Antimicrobial Resistance

Today we are talking with Dr. Virginia Fajt from Texas A&M University  and Dr. Paul Plummer from Iowa State University about the development and monitoring of antimicrobial resistance and how it relates to food-producing animals. 

Topics discussed include: The significance of antimicrobial resistance in food-producing animals; the difference between antibiotic residues and antibiotic resistance; how resistance develops and how to prevent it; antimicrobial resistance monitoring, and much more!

Helpful Links:
AVMA Antimicrobial Use and Antimicrobial Resistance:
https://www.avma.org/resources-tools/one-health/antimicrobial-use-and-antimicrobial-resistance

AVMA Antimicrobial-Resistant Pathogens Affecting Animal Health:
https://www.avma.org/resources-tools/one-health/antimicrobial-use-and-antimicrobial-resistance/antimicrobial-resistant-pathogens-affecting-animal-health

AASRP Guidance for Antimicrobial Stewardship
http://www.aasrp.org/resources/AASRPantimicrobial3F.pdf

Food Animal Residue Avoidance Databank for estimated withdrawal intervals for extralabel drug use:

http://www.farad.org/

Antimicrobial resistance genes found in bacteria used as probiotics:
https://www.sciencedirect.com/science/article/pii/S0168160519303198

AVMA Committee on Antimicrobials:
https://www.avma.org/membership/volunteering-avma/councils-committees-task-forces-and-trusts/committee-antimicrobials

National Institute of Antimicrobial Resistance Research and Education (NIAMRRE):
https://www.niamrre.org/

**We want your feedback! Email DairyGoatExtension@iastate.edu and let us know how you are involved with dairy goats, what you think of the program, and send us questions that you'd like to have answered on a later episode!

This podcast is sponsored by the American Association of Small Ruminant Practitioners as well as USDA National Institute of Food and Agriculture, Agricultural and Food Research Initiative Competitive Program, Antimicrobial Resistance grant # 2020-04197.

Questions or comments about today's episode can be directed to DairyGoatExtension@iastate.edu

Transcript

Michelle: 0:33

Hello, I'm Dr. Michelle Buckley from Iowa State University's College of Veterinary Medicine. Thanks so much for joining us on Baas and Bleats, sponsored by the American Association of Small Ruminant Practitioners. Just a quick note before we get started, this work is also supported by the USCA National Institute of Food and Agriculture, Agricultural and Food Research Initiative Competitive Program, Antimicrobial Resistance Grant Number 2020-04197, which funds my research on improving antibiotic stewardship in dairy goats to assure food safety and milk quality. As always, if you have any questions about any of our episodes, please email them to dairygoatextension at iastate.edu. I hope you enjoyed today's show. Thanks for joining us today on season one of Boz and Bleats, the American Association of Small Ruminant Practitioners podcast. This season, we're focusing on improving milk quality and food safety in dairy goats. Today we have Dr. Virginia Fate from Texas AM University and Dr. Paul Plummer from Iowa State University, and we'll be discussing antimicrobial resistance in dairy goat production. Thanks for joining us today, everyone. Let's start with some introductions. Dr. Fate, you were our guest on the previous episode about how to use drugs appropriately in dairy goats, so welcome back. For the listeners that missed that episode, could you give us a little refresher on your background as a veterinarian and working with antimicrobial resistance?

Virginia: 2:26

Sure. Hi, um, Michelle. My name is Virginia Fajt, and I am a veterinary clinical pharmacologist at Texas AM University. I deal with lots of um issues related to drugs um in animals. Particularly, I have an interest in drugs that are used in food-producing animals, um, and specifically antibiotics, which is where my interest in antimicrobial resistance comes about. I am a um district director for the American Association of Small Rubin Practitioners, and I am the um AASRP's uh delegate to an ABMA committee that has an important role in antimicrobial resistance and antimicrobial stewardship, a committee on antimicrobials.

Michelle: 3:13

Fantastic. Well, I'm glad we were able to get you for this show then. Um Dr. Plummer, welcome. This is your first time on the podcast. Can you give us a little peek into your history with dairy goats as a veterinarian and then uh more specifically your work with antimicrobial resistance?

Paul: 3:33

Sure. Uh it's a pleasure to be here, Michelle. Um, and uh in looking forward to our discussion. Uh as you mentioned, my name's Paul Plummer. I currently am a professor at the College of Veterinary Medicine here at Iowa State uh University with you. And um and uh in my role there, I'm a both a PhD microbiologist and have an active research lab as well as also an internal medicine specialist uh and teach or participate in in most of our um small ruminant electives and and uh clinical rotations here at Iowa State University. I actually did grow up um milking dairy goats and continue to milk dairy goats to this day. So I was born into a dairy goat family and have bred Toggenbergs uh for my entire life and uh continue to milk goats, milk goats this morning before I got on the on the call here. So um they are part of my everyday experience and and milk quality and mastitis is is part of that as well. So um as it relates to antimicrobial resistance, I have the pleasure of serving as the alternate delegate um for AASRP to the AVMA Committee on Antimicrobials with Dr. Fate. Uh I also uh serve as the executive director for the National Institute for Antimicrobial Resistance Research and Education, uh, that is a group of academic and industry folks that's hosted here at Iowa State but represents a national um membership, uh and we work to help uh build collaborations to mitigate antimicrobial resistance development.

Michelle: 5:25

Perfect. So we're talking to two experts today, folks. So to get the episode started, I just want to talk about what antimicrobial resistance really is and why do we care about it. Um I know it sounds big and scary to most people, but let's break it down to a definition. Um, and then I also want to talk about whether just because the resistance might develop in an animal, can it be passed to a human? Can it affect human health as well as animals?

Paul: 5:59

Well, I can provide some initial comments on uh what antimicrobial resistance is, and so kind of in the most um simplified form, we consider antimicrobial resistance when a drug, um specifically in this case, an antibiotic that used to be effective in killing a bacteria loses its effectiveness in killing that bacteria. And so after that happens, we are unable to control the disease uh with that particular antibiotic or control the growth of the organism with that particular antibiotic. So it impacts our ability to keep our animals healthy or humans healthy if it's a resistance that impacts uh humans. In terms of can it be passed from uh from animals to humans? Certainly there's examples where we do see that that can occur. Um there are particular examples, um, for instance, in not related to small ruminants, but uh you know, there's been an identification of antimicrobial resistant bacteria moving from puppies uh to humans and causing disease in humans. Um, there's some other specific examples where uh bacterial pathogens have the potential to move resistance to humans, but on large, those are very you know, very small number of documented clear evidence that transmission can occur from animals to humans. Interestingly, we also have probably an equal number of documented cases of resistance moving from humans to animals with particular organisms as well. And so certainly these organisms can move back and forth. When they move, they have the potential to carry the resistance. But that does not mean necessarily that that organism has the capability to cause disease in the uh in the other species, um, nor does it have the in some cases it may not even impact its treatment because we might use a different antibiotic in that other species.

Virginia: 8:16

Yeah, just a couple of thoughts. Um one thing I w I'd like to add to the conversation about resistance are public health concerns for acquired resistance, um, like Dr. Plummer's talking about, where um for a period of time some kind of bacteria were susceptible to antibiotics and now they're not susceptible anymore. Now they're resistant. There are some uh bacteria drug combinations that are where there's what's called intrinsic resistance. Those bacteria have always been resistant. That's not a new phenomenon, and um, and it's important to separate out um when you see reports about resistance that they're actually talking about acquired resistance, where and what we mean by acquired is those bacterial species have in some way been exposed to and managed to pull into their own cells DNA that leads to the resistance mechanism. Um, and so along those same lines, those genes that cause resistance are theoretically at least can be moved from one bacterial species to another so that perhaps the resistance isn't in um is in a pathogen, a bacterial um organism that causes disease in in an animal, but the DNA that causes resistance could potentially move into another species of bacteria that would then be transmitted in some way either ecologically in the environment or to humans. Those are um theoretical risks of antibiotic resistance, and they they drive some of the decisions at the regulatory level about what antibiotics are potentially um should be removed from use in animals or should be um carefully monitored in animals or humans for that matter. So the the biggest take home from what you've heard so far and what you'll hear for the rest of this podcast is antimicrobial resistance is complicated. It is ecological. There are different kinds of risk factors and pressures that make a difference in how bacteria grow, how they spread their genes, and so on. And so it's a very complicated discussion. So to me, the most important take home is um if you think it's easy to understand, you probably don't or aren't quite grasping it because it is a very complicated. I think think about it as ecology and a system that has multiple inputs and outputs and factors and so on, um, helps understand why we continue to have conversations and continue to have um challenges with making good decisions about how do we make this problem better, how do we preserve the effectiveness of antimicrobials in humans and animals.

Michelle: 12:12

Gotcha. So it sounds like not to simplify a very complicated topic, but um it sounds like just because a bacteria has DNA in it that we know causes resistance to an antibiotic doesn't mean it's necessarily problematic in the species that we've identified it. And we know a lot of these plausible scenarios of how resistance is transmitted based on our general understanding of microbiology, but the true understanding of statistical um frequency and how often this phenomenon occurs is something that's still uh under evaluation.

Virginia: 13:01

Yeah, that's a great way to put it. I think um because so many things about how bacteria work, how they acquire DNA, how antibiotics select for resistant um bacterial populations can be so specific to the individual bacterial species, the individual drug, the um scenario uh where the bacteria are normally living, what the infectious disease is, where that animal or that person um inhabits, what their habits are, and so on. And so there are there have been lots of investigations. There's a lot we know about antibiotic resistance, but much of what we know is about very specific combinations of species of animal or human, bacterial species and drug or group of drugs, um, and and everything changes when you change the bacteria because every back because all the bacterial species are different from each other, they have different normal ecological needs um and and pathways and so on. And so even if we know a lot about, for example, salmonella, we don't know as much about other species of bacteria. Or we know about salmonella in one particular setting, but we don't know very much about it in other settings. And so I think what we there's a lot we know, um, but the universe of what we don't know is really big because of this is such a complicated system.

Paul: 14:27

And I think that becomes a challenge for us at both a regulatory and policy uh level discussion, because you know, as I pointed out in my first comments, yes, there are specific examples where we have evidence of direct transfer and and an impact, but those are very limited. But it can be, you know, it's quite easy for folks to kind of say, well, here's an example, so we're gonna assume this happens with all bacteria, all drug combinations, and and that is an erroneous uh assumption and one that quickly gets us into problems when we start making broad policy decisions based off of a very limited number of uh specific examples. And and so I would wholeheartedly echo uh Dr. Fate's comments that you know really resistance has to be considered as a specific bacterial species drug environment host combination. Um and so there you've got four variables for which you know you could have an almost endless number of possible combinations, and and pulling out one or two examples where we know there's a problem, and then assuming that it happens for all the other multitude of those very quickly takes us down a path of uh perhaps making poor choices or or choices that impact on an animal health or animal welfare just as a precaution.

Michelle: 16:04

Fair enough. Well, I think this is a rabbit hole that we could dive way down into and could inspire someone to pursue a PhD in microbiology someday if they were interested. Um, but let's kind of step back for a minute and talk about who is at the most risk for transmission of resistant bacteria. Um, since we're talking about this in terms of dairy goats and veterinary health, is it the consumer who's buying goat milk at the store if it has resistant um bacteria in it? Or is it the people on the farm that are handling the animals every day? Um where where does the highest risk fall?

Paul: 16:47

Well, I think that's a that's a great question. And and uh as Virginia pointed out earlier, I don't know if there's simple answers to any of these questions. Um so you know, there again, I can give specific examples. Raw milk likely poses a much higher risk. Raw milk cheeses or raw milk in general poses a higher risk of exposure to antimicrobial resistant pathogens because pasteurization's not been performed to um you know to remove those pathogens from those products. So consumers, whether that's a producer or a um a lay public consumer of raw milk or raw milk cheeses, um, certainly would be an area where there could be potential risk for transmission of resistance, resistant campylobacter, for instance, um, or resistant to some other specific milk pathogens. Uh an example of where a producer could be at higher risk, uh, and and this is also going to be a Campylobacter one, but in is in abortion storms. So if you're having an abortion storm on your farm, many of those abortion agents do uh have zoonotic risk and can cause disease uh in the producers if there's a high enough exposure level and you know you're not using good hand hygiene or or uh um you know contaminating through that process. And there again, some examples um like Campylobacter perhaps could cause uh disease. So, really, the the simplest answer is exposure to either the animals that are shedding in high numbers or milk that's not pasteurized would be the highest risk individuals for that potential transmission.

Virginia: 18:39

Yeah, and I think the the unknown amount of risk is um if those antibiotic resistant bacteria like Dr. Plummer just talked about or others that may have acquired resistance in some other way, if those are shed into the environment, for example, they're in the feces and then they're shed into the environment, and then whatever um however the that environmental um contamination is managed, the theoretical possibility of those elements of resistance being transmitted and becoming a general public health risk are really unknown. So we think, well, it's a small farm, I'm a small dairy, I live in rural Iowa or rural Texas or whatever, it can't be that big a risk. And and the the fact is we actually I don't know that there's very good data to actually quantify what that risk is. It's a theoretical risk, it's something we should be considering. Um it's it's one of the reasons that um there's you know discussions about how to manage large operations that have large um, for example, lagoons for managing waste and and what are the environmental regulations related to that. But those are all theoretical risks. There's a lot of conversation about it. I've seen recent studies about you know pharmaceuticals or antibiotic resistance genes in waterways of all kinds, surface water and other things. Um, and identifying their them is a is is useful information, but just because they're there doesn't mean they're either high risk or low risk. We we don't really know. And so I think there's a lot we don't know about who else, aside from the individuals who are directly managing animals who have been either treated with antibiotics or are have exhibited bacteria that have antibiotic resistance. You know, outside of those, I don't know that we know what the risk is. Um and that that's not to be scary, like, oh my God, it's there's a big risk. I don't, I just I just think we don't, it's not quantified very well. And it's certainly possible that that it's a very, very low risk. That would be my assumption, but it's also possible that that it we just don't know that that it's higher than we think it is. So I I I don't know. I think that there's a lot of unknowns about that, about who is really at the most risk, particularly if you're talking about a very specific uh commodity, right? You're talking about if you're talking about goat milk, what's the risk of goats transmitting antimicrobial resistance to people? You know, you start talking about cattle feedlots, much larger populations of animals, much larger waste stream, you know, etc. Um, but we still I think uh it's still unquantified in a lot of ways how much risk that really is to the general public.

Michelle: 21:21

So that's certainly not to say that consuming raw milk cheeses is going to give you resistant um bacteria at all, but that does kind of bring me to my next question. Um Dr. Fate and I spoke recently about avoiding antibiotic residues in meat and milk. And so I think it's important to differentiate how are antibiotic residues different from antimicrobial resistance.

Virginia: 21:48

Yeah, sure. That's a um that's a really it's a really important point, and and it certainly can be confusing when we talk about antibiotics, um about residues versus resistance. And as we talked about in that um podcast, anytime you use a drug in an in an animal or a person, um there's a period of time where that drug is in the animal and then it is eliminated at some um fairly well-known rate. And studies are performed in in drugs that are approved for use in food-producing animals to determine how long food products should be withheld so that they have uh levels of drug that are below um a risk. Um that that's called a um tolerance. We want the level of drug to be below the tolerance, and the tolerance is determined based on uh a bunch of different pieces of information, um scientifically derived information about what is acceptable risk, essentially. And so when you talk about residues, that includes all drugs, that's not just antibiotics. We're trying to prevent the food supply from being contaminated with concentrations of drug that might cause problems in humans, and and antibiotics are the same as all the other drugs that we um that we potentially use in food-producing animals or any animals, and so um that's what a residue is. There is a little bit of crossover, and that may be why there's some sort of mixing up of the two, in that if um an antibiotic residue were to exist in, for example, milk that is then being fed to young animals who are now being exposed to low levels of antibiotic, that then would select for resistance in those offspring. Also a very you know theoretical pathway, um, although there are a few studies about feeding um waste milk with antibiotic residues in it to calves and selection for antibiotic-resistant bacteria, at least in the gut. Um, and so that's where there's a crossover between residues and resistance, but it they definitely are um uh uh it's definitely important that they be separated from each other, and one doesn't cause the other. They they exist um independently.

Paul: 24:11

I think uh Dr. Fate did a good job uh describing that. We just find through our efforts here at Niamory that um particularly out in the public, there's a lot of confusion on those issues, and um, you know, folks um equate that anytime an antibiotic's gonna be given that now I'm gonna have resistance. And and it's no, um, there will be a residue, but our food system is actually very good at preventing those residues, and we have exceedingly low rates of um you know of contamination of food with antibiotics. So consumers don't need to uh you know be broadly concerned as it as it relates to risk. The risk of exposure of consuming an antibiotic and food that comes through our food safety inspection service is is is exceedingly low. We know that. Um, but every antibiotic use does not select for resistance, and um you know testing for antibiotics in the milk will also, or in the meat, will also not eliminate the resistance if it's there. So there's there's just quite a bit of confusion around that, and uh I think it is good to highlight um because there seems to be this assumption that every time we give an antibiotic, then resistance is there, and and that is by no means the case. If that were the case, we never have success treating diseases because we once we used an antibiotic once, um, then it everything would be resistant.

Michelle: 25:47

That's a great way to think about it. Um it's it's not an easy thing to do to make a bacteria change its DNA to be resistant to an antimicrobial, generally speaking. These are uh metabolically expensive processes for the bacteria, otherwise they would be made resistant to begin with. Like some bacteria don't respond to certain antibiotics naturally, but um it's not just something that happens with one use. So it sounds like you're saying we don't need to just stop using antibiotics altogether.

Virginia: 26:27

Yeah, oh yeah, for sure. And um, and I think there there if we were to say you can't use antibiotics anymore in animals, or you can't use them anymore in um food-producing animals, um, the the animal welfare um risks and and in fact potentially even risks to public health from animals that weren't effectively treated for some infection that then ended up in the food supply, could actually end up with um bacterial infections causing problems that way. And so um, but pr but strictly from uh you know from the veterinarian perspective of should we just let animals die from bacterial infections or suffer from bacterial infections, that doesn't seem to me to be the best answer. Um, and it wouldn't necessarily solve all of our problems about antimicrobial resistance. There still will be resistance. There are naturally occurring resistance genes that are have been uncovered from the permafrost. And so antibiotic resistance genes have been around since bacteria have been around. That's that's how they compete for resources in their own little um ecological niches. Um and so that that's not the answer to eliminate all antimicrobial use. I'm sure Dr. Plummer has some words to say about that as well, because I I do think it's a it's an easy out if you don't understand how animals are raised, how animal production works, um, what veterinary medicine is all about, what our obligations are, the oaths that we take, right, to as veterinarians to protect um animal health, um, that those would all be challenged by just saying, you know, heart blanche, remove all antimicrobials from use in animals.

Paul: 28:06

Paul completely agree. And um, as you pointed out, I mean, even removing all antimicrobials from use, we could stop giving all antimicrobials to humans, animals, and and you know, stop manufacturing antimicrobials, and resistance is going to continue to develop um because these organisms, penicillin, is produced. Uh, you know, we now manufacture that, but um, but was originally produced, and many of these antibiotics are produced by the organisms themselves, as Dr. Fate pointed out. The the possibility of stopping complete antimicrobial use uh, you know, obviously impacts a significant um detriment on our ability to keep animals healthy and as well as uh assure good animal welfare. We also do have some data, um, some uh risk modeling, for instance. So Dr. Bing Wong's group at uh University of Nebraska Lincoln has looked at um risk modeling. This is in beef, and and looked at the potential decrease in risk associated with stopping using antibiotics entirely, um, and compared that to the potential decrease in risk for um following good food safety hygiene practices with um with cooking of that meat and demonstrated that the uh the complete removal of antibiotics resulted in less than a 2 or 3 percent impact on risk to the end consumer, whereas good meat handling hygiene and cooking to an appropriate internal temperature reduced that risk by 99%. So, here again, um you know we can have much higher impacts in terms of food safety risk with good handling and good food hygiene and cooking to an appropriate temperature. Removing antibiotics from that mix does not impact that risk nearly to the degree that good handling does.

Michelle: 30:12

Those are fantastic points that you both bring up. And Dr. Plummer, you also touched on something. Um penicillin is a naturally occurring antimicrobial, and there are plenty of natural supplements out there that have antimicrobial properties that can impact antimicrobial resistance. It's not just manufactured drugs that can cause resistance. Um, and and the nice thing about drugs is that go through this, you know, FDA approval process and um and that whole system is that we have a very good understanding of how those work and the impacts that they have on the bacteria that they're affecting. Um, however, with you know other supplements, natural remedies, things like that that don't go through the same rigorous process, we have a very incomplete understanding of the role that they play in the body and how, you know, what systems they affect and how they affect them. So um in my mind, anyway, all those unknowns uh pose more potential for risk.

Paul: 31:20

Oh, you're certainly right. And we do see that um, you know, so for instance, um sometimes the way these resistance mechanisms are carried, there's other environmental resistances, so metals, uh metal concentrations can impact um, you know, the selection and emergence for for resistance copper in the environment, um, copper and feeds, um, you know, other metals as well. And um, interestingly, towards your point on supplements and stuff, there's a growing body of evidence that um some of our probiotics and and um those types of supplements actually have the potential to carry resistance in them. So um, because there's not a screening process for many of those um probiotic uh over-the-counter generally recognized as safe type of products, um we do know now that in some cases there's actually resistance in those probiotic organisms. I don't think that's been uh associated with any sort of increased disease risk in animals or humans. Um, and and so you know what risk that really poses, I don't know. But purely on the um the potential, resistant organisms can be um can be moved through even those supplements as you were discussing.

Michelle: 32:39

Wow, I I had not even seen that uh that data out yet. So that's really interesting, Dr. Plummer. Um, Dr. Fate, you mentioned that we have an obligation for judicious use um and appropriate use uh in maintaining animal health and welfare and balancing that with the risks that we've been discussing today. Um when I was practicing in California, any antibiotic required a veterinary prescription. However, that's not currently the case in most of the other 49 states in the US. Um I understand that rule will be changing in the future, though. So, what does this mean for producers and veterinarians in the rest of the country?

Virginia: 33:22

I'm glad you brought that up, Michelle, because um it is a it is something that's gonna change soon. There are um there are still some antibiotics that are available over the counter. So you can go um to uh tractor supply or um feed store or other places like that and and purchase, particularly most of them are available for livestock. Historically, we're available for producers to purchase on their own without a veterinary order, without a prescription. And all of those products throughout the United States are going to be um all required to become prescription products. And prescription means a veterinarian will have to write um an order, a prescription for producers to use those drugs or to purchase those drugs. And so that's gonna be a big change. Um, in some parts of the country, it it won't make a lot of difference because there's availability of pharmacies and drug distribution centers and so on. Other parts of the country um where there are fewer veterinarians or veterinary access is um problematic, there may be some challenges. And so now is the time um for producers to be thinking about who is my veterinarian, who do I, who do I call for advice, and can I, if I don't have a veterinarian that I regularly call, I need to find someone to establish the veterinary client-patient relationship, that VCPR, so that when I am faced with a problem, I have someone to call and someone who's familiar with me and my operation that will be willing to to help with writing prescriptions, seeing animals, diagnosing disease, and so on. So it's a really good this is an opportunity to to talk about it. Um the FDA is planning various kinds of educational um efforts. I'm sure Niamory is as well, but it is it is gonna be a big change. There was a big change um a few years ago when all of the antibiotic feed additives um became BFD drugs, veterinary feed directive drugs, and required veterinary oversight. Um, but this is this is kind of the the next step of providing additional care with making decisions about antimicrobials and having veterinarians who are trained in animal health and um and uh drug therapy and making decisions about drugs and have the license to do so, um, being involved in making decisions about antimicrobial use in all animals.

Paul: 35:57

For producers that may be listening, the things you might be using that would be impacted here would be over-the-counter penicillins, um, tetracyclines, oxy-tetracyclines, um, tilacin, some of the macrolides, um, that right now you could go purchase as of um next summer, summer of twenty twenty-three, you won't be able to go uh purchase those, as Dr. Fate said. So uh I too would echo the encouragement to find a veterinarian if you don't have one. And um, since we're on the AASRP podcast, um the AASRP website also has an option for find a small ruminant veterinarian in your area. So um would encourage producers that might be looking for a uh a small ruminant vet in your area to go to the website uhasrp.org and uh and look for a local veterinarian to establish a relationship with so that you'll continue to be able to assure your animal's health uh with the use of these drugs when necessary uh after they become uh not available over the counter.

Michelle: 37:02

And I would just add that um the point of this legislation coming through is not to make it so that now producers can just pick up the phone and say, hey, doc, whoever you know is my local vet in town, I have a goat that has pneumonia and I need to give them a shot of whatever antibiotic. Can I come pick it up? There will be requirements for maintaining a regular relationship with your veterinarian where they they see your animals at least once a year and help you to develop an animal health plan. This is not just a hands-off type of scenario. Um and per our discussion today and in previous episodes, it really shouldn't be because we all need to be involved in making these decisions appropriately. So I would also encourage potentially companion animal veterinarians or or vets who work on species other than small ruminants to utilize the resources that we're providing in this podcast and contact myself or any of the guests that we've had on the show with questions to help you feel more confident in dealing with small ruminant species because we do have an issue with getting access to care for a lot of our producers. And it can be a little bit scary to start working on a species that you're not used to, but as a community, we're here to help. And so any questions that practitioners have can be emailed to dairygoatextension at iastate.edu. And uh we want to be a resource to give people the confidence to help serve our small ruminant clients and make sure that we're helping them take the best care of their animals. So a little plug for that as well. I want to kind of shift gears a little bit now. Um we kind of mentioned this earlier, but let's talk about how we are tracking antimicrobial resistance in food-producing animals. Um I know both of you have stated that this is an area where we're lacking a lot of data, but where and how are we starting to collect this data?

Paul: 39:21

Sure. Um, well, uh, you know, you you're exactly right that um we we do not have any um you know kind of systematic national efforts to um to bring that data together. I would say that certainly within some production systems um and and within you know uh a number of veterinary clinics, there probably is a reasonable understanding of what resistance occurs in in those animals that they treat regularly. So um, you know, if I'm a veterinary in in a in a large dairy goat production system and I have significant resistance to an organism that causes disease in those animals, I'm likely to figure that out through diagnostics, but also because of treatment failures. And so I would say that it's not that we have a complete lack of knowledge. It's just bringing that knowledge together on a on a larger scale, um, you know, even at a uh a veterinary pulling all that data together in a in a veterinary clinic or at a state or at a national level. There is interest and and pressure, uh certainly at both the national and the international level, to um start to build those databases. Some countries uh around the world uh have very extensive national databases in which they're able to collect that data. Uh and largely that's most effective in countries where there's uh kind of a much more centralized um veterinary care system for the veterinary data, so that um you know you've you've only got one or two sources where all that data is coming into, and so really pulling it together is is it's almost a you know a misnomer because it was all together to begin with, which is certainly not the case here in the US, where we have so many different veterinarians and production systems. So there also is a complexity here that you know, going back to that concept that Dr. Fate mentioned earlier of complexity, you know, there. Is a lot of risk of comparing apples to oranges when you start pulling these things together from different sources. So there's multiple ways to measure resistance. There's multiple ways to identify the resistance. There's multiple, if you will, definitions, or you know, without getting into too much detail there, determining what exact level of resistance constitutes a resistant organism. So these aren't kind of black and white concepts. And so as you start to pull this data together, you have to be very careful that you don't start making erroneous comparisons and erroneous assumptions when actually it's a difference in data collection or data reporting. So I think I'll end with that and see if Dr. Fate has uh comments.

Virginia: 42:32

Yeah, one of the things I was thinking about is the source of the bacteria which in which you are measuring the resistance. And so if you have a relatively passive surveillance system and you collect the bacterial isolates from, for example, diagnostic laboratories, those samples are already biased because they come from typically they come from animals that have already been treated with an antibiotic, and that's the reason that a sample was sent in in the first place. And so gathering example isolates of bacteria from animals that have not yet been treated for the disease they have in order to accurately characterize resistance in a particular bacterial pathogen is a big challenge and um and certainly isn't routinely done. That's not um how animals, that's not how veterinarians, that's not how physicians make decisions about they don't isolate a bacteria from every single individual that gets treated before they treat. And in order to characterize resistance appropriately, that's almost what you would have to do, right? And so we have to to to be completely accurate. So we depend on other ways of acquiring those bacteria, and some of those ways can lead to biases in terms of assessing the true um proportion of bacteria that are resistant. Um and and there are diagnostic labs that use different systems, and they're and it's challenging to compare not just across drug groups and um individual drugs within groups, but um the same bacteria from different species of animals, and uh, what does that mean and how do we and so I think the the collecting of the data and analyzing it is challenging, and the interpretation is um could easily go awry. Um, and so having lots of discussions about the best way to approach those things to surveil for antibiotic resistance, and not that it's not happening, because it certainly is, um and we need to continue to be cautious about how we're interpreting those data and that we're making appropriate um policy decisions based on data that are not um that may or may not be truly accurate or an accurate representation of um the prevalence of resistance.

Michelle: 45:06

That makes a lot of sense, and it also kind of makes me a little bit nervous because my primary PhD project um has a portion of it that's evaluating development of antimicrobial resistance in dairy goats specifically. But Dr. Plummer, you've put me at ease a little bit because um, and Dr. Fate, because essentially what we're doing is taking samples, cultures, bacterial cultures of goats before they're dried off. And uh based on those results, we'll be treating those that are positive for certain bacteria with um two different antimicrobials. So each goat will get uh one of those two or be assigned one of those two groups. Um and then after they kid, we'll be going back out, collecting another sample. Um, and so any of our goats that don't clear their infection will be uh genotyping them, so looking at their DNA to determine if they have a resistance gene and if that could be the reason that they didn't clear the infection. And so we're looking at the overall prevalence of infection at dry off. We're looking at um cure rates and how effective these antimicrobial treatments are, and then we're also looking at the prevalence of antimicrobial resistance when it's applied on a targeted dry-off treatment. And uh this isn't addressing any kind of blanket treatment like um some dairies might treat every animal at dry-off. Um, so this isn't quite that scale, but just making sure that we're targeting bacteria that we believe to be susceptible to the antibiotics that we're evaluating. So, um, but I'm nervous in that I know that these are very scenario specific. Resistance can be very scenario specific. So something that holds true for my study um here in Iowa uh could be not applicable to a dairy farm in another part of the country. Um, we're also we are also running a portion of this trial in California to see how this compares, but um definitely recognize that there's a lot more data to be collected, and we could run this study on a different dairy in every state, and I imagine we could get a little bit different result. So um, but we're excited to see what the result is and and hopefully inspire more research along these lines later on. So we'll keep you posted on that.

Paul: 47:40

And I would just add that uh, you know, I mean, you in those comments you're you're pointing to the resistance prevalence, um, which it certainly is part of that research outcome, and and that could vary from farm to farm. Um, but you're also evaluating the the targeted antibiotic treatment, um, right? So selection instead of doing blanket treatment, selection of specific animals to to treat based on culture approaches. And those types of outcomes, to the extent that they reduced antibiotic use, many of those animals that, if we do blanket treatment, may not have ever needed treatment. They may not have had an infection, but you know, we're still using that antibiotic. Those types of outcomes still may have a much higher external validity, um, regardless of the exact prevalence of resistance within the farm. Um, so the the impact of being able to reduce antimicrobial use through um selective dry dough therapy also has an external validity that's probably higher than an individual farm prevalence.

Virginia: 48:51

I just want to say it sounds like a really cool project, Michelle, and I'm and that's exactly the kind of work that we need to continue to do to assess the real risk of um of resistance itself, of selecting for resistance, what that looks like over time in um in animals. And so I'm excited that this work is happening.

Michelle: 49:12

Thank you. It's been fun in a kind of nerdy way so far. But it's time for us to wrap up for the day. So if you could both just give us a little recap and summary on how veterinarians and producers can help to mitigate antimicrobial resistance development, especially as it pertains to dairy goat production.

Paul: 49:38

Yeah, sure, I'll I'll start off. And and so, you know, I think um as as we think about this for the practitioners out there, the veterinary practitioners, but also as the producers, um, you know, our goal is to use antibiotics when we need them to assure animal health and animal welfare, but to make decisions and make management decisions and as well as kind of treatment decisions that help us to assure that we uh or make our best effort to not use antibiotics when they're not gonna be when they're not gonna be necessary or helpful. So um as a producer and a veterinarian, things that think I think through in that process are number one, how can I prevent disease in my animals? So um whether that's vaccination, whether that's biosecurity, um, you know, and and making sure I'm not introducing diseased animals into the herd or flock, um, whether that is um routine surveillance, perhaps for you know, on dairies, some intermittent milk cultures, but mitigating disease risk through vaccination and biosecurity helps to ultimately reduce the amount of antimicrobials that we have to use and the potential risk for antimicrobial um emergence. Then the decision around treatment decisions or the process of treatment decisions, and this is why the FDA is moving us towards having veterinary involvement, um, evaluating each animal and making an appropriate disease treatment decision for that animal. Does this animal need antibiotics or not? Certainly, for instance, let's think about kids, um, dairy goat kids with diarrhea. There are some bacterial causes to that diarrhea. Um, even in those bacterial causes, antibiotics are not always necessary. But there's also plenty of non-bacterial reasons for diarrhea for which antibiotics are not going to have any impact. And so just saying that every goat kid with diarrhea needs antibiotics is probably not where we need to be at, and we need to be moving towards more selective treatment process. And so working with their veterinarian to make that decision. And then finally, almost every talk I give on this, um, whether I'm talking to prescribers, like veterinarians or producers, um, you know, my view of this across the One Health spectrum. Uh, in my role, I work with human physicians giving antibiotics, veterinarians, dentists, nurse practitioners, environmental. We use antibiotics in plants and and and crops. And, you know, my take-home message is if we all make the commitment to try and use antibiotics better tomorrow than we did today, that's the forward progress that we need to make. Um, it's each of us making the individual decisions on a daily basis that improves how we use those antibiotics. Um, so those would be my take homes, and um I'm sure Dr. Fate has some great ones to add.

Virginia: 52:50

I'll just follow up by saying um the resources, particularly for veterinarians and um producers. Well, there's certainly, I mean, I could list lots and lots of different things, but I think really good places to start are um the ABMA, American Veterinary Medical Association website. Um there's a there's a section on antibiotics and antibiotic resistance, and there's links to other resources. Um there's really useful guidelines for veterinarians about um all the things that um Dr. Palmer was just talking about, um, and also similar kinds of resources from the AASRP website. So specific to small ruminant practitioners, what how do I think about using drugs, um antibiotics um in a prudent manner? Um, and what makes uh what makes me an antimicrobial steward? How can I um make the best decisions? And um AASRP has continued education sessions and and often they're related to um making treatment decisions, um, some of which involve antibiotics and so um and preventing disease and so on. So those two are are really good resources for the for the veterinarian and for the producer um to share with their veterinarian um uh to get you started to um kind of give the high-level view of what is it that makes um antimicrobial stewardship better from the veterinarian uh perspective.

Michelle: 54:18

Fantastic. And we'll put some links to a few of those pages in our show notes as well. Um and of course, folks can always email uh again dairy goat extension at iastate.edu with specific questions. Um, or if you're not sure if a resource is valid, um, feel free to send it our way and uh we can we can help steer you as well. So that about wraps it up for today. Thank you both so much. This has been a really enlightening discussion. I really appreciate you taking the time to chat with us, and um, I hope we get to have you both back on soon. Have a great day.