How often and for what purposes are antimicrobial drugs given to companion animals? Do existing practices needlessly hasten the evolution of superbugs? If so, what can the government do to support smarter use of important medicines?
In a continuing effort to quell the development in pathogens of resistance to drugs — a leading threat to global health — the U.S. Food and Drug Administration is soliciting public comments on how antimicrobial drugs are used in pet patients and how the companion animal sector can do its part to prolong the drugs' effectiveness. (Antimicrobials include antibiotics.)
The deadline to comment is June 16.
Drug resistance happens when microbes evolve to evade drugs designed to kill them. While evolution is inevitable, injudicious use of antimicrobial drugs, such as administering them for a viral infection or prematurely ending an appropriately prescribed course of the medicine, can speed microbes' development of resistance.
The invitation for input about use of the drugs in pets marks a relatively recent shift in focus by the FDA's Center for Veterinary Medicine (CVM) in its campaign against antimicrobial resistance. For about a decade, the agency concentrated largely on antimicrobial drug uses in animals raised for food, principally, cattle, pigs and poultry. The FDA has moved to limit giving animals antimicrobials for the sole purpose of stimulating them to grow faster — a curious side effect of the drugs — and expanded requirements that veterinarians oversee use of the medications.
In 2020, the agency began giving more attention to the companion animal sector, providing grants of $200,000 each to two research teams to collect data on how much veterinary practices in the country use antimicrobial drugs in cats and dogs.
The funding represents the first effort nationally to quantify and characterize the issue in pets. While the federal government has been required by law since 2008 to collect and make public the volume of antimicrobial medications sold and distributed each year for use in food animals, comparable data isn't collected about household animals.
"We don't have very good information at this point, and are hoping to get better information ... to guide our activities to support better stewardship of antimicrobials," said Dr. Bill Flynn, deputy director for science policy at the FDA's CVM.
Information is coming
Data are beginning to trickle into the gap. FDA-funded researchers at the University of Minnesota College of Veterinary Medicine have started compiling data from a two-pronged approach to tracking antibiotic use in cats and dogs.
The team is conducting a series of national point-prevalence studies, which involve collecting standardized data from many locations at a given moment in time. Last year, 52 hospitals around the country reported one day's worth of patient-visit information, including reason for visit, any diagnostic tests conducted, any antibiotics prescribed and the indication for the antibiotics. The study will be repeated in 2023.
This research builds on a point-prevalence study at 14 U.S. veterinary teaching hospitals conducted by the Minnesota team in 2020 and planned again for this year and in 2024. Preliminary results for 2020 show 36% of cats and dogs were prescribed at least one antibiotic, 94% of prescribed antibiotics were systemic, and 65% of antibiotics were intended for infection treatment.
The researchers will present their first paper on the teaching hospitals study in June at a conference of the American College of Veterinary Internal Medicine. Meanwhile, the team is now enrolling participants for this year's iteration of the study. The study website has information for those interested in learning more or signing up.
The second prong of research is developing a Companion Animal Veterinary Surveillance Network, which will draw data on antimicrobial prescribing directly from practice electronic medical records at the school's teaching hospital and from a proprietary practice information management system used by an unnamed private practice group with 115 clinics.
In terms of potential impacts on human health, better stewardship of antimicrobial drugs in companion animal medicine might be as important as controlling how they're used in food animals. That's because pets live more closely to people.
"We humans and animals are sharing an environment, and potentially sharing bacteria and pathogens because we have a shared environment," Flynn said.
That means a pathogen that evolves in a dog's body to resist an antibiotic could wind up in the dog owner's body. And many antimicrobial medicines made for human use are given to pets, too.
Not a new subject for many veterinarians
Whether it's appropriate to use antimicrobial drugs in certain instances is something companion animal veterinarians have been pondering for years, judging from message-board discussions on the Veterinary Information Network, an online community for the profession and parent of the VIN News Service.
A classic example is metronidazole, an antibiotic developed for human use that is a popular treatment for diarrhea in dogs. Dating back to at least 2009, practitioners on VIN have questioned the wisdom of reflexively reaching for metronidazole to quell upset stomachs, a practice that has conditioned many pet owners to expect a prescription for the pills when their dogs have the runs.
The discussions often revolve around other possible ways of responding to mild cases of diarrhea in otherwise healthy dogs, such as by giving probiotics, withholding food for 24 hours and/or feeding a bland diet (commonly white rice and chicken).
But holding off on the antibiotic may be easier said than done. In a VIN discussion in 2019, one veterinarian admitted that he sometimes uses metronidazole perhaps too readily, to which Dr. Joseph Butterweck responded sympathetically, "I was smiling when I noted you used metronidazole even though you doubted its value. We all do that in practice because we think we need do something."
Butterweck added: "The culture in vet med is use antimicrobials. How do you change that culture? That probably is the biggest roadblock to prudent use of antimicrobials."
In an interview last week, Butterweck said veterinary practices that sell such drugs (not all do) potentially have a financial incentive, as well, to prescribe them. "You get paid for the pills," he said. "You don't get paid if you don't give them the pills. And the client wants something. It's easier to give them something rather than to say, 'No.' "
Butterweck said his own habits with antimicrobial drugs have changed during the 60 years he's been in practice. But as a veterinarian in California working relief, he said he continues to see colleagues dispensing the medications more often than he believes is necessary.
"It's not going to change unless veterinary licensing authorities call it a priority," he said, suggesting that requiring record-keeping on prescriptions of antimicrobial medications and periodic inspections of the records would be more effective than merely talking about the importance of good stewardship.
Another antibiotic-related issue that surfaces frequently in small animal medicine is the availability of the antibiotic amoxicillin, sold over the counter for aquarium fish. It's so common, it has a nickname: fish mox.
A veterinarian identified as Dr. Cheryl Waterhouse, who gave input to the FDA in March, referenced the fish antibiotic in her comment:
"I am a practicing veterinarian of 40 years in small animal medicine. There has been a good progress in reducing the amount of antibiotics used by the general public through restricting them to veterinarians. But clients are still able to obtain antibiotics through alternative sources such as 'fish medicine,' etc. Also, we need a commercial product for ear treatments that is just a steroid and fungal med. Once I started doing ear cytology, [I] discovered that the vast majority of ear infections are yeast only, stopped using antibiotics, since then I have not seen one Pseudomonas ear infection [in] one of my own patients. Veterinarians have been creating Pseudomonas problems, we need less combination products."
Asked about fish mox, Flynn at the FDA said that antibiotics sold for ornamental fish without a prescription is an area that the agency is looking into.
He also said the idea of avoiding combination products is a helpful suggestion for the animal health industry and something that the FDA can influence. "There are things we can take into account when we're evaluating products from not only an effectiveness standpoint ... but also from a safety perspective, and safety assessments can include looking at, 'What are the antimicrobial-resistance aspects?' " Flynn said.
Another veterinarian who submitted a comment anonymously in April acknowledged that antimicrobial drugs are sometimes used too readily but suggested that education rather than regulation would be a better approach:
"I have been in practice as a veterinarian for 13 years now. During that time, I've absolutely seen antibiotics overprescribed by well-meaning colleagues to well intended antibiotic-seeking owners. However, I don't think further regulation is necessarily the most appropriate answer. Education of owners and professional pressure on veterinarians to be better stewards of antimicrobials would lead to improved discretion of their prescription. Owners and veterinarians alike need to be reminded that metronidazole is not an anti-diarrheal and doxycycline does not treat viral tracheobronchitis. I think with more pressure to do the right thing and the normalization of saying 'no' when their use is inappropriate, the profession will correct itself."
Flynn said regulations aren't a foregone outcome of the FDA review. "We've not really laid out any particular preconceived idea in how we're going to proceed on this. We're not necessarily looking at this from the standpoint of there being new regulations," he said.
Broadly, Flynn said, the agency is scouting ways it can support good stewardship and best practices. The fundamental question, he said, is: "How can we use these products in the best way possible to minimize the collateral effects we have on antimicrobial resistance?"
Lisa Wogan contributed to this report.