 So, good morning, good afternoon, or good evening from where you are connecting with us in the world. And thank you very much for the colleagues that took the time to register and to actually attend this webinar. As some of you might already be familiar, we call this Knowledge Dissemination Dialogues on Webinars. It's a series of webinars co-organized by the AMR Working Group of FAO and the FAO Sustainable Livestock Technical Network, where we promote different colleagues work. And at the end, we call it dialogue because we like to be able to look at time for the discussion and potentially open new doors for collaborations between the speakers, FAO, the colleagues attending, etc, etc, etc. So, today we have the pleasure of having our colleague Peter Tambork, he's based in Denmark and he will be presenting some of the work that he has been doing in Denmark with a network called N of Art and the topic will be optimizing veterinary anti-virus use through development of treatment guidelines and clinical breakpoints. Just follow-up rules, please keep your microphone on mute. If needed, we name yourself with your organization and country, followed by your name, the name of the Zoom participant. Please note that the views presented are those of the speakers and not necessarily endorsed by FAO. Please refrain from advertising or services your company or any other commercial product or brand. And please post your questions in the chat. At the end we will read them out and if it's not possible to answer all of them during the webinar today, we'll follow up by email afterwards. A quick note that the meeting is being recorded and that the video and the PowerPoint presentations will be posted on the FAO YouTube channel and shared with the participants. So, with this said, I stop here. Thank you all and the floor is yours, Peter. Okay, thank you George. I will try to share my screen, hopefully it will work. Okay, can you see it? Yeah. Okay, yes. I have the title here, Optimizing Veterinary Antibiotic Use Through Development of Treatment, Guidelines and Clinical Breakpoints, as George said. And I'm very pleased to be here today to present some of the work that I and a lot of colleagues have been doing as part of the Innovate Network. I'm from the University of Copenhagen and Associate Professor in Veterinary Clinical Microbiology. So, what I will talk about will be first an introduction to Innovate to this network that George also mentioned. Because it's, you can say the frame for a lot of the work we have been doing on treatment guidelines and also to some extent the clinical breakpoints that I will talk about afterwards. And it will not just be the actual work on treatment guidelines and clinical breakpoints, but also some of the issues pertaining to that to development of how to do it and also some of the issues and some of the problems of doing it. And then of course afterwards, I'll be happy to take any questions you may have. So Innovate is an abbreviation and acronym for European Network for Optimization of Veterinary Antibiotic Treatment. It's a cost action network funded by cost, which is also known as the European cooperation in science and technology. So it's a EU funded networking. And what is funded is various networking activities including meetings, workshops, training schools, short term scientific missions where particularly young researchers can travel to other labs or other scientific environments to learn new methods and use and do something for Innovate. And then also funding for dissemination activities including publication feeds, webpage, press releases and so on. It's all about networking and no money for research, so that has to be attracted from other channels. Quite often it's existing research being done already in the different labs or different research environments that is being, you can say, put into a higher frame with this cost action network. Currently, we have more than 260 persons from 45 countries attending Innovate. And here you can see a map of the Innovate consortium. You can see most of Europe is covered. All the countries in green are what is known as cost countries, some of them are light green and known as near neighbor countries. A lot of different definitions that I will not go into too much detail about but you can see most of Europe is covered at the moment. People included are microbiologists, pharmacologists, veterinary practitioners, epidemiologists. We have some communication experts and so on. It's essentially no limits as to who can participate and both from academia and private organizations. We also have international partner countries not shown on this map but we have people represented from Australia and Canada, South Africa, Caribbean Island and United States. And it's an open network and a growing network. So it's possible to join the work. If, for example, any of you attending here today will be interested, you are more than welcome to either contact me or to go to the homepage innovate.eu to ask or to subscribe to a working group. So that was a bit about the frame for innovate but the aim of innovate is written here it is to optimize veterinary antimicrobial use with special emphasis on the development of animal and PC specific treatment guidelines and refinement of microbiological diagnostic procedures, combining this with diverse educational activities the action will contribute to build a larger critical mass experts in veterinary antimicrobial stewardship throughout Europe. So, a very long aim, as you can, can hear and see, but I tried to highlight the important parts here it's about development of treatment guidelines of practice guidelines for, and it's my global use. It's about diagnostic procedures, particularly development of clinical breakpoints but also multi tough criteria for bacterial identification, and then about education. And cost actions are known to. Well, if you have a cost action you need inclusiveness so it's a lot about including young researchers it's about geographical diversity, and it's about gender equality gender balance. So, so yeah, we have, especially the educational activities training schools and so on targeting the young scientists. So this is a per chart of the, the work being done by innovate the five working groups, and I'm not going to detail with with all the different squares you can see here. Just highlight some of them. See if I can get a pointer here. Working group one, we have, I will go in, I will mention in a moment as survey we have done on available treatment guidelines in Europe. And then I will mention some of the work we're doing and working group for to develop treatment guidelines, new treatment guidelines, and then I will end up with some of the work from working group three on development of clinical breakpoints. So let's start with antimicrobial treatment guidelines. So, as probably most of you are aware that quite a number of treatment guidelines available. A lot of international treatment guidelines, some of which you can see here books can be web pages it can be. Well, it could be anything leaflets it could be. Yeah, something you can only imagine what it could be. So some of the examples are shown here. And of course these are broadly available, and many of them are made by leading experts in the different fields. And they may be widely used. And because of that may also even establish consensus among beds about how to use and spot it for different purposes. I guess they're good, but there are also some limitations and probably the most important of which is that they don't take into consideration local factors. And some of these are listed here, it can be local resistance patterns, local availability of antibiotics, but also availability of diagnostic tools, local legislation. So different traditions and culture can also affect how these may be used or the effectiveness of these international treatment guidelines. So therefore in many ways, national treatment guidelines are preferable to the international ones. So here's an example of national treatment guideline how it was made using an example from, you can see my own backyard from from Denmark, where I was the editor for the treatment guideline for companion animals in Denmark. And this was some work that started back in 2010, where the Danish Veterinary Organization wanted a treatment guideline for companion animals, dogs and cats. And they gathered a lot of experts from Denmark on different fields or an expert on urinary tract infections, skin infections, and so on. Each of these experts had to write a chapter for their own expert field, and then they would need an external reviewer to assess that everything was fine. And then I as editor I tried to glue it all together and make it into what was in the first edition of the treatment guideline. I was inspired from the Swedish national guideline for companion animals at that time. That was because I was one of the few ones available back then. Then five years later, we wanted to make an update. So first we thought it would be a good idea to make a survey on how it had actually been used and if there was any impact on on this treatment guideline. And this survey was conducted amongst veterinary practitioners, and it showed that at least according to their response that there had been some impact that those who had actually used it and read it actually had a different practice towards use of antibiotics and in a good way, we would say. That was of course based on their responses, but we also could see from the Danish surveillance system, Dan map that you may know that the use of antibiotics that also changed in these five years that actually use of sephalosporins for companion animals had declined by two thirds in that time. So based on all that we made an update using more or less the same approach, almost the same authors told them to look at the available evidence see if there was something new, and an update the chapters and I think I also a new chapter was made apart from that. And you can see here this is a Chinese version you can see on the right here. And of course we didn't decide to make it in Chinese from the beginning we made it in Danish and then later we translated into Chinese, Polish, Slovene and English based on requests from from other veterinary organizations. And of course we are we are proud of this we are we're happy that it's being widely adapted but it's also, as I told you before it's not necessarily a good thing. Because Danish standards Danish drugs are not the same as necessarily the same as in other countries. Of course this may be better than nothing in some of the countries if no other guy exists but it's not ideal. And at the same time. This was even you can question the approach we used for making the guideline it was not. Well, it was our own approach. This was what we thought would work. And I think we have a good guideline but well it was not a standardized systematic approach. And this leads me to the next to the study here of innovate. This is a study by working group one, looking at the available guidelines in Europe for also for companion animals. Sorry, it's a lot about companion animals animals right now I promise there will be more on food animals later. But but this is a survey that was done and published last year. And this survey was to see what is, what are these, which guidelines exist what is how are they made what is the structure and what can be what can we learn from that. And here on the right. Maybe I should first acknowledge focus Alison you can see in the lower left he was from the UK Dr focus Alison was in charge of this study. We exploited the network of innovate, we had country representatives who checked in their home country if a national guideline existed and report it back. And then we, we, well, we tried to see what was out there in Europe and also contacting people from other countries not in innovative. So 40 countries were contacted, as you can see here. And then we had to omit some of them for not being sorry. First of all, I will say we got a response from seven 17 countries with some sort of guidelines. Afterwards we had to omit some of the available guidelines because various reasons are not eligible. Maybe they didn't provide specific recommendations for more overall general approach to antimicrobial stewardship. So, we ended up with 15 guidelines from 10 countries. And these were evaluated both in an objective and a subjective way. And here are some of the results some of the things were found from the evaluations on the objective results you can say it was shown that 11 of the 15 guidelines had suggested dosages. 14 had three suggested treatment durations 11 had potential adverse effects listed offense microbial use. And then we actually showed examples of when not to describe as microbes, because of course that's an important part of stewardship it is also to decide when it's not necessary. And then this table here you can actually see some of the examples of when and microwave should not be used at least some of the recommendations here, for example acute diarrhea and dogs. And one thing that all of them recommended not to use was another indication subclinical bacteria was something only approximately half of them recommended. And I can just mention, when it comes to treatment duration urinary tract infection in dogs recommendations was anything from three to 14 days for sporadic urinary tract infections infection. And of course this is a big change a big difference between the highest and lowest duration. And we could see that the newest guidelines with those with the shortest durations recommended just showing that over time recommendations actually change. So the authors raised some concerns based on this survey. First of all, relatively few countries in Europe have national guidelines. They were initiated were initiated by government mental initiatives that were all by other initiatives could be from veterinary organizations or something else but not from governments. There were large differences in structure and recommendations. Anything from leaflets to books were published. There was general failure to declare the evidence base and conflicts of interest. And then there was not enough follow up on implementation and effects of advanced microbial use. So it was concluded that the study provided a framework highlighting some of the fundamental stewardship principles that should be integral to future stewardship guidelines. And that a greater awareness of the need to use a structured approach to guideline development could improve the quality of such guidelines in the future. And this structured approach is actually what is central for working group for of innovative because working group for has the objectives you can see here. First of all to draft a standard for veterinary practice guidelines, and this has actually been done already and available on this link you can see here on how to make these guidelines. And remember here I call them practice guidelines, because it's not only about treatment is also about how to handle animals with infections in a broader context. And then provide high quality species and disease specific veterinary practice guidelines in a structured and transparent process and here, again a highlight, it should be a structured but also transparent way it should be made. And then promote these innovative guidelines international or local guidelines. This is work being done collaboration with different organizations we have the estimate study group for veterinary microbiology, the world small animal veterinary association and then also the international society for companion animal infectious diseases being involved. The organization of the work is shown here. In fact, you can see the spirit and yes, who is the chair of working group for coordinating all the work. And she is chair, you can say of seven drafting groups you can see below here. So the drafting groups are post weaning diarrhea, bovine mastitis, born respiratory disease, poultry coli bacillosis, surgical prophylaxis and hygiene, canine acute diarrhea and canine pyroderma. So, each of these groups I have to make some recommendations for for these different infections and so on. And they're not just let loose during their own thing they are under the control you can say of a methodology task force led by Dr. Lewis come. And this task force is made is established to ensure that it's done in the same way in a structured way. How did we select these topics. Well, they were based on the criteria you can see below amount and critical importance of antimicrobial used for treatment of the disease condition. Potential to impact animal and public health from antimicrobial use and then lack of similar European guidelines and I think you can all realize that for example, in cattle mastitis and respiratory infections are some of the most important infections requiring antimicrobial treatment. So the persons involved in each of these drafting groups were carefully selected by the leaders to have complementing expertise, both pharmacology and microbiology but also clinical clinicians were important, or are important. Had to fill out transparency declarations to make sure that it's all clear what what is their interest and what is their work. And then the group should include animal owners. So, not just scientists necessarily but also animal owners, for example, farmers, small animal owners and so on. I don't think any of the groups have them involved at this point, but they will have to be involved according to the process later when the guidelines are being evaluated. So this is the process. You can see here of the guideline development and sorry it's a little bit blurry but but I will just guide you through what we're doing. First of all, initially, the groups had to all the seven groups had to make foreground questions on management and interventions of infection. So, to raise all the questions of what do we want to achieve. What do we want to, where do we want to make an intervention and so on. The questions raised then had to be reviewed and first they prepared a protocol to be together with this methodology task force to make the right search strings and so on. And then, this is where we are now the groups are making reviews of the evidence pertaining to these questions. And finally, which will be by the end of this year and next year. This, these reviews will then be used in something called the great approach which is, you can see down below here grading of recommendations assessment development and evaluation. This is a systematic approach used previously for human treatment guidelines but now for the first time for veterinary guidelines, where the evidence for different recommendations are rated as good moderate or low direction of the recommendation, are we for or against this recommendation, and then the strengths of recommendation is also evaluated. And finally, after this great process the guidelines should be ready. And just to mention that it's okay that not everyone in a drafting group agrees but it will be transparent will be evident from the final recommendations if there is some disagreement in the groups. And finally just want to mention here that these reviews will be available, as I said, later this year or next year, and then the guidelines will follow in separate. I think articles, everything to be published in the veterinary journal. So, so look out when, when they arrive. Finally, we want to take these a little bit further because these are European, we call them treatment guidelines from European stakeholders. But we also want to make them national we want to help countries to adapt these general recommendations and make them international treatment guidelines and of course it's a European initiative but it's something that could go beyond. So, so I would just say that this is something that hopefully can have an impact beyond Europe. Okay, and I can see time is running fast but I will hopefully not go too much over my 30 minutes, I will jump to the next point which is clinical breakpoints, which is the use of zone diameters used by diagnostic laboratories to cast grass susceptibility testing results as either susceptible intermediate or resistant. So whether or not you can treat an animal based on diagnostic tests treat with antibiotics. So the clinical breakpoint should be specific for animal species, infection science bacterial species and the dosage you intend to use. Just an example here, we have a breakpoint here it's for pastorella motocida from respiratory infections in cattle. It's morphinical and here the breakpoint is MIC below or equal to one milligram per liter means that an isolate pastorella is susceptible to this drug. So just highlighting we have the bacterial species infection animal drug and the dosage. So I think in the interest of time I think I will go quickly through this is better on how breakpoints are defined using the vet cast approach. I'm chair of that cast which is the you cast veterinary subcommittee for susceptibility and this is the approach used to make clinical breakpoints you need three cutoff values MIC cutoff values and essentially based on these you decide on the clinical breakpoint. And instead of explaining a whole lot about what these cutoff values are just mentioned that it's actually a lot of data needed to create them a lot of MIC data pharmacokinetic data for animal trials and and so on. So the internationally recognized clinical breakpoints existing. Well, it's not a lot. We have we have, I would say, in my view, what I know of, at least is the CLSI breakpoints that you can see here this is the latest edition as I recall the beta one s. And they also have other documents CLSI but they're not the breakpoints there are not as you can say validated as a once in this beta one s document. A bedcast is also working on clinical breakpoints currently you have one for floor clinical and we are working in progress to create other clinical breakpoints. So this table you can see here on the right. It shows the available clinical breakpoints in veterinary medicine for from CLSI. And you can see on the top row here can see the different animal species. And then you can see on the left you can see the different antibiotics for which breakpoints exist and then you can see in the actual table, which target pathogens and which infections these breakpoints are directed at. I think it's pretty clear that there are some gaps. So, some of all the empty fields means that there is no breakpoint for this animal species, for example, for cat and cifridoxin it's empty meaning no clinical breakpoint. And in some cases it makes sense. Because some of the drugs are specific for more or less only used in some animals, for example, go down to some of these to less from icing for example it's not used for companion animals. So it makes sense we don't have breakpoints for for those, but instead for production animals, food animals, but in other cases, well we need the breakpoints so what do we do when we have a situation where breakpoint is missing. And we just use another breakpoint, or what. And this is not super easy answer question to answer, I will just mention that it can create problems and I have an example here illustrating this. So here you can see part of this CLSI breakpoint table you can see on the top here we have breakpoint table for pastoral and we'll talk to that in cattle. And below here, we have a table for actinobacillus bleodemonia in in pigs. And the table here, the tables are both actually show breakpoints for to less from icing against respiratory infections, both for cattle and for pigs. But at the same time they also show different breakpoints. So here, you can see the breakpoints for this diffusion, what corresponds to susceptible intermediate or resistant is not the same as you see in in pigs so cattle and pigs are different. So this means that, for example, if you have a zone diameter of 12 millimeter when you test susceptibility to to less from icing. Pastoral and will talk to that would be resistant. If it's from cattle but if it's an actinobacillus bleodemonia it would be susceptible. In other words, you can say this is fine. I mean now we have the breakpoint so why care about this but just imagine if we didn't have the breakpoint for for example cattle. There would be a risk. If we just use to the pick breakpoint that we would have it false susceptible and we would treat with an antibiotic when it was not possible. It's a situation that you risk when you use breakpoints from other animal species or other infections. So what to do when you lack a clinical breakpoint. Well, what you saw is actually one of the possibilities to use a clinical breakpoint for another animal species, but also it could be for another bacterial species in the same animal. The infection site for humans could be an egg off. It could also be for another dosage or though that's not really recommended because these breakpoints are highly specific for certain dosage. Actually the best thing would be to report no interpretation. If you lack a specific clinical breakpoint. We're not really interested in that it's diagnostic labs we want to report a result. And I just want to highlight here again CLSI has made a document called the bed online, giving some general recommendations and suggestions on what to do when a breakpoint is lacking. So this is at least one way to go where you can see what would be recommended in a specific situation, but even that document has no real solution so we need to develop new clinical breakpoints. And one of my last slides is just to highlight that that cast is working towards new clinical breakpoints of course CLSI is also continually doing that but I'm not from CLSI so I cannot mention too much about what they are actually doing or planning but the cast is prioritizing clinical breakpoints in different ways. Of course we're looking at the data gaps, where do we have the gaps in the table. What is highly needed, what would be have a big impact if we made a breakpoint here. So we need to be realistic and look at what do we have data for funding for because it's expensive to make breakpoints and that cast is not funded in any way, except for donations or whatever we can attract, but it's not. It doesn't have a basic funding for anything. So we have to look at data being available already, or we have to design new research. Of course we also have to consider what we have the expertise for, because it's not always that easy to make clinical breakpoints for animals, because we have to consider other things. We have to consider flock treatment, which is of course not a thing in human medicine, and so on. There are a few things that are different in veterinary medicine. And we produce data, pharmacokinetic data from animal trials, MIC data, and then we model data, PKPD modeling, and then we make the PKPD breakpoints, and then decide on the clinical breakpoints in the end. And this work is done in collaboration again with Enovat, this time the working group three. And you can say there's a lot of overlap between bedcast and this working group, some of the same people being involved. But Enovat has a capability to also fund training schools. So we have Enovat has made a training school, this is what you can see here, a picture from part of last year, where we had just over 20 people attending a training school in basic PKPD. So one of the quite important topics to make breakpoints, for example. Working groups three of Enovat has also made a survey to ask what breakpoints would actually be needed or wanted by end users. So clinicians or microbiologists from diagnostic labs and so on. And I will just end up with the results here, because this is not yet published but this is what came out of this survey. Because one thing is what a little steering committee wants in terms of breakpoints. Another thing is what the wider community would like for breakpoints. And here you can see results for cattle and pigs. So for cattle. First of all, there was a demand for breakpoints for respiratory tract infections and mastitis and for pigs, mainly for gastrointestinal infection and respiratory infections. And here you can see the two figures here, you can see what drugs, which drugs the responders would like breakpoints for. You can see, both for pigs, but also for cattle, the two most wanted drugs are sulfur, trimethoprim combinations and penicillin. This is actually, well, it's understandable, because sulfur TMP is something for which there are no veterinary breakpoints at all. So whenever you test for sulfur TMP susceptibility using veterinary isolate, it would be a human breakpoint. So yes, I understand why it's in demand, but it's also complex, because it's a combination and there's a synergy between the two drugs. So it's not very easy to make a breakpoint for this combination. But it's, at least we have noted, hopefully we'll publish it and maybe we'll have the time and the funding to use or to work on such breakpoints. Also for gastrointestinal infections in pigs, it's interesting because there are no breakpoints for gastrointestinal infections. It can actually be considered topical treatment almost because you take a pill, you ingest powder, whatever. And then it ends up directly where the pathogens are. And actually, this is not a typical, you can say, way normally is for systemic use of antibiotics when we make clinical breakpoints. So this is also something new that we need to have a look at if we can make breakpoints for gastrointestinal infections. Okay, and that cast is of course the European initiative under the under you cast. But again, I would like to emphasize here that is not a closed group European group is something anyone can contribute to probably a lot of you know already that you cast is also expanding worldwide and that cast I don't see any reason why that cast cannot do so also. So if anyone is interested, we're always open for people interested in collaborating, providing data. Helping with modeling of data, providing input, expert input or questions on some certain topic, but also for teaching, we can, of course, consider people from outside Europe. And of course, when our breakpoints become available, they can be used anywhere as long as the protocol and guidelines of that cast are followed. And I think that's it from me and I apologize for going a little bit over time. But yeah, I'll be happy to take any questions. Thank you very much, Peter. It was excellent. And you made it. I think many colleagues both clinicians and working on regulatory aspects, for example, could relate with many of the aspects that that you raised. You opened some interesting doors for collaborations in the future. So thank you very much for that. We have several questions about minutes for questions. We'll try to address most of them. And if not, as we said in the beginning, the materials will be shared on the field channels and we'll follow up by email on the questions that we cannot address in the webinar. One of the first questions that came in was if you could please clarify the relationship between if there's any between NOVAT and the clinical laboratory standards institute, the CLSI. If NOVAT is affiliated with CLSI. No, it's not. So you can say NOVAT is about... Well, we have the working group three working on clinical breakpoints, as I mentioned, and you can say actually originally NOVAT was the idea came from bedcast that we wanted to make a cost action. And then it was just broadened into something with treatment guidelines and so on. So it's based on an initiative from bedcast. But it doesn't, of course, exclude CLSI. So I mean, bedcasts in general, but also NOVAT is interested in collaborating with CLSI. And we have contacts. I have contact with Mike Papich and other people from CLSI. We regularly interact. But of course, they do their work and we do our work, but every now and then we exchange views and so on. Okay, thank you very much. Then we have a question that many clinicians face in the field. If there's any guideline about when you should switch to a second or antibiotic, meaning you are thinking, for example, a respiratory tract infection, you tried the first antibiotic of your choice and then it didn't work. So the colleague was wondering if you came across guidelines on when should I switch or should I try something else? Yeah, that's a good question. And actually, I sometimes wonder myself because we have in Denmark a treatment guideline for horses where we have the first, second and third choice. And sometimes I wonder when did you ever select the third choice? But I would say, first of all, I am not aware of the specific guideline because they can be made in many different ways. But in general, I would say a second choice would be if you have tried before treating an animal with the first choice and you have, you've seen it didn't respond and you want to treat it empirically again. I think then you can argue, okay, maybe I should use a second choice because the first choice didn't work. You can also say if it's an animal that it's from, I mean, it has an unknown treatment background. You can also say, okay, well, we know it's been treated many times it failed. So maybe we should go a little bit higher this time. But it could also be a seriously ill animal. It could be an animal that where you cannot, a failure is not an option, a highly valuable animal maybe. And then it would be worthwhile to go with the second or third choice, which would usually be more broad spectrum or more critically important. I don't think there's a clear definition, but actually it's maybe some one of the things that should be more clear from from the guidelines actually when you can go for that. I think this is an important point. All right. Thank you very much. That's there's some questions that several colleagues asked if the CLSI guidelines are available for public download my impression is that they aren't. But can you please clarify if the colleagues that are interested in downloading them. The last question that you presented, are they publicly available or not. Well they are. I think they're not. It's not easy to find them but actually you can go to the CLSI homepage and then you can. I'm not sure you can download them as such as a PDF, but you can actually go page by page and see the recommendation which is a little bit tedious. But I think that should be possible. But I would recommend that you contact the CLSI to to get that information but but certainly actually after that cast started some years back. This was actually a criticism of CLSI that was only available for purchase and then since then, to my understanding it has been available. Access and public availability. A couple of questions on alternatives if you if you have come across if there are guidelines for any alternatives to antimicrobials in the treatment of animal species so guidelines for alternatives to antimicrobials if you have any experience on this or availability on them. Well, I'm not sure I have a guideline specifically on alternatives. At least I'm not aware of that. But I think definitely guidelines like I mentioned before that they should. As I wrote, as I mentioned before that 15 out of 15 guidelines had examples of when not use antibiotic treatment, and they should, of course, also mention what could be done instead. And I know for Danish guideline for companion animals, for example, acute diarrhea. I think we've listed six or seven other alternative options on what to do when you face an animal with this problem. We don't just say, don't, don't treat with antibiotics and then find information elsewhere. So I hope that most other guidelines to the same, but I'm not aware and I'm not aware of any specific guidelines for completely alternative treatment. All right, great. There are several places which is wonderful to see many colleagues are interested in further collaboration, and also engaging in teaching and research. So you mentioned that the colleagues can join via the website that you mentioned and we will share the presentation. And at the end, we will also share the contact information if colleagues want to follow up. So that's, that's very good to see the purpose of one of the purpose of this webinar. I have a question from a colleague that is mentioning that they are monitoring the prevalence of resistant commensal E. coli from dairy cow feces through microbroth dilution method. Can they use the forecast clinical breakpoint. Well, that would be then for for human infections and actually, well, you can use whatever break point you want. I mean, you can say, you can argue here that if it's a commensal, it's not for, I mean, you're not talking clinical treatment anyway. It doesn't matter so much if it's a veterinary human breakpoint. I think the most important thing is that you're whenever you publish something that you're very transparent about the breakpoints you use and mention why did you use these and not those. And then for surveillance in many cases the, it costs the epidemiological cutouts would be a good choice, because it shows the distinguish between wild type and non wild type and I think that, at least for surveillance purposes would be a good choice and that's you can say universal that's not between veterinarian human. One is sometimes confusion on this and I think that you can help all of us clarify in this point. What is the relationship between the clinical breakpoint and the antimicrobial susceptibility testing. So there are two words that use a lot and we hear a lot. If you could clarify what does it mean or how they are related determining the clinical breakpoint and when we speak about antimicrobial susceptibility testing. I'm not sure I understand the question. Can you repeat it or I mean the relationship between clinical breakpoint and susceptibility testing. Yeah, that is the question. I will try to answer but but I mean you do susceptibility testing you get an MIC you get at this diffusion zone diameter, and that you need to interpret. Of course you can say one is lower than, than 18 and then something. But what does it mean. So you need some of these limits to define whether it's susceptible or resistant or intermediate meaning that you could probably increase the dosage and have an So that's the sort of, yeah, borders of when it's on how you can interpret your results but but it's a good question and it's something. I think a lot of people, I mean, I know personally vets who do their own, for example, this diffusion in their own practice and then they look at the zone diameter of the plate. Okay, there's a large zone diameter, okay, it's susceptible and a small zone diameter or no inhibition zone, then it's resistant. And, and this is something I mean that you can say it makes sense intuitively, the more inhibition, the more efficient the antibiotic is, but it's just not good enough you need, because it doesn't correlate to necessarily what happens in the animal. So you need some breakpoints and also the needs. I mean it could depend on the strengths of the disk you use on the disk diffusion. So you really need to use some breakpoints when you want to use it for guiding treatment. Okay. So this is, you come across these different guidelines, and a click is asking, okay, so that has these different possibilities, and which standard to use when performing antimicrobial resistance surveillance the your cast and or the CLSI and why. So that that might be a question that comes up. Like, we know the options, which ones to use and why. Yeah, I think again it depends on the scope of the surveillance. I think if it's, when we talk surveillance of indicator bacteria again it could be you can use it. And then depending on the logical cut offs and then I think those that you can find publicly available often you cast but they inferior they should be universal they shouldn't be different between organizations. But when it comes to clinical breakpoints, I would say, I mean, the only validated clinical breakpoints are those from CLSI when we talk about animal infectious agents about animal bacteria. So, I would say then use those whenever they are available. But then the problem is if you have, let's say you have a Nikolai from whatever pig thesis, for example, from from infections from diarrhea and pigs and you want to make a table of resistance. So let's just face that we made something similar. Just a few days ago for the Danish surveillance at Denmark report we have 150 clinical E. coli from pigs diarrhea. And then we want to publish resistance data, and it's not easy because you don't have a breakpoint for. First of all, as I said, we don't have any insertic breakpoints. And then we have to use other breakpoints from veterinary side, but sometimes we don't even have a veterinary breakpoint. If it's from a, you know, some drugs are only for human use. Then we have to use a human clinical breakpoint or any cough. And it's actually, I don't have a universal idea of what is the best approach, except to write what breakpoints you actually used. And especially if you want to compare data to previous years like we are doing, then you have to calculate it in the same way or if you want to compare between studies, be very careful, because often when you compare between studies breakpoints are different. So it's a lot of potential risks of over under interpreting data. Yeah, I know it's another is not very clear answer, but it's also very complex area. Since we have a global audience. The question is, are the guidelines that you have been mentioning location independent, that is, in the same guidelines be applied in any week and this is particularly relevant. So I think you mentioned this in your presentation, but could you please clarify this if there's guidelines in one region can or should they be applied in another region of the world. I think if it when it comes to the innovative guidelines that we are making now. I mean, they are, they, we call them European guidelines because it's a European initiative and most of the people working on it are European but they don't look for European literature. I mean they look for literature at the reviews right now across the world. And they also have experts from outside Europe. So these guidelines when they become available for these specific infections infections post weaning diary and pigs and cattle respirator infections and so on. Then they can be applied anywhere and be, you can say, adapted into national guidelines and the principles of those can be taken and used to make national guidelines. So, but, but of course if a certain drug is recommended and it's not available in your country. Well, then you would need to, of course, adapt it and maybe consult with those who made the guidelines and ask if it's not clear what could be another option for treatment here. Great. Thank you, Peter. A question on some some these two words sometimes get mixed and if you could please clarify the difference between a clinical breakpoint and they cough the epidemiological cutoff. And when do we exactly should use each one of them. I think this is a question about that many colleagues have so if you could please use this time to clarify that. Okay. Yeah, so I make off is is. Well, maybe I should, I actually omitted a slide on this because I thought it was a bit too complex maybe I should have included it as a backup slide but anyway, and it covers is defining the upper end of the wild type population so population of bacteria without a quiet resistance. So the highest MIC you have amongst the wild type without this acquired resistance, these phenotypically detectable phenotypic resistant that's the a cough. So it's very, you can say, well, it's not based on anything related to how the drug is absorbed and how it reaches a certain infection site and, and so on. So that's, you can use it for surveillance you can say well it's resistant or not resistant it's a quiet resistance or not. But a clinical breakpoint is something that's supposed to guide treatment of infections. So therefore you need to know I mean one thing is that it's, let's say it's susceptible according to an a cough. Okay, so if it's susceptible according to a neck of it's a wild type organism. But, but let's say if it's not absorbed from the God, and you want to treat it as respiratory infection. Then it doesn't matter if it's a set susceptible according to the a cough, then you cannot use it anyway, so it's resistant according to the clinical breakpoint, because it takes into account the absorption the distribution elimination and all sorts of other things that are not taken into account by any cough and this is also why the clinical breakpoints have to be specific for animals and so on because different animals have different rates of absorption and other pharmacokinetic traits. Thank you Peter and we are very thankful for all the questions that the colleagues posted that reflects the interest on these topics. And we will not unfortunately be able to address all of them policies in advance for that but we can follow up by email and Peter is available we are available to make the further connections. The last question before we close up is on the, you mentioned that one of the conclusions if I understood correctly was on the leg that there is these guidelines but then there's a still a lack on the follow up on the actual implementation of the guidelines and even more than that the actual impact on the different antimicrobial use. So the question would be, is there any planned work on to cover these these gaps that the implementation gap of some of the guidelines that you came across. And if they actually are reflected on the different antimicrobial use in meeting quantity or the different classes used if there's any planned work on these aspects. So I guess it's about the end of that guidelines of implementation of those. Yeah. I'm afraid we are running out of time when it comes to innovate also, because we have until the end of next year. So we have still one and a half year almost to complete the reviews ongoing and the guidelines. The plan is in the objectives is also to try and implement the guidelines in countries that don't have guidelines so, so we will help with that is a bit diffusely described in the application in the memorandum of understanding. So that's certainly the plan. So, so hopefully next year and actually we have a possibility to extend the action half a year so maybe with a bit of luck we have two years left. Hopefully we can, we can once the guidelines are ready try and help to move them a bit forward because one thing is to have a European and innovate guideline but it I mean you want we really want to implement them we want to have to make them work. I mean, it's not just a publication to us it's also something we want to be used. Yeah, so it's to. So it's not any concrete not any specific plans, but certainly something that we will end to do probably I would say in a year's time from now we'll start considering that because hopefully by then, most of these treatment guidelines should be available. So thank you for your presentation and for the fruitful discussion and all the collaborations that all the clarification I think it was very useful to some common understanding of terminology of the concepts and and the work that you congratulations to all the network colleagues that they've been working hard and as you said, this is a network so you have all have to put your own time to come up with these answers and find funding for the work that you do. I think we as a technical community can be thankful for the work that you are doing so thank you for participation on this. And just before we close up sharing what's coming up for next to this webinar the knowledge determination dialogue are organized always in the second Thursday of the month. And so the next one is 11 August, and it will be on antifungal resistance in agriculture by the colleague Lawrence could reach based on the anniversary of wealth in Canada so at the same time the lunchtime in the central European and August 12 also the second Thursday and many colleagues expressed interest in following up on different topics so you can always reach us via this email.com or will slash iPhone resistance at fio.org to if you have speakers or any other suggestion will be happy to take them on board. So thank you all, and we'll follow up in the field.