To Combat Superbugs, All Animal Antibiotics Should Have Clear, Science-Based Durations of Use

Many antibiotics do not meet FDA’s current definition of judicious use, which must be strengthened

Article May 6, 2021 By: David Hyun, M.D. & Helene Sherburne Read time:

Projects: Antibiotic Resistance

Combating the global health emergency posed by antibiotic resistance requires responsible use of antibiotics in all settings, including animal agriculture. That’s because all use contributes to the emergence of drug-resistant superbugs. And using antibiotics for the shortest appropriate duration is critical to reducing the spread of resistance and protecting animal and public health.

However, many food animals continue to receive medically important antibiotics for unnecessarily long periods of time—or even indefinitely. Such practices do not meet the two principles set by the U.S. Food and Drug Administration (FDA) defining judicious use in these animals, which say that:

Medically important antibiotics should be used only when necessary for assuring food animal health.
Veterinarians should oversee or be consulted on the use of medically important antibiotics in food animals.

FDA has made progress in ensuring that animal antibiotic use is aligned with these principles, but it has yet to impose firm rules to prohibit the administration of medically important antibiotics to food animals for indefinite or unnecessarily long periods of time.

A brief published by The Pew Charitable Trusts in April shows that nearly 60 animal antibiotic label indications lack duration limits that spell out how long specific antibiotics can be used. Others have questionable or scientifically unsubstantiated guidance for veterinarians. These injudicious uses should be addressed through the establishment of fixed, evidence-based duration limits to be included on drug labels. That would give veterinary prescribers clear, data-driven instructions on how long a drug may be administered to achieve the intended clinical outcome, minimize the risk of antibiotic resistance, and protect animal health.

Table 1 shows FDA’s principles for defining judicious use, what progress the agency has made toward meeting these definitions, what injudicious uses remain to be addressed, and what the agency can do to align antibiotic use with its principles.

Table 1

FDA Principles for Judicious Antibiotic Use in Animal Agriculture

Agency has made progress, but significant injudicious use remains and must be addressed

Progress in meeting this principle	Injudiciously long uses that persist	Recommendations for FDA action
FDA principle for judicious use	Medically important antibiotics should be used only when necessary for assuring food animal health.
FDA has prohibited growth promotion claims on medically important antibiotic labels, meaning the drugs cannot be used for indications such as “increased rate of weight gain” and “improved feed efficiency,” both intended to enhance animal production.	In some cases, antibiotics are administered for months at a time, which is usually not necessary for animal health. The decision to treat animals for extended periods is often driven by production factors that depend on the long-term use of macrolides (a drug class critically important to human medicine) to prevent liver abscesses. Certain animal diseases, such as anaplasmosis, can be managed without long-term use of antibiotics but require improved management practices and access to effective antibiotic alternatives.	FDA must ensure that drug labels do not allow food animals to receive unrestricted or unnecessary treatment for preventable illnesses when the underlying condition is effectively a byproduct of producers’ injudicious animal management practices. FDA and other agencies should identify and fund an expansive animal health research agenda to provide veterinarians and animal producers with a wide selection of non-antibiotic alternatives and better management practices to prevent and treat such conditions.

Progress in meeting this principle	Injudiciously long uses that persist	Recommendations for FDA action
FDA principle for judicious use	Veterinarians should oversee or be consulted on the use of medically important antibiotics in food animals.
In 2015, FDA issued a final rule on the Veterinary Feed Directive (VFD), which required a veterinary order to distribute animal feed containing medically important antibiotics. FDA requires a valid veterinary-client-patient relationship before antibiotic administration. Veterinary oversight is required for feed, water, and injectable products. A proposal currently under administrative review would require veterinary supervision for the remaining medically important antibiotics still available over the counter.	Veterinary oversight remains limited by the guidance available to veterinarians on animal drug labels, and effective treatment decisions are undermined when these labels lack defined durations of use.	FDA must ensure that veterinary prescribers have the tools needed to make the best decisions possible for animal and public health by requiring animal-drug makers to quickly establish clinically validated duration limits for all medically important antibiotics.

FDA needs to consider a broad array of factors when deciding how to apply its definition of judicious use as it relates to how long these drugs are used and whether use of antibiotics is appropriate at all:

Use of medically important antibiotics in animals should be guided exclusively by science-based data on appropriate duration, dosage, and intended use. Veterinarians need evidence-based guidance validated in clinical studies or field trials on the shortest fixed duration needed to achieve the desired clinical outcome. A recent FDA proposal on duration limits does not sufficiently address this issue and could leave prescribing decisions for some medically complex diseases to veterinarians’ discretion. As currently written, this approach would take years to implement and lead to potentially subjective and injudicious use of these antibiotics. With science-backed limits in place, veterinarians could make sound clinical decisions based on relevant diagnostic information and peer-reviewed research to minimize the risk of antibiotic resistance and protect animal health.
Medically important antibiotics in animals should not be used in instances when improved animal management practices can reduce the need for antibiotics in the first place. Certain animal diseases can be prevented through improved management and animal raising practices, which can reduce or eliminate the need to administer antibiotics. Increased funding for research on management practices and antibiotic alternatives—and for veterinarians and other experts supported by the Department of Agriculture who provide services directly to growers at no cost to support producer decision-making and overcome rural veterinary shortages—can give producers and veterinarians the tools needed to raise healthier animals with fewer antibiotics.
Data about antibiotic use in food animals—which is critical to understanding and improving antibiotic stewardship and judicious use—remains limited, underscoring a need for improved, comprehensive data collection and monitoring. The available federal data illustrates only antibiotic sales, which are an imperfect substitute for information on actualuse. Producers, veterinarians, and animal-drug makers do not know enough about antibiotic use and resistance patterns that could influence infectious diseases important to human health, or about host-pathogen interactions. This data would improve animal husbandry, biosecurity, and the use of effective alternatives to antibiotic use. Expanded collection of on-farm data that links antibiotic use with health outcomes, prioritizes improved record-keeping, and makes better use of veterinary diagnostic data would help prescribers and producers make smarter choices. In addition, support for federal programs such as the National Animal Health Monitoring System, the National Antimicrobial Resistance Monitoring System, the National Animal Health Laboratory Network, and the Veterinary Laboratory Investigation and Response Network will improve general understanding of antibiotic use and resistance, which should help policymakers and scientists make informed decisions in the interest of public and animal health.

Aligning current animal raising practices more closely with FDA’s judicious use principles and integrating these recommendations into the agency’s definition and regulatory framework for managing animal antibiotics would reduce unnecessary antibiotic use, a critical step toward combating antibiotic resistance. That starts with establishment of science-based duration limits for all medically important antibiotics and improved animal management practices.

David Hyun, M.D., leads The Pew Charitable Trusts’ antibiotic resistance project, and Helene Sherburne works on the project.