Thank you very much. So, yeah, as Bruce has introduced me, I'll be talking to you guys about, cutting the use of antibiotics this evening. And, just to introduce myself, I, like Bruce said, said, I'm a first opinion practise vet, I'm working for Langford Vets, which is associated with the University of Bristol.

And before that, I did a residency here at Bristol working towards a European College diploma in bovine Health Management. And during that time, I managed to gain an awareness of evidence-based medicine and hopefully using that now, and I did a research project into reducing The use of high priority critically important antibiotics on dairy farms. And so what, some of the research I have been involved with as well as that, has been looking at stakeholder beliefs about antibiotic use in livestock and measuring antibiotic use on farms using different metrics.

So I guess that's one of the reasons I'm speaking to you guys this evening. But actually, like I said, I am ultimately just the first opinion practise vets, but I do work with a really great team of people here at the University of Bristol. Here's a picture of some of them.

And I've managed to work with A lot of them writing papers, talking to them, and these guys really are working at the forefront of this area of antimicrobial use in livestock systems. And in talking to them and working with them, I've been able to learn a lot from them, and I've been able to organise some of this information and ideas that They have, and, I've managed to think about some of these bigger questions about antibiotic use and antibiotic resistance. And some of those ideas and thoughts are filtered down into my everyday practise and how I think about my practise and how I teach the students that I work with and how I communicate with the farmers that I work with.

And so what I'd like to do in this webinar really is just try to distil some of those thoughts and ideas and questions that I've got and pass them on to you guys. Although I do have to warn you that you probably want to end up with more questions than, at the end of this webinar that you have at the beginning, because that is the nature of this area of research, I'm afraid. So just an idea of what I'm gonna be talking about this evening is to firstly know what the high priority critically important antibiotics are and why they're categorised as such.

And also to be aware of different metrics that you can use to measure antibiotic use on farm. I'm gonna talk about. That in quite a practical way, hopefully.

And to be aware of the advantages and disadvantages of those metrics, to be aware of different ways that the metrics can show a reduction or change in antibiotic use and how that can appear using different metrics. And also then go on to consider how changing antibiotic use might influence antibiotic resistance prevalence on farms, as well as in the environment and even in the human population. And the first four points of the web are gonna be the first half of the webinar and the last one really is kind of the second half of the webinar.

So let's start with the bigger picture. As I'm sure you're aware, the predicted, threat of antibiotic resistance to humans is really a global concern. And this figure is reproduced from the O'Neill Commission report which was published in 2016, and this report predicts that the impact of antimicrobial resistance.

Will be so great going forwards that by 2050, antimicrobial resistance will be the biggest cause of human death, surpassing even cancer. So you can see that the scale of this issue is huge and there's increasing calls for action to be taken now in all sectors, not just the medical ones. And so, in the livestock sector, at the beginning of the year, the government published an updated plan on the government strategy to contain and control antimicrobial resistance.

And within this, there was a section specifically relating to the use of antimicrobials in the livestock sector. And in it, the government commits to working with vets and farmers to reduce antibiotic use in animals by 25% between 2016 and 2020. So time is ticking on this, and the government and the public do want us to do something about it.

Now with the current estimate being that about 7% of all antimicrobials being used in animals in the UK are being used in pets, that leaves us farm vets responsible for probably much of the remaining 93% of antimicrobials being used in animals. And so it's definitely something that we should, as a profession, be aware of. So before I continue, I just wanted to clarify one term that you'll hear me repeat and refer to quite a lot through the webinar, and that's the high priority critically important antimicrobials, or the HPCIAs.

This is a term which has been defined by lots of different groups and agencies, and you can see here the definition for which according To the European Medicines Agency, and that is that these are antimicrobials for which the risk to public health from veterinary use is only acceptable, provided that specific restrictions are placed on their use, and that they should only be used when there are no alternative antimicrobials authorised for the respective target species and indication. And just to be clear, in the UK these are the fluoroquinolones, the 3rd and 4th generation cephalosporins and calistin. So It's also worth knowing that this is, this list is often reviewed and regularly reviewed, but that there are other groups of antimicrobials which are kind of on the watch list and there are other agencies, namely the World Health organisation that's categorised other classes of antimicrobials as being highly important to human health.

For example, you can see here in this table, which is lifted from the NOAA briefing on CIAs. And this lists aminoglycosides and broad-spectrum penicillin, so that would be coamoxyla, for example. They're listed there in brackets, and that's because these classes of drugs are still under review as to whether they should be classed as category 2.

And class category 2 drugs, as you can see, are should be restricted to use where there are no alternatives or response to alternative, alternatives is expected to be poor. And so like I said, there's no currently no advised restrictions on the use of those antimicrobials, but it's just worth being aware that these things are being reviewed constantly. So now we know what their HPCIAs are, we should be aware of what steps are being taken to reduce the use of them in the livestock sector more broadly.

There have already been big inroads made in the poultry sector, particularly. The British Poultry Council, which is responsible for 90% of All UK poultry meat has already implemented bans on cephalosporins and flocks for poultry meat, bans on fluoroquinolone use in DL chicks, and a cease in cholein use. And that's resulted in 82% total antimicrobial use decrease between 2012 and 2017.

And as you can see, 91% decrease in the critically important antimicrobials. And there's also in other those sectors, the egg sector, there's mandatory reporting of antibiotic use and in the pig sector there's mandatory reporting via an electronic medicines book. So these sectors already have quite good ability to accurately measure the antibiotics being used in that, in these sectors.

So what about cattle and sheep? Well, there's already been requirements to at least review our medicines use in this in these sectors, and ideally to reduce our medicines use. And the use of certain antibiotics has already been restricted by some retailers.

And the red tractor scheme, which enforced a restriction on the use of the HPCIAs in June of last year, did really go quite a long way to, to implement the restriction of these certain antibiotics. And I think, made these changes and talking about These changes in antibiotic use on these farms, kind of a social norm for both vets and farmers. So things are changing, but the question is, are we or are the farmers changing antibiotic use just because we have to or because we want to and we want to understand that?

And are we as vets using these opportunities that these changes enforced changes provide to have constructive conversations with farmers about antibiotic use on their farms? And I think as a profession, we should be looking beyond these enforced changes in antibiotic use and start thinking about what more we can do to use the antibiotics responsibly. But the question is, how do we know what we should be doing and what changes actually make the biggest difference?

So even if we're just working with a few farmers and doing the red tractor schemes, we are all doing these medicine reviews now. But are they just a tick box exercise and do we use them to their full potential? So I think to be able to use the information, you need to be able to collect it and vet practise sales records are likely to be the most accurate and easiest way of doing.

In fact, a colleague of mine at the University of Bristol called Gwen Rees is about to publish some work from her PhD thesis, which demonstrates that vet sales data is the most reliable way of measuring antibiotic use on farms. And I'm sure you could all predict in her study, she found that on-farm medicines records were commonly significantly different from actual antibiotic use on the farm. So as a minimum requirement, at least a red tractor, you need to have a list of product names that are being used on the farm.

In the simplest form, this could just be a tally of bottles or tubes. This, of course, only gives limited information. And so one other thing that you could do to add value to doing this with the farm is also to look at the list of medicines used in the previous 12 months.

And so that can give you an idea of how things might have changed year on year. Of course, just doing a tally of bottles or tubes does assume that the number of animals on the farm is the same year on year. But you can, if you know that the number of animals has changed significantly, you can just do kind of a quick calculation and divide the medicines used by the number of animals on the farm, and it's kind of a reasonably simple way of just working out a bottle per animal per year kind of a rate or similar.

And then you can measure, the antibiotic use on that farm in a, in a meaningful way. So that's fine if they haven't dramatically changed antibiotic use over time, and it's kind of a quick and dirty way of assessing antibiotic use, but it might reveal more about what's changing on the farm, rather than just a list of one year's, one year's use. So now we've already talked about calculating more than just the bottles or tubes per year at the top there.

And as I mentioned, to compare for a changing population, you might need to divide by the number of animals on the farm to use like a bottles per year, per animal per year metric. But there's lots of other ways to pull out different information and it might, that might be more suitable for different situations or different systems. So for example, if you wanted to compare the total amount of antibiotics used year on year, you might want to look at total milligrammes used per year.

But as I've already said, this would be highly influenced by the number of animals on the farm. So milligrammes per kilogramme is another metric that's commonly used, both in the literature and in like industry stats. And of course, this does require an idea of how many animals are on the farm, which might be easier for some systems than others, and also how much these animals weigh, which generally isn't so easy.

And this is why the standard weights have been advised by the veterinary medicines directorate and to be used in these kind of calculations, and the weights for different animal species and different stages of production have been given an average weight of an animal over its lifetime. So you can see in the graphic here. Yeah, it's a little bit small, but you can see that there's some examples there of different average weights which have been assigned to different species and different production systems.

And so you can use that and that allows a kind of a 1 milligrammes per kilogramme calculation to be done just according to the average weight of animals in a specific population. And this calculation is known as the Migs per PCU, which is the population corrective unit. So you might see that on some of the industry statistics.

And the eagle-eyed among you will have already spotted that that was a metric that was shown in the graphs I showed you before from the British Poultry Council antibiotic report. So just to be aware of that metric and what it means really. So so far I've just spoken about measuring total milligrammes or milligrammes per kilo.

But of course, depending on what antibiotic is used, a certain number of milligrammes could treat very different numbers of animals. So some are at a dose rate of 10 mg per kg, whereas other antibiotics are used at 50 mg per kg. So for this reason, dose metrics have also been widely used and They have both advantages and disadvantages, but probably it's more important to know what the limitations are of such a metric than actually what we're using it for.

So the graphs here demonstrate the same data, which is the main antibiotic use on 7 dairy farms across the 5 years shown there. And you can see on the left axis shows the data in milligrammes per kilo, and you can see the amount of critically important antimicrobials shown in orange represents quite a small proportion of the antibiotics used on those farms, whereas the right hand graph. Shows the same data but in a dose doseba metric.

And you can see on that, on these on that right hand graph, the critically important antimicrobials accounts for a much larger proportion of the doses of antibiotics prescribed to animals on these farms. So we do need to think which of these metrics is quote unquote better. But it depends what you're using the information for.

If you're trying to argue that these farms haven't used many critically important antimicrobials, then you want to be looking at the left hand graph. But maybe the right hand graph is a bit more of a real term descriptor for vets and farmers who can, you know, we can get our heads around the ideas of numbers of doses in animals a little bit easier. The problem with both of these metrics, which are obviously farm level, is that you don't know still what animals the medicines actually went into, or what constitutes a dose on an individual farm or how frequently the antibiotics were given and in what form.

So all that information is still information that you would have to extract from the farmer whilst doing a medicines review to really, get down into what's really going on on the farm. And while there are standardised dose metrics, like you might have heard of animal daily doses or defined daily doses, it's also possible to calculate a dose-based metric just for an individual farm, particularly if a farm uses certain medicines to treat a certain population or certain condition. And yeah, so these dose-based metrics are particularly useful if a farm is changing its medicine use over time.

So I've just, put out an example here for you. So I'll just talk you through it. So you can see this is a farm that you might be doing a medicines review from 2017 and 2018 and have that data to 2018, 2019 and have that data.

And maybe as per red tractor recommendations they've they've used from, moved from using a combination of both pen strep and ceftiure as systemic and injectable antimicrobials that they use in their animals towards using more first line pen strep. And moved away from the use of fuel. So you can see here that if you've ever used 5 bottles of hand strap and 9 bottles of cetyfu, that will have been sold in 14 bottles of antibiotic in total.

And just over here, you can see how I've calculate the dose doses of that. So, based on a meal per 25 kg and a 600 kg cow, they've used 20.8 doses of henstrep and 75 doses of Satyure.

Whereas in 2018 and 2019, they've moved to using a lot more pen strep, 20 bottles, only one bottle of Safiaure. But that has actually upped the number of bottles that they've been sold to 21. So if you're just looking at bottles of medicines, you might conclude that they're using almost a third, again, the antimicrobial use in this year than they did last year.

Whereas actually because of the The way that they're using and the different types of antibiotics they're using, the doses of antimicrobials they used has stayed very similar and actually slightly decreased between those two years. So again, it is important that you just understand the numbers or sort of the information behind the numbers that you're calculating or given by certain, reports that you might be looking at. And so you don't have to do this necessarily for yourself.

There is an online calculator, I'm sure you're aware, that's been produced by the AHDB dairy alongside Nottingham University. And so you can just have a look at that, type in the, you know, bottles that are being used on a farm, that will give you those space metrics which might make more valuable information for you to discuss with your farmers. So these graphs just demonstrate how different analysis will affect a different farm's performance when benchmarking farms against each other.

So you can see here that you've got on the left-hand graphs, the total use of antimicrobials across different farms represented by different letters. And on the right-hand graphs, just the high priority antimicrobials, and that's how they've been benchmarked. Top graphs are total milligrammes per kilogramme, and the bottom graphs are dose space metric defined daily doses.

So you can see here that when measured in total milligrammes per kilo, farm E is the highest user of antimicrobials, whereas farm A, it uses the highest number of doses of antimicrobials. So. Not only might this information tell us more about how the antibiotics being used on the farms, but it should also make us think about which of these situations is most biologically important.

So are we concerned more about the total amount of milligrammes going into animals on a farm, or are you more concerned about the number of times animals are exposed to a dose of antibiotics? And at least to my mind, every dose of antibiotics is another time that bacteria are exposed to the antibiotics and another opportunity for resistance to build up. Whereas, conversely, an inappropriate underdosing would result in fewer milligrammes of antibiotics going into animals.

But then, as we know, that could accelerate development of resistant bacteria. Similarly, look, just looking at the right hand graphs, you can see that the benchmarking is according to high priority CIA use and that farm A, while it uses the highest number of doses total of antibiotics, actually isn't using any HPCIAs. So again, we need to think which of these would be most Biologically important.

And in reality, it probably mean that as a vet, you're gonna have a conversation with Farm, F about having, trying to reduce HPCIA use, whereas you might have a conversation with Farm A about just reducing overall antibiotic doses that they're using on their farm. So that's kind of a, a summary of what I've told you so far is regarding trying to calculate and use medicines audits most appropriately is that a basic tally of bottles or tubes in its simplest forms might be a reasonable way to look at this if there's no significant change in animal numbers or medicines used between years. But if animal numbers have changed, then you really need to divide by the number of animals on the farm as best as you know that information.

And if medicine use has changed between different drugs and different classes of drugs, then you really need to calculate doses that are being used on a farm. And that will give you a much better idea of the sort of real use on a farm. So as you can see, I've kind of covered the 1st 4 points that I wanted to discuss with you guys this evening, and now I'm going to move on to considering how changing antibiotic use might influence antibiotic resistance and prevalence both on farms, in the environment, and potentially in the human population.

So these are some of the questions that really are driving research forward in this area and I'm not really so much gonna try and answer these questions for you in the coming slides, but more give you an idea of how far along the research is in this area and how Yeah, and, and where we are and what answers we have and what we don't have at the moment. So thinking about the effects of cutting antimicrobial use on farms and animals, what happens to resistance prevalence of animal is that's if we reduce antibiotic use on farms, which antibiotic use changes have the biggest impact on resistance, and what happens to animal health if we reduce or change antibiotic use on farms? And then do humans acquire resistance from animals?

And if so, how does this happen? And how much effect would changing antibiotic use on farms actually have on resistance in the human population? So, to tackle the first question of what happens to resistance prevalence if animal in animal islets, if we reduce antibiotic use on farms, we can look at other countries which have already reduced their antibiotic use in recent years, as well as have antibiotic resistant surveillance in place.

And one of those places in the Netherlands, and there they've had restrictions on the use of antibiotics in livestock since 2011, and that's resulted in antibiotic use being cut by 68% since, since then. So you can see on the graph here that antibiotic use in turkeys, veal calves, broilers, pigs, and dairy cattle, as represented by the different coloured lines overall have all decreased through those years. And they've also got some resistant surveillance data from the same period.

And in some cases, resistant prevalence does seem to also have decreased alongside the reduced antibiotic use. So these graphs show the trends in the proportion of resistant E. Coli isolated from broilers, slaughtered pigs, calves, and dairy cattle.

And you can see that there sort of seems to be a general decreasing trend probably since about 2011 in some cases. However, in other cases, the resistance data doesn't really seem to correlate so well with the trends in antibiotic use, and here you can see these are graphs showing trends in resistance of salmonella typheurium isolated from humans and from food animals. So you can see that there's not a clear picture always.

There's not necessarily a direct correlation between antibiotic use and resistance prevalence, at least to some of the antibiotic classes, even in the animals that they're being used in. However, on the flip side, that the enforced reduction in antibiotic use in livestock in the Netherlands has impacted antimicrobial resistance levels in animals and in humans in some of the isolates that are being monitored. So another case study is Belgium, and the paper here is, was published in Preventative Medicine Journal last year.

And the background to that paper being that the Belgium policy on veterinary antibiotic use set objectives for antimicrobial use reduction compared to their 2011 use. Which called for 50% lower use of medicated feed by 2017, and the 50% lower total antimicrobial use, and the 75% lower use of the critically important antimicrobials by 2020. So what happened?

Well, as you can see that during those years following 20 following 2011 targets were announced, the veterinary antimicrobial use of the majority of antibiotics decreased. So the overall use decreased by about 15.9% between 2011 and 2015.

As you can see here, flosenacols were the only antimicrobial group for which, the use didn't decrease. And you can see here from these graphs, these show the average antimicrobial resistance prevalence again of E. Coli in food producing animals in Belgium between 2011 and 2015.

And this is shown as a resistance to each of the panel of 11 antimicrobials that the islets were tested against, each of which shown by a different coloured line on these graphs. And again, you see, you can see there seems to be an overall decreasing trend of resistance prevalence alongside the decrease in antimicrobial use. So it would seem from these studies at least that antimicrobial use in livestock does to some degree drive antimicrobial resistance prevalence, but that the relationship is much more complex than just a straightforward cause and effect.

And likely there's lots of other influencing factors that are happening out there on farms. So the questions are, what are these factors? And the answer is we're not really sure yet, but there is a study happening here at the University of Bristol, which is trying to find out.

The study is called the OStar Project, and that's stands for One Health selection and Transmission of Antimicrobial resistance. In the study, they've got over 700 farms enrolled onto the study in which antibiotic use and resistance prevalence are being monitored through time, and they're also looking at the farm husbandry and management practises, and that's going to be taken into account. And the main questions being asked by the study are what are the levels of antibiotic resistance on dairy farms in the normal bacteria in the UK?

What are the farm factors most associated with higher levels of antibiotic resistant bacteria? And does reducing antibiotic usage, for example, doing selective dry cow therapy, actually reduce the level of antibiotic resistance on a farm? So for example, Is there any point in you and the farmer struggling away with selective dry cow therapy if it turns out that feeding calves waste milk with antibiotics in has a bigger impact on the spread of resistance and of resistant bacteria, or maybe they have an equal effect and we should be highlighting both of these practises to farmers equally.

And of course, there are endless management practises, which may or may not be conventional, that might contribute to increased or decreased prevalence of antibiotic resistance on farms. So there might be from the farmer that uses two intra mammary tubes rather than 1 for every treatment of a cow with mastitis through to the use of other substances around the farm like heavy metals or disinfectants. So a measure, I'm sorry, I mention these other factors as possible drivers of resistance because I'm sure you're aware that the spread of resistance between bacteria can happen in more than one way.

So one way is by an evolution or mutations within an individual bacteria, and that might make them resistant when they happen. And that then can be passed on genetically as the bacteria replicate, and that's a more limited and a more slow process. And the other way that that resistance can spread is via plasmids.

And these are pieces of genetic material that bacteria have that can make them resistant. Now two important points to note about plasmids. One is that they can move horizontally between bacteria and between bacteria species.

And that they're not just selected by antibiotics necessarily. So, here in the diagram, you can see this is a diagram of a plasmid that has been discovered. And on this plasmid, there's a section that confirms antimicrobial resistance to variants of varying sorts.

And you can see that there are other certain sections which, confer resistance to other substances, so copper or silver, for example. And since these sections are all on a plasmid that also carries genetic material that codes for antibiotic resistance, it would be feasible that if you're using heavy metals or products on the farm that could increase the relative survival of bacteria with this particular plasmid, you'd also increase the survival of these kinds of resistance in those bacteria. And these sorts of interactions are things that, well, we should all be aware of, of, of having the potential to affect the prevalence of antimicrobial resistance on farms.

But unfortunately at the moment that we really don't fully understand at this time. So I guess the the the answer is watch this space for that one. But of course, it's also worth considering what and how big the impact of antibiotic resistant isolates within livestock could have both on the health and welfare of animals and the animals that we're treating, and, subsequently the economical impact on the farms that we're working on.

And also how much impact the presence of resistant isolates in livestock could have on humans and on human infection and infection risk. So considering the effects on animal health and welfare, of course, we could, with more resistant bacteria be looking at increased resistant failure and treatment failure, sorry, increased time to cure if we're treating with one antibiotic and then having to change treatment plans. And of course, increased cull rate of animals that don't recover.

For the livestock sector, this would mean lower productivity and increased, increased cost of treatment with repeated multiple treatment choices and options, and of course, increased losses. Of course, the use of antibiotics is essential for the treatment of clinical disease, and that's what we're using them for and should always be used appropriately. And there are concerns that reducing antibiotic use in livestock just for the sake of it really could result in a decreased animal health and welfare problem.

So in a study of factors affecting dairy farmers' attitudes towards antimicrobial medicine use in cattle in England and Wales, Jones and colleagues found that although over 70% of farmers questioned in their study thought reducing antibiotic use would be a good thing to do. They still had considerable uncertainty, as to what would happen to animal health on their farms, and 50 56% of them were not sure, and 20% believed that the health of their animals could be worse if they reduced the use of antibiotics on their farms. It should also be known that there was also uncertainty over whether reducing antibiotic use would even reduce the incidence of antibiotic resistance, and 45% of farmers were uncertain about that, and 18% of farmers thought there would be no decrease in resistance if they changed their antibiotic usage.

So I think just being aware of these concerns is important as vets and as vets we can allay these fears where appropriate and we need to be able to have the confidence in our own ability to reduce antibiotic prescribing without compromising animal health and welfare. And of course, if an animal has a bacterial infection, then antibiotic treatment is needed, and withholding treatment would increase suffering and, and reduce welfare. But reducing or even just changing antibiotic prescribing in favour of more responsible antibiotic.

Can be done with, without a decrease in animal health or productivity. And that ultimately was the outcome of, the study that I did, a retrospective study I did, with my colleagues here at the University of Bristol, and finding that these dairies could reduce the use of high priority, critically important antimicrobials and, in fact, stop the use of these drugs without influencing animal health, welfare, or productivity. And similarly, some work has been done again in the Netherlands showing that there was no decrease in other health parameters in herds where selective dry cow therapy had been essentially enforced onto farms.

So of course there have been various studies also trying to pull apart the questions regarding whether antimicrobial resistance in humans, comes from livestock and how much of a role resistance in livestock could contribute to resistance in humans. 11 of these studies is this One Health for Food ESPL attribution analysis, and this was a public-private partnership project, that happened in the Netherlands, and they were looking at the prevalence and sources of, extended spectrum B tactams, that's ESPL bacteria in the human population. And they looked at the prevalence of ESPL carriers in the general population and then looked at the risk factors for carrying ESBL E.

Coli. So they looked at things like owning pets, preparing food and meat products, pastime activities, as well as access to livestock species. And this is one, figure from that study.

And the outcome found by the study was that basically different people carry, sorry, predominantly different species of the SPL bacteria, and that some people are at a higher risk of contracting resistant bacteria from livestock than other people. So you can see from this figure that, farmers tend to have similar ESPL species. To their animals, so the chicken farming community carries similar ESPL species to chickens, and as you can see just looking at the little dots and the colours on that graph.

These guys are up here. And that the pig farmers carry quite similar, ESPL species to the pigs. And also that human-centric ESPL type bacteria tend to be found in the human population and, and are kind of distinct from the animal populations.

And that, that is just showing that, wastewater often has similar human ESPL species. So this could lead you to thinking that if livestock do develop an increased prevalence of resistance that it still shouldn't really affect human health. Well, I think one thing is vets, we should remember is that if resistant isolates increase in prevalence in livestock, then we are going to be the ones that will have those resistant isolets too, as well as our families and loved ones.

But beyond that, we need to think about how a human commensal or pathogenic bacterial isolate might come into contact with these animal bacterial isolates to achieve a plasmid transfer because as soon as that happens, the resistance will jump into the human population from an animal. And, you know, that could jeopardise not only human health, but also the industry that we work in potentially. So how might this happen?

This is a figure that's been lifted from a report by the European Medicines Agency. And this flow chart shows, as the text says above it, the chain of events that may lead from the use of antimicrobials to, in animals to a compromised antimicrobial treatment in humans. So if you just look down that list of events, the thing is that we already know that every stage in that list is already happening.

So we need to think about reducing the risk at each stage, not just the first stage. So how might Human bugs get resistance from livestock bugs. So we need to think about not just farmers, farming communities, but just Joe Bloggs out there.

And if they live in London or any city or urban area, how would they come in contact with livestock, bacterial isolates? Because that's the reality for the huge, you know, majority of the population. Maybe it's from drinking unpasteurized milk or travelling around the place.

Is it from preparing food, particularly meat products? Is it contact with their pets? If they go for a run in the countryside, across a field with cows in it, or swimming in water with the runoff from local farms?

And if we can understand what the risk points are for people, not only can we try to reduce the development of these resistant islets in the first place, but we can also try to reduce the methods by which the isolates would be spread from livestock to humans. So this is just an example of a study done in the Netherlands by others and colleagues, which just aim aim to look at the quantify the E. Coli exposure of humans through the consumption and preparation of meat from different food animals.

And you can see here that different animal products do contribute to, the exposure of the human population to these E. Coli isolators. But they quite commonly, the preparation, the preparation of the food products, the actual risk drops as the, as the products are prepared.

So food preparation is a risk factor for transfer of resistant bacteria, but how much of a risk factor compared to others, for example? Well, back to the ESPL attribution analysis. And that found that the main outcomes were that ESPL types from the general population and hospital patients show large genetic similarities.

So the largest exchange of ESPL bacteria is from human to human. And while types from livestock, both in animals or on meat, are substantially less similar to those of humans, the difference is found between ESPLs in humans and in livestock farming suggests that farmed animals make a relatively small contribution to purely ESPLs that occur in humans compared to the human contribution. So, and as a sorry, poultry, so ESPLs found in poultry and non poultry meat, as well as in surface water, were the highest percentages of ESPLs found, .

About the place. And as a result, both swimmers and consumers of meat are exposed to, to quite low concentrations of ESPLs. But at present, there are no epidemiological studies that show that exposure through meat eating or swimming leads to an increased risk of carrier status in the general population, or infections in inpatients.

But of course this is a concern and something that should be looked at and continue to be considered. And we should also remember that vets are not only responsible for antimicrobial resistance in livestock and food, also, as I mentioned before in pets, which are constant, currently an unknown contribution to, antimicrobial resistance in humans. And to some extent, antimicrobial resistance in the environment via things like surface runoff from farms, and particularly from slurry spreading, if that slurry has antimicrobial waste milk in it, and even from the livestock that are in the fields that could have direct contact with the general public.

So how much attention should we be paying to putting antibiotics into the environment around us and how they get there? And certainly the microbiologists here at the University of Bristol have tend to have more of a concern for the antibiotics which end up in active, still active in the environment as opposed to antibiotics which are going into animals and being metabolised. So this is something that we need to think about and we need to think about all routes of antibiotic transmission to humans.

So I've just outlined kind of a few ideas that some people are having about mechanisms by which antibiotics might end up in the environment around us, and how we might be responsible for those antibiotics getting there. So long-acting antibiotics, of course, are great because they mean that you can treat, you know, a crazy beef animal for a long time. But in doing so, they also may be present in this animal under the what we call the mean inhibitory concentration for quite a long time.

So do they underdose that animal for a long time? They're also therefore excreted into the environment for a long time, and we don't really know what effect that would have. Similarly, it is true that different antibiotics actually persist in an active form in the environment for different amounts of time.

So antibiotics like fluoroquinones and macrolides persist for longer in the environment than, for example, the penicillins. And there's also concern, like I said before about antibiotics running into water courses through slurry spreading and just water runoff. And this is just a graphic of how all the different methods by which antibiotics and antibiotic resistance can come back to humans.

And if you start to think about it, vets can be involved in quite a lot of the different stages that you can see here on the graphic. And again, I don't have the answer as to how we can necessarily reduce those risks, but I think it's just worth us being aware that there's multiple ways that that can happen. So does antimicrobial resistance in livestock really affect human health?

Well, probably right now, for the majority of at least the UK population, there's probably a reasonably weak link, which is a good thing. For livestock workers, there's probably a stronger link. And if antibiotic resistance were to increase in the livestock population with more antibiotic use, and hence the risk of, a human specific isolets coming in contact with resistant animal isolets, then there probably would be a stronger link going forwards.

But not only does the increased prevalence of resistance result in increased risk of humans being susceptible to colonisation with resistant bacteria, there's lots of other human factors which would currently influence this kind of risk and will increasingly do so in the future. And these things are potential, you know, out of our hands, but something again that we should all be considering and aware of. And that is that medical advances of recent years have resulted in increased numbers of invasive medical procedures, and increase in the number of immunocompromised individuals and patients with chronic debilitating diseases out in the community.

So again, people who are more susceptible to these resistant bacteria, so increasing reasons why we shouldn't, like we would want to keep them low in the general population. And also increased worldwide travel with people and food products, the increased mobility of people, as well as reduced environmental and even social barriers have meant that there's raised increased risk of the spread of antimicrobial resistance in a worldwide setting. So we're all aware of those people that we're gonna be working with and what you'd maybe call the laggards, and that consider that a dose of Pennstrep is cheaper than a dead cow and would, you know, validate the, the use of what we'd call defensive prescribing for the animals that are in front of us and that we're treating.

Or farmers or people that we're working with that don't consider that they have resistance on their farm, or that the antibiotics are still working and so why should they bother changing? Or that they're just people, and now you guys who are aware that maybe the direct threat to human health is relatively small at the moment. And what do we say to those?

Why should they still try to reduce their antibiotic use or why should we do so as an industry? Well, There is obviously the threat to animal health going forwards. There is the threat to human health, which ultimately could be massive, and we don't want to increase any more than we have to.

But, but as well as that, there is just public perception, and already you'll always be aware that these kind of headlines do make it into the papers and the public have this concern about the food that they're eating. And as an industry, we need to realise that while there are likely benefits to reducing the use of antibiotics in livestock, and one significant reason for making these changes in the short term is also public perception. And in other industries, companies will do things that don't necessarily improve the product that they make, but purely improve the public perception of the brand.

So, for example, why in 2015 did Nike give 1.9% of their pre-tax income to community initiatives? Do they think that making children in China more physically active will improve the quality of the training that they're making and selling?

Of course they don't, but they know that they need to improve their public perception and they're trying to gain public confidence. And we all know that the public are becoming more critical and more knowledgeable about where they get their food from and about the farming. Sometimes this is misinformed, but just like any of these companies, we are selling a product to a consumer and just like them, we need to build our our consumer confidence in the products and in our industry.

And I think that. As vets, our role is not just to be proactive in our responsible antibiotic use in our own practise, but to push our farmers and push our industry to being proactive, being responsible, and also for us to be knowledge about antibiotic use and antibiotic resistance, so that whoever we talk to in the community and in the public is gonna increase their confidence in us and our, industry and our profession. So I hope that this webinar has done something to increase your confidence in your responsible antibiotic use, and in your confidence to talk to farmers and anyone in the public who asks about antibiotic resistance and what it is and where it comes from, and maybe what we can do to reduce the threats or just be aware of all the things at least that we don't know what we.

We can do, and the answers that we don't yet know, but what, what, you know, research is going on to try and work out those answers. Because I do think that this antibiotic use and antibiotic resistance issues, these, this issue will define the industry in the, in, in the years to come. And I hope that you will feel a little bit more prepared and a little more, a bit more confident in talking about it now.

So, That's me, that's my wrap up. Thank you for listening and then I'm sure if you have any questions, they can come my way now. Andrea, thank you very much.

That was absolutely thought provoking and as you say, it's not only about what we know, it's also about what we don't know. And it reminds me of all the levels of of development of, of things of unconscious incompetence and conscious incompetence going up and I think if you've done nothing else tonight but stimulate us all to think more about reaching for antibiotics and and certainly to discussing it with the farmers, you know, and if, if nothing else, just get measuring and and then see. You know, my favourite saying is what gets measured improves, and if you're not measuring, how would you know?

Yeah, exactly, exactly. But it's not always that obvious how to measure. So, again, hopefully just, even the simplest ways can be effective, but only if you understand what what you're trying to measure, really.

So. Yeah, absolutely. I, I did love your graphs, you know, with the, the same results presented in two different ways, giving you two different answers, because, statistics are great, but, yeah, you can manipulate them to say pretty much whatever you want them to.

Yeah, absolutely. You know, we both, you know, that goes both ways. We can, if we're doing the calculations of that for these farms, we can manipulate those statistics, but similarly, you know, those benchmarking data more and more.

Frequently as vets, we get given those kind of benchmarking data from the farmers who have been given it by their retailers, and they're struggling to understand, you know, why they are where they are on the, on the graph. So I think it's important not just for us as vets to be able to produce that kind of information, but just to be able to understand it because it is being produced for us by more and more roots and avenues these days. And as the vet, you know, to these farmers are sometimes a little bit baffled by it.

So hopefully everyone will be slightly less baffled now by it when they when they're presented with that. Yeah, and that calculator seemed like a good idea. I've never looked at it, but it seemed like a good fields.

Yeah, absolutely. And I think, like I said, sometimes it's it it won't be necessary and even Myself, you know, for the smaller farms, I will just do a quick tally of bottles, but it's really knowing when that is an appropriate way of measuring things and when it's not. And when it's not, those that kind of, you know, calculator is really useful because you don't have to do it yourself.

You can just go in on there, plug in the numbers and it will give you some answers that you can then go and discuss with your farmers. So, yeah, it does, those sorts of tools do make life easier for everyone really. And and highlights a very, very important topic, brings it out in the open and gets everybody talking about it.

Yeah, absolutely, and I think that's the thing. I think it can be a little bit overwhelming and definitely I'm, you know, still have lots of questions and there's still a lot that You know, everyone working even, like I said, at the forefront of this field, there's lots of questions that we don't know the answers to, but I think we also kind of have to be honest with ourselves and honest with our farmers sometimes to say, yeah, we actually don't know the answer and we actually don't know what other things are gonna increase or decrease antibiotic resistance, but we should be aware that There might be other things and keep looking out for, for the information as and when it comes around. So, yeah, definitely just hopefully allow everyone to kind of open those conversations a little bit more with their farmers and and start just making everyone think about it because you're right, once you're monitoring it and talking about it, then things seem to start miraculously improving, so.

Yeah, I was, a couple of months ago I was reading an article that was talking about antibiotic resistance in the veterinary industry and the human industry and it's no surprise, but the vets are way, way, way ahead of the doctors in a lot of these aspects. Yeah, yeah, absolutely. And, and then and, and, but not to say that the doctors aren't.

Definitely kind of tackling these issues and there's, there's some really interesting kind of research done from the doctor's side on the kind of more socioeconomic, and the psychological aspects of prescribing and things like defensive prescribing and the fact that GPs tend to prescribe antibiotics more frequently in the hours before lunch and before they go home just to get people out of the door. And I think That is kind of, those kind of things should also be considered and probably haven't really been quite the same degree in, in veterinary medicine. And it's just worth thinking as a first, you know, as a practising vet, you know, what are the times when I'll just shove a bottle of antibiotics at it to kind of make the problem go away.

And, I think we're probably all a little bit guilty of it, but just to know and be aware that we're doing that is just as important, really, about starting to think about how to, to stop doing that, really, yeah. Yeah, absolutely. But it's, it's, it, it's nice to see even adverts on TV, you know, with the little capsules dancing around saying don't, you know, if you've got flu, don't ask your doctor for one of me because I'm not gonna work.

Yeah, absolutely. And again, that's what I was talking a little bit about the idea of the social norm of people knowing now about antibiotics, about antibiotic resistance, and that actually. You know, being the person to say, I don't want to use antibiotics in this fact for these reasons is now a more acceptable thing and that's also happening within farming now because of these changes that the retailers are making and You know, the, the farm assurance, red tractor Farm assurance has kind of forced that issue out onto the farms.

And again, it is becoming more of a social norm for farmers to actively be trying to reduce their antibiotic use. And we're not quite at the stage where they are in the Netherlands where the majority of farmers would know, for example, their animal daily dose of, of antibiotics for their farm. But we are at the stage now where it's quite, like most of the progressive farmers will be actively trying to reduce antibiotic use.

They know what the critically important antibiotics are. They know what they should be doing to try and reduce their use in the biggest areas. And, you know, we should be, as a profession, really trying to push that forward onto both all farms and push those farmers to do more, really.

Yeah, yeah. Susan's come up with a very interesting question. She says, superb talk, thank you very much.

She says, I apologise if you've already answered this, but is it, is, let me put my teeth in and try that again. But is the best option to use a realistic therapeutic dose for as long as it takes to achieve recovery or do what the medics do and give minimal doses for the shortest time? And thereby the infection recurs in a constant cycle with us building resistance.

Yeah, well, I haven't, I haven't, answered that question. I guess, the answer, well, we, we don't have any definitive evidence within the veterinary literature, but it is to say that Susan is right in the sense that the medics are being, encouraged to use, the proper dose for shorter amounts of time, and that is likely something that we should. Be considering doing so making sure that we are properly dosing and not underdosing animals with appropriate antimicrobial treatment and using a shorter dose as is possible.

I would just say though that like that is under the caveat of the short dose needs to be a dose that is effective. So as Susan said, you don't want to underdose for a very Short amount of time and therefore end up with a recurrence of the infection. So these farmers that give just one dose, a one-off dose of Pen strep, that's probably not helping anything.

It's probably counterintuitive. And so training farmers to give an appropriately long dose of, say, 5 days of antimicrobials is important. But the evidence in the In the medical literature does show that, for example, a 5 day dose for acute sinusitis infection or acute, you know, ear infection.

I was literally reading this. My partner's a doctor. I was reading this only yesterday in one of the medical journals.

Those short 5-day doses have been shown to be effective. And so maybe we really, we just need the literature. To, to, to tell us as vets how short we can get away with.

Unfortunately, that literature is not available at the moment. But again, something that we should be aware of that probably we should be using short, good doses, but we don't want to underdose for too short amount of time. I can't tell you what the length of those optimal dose would be though.

So sorry about that. Excellent. Again, it's about, excuse me, getting the discussion out there and talking about it and and getting somebody to do the research for us.

Yeah, absolutely. And, and yeah, we, we need people to do that research. And it is true that unfortunately, all research takes time to philtre through, but again, as long as we're all kind of talking about the subject, and we can learn from each other and we all learn to some extent from experience, but hopefully we can start to learn from other people's experiences.

Or we're discussing this both within veterinary, both veterinary medicine and across, you know, like, you know, two other sort of medical disciplines. So, the medical literature can inform us to some degree as well, and we probably need to be starting to open conversations with the medics as well. Yeah, yeah.

How do you feel about visiting California in the US Andrea? Because it seems like you got a bit of a subtle invitation here. Min Mina has written excellent presentation.

Here in California and the whole US. We are still in the dark ages about antibiotics. Where the farmers are in the decline, but the big cooperrations are increasing.

They are for profit first. Never mind the resistance to antibiotics. We need your help.

I'm sure they don't just need my help. They are much more important, wise and informative people than me out there. But yeah, I mean that and that is the that is the problem and and similarly has been the problem in the UK.

I mean, ultimately that, you know, the people and Who are selling the the antibiotics and selling the drugs of the people that are making their living off it. And that is true of vets as well. And so I think if we are the responsible vets, if we're going to be the responsible vets of the future, then that is something that we need to address as well and just be open and honest with our farmers about that.

And if that means changing our pricing structure. To properly, charge for our professional time as opposed to making profits on antibiotics, and we need to really promote that quite strongly. And, you know, before we get to the state where, prescribing and sales of antimicrobials are decoupled, which has been threatened across different parts of Europe at least.

So. Yeah, I, I appreciate that there's lots of different, stages and lots of different places that, places are out with their antimicrobial resistance, tackling this, this problem, and. I don't think the UK is, is, necessarily ahead of the curve, but I think it's, it is a global issue and everyone, everyone unfortunately is going to have to play their role at some point.

You might just have people taking up their responsibilities slower than others, I think. It's interesting that you, the comments you were just making because I was at a CPD event a couple of weeks ago, and it was all about business and and business profits and everything else. And it was very interesting to hear the speaker who was saying that if he had his way, he would get all vets to double their fees and stop selling drugs.

He said, make your money out of what only you can do because the online pharmacies and The, the, you know, the the co-ops and that sort of thing, that they, they can outbid you by, you know, volumes and all that sort of thing. And maybe you know, if we did make less money out of the medicines, it, not everybody obviously, but there would be some people who would be less inclined to, you know, add in the extra bottle here or there or do those kinds of things. Yeah, no, absolutely.

And I think that, you know, in, in an ideal world, that would be the case. And I think people are, and, you know, practise managers and partners definitely are coming around to that day and probably have wanted to do that for quite some time, but the reality in the kind of cutthroat world of industry is, is not quite the same. But I think as long as, as As as much as we can for the profession, we're all singing from the same hymn sheet and telling farmers that we don't want to be making the profit from their antibiotic sales and we'd rather be making it from, you know, preventative herd health and the like, then, hopefully we can, we can push that, that kind of whole issue forward a little bit.

Yeah. Interesting comment that's just come through from CI. Cy says, just to say hello from Norway, vets here are not allowed to make money on medicine sales, so there's no economic motivation for us.

Yeah, absolutely, and I know that that is what is happening in some parts of, of the world and is being sort of questioned as to whether that should be happening in more countries. I don't really, can't really comment on if that would work, in the UK or in other parts of the world, in the same way, but absolutely it is, it is the case that that is already happening in some parts of the world and, and should definitely be considered, . You know, because we ultimately shouldn't just be here to prescribe antibiotics, we should be here to maximise animal health and welfare, really.

So health and prevention rather than treatment. Yeah, yeah. Easier said than done though, as we all know the reality of of out on the farm, and I, like I said, I am a practising vet on a day, so I, you know, try to, to have a practical approach, you know, when I'm out there on the, on the farm, I'm, I'm also, being pressurised, you know, by the threat, you know, the ease of defence of prescribe.

And thinking about, you know, am I gonna make my wage this month, but ultimately, I think we have to just inform ourselves and our clients that there is a much bigger picture here to be worried about than just a profit line, really. Yeah, absolutely, absolutely. Always easier to do from the armchair.

It's like what do they call the morning. Quarterback, you know, analysing the game from not being on the field. Yeah, exactly.

And you know, this whole concept is kind of nebulous and, and, elusive to think of. And when you've got that one, the farmer's favourite cow in front of you, it's very hard to weigh those two things up in your head. So.

Yeah. Well, Andrea, thank you so much for your time. It has been absolutely fascinating and thought provoking.

I think is the, the one word that or one statement that keeps coming to mind for me. So we really do appreciate your time. I know this was your first visit to the webinar vet a brilliant one at that, and we look forward to having you back on this, with us again in the future.