Veterinary antibiograms for empiric antimicrobial selection

Drs. Claire Burbick and Edith Marshall authors of "Benefits and challenges of creating veterinary antibiograms for empiric antimicrobial selection in support of antimicrobial stewardship and advancement of one-health goals in: American Journal of Veterinary Research - Ahead of print (avma.org)" discuss veterinary antibiograms. Hosted by Associate Editor Dr. Sarah Wright and Editor-in-Chief Dr. Lisa Fortier.

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Transcript

Sarah Wright: 0:00

You're listening to veterinary Vertex. A podcast the AVMA journals. In this episode, we chat about the benefits and challenges of creating Veterinary antibiograms with our guests, Edie Marshall and Claire Burbick.

Lisa Fortier: 0:19

Welcome to Veterinary Vertex. I'm Editor-in-Chief Lisa Fortier and I'm joined by Associate Editor Sarah Wright. Today we have Edie and Claire joining us. Edie and Claire, thank you so much for taking time out of your very busy schedules in the very end of summer, when nobody wants to be working, everybody wants to be on vacation and getting ready to send their kids off to school. And thank you so much for taking the time to be here with us today.

Claire Burbick: 0:44

It's a pleasure to be here. I'm really excited.

Edie Marshall: 0:47

Yeah, thank you for doing this. I'm excited as well.

Sarah Wright: 0:52

Edie, your Currents in One Health manuscript in AJVR discusses the benefits and challenges of creating veterinary antibiograms. Can you explain to our listeners what antibiograms are?

Edie Marshall: 1:03

So antibiograms summarize cumulative antimicrobial susceptibility testing data, which, for some of our listeners, that's just a lot of syllables. Essentially, when a veterinarian collapses sample from an individual animal and runs the culture and susceptibility testing, then that is a result for that individual animal. And what the antibody programs do is take a whole bunch of those test results from multiple animals over a defined period of time. And for a specific pathogen, and summarize that like combine all the data together, so that veterinarians can see sort of trends in resistance. And they may be able to use that information when selecting an antibiotic early in therapy, before their own test results for that individual animal have come back from the lab or if they're not going to be able to run those test results.

Sarah Wright: 2:07

Thank you. And Claire, what are some important findings from this study?

Claire Burbick: 2:13

I really struggled to kind of pick out sort of a small list, I think the most important findings to me, really are sort of refining some of the gray area regarding an individual antimicrobial susceptibility testing, because I think there's some nuance there and in the data in regards to what's an MIC versus what's a breakpoint, which I think are super important concepts for veterinarians to understand. And then also that the individual susceptibility test data can actually be used again, which is kind of amazing, to be able to really help guide empiric therapy, which I think is always, you know, something that literally every veterinarian is doing every day and to have the confidence that the drug that you reach for, for urinary tract infection, you know, kind of the common things that are treated with antimicrobials. You can feel that kind of extra level of confidence to say, I know, the pattern within my population is x, y, and z. And so my choice of this therapy is going to be how I will have the most confidence and the efficacy, you know, based on this pattern, so it just gives us kind of that additional layer of usefulness, within, you know, antimicrobial use and stewardship, which I think just has, you know, so many benefits for the practicing veterinarian to make those good choices. And so I think that's on the one side, I think the other side, is that really, you know, we have a lot of challenges. And I think, you know, half the paper is really addressing a lot of the gaps and challenges and limitations we have, which, you know, I struggle when I talk about this, because I'm like, I'm just a really negative Nancy person, and we have all these challenges. But, you know, I don't know that, you know, this is really well known within the veterinary practicing community that we do have gaps in breakpoints, and that really limits our ability to, you know, accurately predict clinical outcomes, like we think we have, that the data is is pretty complicated. And you do you have to have kind of some background and what that means. And that also, you know, we kind of have some structural lacks within our profession, which aren't as big of a problem on the human side. So they have funding that's tied to doing antimicrobial stewardship work like funding, you know, we have insurance we have government regulations that really support doing this type of testing, compilation of data, you know, educational outreach, all of those things on the human side that we really don't on the vet side. And so, you know, I think there's a lot of things that need to be addressed to be able to really have the level of of antimicrobial use comfort and stewardship that we would really like to have, and that maybe people don't quite know. And I think so, breakpoints is a big one, the lack of specialists that are trained in this area might in microbiology, also in pharmacology, and, you know, the infrastructure, along with the finance and financial support there, I think one of the things that's important to remember is we're relying on animal owners or producers to provide this data for us. And so it can be very complicated to even get susceptibility test data to put into these antibiograms. For us, because we're relying on, you know, the, the farmer, we're relying on the, you know, the cat owner to make this data available to us. And so, you know, those are some challenges. And then, you know, as we are in such an IT society, and we're looking at these big data sets, we really also need support in managing the data, getting access to the data, you know, I work in a diagnostic lab, and it's not actually that easy to pull data out of our systems. And so there's just a lot of kind of, like, sort of the boring details that that we just, you know, kind of take for granted on the human side that we really, you know, are challenged by on that side, and so even though it is a bit of a laundry list, I think, you know, these are important things to kind of get out into the discussion of how do we want to do stewardship? What do we need to support that? You know, how do we get data to either treat individual animals effectively, or, you know, regions or, you know, areas of practice? How do they get antibiogram data to really help with this process. And so,I like it, because I feel like it's a soap box of, you know, all the things that microbiologist and the pharmacologist worry about. And so, you know, kind of, you know, what we could do with this magical data. And then also, you know, some of the challenges in getting some of that data.

Lisa Fortier: 7:24

Yeah, for sure. I've been, you know, I was at Cornell for 32 plus years, and super spoiled to be able to call people like you all the time when we're in the diagnostic lab, or even on Saturday morning and be like, what do you have for me? You know, and if some of the listeners are my age, it was antibiotic sensitivity. Right. Now, antimicrobial susceptibility. And so there's some different ways of thinking. And Claire, you mentioned that breakpoint and MIC are super important that I think, if you wouldn't mind reminding listeners, what those what the differences are.

Claire Burbick: 7:59

Sure. So I think MIC and the breakpoints sometimes get sort of combined, but they're very unique things. So the MIC is really the value that we're producing in the lab. So we have the bacteria that we isolated from whatever, you know, what if it's your own, or pus or whatever, that we have considered significant for the case. And so we do this in vitro testing. So it could be a broth microdilution, where we get that MIC. It also could be just a fusion, which was mentioned in the paper, which is an Agar based, Kirby Bauer, kind of the older school method that I think that's are probably learned in vet school back in the day. And so we're producing in vitro data. So we put a drug in contact with the bacteria. What happens? So does this level inhibited? Does this level inhibit it? And so we're just trying to measure what drug is going to be impacting our bacteria within either testing modality. And so when we're doing broth microdilution, we have these dilutions of drug that we grow our bacteria in, and then the MIC are the minimum inhibitory concentration is where we visibly see no growth in the well. And so that's what we call our minimum inhibitory concentration. And so we get this value. And then we have to go to the big document that is produced by the Clinical and Laboratory Standards Institute, which sets breakpoints for veterinary medicine in the United States. And so the breakpoint is actually a combination of properties of the bacteria, properties of the drug itself, is it time or concentration dependent, and then, also the pharmacokinetics and the animal species. So it's really combining a lot of different types of data to predict that, yes, we can achieve this level of the drug in our patient and at that level. We believe, through our modeling and all of the calculations and studies that are done would be able to effectively treat this specific bacteria with this specific dose route and frequency of administration of that drug. And so it's really not just like, oh, bug drug, it's bug drug, you know, it's drug in the animal. It's all the calculations and math, which makes my brain hurt really bad. But it gives you that clinical prediction. And so that's why the breakpoint is so absolutely critical, is that it gives you a clinical prediction. So the MIC does not in and of itself, give you that, but it gives you a placeholder to then assign an S, I, and R, which has been determined from all of this data. And so that's why when I think veterinarians look at it, and they say, Oh, I have an MIC you know, that should give me the information I need. But really, we have to have all of this background data in order to contextualize that MIC. And so, what we need are breakpoints, but they're kind of hard to do, because you know, we have to have all of the studies, we have to do all of the analysis. And when you think about, you know, if you have E Coli in a rabbit, you know, that's a whole different analysis versus E. coli, in a horse versus E. Coli in a dog. And so all of these kind of species specific parameters are baked in to that breakpoint. And so it gets to be on the vet side, very, very overwhelming. On the human side, you know, you have E Coli in a person, boom, you're done. On the vet side, it's like, well, what about reptiles? What about, you know, rodents? What about, you know, birds? All of that it's very different. So that's why, you know, having people understand the breakpoint concepts and the complexities of it and our lack of breakpoints for for most things, I would say, it's kind of important to get some advocacy out there to support getting more of those.

Lisa Fortier: 12:23

Yeah, well, no shortage of future research projects for anybody in the diagnostic laboratories. The other thing you talked about was, you know, it's difficult to get your information out of any system. When you're doing a retrospective, and in equine surgeries, I would do that but then your hospital changes systems. And then you're like, wait, what? And I can that can really set you back. But Claire, what sparked your research interest in antibiograms?

Claire Burbick: 12:51

So it's a little bit I think it was born from frustration. So which is kind of, again, try not to be like a negative Nancy here. But so in Washington, which is where I'm located, we have a lot of people in the universities here, University of Washington, WSU Department of Health, that are really, really interested in that one health concept. And part of that one health concept was focused on antimicrobial stewardship, and monitoring of resistance. And so we had this really beautiful plan to combine datasets, so we'd have human clinical data, we'd have that clinical data, we'd have data from the environment, because we can't ignore that part either. And then we would have these kind of antibiograms that would be, you know, allow us to really look holistically in the kind of a One Health approach to looking at this data. And so great, wonderful, we're compiling all this data, and then we're looking at it. And we're like, how do we do this? This is like, actually quite complex, because do we look, you know, are we looking at it for through the human lens? Are we looking at it through the veterinary lens, like which breakpoints do we use? Because if we're looking at it, you know, resistance impacting human health, then using vet breakpoints don't make a lot of sense. We also have breakpoints that are formulated a little bit different on the vet side, which might make things look a little bit more resistant than they actually are. And so it got to be very, very complicated. And actually, we had kind of a lot of angst over how to really do one health antibiograms, which I think is still a very, very worthwhile thing to pursue, but it really, and I think when you read the paper and you see, you know, you can't just use, you know, the state level data to really look at your individual practice. And so you're trying to figure out what population Are we talking about, you know, how does this impact my practice when we're looking at maybe tertiary care data, that's going to have a lot more potential resistant bacteria in the data set. And so it kind of that was sort of the genesis of being like, we really have to be very, very careful and transparent about what data is populating these antibiograms, how we're applying breakpoints appropriately, is it? You know, how are we using it? So we really have to have a very clear fit for purpose for how we do it, where the data is coming from, what breakpoints are appropriate for that particular situation. And so that was really kind of the start to, you know, trying to wrestle with, how do we do antibiograms in veterinary medicine that makes sense for people to actually use? Because I think that's really what we we would like to have is them provide that, you know, either clinic, or local or regional, you know, data that can really be used in practice, because, you know, as I've talked with veterinarians, especially recently, you know, they're they're very much, you know, have stewardship in mind, but they need it to be very applied, like they don't need to have, oh, yes, I mean, they know, it's a big problem, but they also are like, I need to actually treat a patient like I can't, that's really where my priority is. And so, you know, I think that's, that's where you go down the rabbit hole of trying to figure out, you know, how do we make this very relevant and useful. And we actually have to be very, very careful with how we put these together so that people can can really utilize them appropriately.

Lisa Fortier: 16:47

That's pretty complex, at over there awful quiet. What inspired you to get involved in the veterinary side of antibiograms and to write this manuscript?

Edie Marshall: 16:59

My program in California, has looked at trying to produce more tools for veterinarians in antimicrobial stewardship, you know, we became aware that on the human side, they use antibiograms, and they're often done maybe at a hospital level, or sometimes even in a department, like the ER, within a hospital. And how could we, as a state level programs start to try to move things in that direction. And we kind of talked about that in our the sister article that we have in JAVMA, and it'll be covered in a different podcast episode. But through our explorations of antibiograms in a one health context, we became familiar with all of the things that Claire has talked about just these complexities, the gaps, the need for additional information and resources to develop this information. And so in chatting with you, Lisa, about, you know, potentially publishing on our experience, the antibiograms, you had the idea to, you know, to make it a Currents in One Health article, and I really saw the opportunity to give people like Claire, who really in the depths of of these nuances, this opportunity, and as I think Claire said, a soapbox for kind of airing and bringing up all of these issues and discussion, so that it is transparent, so that we are aware of the pluses and minuses there. And what else is needed to really make these antibody programs and effective tool for veterinary antimicrobial stewardship.

Lisa Fortier: 18:42

That's fantastic. soapbox or not, it's all incredibly important information. Edie, what do you think is the most surprising finding from your manuscript, it might not be the biggest take home message, but what do you think was the most surprising?

Edie Marshall: 18:58

I think the surprising thing was how much we rely, to be honest on antimicrobial susceptibility test results. Without necessarily all of as Claire has also mentioned, the information we'd like to have to make those as fully useful as we want. So the realization that where an interpretation is provided that something is resistant, but actually that interpretation is based on human data, or data from another animal species. I think that's been really eye opening. For me, as a veterinarian throughout all of this and having been unaware of those kinds of things when I was in practice, and and using this susceptibility test data on a daily basis, and just not knowing necessarily what the limitations were. So I think, looking at that bigger picture and the complexities of it sort of like you can see where, you know, it becomes challenging and potentially a little frustrating to know where to go with that. And that's why we need to elevate this conversation so that we can start to fill those gaps.

Sarah Wright: 20:13

Talking about MICs and breakpoints really brings me back to second year vet school. Those words are almost like trigger words right now. My background is in zoo and aquatic medicine that was so I definitely appreciate you guys bring up the species nuances like you would, I guess, start my morning getting susceptibility results back from a bottlenose dolphin, and then a female Anaconda in the afternoon and then you have to have the data etc. So appreciate all the hard work that you're doing really means a lot. So Claire, how did your advanced training prepare you to write this manuscripts?

Claire Burbick: 20:46

I was thinking about this one a lot. Because I think, in a way, I mean, I think in general, one of the things that I realized as I did, you know, go through my residency and clinical microbiology and, and kind of all the nuance that you start to appreciate, in diagnostic testing. You know, I think a lot of times, we don't maybe remember the statistics that are behind things, the gray areas that are behind things, maybe we don't have the level of confidence and information and research for certain things that we think we should. And so I think, as I moved through my residency, and I'm like, oh, clearly, we know all the things about, you know, this pathogen, and we know all the things about that, and realizing, you know, as I kind of get into the weeds, that we don't have as much data, we don't have as much research. And so I think that, you know, kind of lit a fire, especially as I started wrestling with the susceptibility test data, what's there, what's not there? What does it actually mean? How confident are we in these predictions that are being made, that that's really, you know, kind of been the part that's allowed me to sort of, you know, go down the rabbit holes of this as, as I do, and realize that, you know, I'm in a unique position to do that, and then try and translate it so that other people don't have to do that, because it's, it's not something that I want veterinarians to have to do, because they have so many other things that are important. And so, you know, I think, how do we, you know, as specialists in these areas, try and become that translator so that the veterinarians can actually understand very concisely, like, what is the susceptibility test report mean, or not, you know, what, our breakpoint origins or not, you know, how do we, you know, make it more accessible and understandable to people that are actually utilizing the data. And so I think it, it's, you know, I didn't actually get very formal training in antimicrobial susceptibility testing. It's, I think, for us, as a profession, we don't, I think we're getting more people that are able to pass on this information, but, but I think we really are still kind of self taught in a lot of ways. I'm not sure I answered the question, great, but but I think it's, you know, it's more just being willing to go down those rabbit holes, and then try and translate that for, you know, people who aren't getting specialized training in clinical microbiology and what not.

Sarah Wright: 23:36

Being more on the clinical side of things, I can say, I appreciate you doing the translation and helping to understand what that means. Because, you know, you get reports back and and so many numbers, you're trying to figure out what's the best choice for my patients?

Claire Burbick: 23:47

It's like, you know, even just saying, like, to the best students, like, does this, you know, if a number eight is, you know, bigger than a less than or equal to point two, five, does that make you change? What drug you would choose? And they're like, yes. And I'm like, No, you don't, the numbers do not work that way. And so even just saying, what does an MIC mean? Do you have, you know, does that use, is it useful in, you know, making a clinical decision? And so, you know, it's like that kind of just very simple explaining the numbers, what are the definitions of S, I, and R? Because that's not totally, really clear. I think for some people, they might have some, some assumptions there, too. So, you know, I think there's just, you know, do I want them to, like go through and understand how breakpoints are, you know, generated and be able to do it themselves? Absolutely not. Do I want them to understand that there's, you know, all these different components that go into that? Yes, I think that is important. But so yeah, I think it's just trying to, to be able to provide as much of a resource for vets as possible for sure.

Sarah Wright: 24:55

And then this is a very important question if our listeners. Edie, what is one use information the veterinarian should know before discussing this topic with a client?

Edie Marshall: 25:04

I think it's really important for veterinarians to know that antibiograms are not meant to replace individual and microbial susceptibility testing, they are an adjunct, they are meant to kind of be another piece of information that a veterinarian might weigh, when they're making that therapeutic decision for an individual patient. Without doing that individuals susceptibility testing, then we don't have data to make antibody programs. So having antibiograms doesn't mean that you stop doing individual testing. In fact, you won't have antibiograms, or you'll have bad antibiograms if people don't continue to do individual testing. So it's important to keep doing that individual testing as much as possible and to help the clients really see the value. And then were available, using applicable antibiograms for your population to maybe help start that empiric therapy, just another tool in the toolbox, but not meant to replace individual animal testing.

Sarah Wright: 26:15

As veterinarians, we sure do love our toolboxes. And then from the other side of the relationship, what is one piece of information the client should know about this topic?

Edie Marshall: 26:26

I think clients have some awareness of resistance, I'll get on my own little soapbox here for a second. And when it comes to food animals and the food system, I think people do not understand the difference between residues and resistance. But I will now step off that, that soap box. So I think there is a little bit of an awareness out there. And I think it's worth veterinarians taking the time to explain to clients why resistance is important. And why doing this testing, then helps the veterinarian make a drug choice that will be best for the patient, but also for the population as a whole. Because if you pick a big gun in this animal, a big gun antibiotic for this patient, and it might work this time, but by using that more and more, it might not work in the future, and that's not going to come back, once you've got a lot of resistance, it's hard to get that to come back. So I think for clients is really important to recognize that there is antibiotic resistance out there, it is a real deal in individual animals and within households. And so doing this antimicrobial susceptibility testing, when recommended by the veterinarian can really help to tailor the treatment specifically, in ways that hopefully will help to try to prevent the development of resistance to those jobs.

Lisa Fortier: 28:02

Yeah, thank you both very much. We'd like to give our listeners a little flavor. And we like to learn a little bit more about the personal side. So we'll go back to Claire for a moment and say, you can clearly hear and feel your passion for your work, Claire, and you're obviously very accomplished Where did your resilience come from?

Claire Burbick: 28:22

So honestly, I think it's really just been kind of that intellectual engagement that has been has really driven me and I think also sort of the in I don't know that I called it one health, but the reason why I went to vet school is really because I felt like I could be more effective in medicine if I worked with animals, because I felt like there was so much interconnection between human and animals and disease that I just felt like I could be I don't know, I guess, more useful on the veterinary side than going into the human medical side. It just felt like I could accomplish a lot more diverse stuff and impact a lot more more in the world of infectious disease working on the animal side. And so I think I'm actually a horrible introvert, horrible social anxiety, so many of those things, but I think what's really, you know, kind of driven me to, to get out there and do this is it's just so interesting, it's so complicated. It's so impactful of an area for really being able to continue the level of you know, medicine and care that we provide and human and veterinary medicine. And so, to me it that kind of overcomes my own shyness and whatnot to just say, you know, this is so important, and we need so many people to be, you know, passionate and working in this area, and I do want to participate in all those efforts. And so I think that's really sort of tipped me towards It's, you know, really, you know, continuing to try and do you know what I can in this area. And thankfully there's, you know, more and more people to partner with and this and I really want to give a huge shout out to California for for really supporting this in a more structural way for the state. Because I think they've, they've been able to do a lot of work that a lot of states aren't are not able to do in this area. And so I really appreciate that they've brought in a lot of other folks into the, you know, working with them, it's been really great. And yeah, just having more partners is super critical. But yeah, so I think it's just more just like, oh, this is so interesting and exciting. The people working in this area are so passionate, and it's just been, you know, a really, really great area to work in.

Lisa Fortier: 30:51

Oh, thank you, as I said earlier, like, there's no shortage of items for you guys to solve, especially in veterinary medicine, eating the other one that our listeners love to listen to. And Sarah, and I always love to hear the answer to this to what is the oldest of the most interesting thing either in your desk drawer on top of your desk?

Edie Marshall: 31:10

So back when I was in practice, I would have clients say, Well, geez, Doc, can't you just, you know, prescribe something? Do you really have to do all those tests? And I would say, Well, you know, I wouldn't have to do those tests if I had a crystal ball. But I don't have a crystal ball. So now we need to do the tests. But I did wind up one day with a crystal ball, I'll be a small one. And actually along, it is now on top of my desk, but within my desk drawers is a magic wand. So for for those who don't want to go the science route, then we could bust out the crystal ball and the magic wand and hope that you know something magic will happen. Unfortunately, those things still don't serve me as well as I would have liked back when I was in practice.

Sarah Wright: 32:06

That's an awesome answer. We have not heard that before. That is a first and we have a lot of episodes right now. I think we have over 70. So kudos for you. That's That's excellent. Thank you very much. Claire and Edie, thank you again for joining us today and sharing your knowledge with our listeners and for sharing your manuscripts with AJVR.

Edie Marshall: 32:26

Our pleasure. Thanks for giving us this, you know platform not just with the podcast, but with the publications because I'm really excited by the opportunity to elevate into the conversation around antibiograms. And to been able to bring in experts like Claire to really help kind of make this more transparent and put it out in front of the veterinary community for further discussion.

Claire Burbick: 32:54

Yeah, thank you so much. This is this has been really great.

Sarah Wright: 32:58

And to our listeners, you can read Edie and Claire's manuscript on our journals website. I'm Sarah Wright with Dr. Lisa Fortier. We want to thank each of you for joining us on this episode of the veterinary vertex podcast. We love sharing cutting edge Veterinary Research with you and we want to hear from you. Be sure to leave us a rating and review on Apple podcasts or whatever platform you listen to.