Healing or harming?

Photo: Christina Weese.

Imagine you’ve been battling a relentless respiratory infection for days. Exhausted and desperate for relief, you head to the doctor, expecting a quick fix from a course of antibiotics. Instead, you discover that the bacteria causing your illness are resistant to every available drug, leaving you with no effective treatment options.

This frightening scenario could become a reality due to antimicrobial resistance (AMR), an issue deemed a major global threat by the World Health Organization.

Antimicrobial resistance (AMR) happens when microorganisms — such as bacteria or parasites — evolve to survive treatments that once worked. The issue is driven largely by the misuse and overuse of antimicrobial drugs in both humans and animals.

While AMR is well studied and documented in human medicine and some food-producing animals, there are few peer-reviewed studies focused on companion animals such as horses. Two new equine research projects at the Western College of Veterinary Medicine (WCVM) aim to address this gap.

Probing antibiotic prescribing practices

Dr. Lorena Santos (DVM), a Master of Science (MSc) student and resident in large animal medicine at the WCVM, is conducting a retrospective study that looks back on antimicrobial prescribing habits involving horses that were patients at the college’s Veterinary Medical Centre (VMC) between 2019 and 2023. Her research team includes her supervisor, Dr. Fabienne Uehlinger (MedVet, PhD), a board-certified specialist in large animal medicine, and Dr. Joe Rubin (DVM, PhD), a veterinary microbiologist at the WCVM.

“The main goal of the project is to try to collect data from medical records of all the antimicrobials that were used in those equine patients and try to see the patterns of these prescribing practices among the clinicians,” says Santos.

While Santos is looking into all cases of antimicrobial use during the five-year period, she’s paying “special attention” to cases involving prescriptions for ceftiofur. The antibiotic drug is widely used in veterinary medicine and is valued for its broad-spectrum effectiveness and versatility.

Ceftiofur belongs to a class of antimicrobials called cephalosporins. These semisynthetic antibiotics are grouped into generations based on their spectrum of activity (what microorganisms they kill) and defence against antibiotic resistant enzymes. As a third-generation cephalosporin, ceftiofur should not be used as a first line of defence for treating common infections. Instead, it should be reserved for more serious or resistant infections in animals, making resistance to this drug particularly concerning.

“We might be using it [ceftiofur], I would say a little bit more maybe than we would need to sometimes,” says Santos. “We want to see when we are using those third-generation cephalosporins: which type of cases they are [used for] and if there are justifications for using them.”

The WCVM study encompasses medical records from various large animal clinical services at its teaching hospital, including large animal internal medicine, surgery, field service and ophthalmology. But Santos says incomplete or inaccurate medical records is making it difficult to track the use and justification of ceftiofur and other microbials.

“One of the biggest issues that we have found … is that in ceftiofur prescriptions, it’s usually not accompanied by a bacterial culture to justify its use. Sometimes I just find the prescription in the system, but there’s no other information,” says Santos, adding that it can take hours to track down and analyze each medical record.

Despite the challenges, Santos is determined to build a foundation of knowledge for future research.

“At least in Western Canada, there are no studies looking at this [prescription practices in equine medicine] at the moment,” says Santos. “There’s a lot of information in small animals, and of course in human medicine, but we don’t know statistics in equine populations, which has a direct impact on human health.”

Investigating antibiotic-resistant E. coli in horses

Antibiotic prescribing practices in horses at the WCVM aren’t the only area of interest for researchers. One of the projects complementing Santos’ work focuses on antimicrobial-resistant Escherichia coli (E. coli) isolated from horses treated with ceftiofur.

Dr. Mónica Arévalo Naranjo (DVM), a MSc student and large animal medicine resident at the WCVM, is undertaking the study alongside her supervisor, Dr. Valentina Ragno (DVM, MSc), a board-certified specialist in large animal internal medicine. The college’s Townsend Equine Health Research Fund (TEHRF) is providing financial support for the study.

“Whenever we use an antibiotic, we want to kill the bacteria causing the infection,” says Arévalo. “But sometimes we forget that within our bodies — and an animal’s body — there are bacteria living harmlessly, without causing problems. These antibiotics can also affect those bacteria, which may then develop resistance.”

Arévalo explains that some bacteria — harmful pathogens or harmless commensal bacteria — have evolved to produce enzymes called extended-spectrum beta-lactamases (ESBLs). These enzymes are what resist the antibiotic by breaking them down and rendering them ineffective. While this resistance poses immediate challenges for treatment, it also has broader implications.

If commensal bacteria survive antibiotic exposure, they may have developed resistance and will continue to multiply. These resistant bacteria can then share their resistance genes with other bacteria, including harmful pathogens. Over time, this process can turn the animal’s entire microbiome (the community of bacteria in its body) into a reservoir of antibiotic-resistant bacteria.

“This is very concerning,” says Arévalo. “This genetic information can jump between different bacteria and also between animals and humans. Since we share the same environment and have constant contact, I have the potential to transmit my resistance to these animals and they can also spread to me.

Arévalo’s research involves collecting fecal samples from horses treated by the VMC Equine Field Service team and testing the samples for antibiotic resistance.

Her team will study three groups of horses: those directly treated with ceftiofur, those exposed to treated horses in the same environment, and those with no exposure to the drug. In total, the study will include 120 equine patients.

The team will take two fecal samples from each horse in the study, one sample before treatment begins and another three weeks following the initial dose of ceftiofur — allowing the researchers to observe any changes in the presence of resistant E. coli. Samples will then be tested in Rubin’s lab to first confirm the presence of E. coli and then to test for antibiotic resistance.

If a sample does show antibiotic resistance, further tests will be conducted to identify the resistant genes.

“Through the DNA material, we hope to have a better understanding of what gave the power to the bacteria to have this resistance against this drug,” says Arevalo. She adds that few published studies focus on the subject of E. coli producing these ESBLs specifically in horses.

“Our hypothesis is that resistant E. coli will be more prevalent in horses treated with ceftiofur compared to those that are not,” says Arevalo. “This information can help veterinarians make more informed decisions about antimicrobial use.”

Both researchers agree that studies like these are key to understanding the delicate balance between effectively treating infections and inadvertently fueling antimicrobial resistance.

“It’s very important to have this information and to communicate it,” says Arevalo. “Sometimes the community doesn’t know, and they just think, ‘Oh, my horse is ill so let’s give antibiotics,’ which can be dangerous.”

“Every time we use an antimicrobial on any of our patients and we have either direct or indirect contact — touching our patient, touching their blankets, buckets of water, even our vehicles — there can be a transfer of some resistance genes or some resistant bacteria from the patients to us,” says Santos.

“If we are not using these drugs adequately, there’s a direct impact in how useful they will be when we decide to use them ourselves.”