So James graduated with honours from the University of Bristol as a Bachelor of Veterinary Science in 2005. He spent 4.5 years working as a veterinary surgeon in First Opinion small animal practise before joining ADM Protection in 2009.

James has worked as the International veterinary manager, veterinary technical manager, and veterinary director before assuming the role of commercial director in animal health in March 2020. Overseeing the company's veterinary division. James is passionate about all all aspects of small animal internal medicine, but has a particular interest in gastrointestinal disease, urinary health and feline geriatric medicine.

Outside of work, James enjoys a variety of sporting activities, including running, cycling, football, and CrossFit. He has a black cat called Hugo, who was rescued at the age of 3. Hugo has a strong personality, but has found the perfect home with James and his partner, Sheila, who is also a vet.

Hello and welcome to this talk entitled Acute diarrhoea and Dogs and Cats, Considering the use of antibiotics. My name is James Cuffin. I'm the commercial director for the animal health divisions at ADM Protein, and I am a vet, although it's been a little while since I was in practise, and I really appreciate you joining this talk all about poo.

I know it's not the most, you know, delightful of subjects, but it seems to be all I talk about in at work, at home, obviously I don't, but no, I appreciate you joining us and let's get into the presentation. So I'm sure you all know this, but just to kind of orientate ourselves and give us a good place to start, diarrhoea is an increase in the frequency, fluidity, and volume of the faeces. And when we're talking about acute diarrhoea specifically, the definition is diarrhoea that's been, that has been present for less than 2 weeks.

And we know that acute diarrhoea does commonly self resolve, and you know there are things or interventions that we can introduce to help speed up that resolution. But in the majority of cases, you know, if we did nothing, they would get better, but obviously we want to try and get things better quicker if we can. So why don't do that, you know, they're probably concerned about their animals' welfare, their quality of life.

They probably don't realise necessarily that it is a condition that will self-resolve, so they want to come to us to see, you know, is there a way that they can get their animal back to normal as quickly as possible. Obviously that's a concern for the welfare. They're probably also concerned with how much diarrhoea there is, in the house, potentially in a litter tray outside, something that they're probably manage struggling to manage anyway.

Yeah, like I say, maybe they're not aware that it will self resolve and they're kind of concerned that their animal is never going to get better, so we need to provide them with the reassurance that it will and that we can hopefully speed things up for them. So let's talk about the prevalence of diarrhoea, you know, I know from People working in practise, they've probably got in their own mind how common diarrhoea is, but just to sort of highlight a couple of studies that were done to show that 14.9% of dogs had experienced episodes of diarrhoea in the previous two weeks.

28.6% visiting the vets had diarrhoea as the primary complaint or had had an episode of diarrhoea in the previous month. In cats, you probably less likely and less data available to refer to.

This study from Alex German was monitoring the litter trays of cats in a rescue shelter over different time points and looking at the kind of, yeah, the incidence of diarrhoea in the litter tray in those in that population of cats. There are certain factors that have been shown to increase the risk of dogs developing diarrhoea. A study by Stevvischieal looked at, you know, what factors these were and what could be kind of having an impact, and what they found is the ones that were statistically more likely to be associated with diarrhoea were a recent diet change, a home cooked diet, living in a multi-dog household, and a recent stay in kennels.

So all factors that again, you know, maybe. Raise some alarm bells for us if if this was reported by the owner, then obviously we would think this could be linked to why they've developed diarrhoea. Given the self-limiting nature of acute diarrhoea, we often don't identify the underlying cause for a lot of these cases.

We might think that it's due to a dietary indiscretion. This probably accounts for the majority of the cases that we see and we might suspect that they have been scavenging, so whether that's out the bins at home or whether they've eaten something out on a walk. We might think there's an intolerance or a hypersensitivity, you know, a specific ingredient in the diet that the animal is allergic to or intolerant of.

So whether that is a protein source, carbohydrate source, or maybe some additives or preservatives that are in there. There might be a case that the diet has changed suddenly, so the pet owner might you know, admit that they've changed the diet without a period of transition. They haven't allowed for, you know, a period of adaptation from the old diet to the new diet, so we might be suspicious that's the reason.

There can obviously be infectious causes parasitic protocell, bacterial, and we'll talk about those more a little bit later. There might be an underlying medical condition, so it could be Addison's or pancreatitis. There might be an obstruction, there could be an interception or could present with diarrhoea as the, 11 of the clinical symptoms.

We might suspect stress being involved, if there's been a recent stay in the kennels or a cattery or a car drive, you know, stress might be something that we've identified as a potential trigger for the acute diarrhoea. They could be exposed to toxins or medicines that could contribute, and the example I've given their antibiotics. Obviously given a course of antibiotics, you don't really discriminate whether they're going to kill good bacteria or bad bacteria in the gut, the sort of commensals or the pathogens, so we might be developing a dysbiosis by using antibiotics in our patients.

There are numerous possible infectious causes of acute diarrhoea, so you've got the parasitic proce, viral or bacterial, something like Giardia, you know, we, we might think that we see on quite a regular basis. Parvo virus stands out as being potentially a fatal disease in young puppies. And then we have quite a few different bacterial causes and the important thing to note here and as we'll talk about later in the talk is although some of these might be identified and might be present in the faeces, they're not necessarily the cause underlying cause of the diarrhoea, and like I say, we'll touch on that a bit more later on.

I think we're all pretty happy with the management of parasitic or proton infections. Parasitic infections are much more common in the younger animal, and if we were to perform faecal analysis on a young patient with diarrhoea and identified worms or eggs, then we'd treat them with the appropriate end of parasiticide. Protozoal infections can be subclinical, so it might be something that we pick up on on faecal analysis, but not necessarily causing any clinical symptoms.

But if it is detected in a diarrheic animal, then obviously it is recommended that we take appropriate treatment management, and that could be metronidazole for jaardia often used alongside something like febendazole. When do antibiotics become relevant in viral infection might seem like a bit of a random question because we know that antibiotics are not effective for treatment of viruses, but there are situations with viral infections where we may see an increased risk of sepsis. So obviously if the patient is immunosuppressed or if we think that the viral infection has caused damage to the GI mucosa, you could then get translocation of.

Normal bacteria that reside in the gut. If they were to get them into the bloodstream, then obviously that would cause sepsis. So that would be an indication where antibiotics would be recommended and would be indicated if there were obvious sepsis in the patient.

So we could see an increase in rectal temperature. We might see blood in the faeces which could give us a suspicion that there might be. Potential sepsis or sepsis has developed or the potential that sepsis could develop.

OK, so if we now look at the significance of potentially pathogenic bacteria in the faeces of dogs and cats. When you're sending faecal analysis away to an external laboratory, they'll have different testing that they offer looking at these potential pathogens. So what we've done here is we looked at a few different bacteria, and what we have done is gone away and looked at the clinical studies that are available for the prevalence of these bacteria in healthy dogs and cats and dogs and cats that have got diarrhoea.

So the reason for the ranges that you see is there are different studies or a range of different studies. So for example with that Campylobacter in healthy dogs, there would have been one study that identified a prevalence of 21% of healthy dogs having Campylobacter in their faeces, whereas another would have identified 76% of faeces from healthy dogs containing Campylobacter, and there may be multiple other studies in the middle there as well. So we've just taken the range.

The reason for that variation it could be the way in which they're testing for the Campylobacter, or it could be the populations of animals they're looking at, you know, are they different countries potentially, you know, do they live in an urban area or are they living in a rural area, all factors that could contribute to the, the levels of of these bacteria in there. But the important thing to really kind of notice here is that, you know, there's not what they're present in healthy dogs in the first instance. So, you know, if, if, if they are pathogens and they, we are worried about them, how can they be present in a dog that is seemingly well.

The other thing to kind of pick up on, I suppose, is that, you know, in some situations you might be more likely to find clostrogen difficile in a healthy animal than you would in a diarrheic dog. So really what highlighting is just because it's present, you know, is it a coincidence or is it actually causative of the diarrhoea? And that's the kind of big decision that we need to make, when we're looking at these tests.

So the difficult thing is to is to decide whether the presence of these pathogens in the faeces is of clinical significance? Is it the sort of reason that this dog or cat has got diarrhoea? Because really, you know, it's worth bearing in mind that A healthy microbiota is a very diverse microbiota, so we should have a mix of lots of different bacteria, and that bacteria would include these potential pathogens as well.

It wouldn't be healthy if you just had, you know, a microbiota that's full of lactobacili and bifidobacteria which are the sort of friendly bacteria. It's very normal and very healthy to have this diversity and which, like I say, does include some of the potential pathogens. So I suppose sort of summarising really what the previous slide said it's highlighting that potential pathogens were isolated from 22% of faeces from healthy dogs and 30% of samples from dogs with diarrhoea.

So there's not much difference between the two, and like I say, that's our difficulty is working out whether you know the faecal sample we've got is indicative of what this potential underlying cause could be. And I think the reason for this difficulty or what makes this more difficult is that a positive faecal culture alone doesn't mean an awful lot, so. That if you've identified E.

Coli in the faeces, you know, there are lots of very normal commensal E. Coli that are not pathogenic and you know actually perform a very positive effect in the gut. There are obviously lots of different species of Campylobacter, and you know, coli and duni are potential causes of diarrhoea, but something like upsaliensis is, is not, you know, it's again a normal commensal bacteria that we'd find in the vast majority of the canine and feline population.

So I think when we You get a faecal analysis back. I think most of the time it might just say Compylobacter species, but really what we need to be thinking is can we be more specific? Is there additional testing that we can do to look at specific toxins, for example, often used with E.

Coli and Clostridia, where you can identify specific toxins that these bacteria or pathogenic bacteria are producing, or should I say the pathogenic versions of these bacteria are producing, and then can we do additional PCR to actually see what species of Campylobacter is present? Like I say, if you do that and it's a saliensis, then that's not what is what is causing the diarrhoea. But if you do get a positive test for coli and Juni, then yeah, definitely I'd be looking to treat that.

But we don't see that routine on routine faecal analysis, so it might be something that you need to speak to the lab about, see if it's something that they offer as an additional level of testing. So just to confuse matters even more, we need to remember that the bacteria in the gut is a balance between, like I say, you know, all the different microorganisms that are present. It's a sort of fine balance in that GI environment and we can get an imbalance there.

This is what we term a dysbiosis where you get increased prevalence of certain microorganisms. But actually, you know, that imbalance in the first instance could be caused by . Another underlying condition.

So it might be something else that's going on, whether that is hypersensitivity or intolerance to certain ingredients that could then drive a dysbiosis. So if we are doing our tests and an example that I always keep using the Campylobacter. That increase in levels of Campylobacter could actually be as a result of something else that is going on.

So although the Campylobacter is increased, you know, that might not be the cause, that just might just be the consequence of some other other underlying problem. Given the self-limiting nature of acute diarrhoea, it's probably no surprise to you all to hear that foetal analysis isn't commonly undertaken in acute diarrhoea patients. So this study by Jones Eta in 2014 found out that further diagnostic testing in acute diarrhoea patients was only carried out in 16% of cases, and this commonly was blood tests or foetal analysis.

A more recent study found out that faecal analysis was carried out in 7.8% of dogs and 6.8% of cats presenting with acute diarrhoea, so relatively low numbers.

So why would we want to be looking at doing faecal analysis in acute diarrhoea cases? Really, it does guide treatment, you know, in some situations, like I said, you know, the bacterial element is, is sort of questionable, but obviously if you identify parasites or protozoa, then, you know, we need to treat those. You can also provide us with some prognostic information.

So the extreme example here being that if Harbo virus is identified, then we need to offer a very grave or cautious prognosis to the pet owner. So here are some examples of when you may want to consider faecal analysis and really, you know, I'll show you the list if there's a sudden onset of acute hemorrhagic diarrhoea, evidence of sepsis, diarrhoea after Kal shows, multiple pets in one geographical area affected, multiple pets in one household affected, owner also affected. So really kind of what we're saying here is that if we're really suspicious of an infectious cause.

Do faecal analysis. If you know there's a clear history of you know the dog eating something on a walk that it shouldn't do and you know does that commonly and usually resolves and then you're probably not going to want to look at foetal analysis. But like I say, if you've got any of these potential red flags, then I think infectious causes becomes much more likely and I think it would be a good idea then to perform the faecal analysis.

So we've talked about the diagnostics behind acute diarrhoea, but if we start getting into the treatment a little bit more now, so looking at antibiotic prescriptions for acute diarrhoea, and a study by Alex German in 2010 found that 71% of dogs that are presented with acute diarrhoea at first in practise were given antibiotics. So it's quite a high level of antibiotics that are used, you know, maybe the situation is improving in 2019, a similar study showed that 49.7% of dogs were given antibiotics.

Again, that still feels like quite a high percentage, you know, some of these dogs did have some diagnostic testing done, but the majority didn't. So if we're kind of thinking back to our potential underlying causes of acute diarrhoea, you know, bacterial is on there, but it definitely doesn't represent 50% of cases. So what we're kind of wanting to avoid, given all the issues around antibiotic resistance is this sort of indiscriminate use of antibiotics in our patients.

I'm sure I don't need to tell you this, but you know, when and why are antibiotics prescribed? Obviously we should be using antibiotics only to know to treat unknown bacterial infection or septicaemia. I say, I think we all know that, and, and in an ideal world that's what's happened.

But in reality, I think, you know, what we do. Often think about is, you know, could this speed up the resolution of the diarrhoea by using antibiotics is, you know, if I give my patient a course of antibiotics, you know, will they get better than if I did nothing. That's probably a question that's in people's minds.

There may be a concern over zoonotic disease and that's obviously a very valid concern, especially if there are humans in the household that are immunocompromised. But is there pressure from the owner? Are they expecting it?

And obviously that's not something we should give in, and we should try and educate and, and sort of explain to the owner why we're not going to give antibiotics for this, this case. So let's look at these in a bit more detail. So if we're thinking of accelerating the resolution of diarrhoea quicker by using antibiotics, you know, I think there is a good argument there.

So this study in 2019, 31 dogs reported that given metronidazole had a short time to resolution of the diarrhoea compared to the controlled dogs receiving a placebo. So there is some evidence that yes, maybe antibiotics could speed up the resolution of diarrhoea. There was another study, a bigger study with 60 dogs again sort of looked at this and showed that the metronidazole group recovered slightly faster than the placebo group, but good for protecting, I suppose, and good good for anyone who likes probiotics.

Actually, the group that were treated with probiotics recovered the fastest of all of those. There's been multiple other studies as well looking at probiotic formulations and how they can accelerate the resolution of acute diarrhoea compared to placebo. So, you know what we say in there, I suppose if you want to summarise this slide, antibiotics good, probiotics better for the resolution of acute diarrhoea.

Not that I'm biassed or anything. So yeah, given the concerns about antimicrobial resistance, maybe nutraceuticals are a more appropriate choice, and we did a study with our proco in advanced, and you can see there that there was a statistically significant improvement in the time to resolution in the procoing group compared to the placebo. The thing that's not on this slide is the group that received the procon in advance were also much or significantly less likely to require other medical intervention.

So this varied obviously from case to case, but it could be antibiotics, some steroids, some wanted to give others sort of anti-diarrheal treatment, but those that were in the placebo group were much more likely to need that in secondary intervention. Whereas the proco advanced group where I think there was 1 out of, I think 50 in the procoing group that needed some additional treatment to try and get on top of the, of the diarrhoea. So what about if we're worried about zoonotic disease?

I think you know if, if, if we're kind of really are thinking that you know this dog has got sepsis, it's really severely affected, you know, I am worried about, you know, kind of an underlying zoonotic cause, and then antibiotics could be sort of justified in those cases, although ideally we'd want to back it up with faecal analysis to show that there is some underlying cause there that is a zoonotic potential as well. If the owner is reported that they are affected at the same time, then again, sort of suspicions are raised, and if the animal shares a home with young children or immunocompromised people, then again, there is a risk there and we need to take that into consideration. However, it's important to point out that there's no evidence to support the continued use of antibiotics until multiple faecal samples are clear.

I know this is a sort of protocol that some people might use, but there's actually no evidence to support that. And again, you know, given just antibiotics to healthy animals, we don't want to be doing that either, because we know that that could promote the development of a sub subclinical carrier status or lead to any sort of pathogenic bacteria that might be present and developing antimicrobial resistance. And then what about the situation where there's sort of owner expectation or or owner pressure, that you kind of tell them telling us that their animal needs antibiotics and You know, I, I had a similar situation like this when I was in practise, which was many years ago now, but, you know, I saw a case of acute diarrhoea and I managed it as I was taught to.

So, you know, I think at the time I recommended, Easily digestible diets. I hopefully recommended some probiotics as well. I can't remember now, you know, 24 hours it was improving, but you know, the owner, it wasn't fully back to normal, so came and saw the older partner in the practise and dispensed antibiotics and lo and behold, sort of 24 hours later it got better.

I'm sure it would have done anyway if they just kind of persevered with my treatment plan, but that sort of situation creates this expectation or pressure, I suppose that, you know, we need to dispense antibiotics, but No, we shouldn't, we shouldn't be looking at antibiotics, you know, this is not a valid reason to be given antibiotics because people expect it. Like I say, we need to think about having these sort of courageous conversations with people and explaining why antibiotics are not indicated or shouldn't just be given out like Smarties to be used in any case that comes in. So our antibiotics always indicated if there is a potentially pathogenic bacteria.

So we've done the testing, we've found a potential pathogen. Should we always use antibiotics in those situations? And the answer is no.

You know there are situations where we wouldn't want to use that, and so we will go into that in more detail. I'm not just going to say no and just leave it at that. So let's go into those.

So salmonella In people with salmonella, what they found is that antibiotics have not been shown to provide any clinical benefits in diarrhoea situations with salmonella involved, and actually the antibiotics may increase the incidence of adverse effects and actually may prolong shedding of the salmonella in the stools. But what about dogs and cats? Unfortunately we don't have, you know, a lot of data to go off.

There isn't any evidence to show efficacy of antibiotics in cases of of salmonella. And we know that salmonella is very likely to develop antimicrobial resistance, so that is a real concern. And also, you know, they can go into this carrier state which we know, dogs and cats can, can happen to them as well.

Campylobacter. Interestingly, Campylobacter enteritis in people, the, the main recommendation for treating is just to maintain hydrate hydration and electrolyte correction. So antibiotics aren't indicating in the majority of these cases.

The only time they would be used is if there was pyrexia, hemorrhagic diarrhoea, more than 8 stools a day, symptoms more than a week, immunocompromised, kind of, and I think these are quite reasonable criteria for using antibiotics in dogs and cats too with compylobacter, you know, if we've kind of Ideally, like I say, we'll have done our faecal analysis. We'll have seen Campylobacter present and high, ideally we would then go and do PCR and identify exactly what species it is, but if we couldn't do that for whatever reason, I think if we had these symptoms or signs associated with a positive faecal analysis, then yeah, I think we could reasonably argue that antibiotics are indicated. But a couple of other things that are quite interesting.

And in children with Campylobacter, there was a positive effect if antibiotics were used very early on in the disease process, but if the intervention with the antibiotics was delayed for a few days, then it didn't have any positive effect. There was no sort of difference to not using antibiotics. So I think if we are going to think about it again, probably if we extrapolate this to dogs and cats, we want to try and get in there early with the antibiotics.

What about E. Coli? Well, the use of antibiotics in E.

Coli remains very controversial in both humans and animals, and there's evidence to show that using antibiotics can increase shigella-like toxin release from E. Coli 0157, which obviously will worsen the disease process. So we want to try and avoid that.

And also we know that. Antimicrobial resistance is intrinsically high in E. Coli naturally, so we don't want to increase the risk of this developing, in, in our patients as well.

With clostrogen profringents, the presence of the clostrogen profringents enterotoxin has been significantly associated with diarrhoea in dogs, although it can still be found in the stools of healthy animals as well. So the presence there doesn't necessarily mean it is the cause. But the antibiotics may be indicated if the disease is moderate to severe.

So I hemorrhagic gastroenteritis. But obviously in the back of our mind, we still need to be mindful of the antimicrobial resistance. So, yeah, I think with these situations, you probably would be veering towards them if the disease was, was like I say, moderate to severe, but just be, be cautious.

And then finally in our tour of pathogenic bacteria we've got Clostridium difficile or C. Diff as people sometimes refer to it, possibly well known from the human side where it is, you know, a serious cause of diarrhoea, really kind of high morbidity mortality rates with with C. Diff in people.

The first line treatment is actually metronidazole, and then vancomycin is reserved for those refractory cases. You know, vancomycin is, is kind of needs to be preserved. It is an effective treatment, but we don't want to be developing antimicrobial resistance, you know, against vancomycin in C.

Diff. Interestingly, there has been a lot of work recently and a lot of publications about the use of faecal microbial transplantation, for patients with, with C. Diff and some really, really promising results.

Some people, for people that aren't aware of faecal microbial transplantation or FMT. It's essentially drinking poo. It's not quite, you know, as simple as that.

What we're talking about really is a donor patient would provide their faeces, and the donor is often someone that is either related to the patient or lives with the patient because they're likely to have a very similar microbiota. So their faeces is screened and checking for pathogens and anything else that we don't want to be passing on. It's then processed into a faecal slurry and rather than drinking it and downing it, and it's more likely to be administered by a nasogastric tube, so it gets, you know, you have to taste it, it gets into the stomach, and the idea being that, you know, it's a way of replenishing and replacing the microbiota of the patient and hopefully then competing with the, the, the C.

Diff. A probiotic, for example, it might be 14 different strains, but what we're talking about here is, you know, essentially a sort of probiotic mix containing thousands and thousands of different bacteria and, and hopefully a really nice balance already. So it's a really effective way of managing these cases.

In dogs and cats, we don't really know whether C. Diff is a cause of diarrhoea. There's definitely been no link to hospitalizations like there has in people, and so we don't know if treatment is required.

I think given the information that we have about FMT and humans and the use of probiotics, then that's probably a better route to go down and we certainly wouldn't want to be using the vancomycin in any cases because you know that really needs to be reserved for the sort of serious refractory cases that have not responded to metronidazole. So we don't want to be kind of contributing to antimicrobial resistance from from animals by giving vancomycin to these cases. So to summarise, I suppose all that, the empirical use of antibiotics is not recommended in uncomplicated acute diarrhoea.

You know, if it just seems like a very straightforward case, and you know we're not at all worried about anything else, then we wouldn't be using antibiotics just sort of first line. The reason that we would want to use them is if we have detected a bacteria that is known to be pathogenic to dogs and cats, or you know we've found it's toxin in the faeces and they have got acute severe disease, then definitely we would want to be looking at antibiotics. And if also if we're kind of worried a little bit about sepsis, so if they are pyrexic, if it is hemorrhagic diarrhoea, then again that might kind of tell us that we need to be considering antibiotics.

And ideally it should be based on in vitro sensitivity testing, making sure that we're choosing the appropriate antibiotic for the bacteria that we're trying to treat. So link into that point about sepsis, should we always be using antibiotics if we are concerned that bacteria could be translocating from the gut into the bloodstream? And the answer is not always, and again, I'm not just going to leave you with that.

Let's go into that in a little bit more detail. Firstly, let's just make sure we're sort of clear on the definitions of different terminology that we're going to use here. So I mentioned bacterial translocation.

This is the movement of viable bacteria or their products from the lumen of the gut to extraintestinal sites. So essentially moving out of the gut into the rest of the body, you know, there are millions and billions of bacteria in our gut, and you know it's not. And unusual I suppose for some of those to be able to get through the gut wall into the, into the systemic circulation.

And if we see those bacteria in the blood, then that would be what we term a bacteremia. This would be confirmed by blood culture and to identify bacteria that are present and obviously in particular pathogenic bacteria. Septicaemia is the systemic disease caused by the spread of these microorganisms and their toxins in the circulating blood.

And then sepsis is the life threatening, effect of, of septicemia. So when we get organ dysfunction and usually due to, The sort of immune response to the infection and you know the kind of knock-on effects that that has in terms of antibodies getting into different organs and causing them to stop functioning as they should be. Obviously if we've got those bottom to the septicaemia and the sepsis, then you immediately require parental antibiotics.

So if there is a, you know, high suspicion or if we've got test results that indicate that there is a septicemia, and then we'll definitely be looking to start parental antibiotics ASAP. The thing that can stop bacterial translocation is a really healthy, highly functional gut barrier. I'm not going to go into the gut barrier in a load of detail now, but essentially it's, you know, it can be made up obviously the epithelial cells that form the wall of the of the intestines or other parts of the gastrointestinal tract.

But also it's the immune system that's associated with those cells. It's the bacteria that are surrounding the cells. So if we have a normal balance of good and bad bacteria, then that helps to keep everything functioning normally and working as it should be.

So if we get a situation where we get a dysbiosis, so that imbalance of the between the good and the bad bacteria, then that does have an impact on the health of the epithelial cells. For example, bacteria in the gut can ferment certain compounds, certain soluble fibres, to produce short chain fatty acids, and those short chain fatty acids are used as an energy source for the androcytes. So you can sort of envisage that you know, if you haven't got those fermentation products being produced, then the epithelial cells are not getting their energy and their food that they require and therefore they're not functioning quite as they should be.

As I mentioned, the immune system is important, you know, the, the gut associated lymphoid tissue is a term that you might be remember from university days. So if that is not functioning, if we are immunosuppressed for whatever reason, then that again is going to not be able to stop pathogens from getting across the the gut barrier into the into the bloodstream. And then obviously if there's a primary damage to the gastrointestinal epithelium, so that could be infectious damage, you know, a viral bacterial producing toxins, and these toxins, you know, will, will damage epithelial cells and obviously if there is hemorrhagic diarrhoea, then that could be suggestive that there is damage to the gastrointestinal barrier.

Obviously, if there's blood going out, and then there's the chance that bacteria could go in, of the, into the blood vessels. So if we've got bacterial translocation or we're suspicious of it, Is it always gonna cause clinical disease or is it gonna kind of worsen the prognosis for the patient? And again, the one word answer is no.

Because there has been a study that was done in healthy dogs just undergoing routine ar hysterectomy, and they found that 52% of those had bacterial translocation. You know, it's not unusual if you think you know what dogs and cats eat, what's going on in their gut in terms of the bacteria they have in there. We mentioned that a lot of Bacteria that we often consider to be pathogenic are present in healthy dogs.

So, you know, there must be some protective measure to ensure that, you know, if some of those bacteria get into the bloodstream, it's not going to result in overt disease every single time. I didn't highlight it on that last slide, but the study that I mentioned there was from 1997. This one is a more recent study, this is from 2015, and this was looking at .

Dogs with acute hemorrhagic diarrhoea syndrome. They looked at 87 dogs with acute hemorrhagic diarrhoea and then 21 healthy dogs as well. And what they wanted to do was look at the, Blood culture, from these patients to see, you know, is there evidence of bacterial translocation.

And what they found is that there was no significant difference in the incidence of bacterema between patients with acute hemorrhagic diarrhoea and the control group. And they also showed that there was no difference in the severity of clinical signs, laboratory parameters, duration of hospitalisation, or mortality between the blood culture positive and the blood culture negative dogs that did have the acute hemorrhagic diarrhoea syndrome. So they went on to conclude that bacteremia does not influence the clinical course or survival and that antibiotic treatment is not indicated to prevent sepsis.

So kind of a really interesting study and a really kind of profound finding from this work that they did. So to go back to our question about whether antibiotics are indicated, if there is a concern about bacterial translocation, I think that last study was quite clear with their conclusions, but just a sort of few more interesting points, from, from human medicine. Actually they found that antibiotics given to human patients can actually cause translocation of normal bacteria, so they actually contribute to that translocation.

And they can increase the inflammatory response associated with that translocation, and we've touched on this one already. They can also increase the release of Shigella-like toxin from E. Coli 0157.

So kind of making those, if for example, E. Coli 0157 is in the bloodstream and we give antibiotics, then you know potentially we're going to worsen, worsen the situation. And actually the presence of anaerobic bacteria in the gut may even prevent bacterial translocation.

So we talked about having a healthy balance of bacteria in your gut, a nice balanced microbiota, and that does seem to contribute towards preventing this bacterial translocation. So if we were to kind of look at Antibiotics that selectively killed anaerobic bacteria, then you know we could make that situation worse and that's actually been demonstrated in a mouse study that looked at this. They gave mice metronidazole and they had increased.

Dissemination of intestinal bacteria into their, I think they looked at, yeah, they looked at the mesenteric lymph nodes and found that those that had had the metronidazole had much higher levels of bacteria in their mesenteric lymph nodes compared to the control group. So this is a slightly older study than the one on the previous slide, but and you can see that they're using the older name of hemorrhagic gastroenteritis, but it's the same as what we were talking about earlier, which is the acute hemorrhagic diarrhoea syndrome, which seems to be the sort of terminology that's more widely accepted now. So, obviously doing this remotely, I can't ask everyone to put their hand up in terms of how many people use antibiotics for, these, these conditions, these cases of, of acute hemorrhagic gastroenteritis or acute hemorrhagic diarrhoea, .

But this study was looking at that those cases, so 60 dogs in total, and they were randomly assigned to either receive amoxicillin clavulanic acid for 7 days or a placebo and they looked at the severity of the signs and what they found is that there was no significant. The difference between the group that received the antibiotics or the placebo group in terms of the mortality rate, dropout rate, duration of hospitalisation, or the severity of the clinical signs, so they concluded that in some dogs with hemorrhagic gastroenteritis or hemorrhagic, I'm getting confused now, acute hemorrhagic diarrhoea syndrome, that they, when they're not showing any signs of sepsis, and I think that's the important differentiation. Antibiotics may not change the case, outcome, or time to recovery.

So this kind of again leads back. They've got blood in their faeces, so we think, you know, the gut barrier is damaged, their, their bacterial translocation is, is more than likely happening, but again, sort of using antibiotics doesn't then improve the clinical outcome. So although I've kind of said that you know if they've got hemorrhagic diarrhoea, then they've probably got bacterial translocation.

We don't really have any hard evidence to suggest that there is an increased risk of bacterial translocation if there is hemorrhagic diarrhoea and therefore, you know, kind of leading on to sepsis. And as we've said with the studies that we just talked about. Bacterial translocation alone may not be enough to justify the use of antibiotics, so You know, how do we then differentiate, and I think that's why some people still do choose to use antibiotics if they've got acute hemorrhagic diarrhoea, because we know that septicaemia can be life threatening if it does occur, and you know, how do we sort of differentiate that?

We can obviously look at see if they're pyreexic or not, and that could be an indication. But what if they come in, they're normothermic, they've got acute hemorrhagic diarrhoea. We don't know whether the bacteria is translocating or whether they're sort of starting to develop sepsis, so I think that's why some clinicians do elect to use the antibiotics early in these cases.

But antibiotics can have some negative effects as well. They will disrupt an individual's microbiota. You know, we mentioned that there is a balance between bacterial species residing in the intestines, so giving antibiotics will inevitably kill off a population of those.

And you know what happens after that is you create a bit of a vacuum, I suppose, and is that going to be filled by some good bacteria or some bad bacteria. And that's why some people, often use probiotics alongside antibiotics or after a course of antibiotics, so that that void is hopefully then filled by beneficial bacteria rather than, you know, the, the other, other option. So yeah, this can result in adverse effects, you know, obviously disrupting the microbiota can have lots of negative impact.

We talked about the fact that they might be more likely to develop bacterial translocation and therefore sepsis if we're killing off the anaerobic bacteria. And the big thing that we keep coming back to is, is the development of antimicrobial resistance, which, you know, is a global problem now that we all need to be mindful of, so we do need to be conscious of our decisions when it comes to the use of antibiotics. So there's quite a bit of evidence for antibiotics having an adverse effect on the gut microbiota and causing this dysbiosis.

This study in dogs, healthy dogs given a two week course of metronidazole, basically found that it did have an impact on the gut health, so reduced the numbers of certain bacteria that we know are beneficial for gut health, and actually these changes persisted even 4 weeks after the antibiotic course had finished. In humans, there's some good stuff, good studies, good stuff, good studies ciprofloxacin in this case been shown to reduce the taxonomic richness and diversity of the gut bacterial populations in people. So again, sort of going back to what I said a bit earlier, that richness and diversity, so having lots of bacteria and lots of different bacteria, is really important for gut health.

So the consequence of this dysbiosis is that we can see gastrointestinal upset people report this quite commonly alongside antibiotics, but it's also been recognised in dogs and cats. Antibiotics aren't, you know, without their risks in terms of something like metronidazole can cause neurotoxicity, even at relatively low doses, and there are some potential. Side effects when antibiotics are used early in a child's life, and it has been associated that they'll develop the following diseases later later in their life things like obesity, Crohn's, asthma, AP, and potentially behavioural disorders.

So the link obviously hasn't been proven in dogs and cats, but it's just bearing in mind that, you know, the long term impact that we can have by messing around with the bacteria in the guts. I don't think we can take it too lightly. And then finally we get onto the biggie, I suppose in terms of antimicrobial resistance and obviously we've mentioned this a few times in the previous slides, but obviously it is a global concern that's increasing, and we need to be conscious that we preserve antibiotics for cases where they are actually needed and there has been some work showing that antibiotic use in animals has been linked to resistant bacterial strains in humans, so.

You know, it's important to remember that what we are doing with our patients could be having that wider impact, across into humans and what effect that might have to the wider population. And this study from 2020 was very interesting, so looking at giving amoxicillin clavullanate to dogs with non-complicated acute diarrhoea. And what they found is that these cases were, were likely to develop E.

Coli that were then resistant to amoxicillin. And those resistant E. Coli were then able to persist for up to 3 weeks post treatment.

And obviously the big thing that we have touched on is that using the antibiotics didn't provide any clinical benefit compared to placebo. So again, you know, it's thinking why are we doing this and what impact is it going to have, you know, on the patient but also like I say, on the wider population. So I've probably reiterated a lot of these points already, but it's always good to have a bit of a summary slide at the end of a presentation.

So just to kind of remind everyone that acute diarrhoea is generally a self-limiting disease and that faecal analysis is a very useful test, but it probably is underutilised at the moment. And I think that probably the reason for that is because the results are quite difficult to interpret. So although that is the case, I think we should be testing, but just when you see the results.

Be conscious of how you're interpreting them and don't sort of jump to conclusions when you see that a certain pathogen is high. Antibiotics are probably too frequently prescribed compared to the percentage of cases where they are actually indicated. I should imagine, you know, the numbers that we talked about earlier, 47% at the moment of acute diarrhoea cases getting antibiotics that is going to be higher than the the times that they are indicated.

And when they should be used is if we have identified a specific pathogenic bacteria and the animal is showing, you know, severe clinical symptoms as well, or if they have septicemia or they're at risk of developing septicemia at some point. And antibiotics, you know, can have adverse effects, you know, we often think of antibiotics as being safe, but again, just sort of bearing in mind that they can have negative effects on an individual basis and with antimicrobial resistance that could extend to sort of global population population levels of negative effects as well. So it is to justify empirical use if it's an uncomplicated acute diarrhoea, you know, you don't think that they have septicaemia or at risk of developing sepsis, then it is difficult to, you know, justify using them and probably maybe worth using probiotics or or something similar in those sort of straightforward cases.

So if you remember nothing else from the last 45 minutes or so, we should be reserving the antibiotics for specific cases where we have, you know, a defined bacterial infection that we are relatively sure is the underlying cause of the disease process and that it could cause secondary complications with bacterial translocation or sepsis if we don't do anything about it. So thanks for listening. Hopefully that was useful or there was a few points that were useful.

If there were, then great, if you have any questions, then feel free to email the address that you see there. That will go to our team of vets and one of us will be able to get back to you and hopefully answer your question. But yeah, thanks again and hope you have a good day.