The First Sixteen Podcast - EP 020

Greg: My family had a close family friend that lived down the road and they had a small pig farm. And they had some really significant disease issues that affected the operation. And eventually what happened is they had to shut down, went out of business, and they essentially stopped being farmers. And for me, I was like, well, how can this be? How can we have something that affects this population of animals so severely that they eventually have to, you know, shut down the operation? And I think that was a really pivotal moment in my decision to become a veterinarian.

Kirk: Welcome to the First Sixteen. I'm Kirk Finken.

Sara: And I'm Sara Boivin-Chabot. You just heard from Dr. Greg Dimmers, a veterinarian whose fascination with population medicine led him from his family pig farm in southern Ontario to working with beef cattle in Picture Butte, Alberta.

Kirk: And joining him, and us, is our other guest: Dr. Tim McAllister.

Dr. Tim McAllister: I'm Dr. Tim McAllister. I'm with Agriculture and Agri-Food Canada here in Lethbridge, Alberta. And the topic we're going to talk about today is one that's dear to my heart because it's really fascinating science and that's related to antimicrobial resistance and how the use of antimicrobials in beef cattle production can influence the nature of the antimicrobial resistant bacteria that may arise as a result of that practice.

Sara: You know Kirk, I was all ready to introduce today's topic, but I think Dr. McAllister has just done that for us.

Kirk: Yeah, we've got an expert with us today, in more ways than one. Dr. McAllister has worked at the Lethbridge Research and Development Centre for close to thirty years in the fields of microbiology and its relation to beef cattle production. And he's also a professional host for his own podcast, Cows on the Planet, bringing you science-based information on cattle and their environmental impact.

Sara: But it's his research into antimicrobial resistance that we're going to be focusing on. Its effect on beef cattle is a big focus both on the farm and in the lab. That's actually what brought Dr. McAllister and Dr. Dimmers together.

Kirk: To all our listeners, you're going to be hearing the word "antimicrobial" a lot in this episode. Antimicrobial, antimicrobial, antimicrobial. It's a bit of a tongue twister. So be patient with us.

Sara: Put simply, an antimicrobial is a product or medication designed to stop the growth of a microorganism. And a microorganism can be anything from a bacteria, to a virus, to a fungus like mold or mildew.

Kirk: And really, antimicrobials are part of human daily life. If you're taking antibiotics to fight off an infection, for example, that's an antimicrobial. Anyone who's a swimmer who goes to the gym and uses antifungals to ward off athlete's foot, which is really gross, that's also an antimicrobial.

Sara: And antimicrobials aren't restricted just to humans. If you're a pet owner, at some point you've probably given antimicrobials to your dog, cat, bunny, hamster, whatever you have.

Kirk: And of course, if you're a farmer, you've given them to your herds or flocks.

Sara: But despite the benefits of antimicrobial use, it can sometimes lead to a less desirable effect: antimicrobial resistance.

Kirk: Thisantimicrobial resistance thing is a whole other beast. That's when a microorganism develops a certain level of immunity to an antimicrobial, which makes the drug less likely to work. See, I wasn't kidding when I said you were going to hear the word "antimicrobial" a lot.

Sara: And I want flag this with a big yellow highlighter: it's not the animals that become resistant to the antimicrobial, it's the disease: the bacteria, the fungus. But there's some fascinating research being done in the field right now to examine both the causes and solutions of antimicrobial resistance. That's what both of the doctors are working on, and it's the subject of today's episode.

Kirk: Let's start with Dr. Dimmers to set the scene. As a veterinarian, he's out in the fields with farmers and their animals. He is one of the first to notice when something's not right. So we're going to take a trip to Picture Butte, Alberta now and find out his perspective on antimicrobial resistance.

Greg: I've been in practice for... what is it, going to be six, seven years, and I think that's a relatively short period of time. I think from a health perspective in the animals, like in the feedlot industry, we do have a pretty strong reliance on antibiotics as a control method for bovine respiratory disease and other infectious diseases. It's a really important tool for us and, you know, even if I look back six or seven years ago, we used to be able to take some of these medications and use them and they had very predictable results. And one of the things that I've noticed in that short period of time is that what used to be a very predictable result when we would use these products is now not always a guarantee. And that's something that the producers and the vets have to be prepared for.

Sara: The fact that antimicrobial resistance has grown so common in only six to seven years must certainly be alarming for producers.

Greg: Yeah. So, you know, feedlot operators are very, very driven by economics. It's a margin business, right? So they procure cattle and set their systems up to rely on margins and try and manage risk as best as they can. And antibiotics are one of the tools that they do rely on. Cattle that we would have normally been able to very predictably say we can use this product and expect this result and it'll translate into this economic benefit or this risk reduction, now, we have to be prepared for the scenario that that, you know... maybe at one time what was the case 100% of the time now might only be the case 80% of the time or less. So it adds an additional level of risk that they have to build into their model, so to speak.

Sara: And farming is hard enough work without adding more risks.

Kirk: So we've got a new problem appearing in a short timeframe that could have huge impacts on producers and the industry. Dr. Dimmers, what was the moment you realized just how much of an impact antimicrobial resistance was having on the industry in Alberta?

Greg: I was doing some consulting with one of my clients here and we were testing for antimicrobial resistance on respiratory pathogens in feedlot cattle, and I was going out and taking all kinds of samples and every single time I was getting the same frustrating result that I got the same resistance pattern time and time and time again. I was like, How can this be? How can we have so much resistance in so many cattle and it all looks exactly the same? So that's when I started reaching out. I said, you know, someone please explain to me what's going on here, why am I getting these results?

Kirk: And that must have brought him to Agriculture and Agri-Food Canada. Because if I know anything about scientists, it's that they love asking questions.

Sara: So through your connections, you were eventually put in contact with Dr. McAllister, right? How did you two team up on this?

Greg: I eventually got in touch with Tim and they helped me out do some DNA sequencing and, you know, helping me interpret my results a little bit more. Tim said, "Well, we don't have any answers to the questions that you're asking, but I happen to have a grant that I'm putting together that exactly wants to investigate what you're asking. Do you want to help us out with it? Oh, and by the way, I have a podcast that I'm participating in. You would be a good candidate for them to ask some questions to." So it's still in really early stages, but it's the start of a collaboration.

Kirk: And just like that, the field meets the science.

Sara: Exactly. Dr. Dimmer and Dr. McAllister didn't realize it, but they were working on two parallel tracks. Both were looking into antimicrobial resistance, each from their own angle.

Kirk: We've heard what this issue looks like from a veterinarian. Now, let's go to the microbiologist.

Tim: The first study I think we ran an antimicrobial resistance was in about 1997. There's one antimicrobial that's used quite a bit in beef cattle production at that time, back in 1997, and that was tetracycline. And that's what we found was just resistance to that one antibiotic. Some of the other antibiotics, macrolides, which are another family of antimicrobials, were also being used at that time. But we didn't find any resistance, or virtually no resistance to those in 1997.

Kirk: I was going to say that's a relief – until I realized 1997 was 25 years ago. A quarter of a century! That makes me feel a little old.

Sara: You and me both. A lot can change for us humans in 25 years. And unfortunately, a lot can change for bacteria as well. Suddenly, they weren't just resistant to that one antibiotic, tetracycline. They were developing resistance to other antibiotics as well. I believe there are two big ones now, Dr. McAllister?

Tim: One is called telithromycin, and the other one is related to another antimicrobial called tilmicosin. Well, tilmicosin was used first, you know, back in the early 2000s. And we started to see increasing resistance to it. So that antibiotic was becoming less effective and it was replaced by a newer antibiotic, telithromycin, both in the same family though, and that antimicrobial was quite effective at controlling bovine respiratory disease. But then as we move into 2019, 2020, we find that that antimicrobial is becoming less and less effective against those bacteria as well. So the general rule is that if you use an antimicrobial quite extensively, it's inevitable that the bacteria will eventually become resistant to it.

Kirk: It's like a never-ending arms' race. Every time we come up with a new way to defeat bacteria, they build a bigger shield.

Sara: Yeah. And what makes it even more difficult is that it's a bit of a paradox. Using antimicrobials against microorganisms enhances the likelihood of antimicrobial resistance. But we can't just stop using them either.

Tim: I think it's important when you get to the broader sector that they realize that antimicrobials do play a role in animal welfare. We don't want a situation where an animal develops a clinical disease and... all animals get sick just like all people can get sick as well, right? We don't want a situation where we then say, well, we know antimicrobials could help control this infection and relieve the pain or suffering that this animal's experiencing, but because we don't like antimicrobial use in livestock, we're not going to use it. You know, that's not a good animal welfare practice as well. So you've got to recognize that antimicrobials also play a role in animal welfare at the same time.

Sara: So it's not that we need to take away the tool, but maybe change it and how we use it.

Tim: Yeah, definitely. Definitely. So if we're talking about beef producers, for example, they need to recognize, which they already do, that antimicrobials are a very important tool that they have for disease management. But they really need to recognize as well that they need to use those antimicrobials in a prudent manner, you know, and not rely on them as a substitute for proper management practices. Because if we use those in an excessive manner, we're going to lower their effectiveness and they're not going to control the disease.

Kirk: Right. Because oftentimes, if producers think there's a risk of their cattle getting sick, they'll give the herd antimicrobials to mitigate the risk. That's known as a prophylactic use of antibiotics: they're being used to prevent future infections, not to treat a current one.

Tim: And that's different than therapeutic use, which is where you see an animal that's clinically ill, showing signs or symptoms of the disease, that you then use to try to treat that infectious disease with that antimicrobial. Once you've identified the animal as being clinically ill.

Sara: Now, feedlots do have sick pens where they place animals that are showing signs of disease, and in those pens they may also receive multiple types of antimicrobials. Is it possible for that resistance to jump to from a bacteria to another, even if it hasn't been in contact with the antimicrobials?

Tim: We don't really know that now, you know, this is part of what I'm talking about as defining the ecology of the antimicrobial resistance and how it moves around. When you don't understand something and how it works, it's really difficult to develop a mitigation strategy that you have a high level of confidence is going to work. And what we're using here amongst the most advanced genomic techniques that are available now. Ten years ago, we couldn't do this work. We had an inability to do it because the tools didn't exist. So the whole area of molecular biology is just expanding at an exponential rate.

Kirk: Wow. So this project is really unfolding in real time.

Sara: Before we move on, Dr. McAllister, I think I have to ask you this question, because I'm sure there are some consumers out there who might be listening and wondering: is it possible that antimicrobial resistance might pass from cattle diseases to humans diseases by consuming meat? Does that pose a risk to human health?

Tim: We tried really hard to find a linkage between the use of antimicrobials and beef cattle with implications for human health. So we used some of the most sensitive detection methods you could possibly find. That involved collection of samples from cattle in their environment, but as well as collection of samples from humans out of the hospitals as well as out of wastewater. You've heard about all of the wastewater detection that's going on for a method of monitoring COVID-19. Well before that, about two or three years before that, we were using that same method to monitor for the types of bacteria that are in wastewater, as well as their nature of antimicrobial resistance. So we conducted those studies and we looked at those various environments, and our overall conclusion was that we could find no evidence that the use of antimicrobials in beef cattle pose any kind of risk to antimicrobial resistance and its implications for human health. But we did find lots of antimicrobial resistance in both of those environments. And really the types of antimicrobial resistance that we saw in the human isolates from those human sources reflected the types of antimicrobials that are used in humans. And the type of antimicrobial resistance that we've seen in the beef cattle reflect that the types of antimicrobials that are used in cattle, and they're not exactly the same.

Kirk: Right. If I'm taking an antibiotic to treat an infected cut on my hand, that's not the same thing a producer is giving to his or her cattle to prevent Bovine Respiratory Disease.

Tim: The other thing that I think in many cases with consumers is that they don't differentiate the difference between antimicrobial resistance and antimicrobial residues. They often think that, you know, using antimicrobials in livestock is going to result in antimicrobials ending up in their food. And that's not the case. Antimicrobial resistance and antimicrobial residues are very different things, and there's already very strict regulatory requirements in place to not have antimicrobials enter the food chain. And producers are aware of that. If you look at the antimicrobials, directions will be on the label saying that there's a required withdrawal time prior to the animal going to processing as food. Then the producers are obligated to follow those directions. If they decide to not follow those directions, they test for those antimicrobials in the processing plant and they will condemn the carcass. The producer will get zero value for that animal. If they do it repeatedly, then the processing plant will stop taking their animals at all. So those are the steps that are taken so that antimicrobial residues don't end up in food.

Sara: So antimicrobial resistance in cattle is not a risk to human health. Good. But it's still a risk to our agriculture sector, and to the health of our animals.

Kirk: We've seen the discovery of this issue. The observations. And now we're in the middle of the research. So what do those next steps look like?

Tim: It's really defining the ecology of antimicrobial resistance. You know, where are the antimicrobial resistance genes? Which bacteria are they in? To what extent do those bacteria exchange antimicrobial resistance genes amongst themselves, which is really a key component. And they actually have what we call mobile genetic elements that help bacteria exchange those antimicrobial resistance genes amongst themselves. And we really think that that's a key part of the equation in terms of solving and understanding antimicrobial resistance and developing strategies to mitigate it, whether they be management or alternatives to antimicrobials or other approaches. The other thing we really need to realize is that antimicrobial resistance from a human perspective is a global issue, right? There's manuscripts published where antimicrobial resistance has traveled globally on planes, much like what we saw with COVID-19. The same idea. And they've identified, you know, the sources of where those originated and, you know, the regulations and the oversight in antimicrobial use, which is very high in Canada, that's not the case for all areas of the world. In some cases, you can just go and buy those antimicrobials at your local grocery store. So, you know, we need to take antimicrobial resistance, from a human health perspective, it's a global issue, just like COVID-19 is.

Kirk: So that's what our scientists are doing. Answering those big questions. Looking at that big picture.

Sara: That idea of how antimicrobial resistance spreads is actually top of mind for Dr. Dimmers as well. And while Agriculture and Agri-Food Canada handles the lab portion of the work, he's thinking of potential solutions on the ground. Let's go back to him and hear his view of the cattle industry's future.

Greg: What has really spiked my interest in this kind of topic in the last, you know, 12 to 18 months sort of timeframe is that I'm really interested to see how we can learn more about how antimicrobial resistance spreads within an operation. And I'm not just referring to how we use antibiotics. I think how we handle and manage and buy cattle and how we set up these facilities to handle cattle does have an impact on how we spread antimicrobial resistance around. One aspect that I think about a lot is we think, how do we identify which animals need antibiotics for treatment? But I sometimes think, how do we turn that on its head and say, how do we identify the animals that really don't need antibiotics? Right? We rely on strategies that we can't identify which don't need it, so we give it to them anyways. And if we could find some really innovative solutions to identify the animals that don't need antibiotics, I think we would go a long way to changing the dynamics of how these bacteria spread within a population. If we can go and say 10, 20, 50, or maybe it's 80% of the cattle that don't need antibiotics, we can keep healthy populations of those bacterial strains in those cattle that are potentially not resistant. And it creates a better competitive environment. And we're not propagating the resistant pathogens by killing off all the ones that are not resistant. It's kind of a novel concept, but I think if we dig into it a little further, we're going to unveil some of those factors. And it might change, you know, for me, going to a customer or going to a feedlot, it might actually translate into recommendations that I can say, hey, you know, manage this a little bit differently and we're going to reduce the impact of antimicrobial resistance in this operation. That's really exciting.

Kirk: So we might not just be talking about changing the use of antimicrobials here, but changing the cultural practices on ranches and feedlots.

Sara: And I like that they are working together and that there are a lot of people working on this question. Because it is a big one.

Kirk: Ya.  One of the things that stuck out for me was when we were talking to Dr. McAllister and he reminded us that the actual evolution of the bacteria and viruses and so on, it's a normal process and the speed at which - we said it is 6 or 7 years, is vastly changing the industry. But that has always been the case. Sara: And we've seen it a lot in the last two years, like Covid has been popping up variants every six months. We understand it better now because we see it a little bit too live. But it's a really big question and I don't think we're going to wrap it up today, we're going to have to visit it again.

Kirk: Yeah, no, absolutely. One thing that you will also need to visit again is our pages for subscribing to The First Sixteen. We've got lots more stories lined up about the new ideas, discoveries, and solutions in the field of agriculture and food processing. It's the best way to make sure you're part of that first sixteen percent of innovators and early adopters who are changing their practices for the better. We're all working towards that bright future, one step at a time.

Sara: And until that future comes, you know what to do?

Kirk: Try something new.