therapeutic use of antimicrobials in aquatic animal medicine

UNDER REVIEW

Introduction

Aquatic animal veterinarians should use all therapeutants, including antimicrobials, judiciously to restore aquatic animal health, ensure the continued production of cultured safe seafood, and minimize development of antimicrobial resistance.

In addition to awareness of and adherence to AVMA's Core Principles of Antimicrobial Stewardship in Veterinary Medicine and Judicious Therapeutic Use of Antimicrobials guidelines, veterinarians should follow these specific principles and recommendations for antimicrobial use in aquatic animals:

I. Disease prevention in aquatic animals

Help clients design health management programs that will reduce the incidence of disease, and the need for antimicrobial therapy.
When there is an increased disease incidence, efforts to identify and correct predisposing factors should be implemented. Effective vaccination and high-quality nutrition will provide health benefits. Water source and quality should be evaluated with an additional assessment of the potential of pathogen transmission from water sources containing wild aquatic animal populations. Biosecurity should be implemented to protect captive populations.
Work with clients and facility personnel to develop written training tools and standard operating procedures on quarantine, diagnostic testing, water quality monitoring, judicious antimicrobial use, withdrawal times, routes of administration, storage, handling, and record keeping.

II. Disease diagnosis in aquatic animals

Submit diagnostic samples to a diagnostic laboratory familiar with the species of aquatic animal being evaluated.
Necropsy clinically ill aquatic animals in populations to update disease/pathogen information for the development of therapy and control protocols.
Determine the in vitro antimicrobial susceptibility of pathogens at the first indication of increasing morbidity or mortality rates in the population. Monitor the clinical response to detect changes in bacterial pathogen susceptibility and to evaluate the efficacy of antimicrobial selections.

III. Antimicrobial selection, use, and therapy in aquatic animals

Licensed veterinarians should issue prescriptions and Veterinary Feed Directives (VFD) only in the context of a veterinarian-client-patient relationship (VCPR).
Properly select and use antimicrobials based on feeding rates and clinical evidence of the etiology of the disease, history, clinical signs, gross lesions, and/or diagnostic laboratory data. Combining two or more antimicrobials for therapy is discouraged unless approved by FDA for combination use.
Clinical and diagnostic records and observations on individual animals or populations may help in developing antimicrobial therapy recommendations. Fish being fed too infrequently or at too low of a rate are not candidates for antimicrobial medication via the feed.

Neither MIC nor disc diffusion breakpoints have been developed for the vast majority of aquatic animal bacterial pathogens. Fish diagnostic laboratories or aquatic disease specialists in close proximity to the bacterial disease outbreak of concern, if possible, should be contacted for assistance with interpretation of susceptibility results.
Although exceptions can occur, antimicrobials should be used in accordance with the product label (indication, dosage, frequency, duration, route of administration, species, and environmental conditions and requirements). Protect antimicrobial integrity through proper handling, storage, observation of the expiration date, and record-keeping.
The product label directions on legally marketed products are established with reviewed scientific data. Veterinarians should read and follow these directions and use the lowest approved dosage of antimicrobials that will reduce mortality and minimize disease recurrence.

Considerations for antimicrobial use in aquatic species include:

Before authorizing antimicrobial administration, the veterinarian should remind the production facility to comply with applicable federal, state, and local laws and regulations (eg. National Pollutant Discharge Elimination System permits).
Use of Veterinary Feed Directive antimicrobials in aquatics should follow the Veterinary Feed Directive rules.
1. Withdrawal times in aquatic animals intended as food should be observed.
2. VFD antimicrobial feeds must be used prior to the expiration of the VFD order. If the order expires prior to completing the duration of use, the veterinarian must issue a new VFD.
Extralabel use of VFD medicated feed is allowed by FDA for minor species, including all aquatic species, provided specific conditions of CPG 615.115 are met.

Conclusion

Many factors influence the incidence and outcome of disease outbreaks, disease diagnosis, and disease therapy in aquatic species. Antimicrobials can play an important role in aquatic animal medicine but they must be used in a judicious and legal manner. Resources such as the AVMA or the American Association of Fish Veterinarians can help navigate the judicious and legal use of antimicrobials as well as the unique aspects of aquatic animal production, management, and therapy.

References

Clinical and Laboratory Standards Institute (CLSI), Methods for Antimicrobial Disk Susceptibility Testing of Bacteria Isolated From Aquatic Animals, 1st edition. CLSI guideline VET03, 2006.
Clinical and Laboratory Standards Institute (CSLI) Methods for Broth Dilution Susceptibility Testing of Bacteria Isolated From Aquatic Animals, 2nd edition. CLSI guideline VET04, 2014.
David R. Smith; et al. (2019) The AVMA’s definitions of antimicrobial uses for prevention, control, and treatment of disease. Journal of the American Veterinary Medical Association, Vol. 254 (7): 792-797.
Compliance Policy Guide Sec.615.115 Extralabel Use of Medicated Feeds for Minor Species
Veterinary Feed Directive 80 FR 31717-31725