Dr. Bill Flynn

FDA photo

Dr. Bill Flynn, deputy director of science policy for the U.S. Food and Drug Administration Center for Veterinary Medicine, has worked on the issue of antimicrobial drug resistance over 26 years with the agency.

Up to now, efforts in the veterinary sector by the U.S. Food and Drug Administration to curb pathogens' development of resistance to drugs have been directed toward animals raised for food.

Now it's Fido's and Tabby's turn.

The use of antimicrobial drugs in dogs and cats is coming under scrutiny in a new phase of a decades-long campaign by the federal agency to promote the judicious use of antimicrobial drugs in veterinary medicine.

"We've been trying to look at this [issue] through a One Health lens, so we recognize the need to look at the uses in all animals," said Dr. Bill Flynn, deputy director of science policy in the FDA's Center for Veterinary Medicine. "That includes needing to pay attention to what's going on in the companion animal sector."

One Health is the concept that the health and well-being of people, other animals and the environment are inextricably linked.

Antimicrobial resistance, also called antibiotic resistance, occurs when microbes such as bacteria and fungi evolve to withstand drugs designed to kill them. Overusing and misusing such drugs hastens the development of resistance, making the medications less effective or not effective at all.

The problem isn't theoretical. Antibiotic-resistant bacteria and fungi are responsible for at least 35,900 deaths in the country each year, according to an estimate in the U.S. Centers for Disease Control and Prevention report "Antibiotic Resistance Threats in the United States 2019."

The report lists the most urgent threats as carbapenem-resistant Acinetobacter; Candida auris; Clostridioides difficile; carbapenem-resistant Enterobacteriaceae; and drug-resistant Neisseria gonorrhoeae. Thirteen more pathogens are listed as serious or concerning threats.

The first step toward examining the role of companion animal medicine in antimicrobial resistance is to get a handle on how the drugs are used in dogs and cats. The FDA announced this week that it will be accepting applications for funding to collect data on the question. Up to $400,000 is available for the work this fiscal year (limited to $200,000 per individual award), with the potential for four more years of funding to continue the work.

It is too early to know how and exactly what data will be collected, and who in the veterinary community will be involved. And officials do not expect the data to provide an immediate picture of antimicrobial drug practices in dogs and cats overall.

"We're not necessarily going into this with the idea that the project [findings] will, in fact, be nationally representative," Flynn said in a telephone interview. "... What we're looking for here is a pilot project; a proof of concept that may not give us nationally representative data but will give us a sort of sampling, or testing out, of methodology that could in the future be expanded in scope."

Flynn observed that while companion animal medicine is similar in many ways to human medicine — with individual pet patients visiting clinics, and doctors dispensing or prescribing drugs directly to the owners — the system is significantly different when it comes to capturing trends.

"There's limited infrastructure in the whole veterinary sector for collecting this information in comparison to the human-health sector ... just by nature of the third-party payment system that exists," Flynn said. "[There are] pharmacies, HMOs and other infrastructure that can be tapped to sort of mine the information. Much of that doesn't exist on the veterinary side. It's sort of starting from a blank sheet."

Between people and pets, a likely mode of transmission of microbes — whether drug-resistant pathogens or benign microbes — is through close physical contact. An ecosystem of microbes present among those who live and work closely together encompasses other species and the environment.

"The bacteria that are swirling around in the human population and the bacteria that are swirling around in the animal population and the bacteria swirling around in the environment that humans and animals live in, [they're] getting shared," Flynn said.

While examining antimicrobial drug use in household pets is new for the U.S., it's already being done in other countries, the United Kingdom among them.

In its most recent update on the issue, the U.K. Veterinary Medicines Directorate reported in October that sales of veterinary antibiotics for companion animals in Britain decreased by 25% between 2018 and 2017; and by 50% since 2014.

The FDA CVM, in a plan titled "Supporting Antimicrobial Stewardship in Veterinary Settings," lays out its goals for the fiscal years 2019-23. The goals include more work on the food-animal side, as well as developing and implementing strategies involving companion animals.

Part of the agency's plan is to solicit public input on antimicrobial-use practices in companion animals and their impact on the development of resistance. When that will happen and in what format has not yet been determined.

Shifting attitudes

The FDA began in 2012 taking steps to restrict the use of medically important antimicrobial drugs in food animals. Whereas livestock producers used to be allowed to feed antibiotics to animals to help them grow faster, today that's not permitted. Moreover, such drugs no longer are available over the counter; their use must be authorized by a veterinarian.

Ten years ago, the concept that veterinarians should oversee all uses of antimicrobial drugs in animals was controversial in the U.S., even within the profession. In 2009, Flynn appeared before the American Veterinary Medical Association House of Delegates to advocate for a resolution that veterinarians should be involved whenever antimicrobial drugs were used in animals. But the House opted not to vote on the resolution, instead asking that a task force study the issue.

Today, the AVMA agrees with the FDA: "Veterinary oversight is and should be required whenever medically important antibiotics are administered to animals, including via feed or water," the organization states on its website.

The association supports the agency's efforts to characterize how antimicrobial drugs are used in pets, as well. "Gathering data on the use of antimicrobial drugs in companion animals is an important step in the FDA's 5-year plan to address concerns around antimicrobial resistance in both animals and people," said AVMA spokesperson Michael San Filippo by email. "The AVMA appreciates the value of science-based decision-making and recognizes that learning more about why, what, when and how we use therapeutic agents is important to making sure we all use [them] as judiciously as possible."

As an FDA official for 26 years, working in some capacity on antimicrobial drug resistance during all that time, Flynn said, "I have seen a pretty significant shift in tone around the issue. ... In decades past, a lot of energy [was] in debating the significance of the issue, or how much any given sector was really contributing to the problem, and 'until we all resolve how much the contribution is, we're not going to make steps to change.' "

Those arguments and positions appear to be in the past, he said: "I think putting it in the context of One Health, that all uses of antibiotics are contributing [to resistance] ... has been a positive, in terms of acknowledging that and saying that it needs to be addressed."

But much work lies ahead in ensuring that effective drugs remain available, he said, adding that the prospect that new drugs will come along to serve in their stead is not assured.

He noted that when "the message is, 'you have to use these drugs judiciously, in a sparing way,' it's not a particularly strong incentive for companies to develop new products."

According to the Antibiotic Resistance Project of the Pew Charitable Trusts, "Today there are not enough drugs in development to meet current and anticipated patient needs, with many major pharmaceutical companies limiting or stopping their investments in antibiotic innovation."

Pew's tracking of drugs in the pipeline shows 42 new antibiotics in development as of June 2019. "These drugs would potentially address many, but not all, resistant bacteria," Pew says. "However, given the inevitability that some of these antibiotics will fail to win approval, and that resistance will eventually develop to those that are approved, it is clear that there are too few drugs in development ..."