Thank you for joining me for this webinar. Most of us will have heard disturbing true statistics about antimicrobial resistance, and many of us, as we should be, are concerned about the implications. We want to practise in a way that helps maintain the efficacy of these medications for treatment of infections in people and horses.

All of the answers as to how to do this aren't you out there, and we can expect guidance to continue to evolve. But there are some things that we know to be helpful or there are likely to be. The scope for a lecture series on some of these topics.

So we won't cover everything in detail here. But my aim in this webinar is to provide an overview of practical considerations in clinical practise, as well as some specific examples. So our objectives are to understand ways to decrease the development of disease in order to decrease the development of antimicrobial resistance.

To become familiar with ways to decrease antimicrobial usage in prophylaxis and disease in order to decrease the development of antimicrobial resistance. And to consider ways to improve our antimicrobial usage to decrease the development of antimicrobial resistance. Firstly, although antimicrobials include both antibiotics and antiseptics, I will use the term antimicrobial to mean antibiotic in this talk.

So what is antimicrobial resistance? Well, it can be divided into intrinsic and acquired resistance. Intrinsic is when all bacteria of a species are naturally resistant to a certain type of antimicrobial.

This is typically when bacteria do not use the mechanisms targeted by that antimicrobial. For example, aminoglycozides are pumped into bacteria where they then interfere with protein synthesis, which leads to bacterial cell death. But anaerobic bacteria do not actively pump molecules across their cell walls.

Therefore, aminoglycosides cannot enter. And this means that anaerobics are intrinsically resistant to gentamicin. But currently, we can't do anything about this, and it's acquired resistance that's of interest to us.

Acquired resistance. This is the resistance that develops following either genetic mutations or the acquisition of genetic material from other bacteria. So here's a diagram to represent this concept.

So on the left in blue, we have one species of bacteria, and on the right we have another in green. The chromosomal DNA of each type of bacteria, so the blue versus the green, is different, but is both represented in. Black.

Then in addition to the standard chromosomal bacteria, the blue species of bacteria have a plasmid which contains a gene encoding for antimicrobial resistance. So we can see that although the green population of bacteria don't. Originally have that, we can get horizontal gene transfer where the plasmid is replicated and transferred.

Via bacterial conjugation to the green species, meaning that subsequently we've got two different. Species of bacteria, now both containing that those genes for antimicrobial resistance, meaning that as both of those populations reproduce and their new generations, both species will now contain that. Mutation for antimicrobial resistance and plasmids are just one example of that.

There are other ways in which genetic material can be transferred to. I think this is a key point, as when we think about resistant bacteria, I think we primarily think of the direct spread of pathogens. For example, zoonotic spread of multi-drug resistant Clostridium perfingen.

But actually, of considerable importance to a spread of the resistance genes themselves. The genes can be passed into different species of bacteria, meaning that bacteria that were previously sensitive to a specific antimicrobial can now become resistant, and this adds to the pool of antimicrobial resistant bacteria in animals, people and the environment. So that species should be sensitive to a specific antimicrobial, but now is not with acquired resistance.

For example, Staphylococcus aureus is intrinsically sensitive to betylactam antimicrobials, including methicillin, penicillin, and ceftifu. However, MRA. Methicillin resistant Staphylococcus aureus has acquired genes encoding for resistance to these antimicrobials.

So which antimicrobial resistance are we interested in? MRSA. ESPL producing bacteria.

So ESPL stands for extended spectrum betylectommase. These are enzymes produced by the bacteria which inactivate betylactam on to microbials, such as penicillin and sty. ESBL production is a particular problem in enterococcus fusion, lepsia and pneumonia, Pseudomonas aeruginosa, and enterobacteria species.

We're also interested in other multi-drug resistant isolates. The exact definition of multi-drug resistance is different for different bacterial species, but it tends to mean that bacteria resistant to at least 1 in 31 in 3 or more antimicrobial classes. And pan-drug resistance, rather scary concept, refers to resistance to all testable antimicrobials of relevance.

So what are the impacts of antimicrobial resistance from antimicrobial usage in horses? Firstly, let's think about it from the, in the context of equine health. Delay in effective treatment.

The more widespread antimicrobial resistances, the less likely that any empirical therapy given is to be is to be successful. Meaning that it might not be until we get cult results that we can instigate therapy that will be effective. Ineffective treatments.

And to microbial resistance in a case might be such that we don't actually have an effective treatment option. Multiple different treatments could lead to an increase in likelihood of adverse drug effects such as diarrhoea. And the implications of these facts are that a decrease in prognosis may be seen.

Costs may be incurred to the client and the welfare may be reduced. So again, if we're thinking about the impacts of antimicrobial resistance from antimicrobial usage in horses, let's think about the concerns in the context of human health. And there are 3 key issues zoonotic transmission of clinical pathogens, for example, as was seen in an outbreak of MRSA associated skin disease in a veterinary team, which had spread to them from a fall.

Zoonotic transmission of opportunistic pathogens. So to use MRSA as an example again, it might not initially cause disease but may colonise people. And when in the future a surgical procedure or trauma occurs, infection can develop.

It's recognised that MRSA is around 4 times more likely to develop to develop in people that carry it in their nose. So this is a particular concern for vets with multiple studies demonstrating a higher prevalence of nasal carriage in them compared with non-vets. Prevalence rates vary across Europe, with figures from 0.7% to 19.2% of vets reported as being carriers.

As we've already discussed, we can see zoonotic transmission or contamination of the environment with bacteria carrying genes encoding and microbial resistance. This could lead to increased future complications for incontact people and their contacts. This could also lead to an increase in morbidity and also potentially mortality for affected people.

There are also wider implications for the human and veterinary populations. We know that in some countries, significant numbers of animal associated MRSA cases, such as infections with MRSA strains, known to originate from animals, have been reported in people that have had no direct contact with animals. Furthermore, we know that exposure to antimicrobials leads to an increase in carriage of bacteria carrying resistance genes, genes which can then potentially be transferred to other bacteria of relevance.

So every time we use antimicrobials, we contribute to this situation, and this is of particular importance when it comes to microbial resistance to antimicrobials that are critically important for human health. A direct impact has been demonstrated between decreased antimicrobial usage in food producing animals and decreased antimicrobial resistance in human pathogens. So let's take a look at the prevalence of antimicrobial resistance in equine practise.

Unfortunately, data are lacking, although there is some information. Reported prevalence is affected by a number of factors. For example, regional frequency of antimicrobial resistance in human infections and the approach to testing, for example, studying hospitalised horses versus those at livery.

The reported prevalence of MRSA carriage and horses ranges from 0 to a staggering 22.5%. In one study, 6.3% of.

Horses carried ESPL producing bacteria in their faeces. And in another study, although less than 1% of E. Coli assets from horses at livery were potentially SBL producers, 48% of E.

Coli islets from hospitalised horses, and 12% of horses at livery were multi-drug resistant. This year, Gina pinchbeck from the University of Liverpool presented some of the results from a combined survey done by the University of Liverpool and beaver into current antimicrobial use in equine practise, and they found that in the year prior to the questionnaire, 15.8% of respondents had had at least one case of MRSA clinical infection in an equine patient.

13% had had at least one ESBL producing entero bacteria SCI clinical infection. But I think it's likely that some vets will have had multiple with antibiograms such as these, thankfully still being a minority, but certainly occurring and demonstrating broad multi-drug resistance. So now let's move on to the main purpose of this talk, to look at what we can do to push back against antimicrobial resistance equine practise.

And there are 3 broad areas for consideration. Decreasing the development of disease that might require antimicrobial therapy. Decreasing antimicrobial usage and prophylaxis and disease.

And improving our microbial usage, and we'll talk about these in further detail. Decreasing the development of disease that might require microbial therapy. There are 3 main ways in which we can do this.

Minimising contagion of conditions which may require antimicrobial therapy. Addressing predisposing factors for bacterial infection. And decreasing rogenic complications through good clinical hygiene.

Minimising contagion of conditions which may require antimicrobial therapy. Helping clients to be aware of the following can make a significant difference. Good biosecurity.

Simple measures like taking your own water buckets when away it shows and not allowing unnecessary nose to nose contact plays a role. Quarantine. Keeping new horses in isolation for 2 to 3 weeks upon arrival at a property.

Monitoring temperatures to enable early detection of infectious disease, enabling appropriate measures to be taken to limit the spread. Having an isolation plan. When symptoms are detected, having a pre-agreed plan that can be quickly and easily rolled out is helpful.

Targeted use of vaccines, for example, being covered for influenza might reduce the likelihood of a horse that contracts flu developing secondary bacterial infection, or even being treated for suspected bacterial infection when there isn't one. There are also other examples like off licence use of vaccines against Lawsonia Intracellularis on properties with recurrent problems, potentially decreasing the requirement for doxycycline therapy. Addressing predisposing factors for bacterial infection.

Ensuring passive transfer involves, therefore reducing the likelihood of opportunistic bacterial infections. Diagnosis and management of chronic pathology. We readily recognise that PPID increases the risk of bacterial infections, but systemic illness may also reduce immune function.

For example, hepatopathy or intestinal disease. The management of local factors can also play a key role. Secondary bacterial infection is a lot less likely if the primary condition is well controlled.

For example, in cases with limb mites or culicoides, like hypersensitivity. Still looking at ways of reducing development of bacterial disease. It's important that we do what we can to minimise the likelihood of iatrogenic complications through good clinical hygiene.

Maintaining good surgical sepsis and postoperative incisional care helps to maintain the minimise, sorry, the likelihood of surgical site infections. Good cathetic care and patients with indwelling catheters. Firstly, avoiding contamination at the time of placement, which is why I've included this image.

As with this tiny click patch, it's inevitable that the junction between the extension of the castle will likely be in contact with the non-prepared area. Also following placements. Little things like ensuring that ports are kept clean, that gloves are worn when catheters are being handled, and that medications are clean when injected.

Can help. Poor catheter hygiene can lead to unnecessary septic thrombophlebitis. This is not only painful but can lead to antimicrobial usage.

A non-surgical preparation is also a consideration. So for example, good preparation prior to urinary catheterization. I just briefly wanted to mention good clinic biosecurity too.

Some highly pathogenic opportunistic bacteria hide out in clinical settings and can cause nose comal infection. Some bacteria can be multi-drug resistant too. For example, locations such as the mats underneath stocks on the back of doors of stocks and other surfaces in clinical areas should be disinfected regularly and between patients.

So let's move on to talking about decreased antimicrobial usage in prophylaxis and disease. I'll tell you the areas that we're going to cover. The first points are listed in dark blue to denote that we'll talk about them further.

Limiting per surgical use. Avoiding use in cases that are unlikely to have bacterial infections. Avoiding use in cases that have bacterial infections, but do not require antimicrobials.

Avoiding the treatment of incidentally cultured bacteria. Addressing underlying causes of bacterial infection. And also there are 3 further points that I'd like to mention, but that we won't go into further today.

Firstly, avoiding the use of antimicrobials in cases that won't recover. This was identified as a key point for minimising antimicrobial use in the American College of Veterinary Internal Medicines consensus statement on therapeutic antimicrobial use in animals and antimicrobial resistance. They made the point that in instances where we know that an animal won't make it, prescribing antimicrobials in order to give the owner a chance to feel like they've tried something is not appropriate.

Also addressing factors that will delay healing, for example, movement of a wounded limb. And finally, let's encourage clients to return antimicrobials of not being given. For example, when the type has been changed, preventing future inappropriate client use.

So let's move on to look at post-surgical antimicrobial usage in more detail. The duration of antimicrobial therapy required depends on the nature of the procedure. With a rather approximate assessment being that the higher the degree of surgical site contamination occurring, the greater the potential requirement for antimicrobial therapy postoperatively.

As one of the, as one of the most frequently performed surgeries, we can use castration as an example. You may well be familiar with the classification system for surgeries proposed by Simmons back in the 80s with clean, clean contaminated, contaminated and infected surgeries. I've included these definitions here because the principles and the conclusions can be relevant to other surgical procedures in the same category.

So closed castration is classed as a clean surgery because there's no inflammation in the tissue being entered. There's no break in asepsis, and the genitourinary tract has not been broached. All the respiratory or alimentary tracts, but that's obviously not relevant to castration.

Open castration is classified as clean contaminated. Meaning that the genitourinary tract has been broached, but no gross contamination is observed. But an open castration, where gross contamination did occur during surgery is classed as a contaminated surgery.

So the key question, of course, is what level of antimicrobial therapy is appropriate for each? For anyone who attended B this year, you might have seen Kaiser Iskren's presentation on the evidence supporting different options for antimicrobial usage for castration. We don't have the scope to go through this in great detail, but I'd like to share some of her concluding points with you.

These don't equate to firm or permanent conclusions, but there were suggestions from somebody who had reviewed the evidence and is well placed to make suggestions. For clean surgery such as closed castration, either just preoperative or a maximum of 24 hours total, antimicrobial therapy is suggested. For clean contaminated surgeries such as open castration, there's an absence of clear guidance.

There are concerns in many cases about clients injecting procaine penicillin and also concerns about switching antimicrobial classes, for example, giving penicillin preoperatively and then TMPS postoperatively, as commensals would then be exposed to antimicrobial classes. Kaiser suggested that perhaps 24 hours penicillin is adequate. I've marked contaminated surgeries in a different colour as the suggestion wasn't made.

However, the example in the Beaver tool kit was discussed, which suggests 3 days of penicillin and gentamicin. Moving on now to look at some different scenarios. I think when we're thinking about reducing antimicrobial usage in prophylaxis and disease, it's helpful to ask ourselves some key questions and we'll come back to these throughout the presentation.

So firstly, is there a bacterial infection or a high likelihood of a bacterial infection? If so, can that current infection be managed without antimicrobials? And if antimicrobials are required, are there supportive treatments or other management measures that could be put in place to decrease the time to resolution?

Risk falls. Is it appropriate to give normal falls routine on microbial prophylaxis following normal falling? If we ask ourselves, is there a bacterial infection or a high likelihood of infection?

The answer seems to be no, in which case antimicrobial prophylaxis is not appropriate. But is it ever appropriate to administer prophylactic microbials to falls? Oh yes, I think so.

In falls considered to be an increased risk of bacterial infection, this is indicated, especially as this is so often associated with sepsis. Studies indicate that although variable, the mortality rate associated with equine sepsis is on average reported to be about 50% in falls. Failure of placid transfer.

Is there a bacterial infection or a high risk of one? I think it's definitely fair to say that fairly passive transfer puts a fall an increased risk of bacterial infection. Can we just address it, reduce this risk through the administration of colostrum or plasma transfusion?

Well, especially if prompt, then yes, quite possibly. But what if there are other risk factors and the fall is already a few days old? I personally do think that in that instance, antimicrobials may be appropriate.

What if the mayor had placenitis? The fall would be considered a high risk of sepsis when born from a mare with placenitsis. Therefore, yes, I think that antimicrobial prophylaxis would be reasonable.

What about recumbency? Yes, I think so. And post-surgically?

Yes, absolutely. And what about aspiration, for example, of meconium reflux or milk? Yes.

What about if there's evidence of a significant inflammatory process, then yes, absolutely, it's the likelihood of sepsis as a consequence is high. So let's think about a coughing course. Let's ask ourselves that first question.

Is there a bacterial infection or a high likelihood of a bacterial infection? There may be historical features that increase the risk of bacterial pneumonia being present and give us a clue. For example, recent general anaesthesia.

Recent esophageal obstruction. Recent long distance transportation or contact with other horses with infectious bacterial respiratory disease, for example, streptococcus aque subspecies epidemic as infections. May also be clinical features consistent with bacterial disease.

For example, permanent nasal discharge, pyrexia, inhapetence, marked lethargy, or even congestive mucous membranes, laminitis. In the acute case, one of the challenges comes in cases, for example, post-transportation, where symptoms could be either viral or bacterial. If symptoms are severe and there are risk factors, initiating antimicrobial therapy prior to diagnostic results is reasonable.

But further assessment is still advisable because if bacterial disease is there, having a culture prior to the initiation of antimicrobials is ideal to ensure that the treatment being given is most likely to be effective. Also, if an infectious disease such as influenza is present, then we need to know about it in order to stop the spread of disease. Chronic respiratory symptoms.

One thing I think we all need to be clear on is that empirical therapy is not a suitable treatment for a failure of response to therapy in an animal with a low index of suspicion of bacterial disease. In a chronic respiratory case with a suspicion of bacterial involvement, further information is likely to be required to facilitate a good prognosis. So we're still on the topic of whether or not this coughing horse has a bacterial infection.

I think it's important to divert into talking about the interpretation of respiratory culture results. And certainly the principles apply to all types of cultures too. I think the key point here is that we want to avoid the treatment of incidentally isolated bacteria.

Respiratory culture results must always be interpreted in the context of the history, the clinical picture, the cytological findings, and the level of bacterial growth. And pure versus mixed growth can also sometimes provide useful information is depending on the types of bacteria isolated and the overall picture, mixed low-level growth may be less likely to be relevant. There are a number of species are common contaminants in tracheal wash samples, for example, alpha hemolytic streptococcus species.

Pseudomonas species, ceraceous species, and a variety of lactose cementing coliforms. It would not be common for these species to be isolated and stand playing horses with equine asthma. Very occasionally these islets might be relevant in cases with bacterial pneumonia, so we can't definitively rule out their relevance without further thought.

But unless we have a reason to believe otherwise, they're likely to be incidental findings and antimicrobial treatment is not appropriate. And then there are the opportunistic pathogens, a variety of bacteria, which again can be incidental, but are more commonly relevant in the context of secondary bacterial pneumonia. For example, Staphylococcus aureus and Clebsiella species.

So the key becomes deciding whether or not pneumonia is present. The factors that we've already talked about may enable us to determine that, but we may also need further diagnostics, such as thoracicaltrasonography. And anaerobes are usually relevant when they're present in a track quash.

And finally, we have the primary bacterial pathogens such as Streptococcus equi subspecies equi and Streptococcus equi subspecies Zooepidemicus. We do know that low levels of some strains of streptococcus equi subspecies Zoo epidemicus can be present incidentally in the airway, but it, depending on the strain and the clinical picture, it can also be a significant finding either in aspiration pneumonia or. As a primary contagious disease.

Actino bacillus auli is also usually relevant when present. And stretomonas multiphilia is also a slightly different one, which has been implicated in some cases of chronic inflammatory airway disease and it may perhaps be relevant even in the absence of specific symptoms of bacterial pneumonia. So we want to avoid the treatment of incidental bacteria.

And a key part of this is interpretation in context as we've discussed. But there are other factors which may also play a role in this. In the AI consensus statement on therapeutic antimicrobial use in animals and antimicrobial resistance, they talked about the benefits of using an accredited microbiology service to facilitate appropriate antimicrobial treatment.

For example, in the UK this will be the use of a lab certified by UCAS. And there are a few points which I think are worth further consideration. Can you get the information that you need from culture results obtained in-house or from an unaccredited commercial lab?

Are the cut-offs for sensitive, intermediate sensitivity, and resistant accurate? When information is available for equine pathogens, which isn't for all drug and bacteria combinations. Will specific multi-drug resistant phenotypes or genotypes such as MRSA and ESBL producing coliforms be identified as such?

I think this is a key part not only of monitoring multi drug resistant infections in your practise, but of identifying cases where isolation is advisable. And also are normal. Flora reported As, as if they are, you either need to be aware of their likely irrelevance or receive interpretive comments.

And do you have access to interpretive support if required? I think another key consideration is our in-house laboratory personnel adequately protected from infection by zoonotic islets and colonisation by multidrug resistant islets. So let's go back to the coughing horse and ask ourselves the second question.

If a horse does have a bacterial infection, can the current infection be managed without systemic antimicrobials? So with the risk factor, and with signs such as severe pyrexia, cough and lethargy, I think antimicrobials are indicated alongside supportive care and further assessment. But what about without a risk factor?

Even with signs such as Moderate pyrexia, cough and cough and lethargy. I think supportive care as assessment only. And what if horse has strangles?

The vast majority of cases will not require systemic antimicrobials, but occasionally, for example, in horses that are in respiratory distress, antimicrobials may be indicated. What if it's primary contagious streptococcus equi subspecies, the epidemicus infection? For example, if we know that this is present on the yard and there are a number of horses showing clinical symptoms.

Many immunocompetent adult horses will not require systemic antimicrobials. And supportive care monitoring is often adequate. However, if there is a failure to to improve despite supportive care, then some animals will require antimicrobial therapy, but they are a relatively small proportion.

If antimicrobials are required. Are there supportive treatments that could decrease the time to resolution. There are no clear cut good evidence-based answers to this, but a few points that might be worth considering could include feeding from the ground.

This may help facilitate mucociliary clearance of bacteria. Maintaining hydration. In dehydrated patients, respiratory secretions may be thicker and more difficult to clear.

And nutritional support, recovery may be impaired by negative energy balance or vitamin or mineral deficiency, particularly in horses that are not eating well. Support might be required. So I'm not going to talk at length about wounds, but whilst we're on the subject of expediting healing, I think wound healing is worth mentioning, as it's the area with most options for supportive therapy.

And in some instances, these therapies may even be able to be used as an alternative to antimicrobial therapy. These are just some examples. Honey.

In the recent published beaver primary care guidelines on wound management in the horse, it was concluded that honey may increase the speed of healing in both acute and chronic wounds. Laser therapy. In the same Beaver review it was concluded that there's currently insufficient evidence to confirm efficacy.

However, this doesn't mean that it doesn't help. But it just that currently there's insufficient evidence to support its use. Lawful debridement with maggots.

In the beaver care guidelines that I've just discussed, we, it was concluded that there was very weak evidence that this is an effective form of debridement. However, there are multiple published human and equine cases that have positive outcomes following larval debridement, despite a poor prior response to other approaches. So it may be something to consider in some cases.

Plasma or platelet rich plasma. Locally derived Hyperimmune plasma has been shown to aid in the healing of infected human wounds. And both Locally, locally delivered PRP and PRP gel have been shown to decrease Staph aureus loads in experimental equine wounds.

And both local hyperimmune and standard equine plasma have been shown experimentally to decrease the binding of MRSA to bone. Local PRP and PRP gel have been shown to expedite wound healing in non-infected equine wounds. Furthermore, in a case report, local PRP treatment was used postoperatively without postoperative antimicrobials in the six week treatment of a severely chronically infected wound following the surgical removal of a boostosis.

This potentially demonstrates a role, not only in reducing antimicrobial use, but potentially in replacing it altogether in some cases or phases of treatment. And there are some gory pictures here of said wound from that case report showing pretty impressive improvement. Diarrhoea in the adult horse.

Again, our first key question should be, is there a bacterial infection or a high likelihood of a bacterial infection? If we consider the possible causes of diarrhoea in the adult horses in the UK, it's only a proportion that are bacterial in origin. With salmonella species, Clostridium profings and Clostridium deseal being our main culprits.

Unfortunately, clinical symptoms alone don't always enable clear clarification as to whether that diarrhoea is bacterial in origin or not. So this is where faecal pathogen testing comes in. So for salmonella.

A key point about faecal pattern testing is that you get out what you put in. So if you take a single faecal sample and expect an answer, you might not be in luck. But if you work within the limitations of testing, expect to test multiple times and preserve samples adequately, you are more likely to get an answer.

So ideal sampling for salmonella culture would be at least 5 separate faecal cultures. Compromise would be at least 3 separate faecal cultures. A further compromise would be at least 3 pooled cultures.

And if you're using less than 3 pooled cultures, then false negative is not unlikely. And certainly if you're just using a single faecal culture, it could be considered unreliable. For C perfringence and C.

Difficile, faecal toxinizes our test of choice, and faeces for these should be sent chilled and should be processed within 24 hours of coming out of the horse. So in addition to thinking about whether or not the diarrhoea could be primary bacterial in origin, we also just need to think briefly about whether there are secondary bacterial complications or a high risk of them. In some immunocompromised patients with severe neutropenia and symptoms of systemic inflammatory response syndrome, some people would feel that a horse is at risk of secondary bacterial complications such as sepsis.

Others would disagree, and in the adult horse, this isn't black and white. My personal experiences that septic complications are rare in the adult horse. And interestingly, a study by Imogen John's back in 2009 found that even in bacteremic courses with diarrhoea, and to microbial administration did not improve the outcome.

So if we look to our second recurring question. If we do think that there's a bacterial infection, can it be managed without systemic antimicrobials? And alongside that, especially with diarrhoea, could antimicrobials have an adverse effect?

So if you think firstly about salmonella species colitis, it's been suggested that antimicrobials do not alter the rate of recovery from salmonella associated acute colitis. Antimicrobial therapy is generally not recommended in acute cases. Although going back to my earlier point about high-risk patients was concerned about septic complications, in some instances, it may be that they're occasionally indicated.

And what about in chronic cases? Well, in a percentage of cases, salmonella infections can become chronic when horses are unable to clear this infection themselves and symptoms such as weight loss and chronic diarrhoea can be seen. In these instances, antimicrobials are often required, but in these cases, it's also important to look at whether there are other reasons for inadequate recovery, and these should be dealt with too.

So let's consider C. Difficile or C perfringent associated colitis. Even in humans, there's insufficient evidence to definitively state that antimicrobial therapy is beneficial.

But it's considered likely enough that antimicrobial therapy is usually advised. Horses this is unknown but confirmed or strongly suspected cases of Clostridal diarrhoea, in my opinion, it would be reasonable to give them to give them metronidazole. So could antimicrobials have an adverse effect?

In cases with diarrhoea, the short answer is probably yes, as they can target the normal flora, a key part of the local immune response to GI pathogens, in addition to targeting the actual pathogens. We know that systemic antimicrobial therapy can prolong salmonella species shedding in experimentally infected animals. Systemic antimicrobial therapy was demonstrated to increase the likelihood of C.

Difficile culture positive faeces in experimentally infected animals. And we also know that antimicrobials have been implicated as a cause of diarrhoea. So with all these considerations in mind, can we draw any tentative conclusions?

For adult horses with acute diarrhoea. Of non-clostridal origin and to microbials almost never indicated. Unless there are septic complications or a high risk of them.

For adult horses with acute diarrhoea of clostridial origin, they could be indicated. For adult horses with chronic diarrhoea of non-bacterial origin, they're not usually indicated. And for adult horses a chronic diary of bacterial origin, they're often indicated.

Now let's move on to look at pyrexia of unknown origin. Are there any clinical or historical derived clues? It may be unknown origin, but if we dig a bit there, there might be something relevant that we can find out.

Is the severity of the clinical picture suggestive of potential for bacterial infection that requires urgent treatment? I think it's a key question is by the very nature of these cases, we can't make informed decisions about the likelihood of infections requiring treatment because of a known clinical scenario, for example, diarrhoea, because we don't know the site. So if we have symptoms such as moderate to severe tachycardia or ypnia or severe lethargy alongside pyrexia then.

In my opinion, yes, antimicrobials are indicated. And further assessment is also likely to be indicated. But if not, then supportive care and further assessment are likely to be the appropriate course of action.

Although there are multiple possible causes for pyrexia of unknown origin, in genuine cases of unknown origin, a significant percentage will either be affected by an infectious respiratory pathogen, have peritonitis, or have inflammatory intestinal disease. So for that reason, I think a nasopharyngeal swab for respiratory pathogen testing, peritoneal fluid analysis, and potentially haematology and biochemistry for organs specific clues can be useful next steps. Still on the subject of reducing antimicrobial usage in prophylaxis and disease, I just briefly wanted to comment on the point about addressing underlying causes of bacterial disease.

The point here is if that we're trying to treat a horse with an ongoing source of bacterial infection without removing that source, we would likely to end up giving multiple rounds of antimicrobial therapy, still not having the outcome that we are the client wants. For example, if we have an apical tooth root infection as a consequence of irreversible damage to that tooth, infection will likely recur without dental extraction. I think this is one of the most difficult challenges that we face in our fight against antimicrobial resistance.

So when a client refuses to address the underlying cause, it puts us in a difficult position. But I think we have to do what we can to communicate the reality to clients, and this ties in with the point about not treating infections that cannot be resolved. So we've looked at some many examples on how we can work towards decreasing the development of disease and antimicrobial usage in prophylaxis and disease.

Now let's take a look at improving our antimicrobial usage. Outlined here in blue will be a number of points that we will cover in more detail. First of all, appropriate antimicrobial selection.

Aiming to achieve effective management of the infection as quickly as possible. We'll also cover optimising the use of culture. And Awareness of limitations and strengths available on microbials.

We'll also talk briefly about dose selection and duration of therapy. I won't say any more about appropriate care of medications other than to highlight the importance of using them within the use by date and within the broach by date. And also that medications should be kept at the appropriate temperature to avoid denaturation and potentially reduction in their efficacy.

Culture A key point in optimising the use of bacterial culture is to sample as early in the disease process as possible and prior to antimicrobial treatment whenever possible. Can you get a representative sample? Sometimes such as in contaminated wounds with internal lesions, or when the location of pathology is unclear, this can be challenging.

Preparation may be required, for example, preparation of a wound, then deeper sampling. To avoid skin contaminants or preparation of a teat followed by midstream sampling in the suspected case of mastitis. If you have a choice between an aspirate fluid from the source of the problem, or superficial discharge, then the aspirate is usually best, as it's less likely to be contaminated with skin commensals or environmental bacteria.

And sometimes blood culture might be useful in cases with internal lesions. Multiple samples can be required though, and you may be more likely to isolate bacteria if samples are taken during a period of pyrexia. And for areas with low bacterial numbers, even in when infections present, so for example in joint fluid, it might be worth considering submitting that sample in a blood culture bottle.

We want to maintain viability of organisms. And we don't want overgrowth of some of the bacteria potentially out competing the relevant pathogen within the sample. So things that can help with this, samples should be processed within 24 hours of collection.

Transport medium should be used for swabs. Eating should be avoided. And we need to be aware that anaerobics can die within 20 minutes of oxygen exposure.

So samples being sent for anaerobic culture need to be processed accordingly. There could be a whole webinar on appropriate ant microbial selection, but I'm going to limit my comments here to a few salient points. There was an excellent review recently in equine veterinary education on the subject of antimicrobial resistance, sorry, not resistance, selection.

And I'd recommend you take a look at this if you'd like further information. Important factors in our antimicrobial of choice include, we need sensitivity of the relevant organism. We need the drug to reach the relevant site, and when it gets there, we need it to work.

Bacteriostatic antimicrobials, such as tetracyclines may be ineffective and immunocompromised patients. We also need a practical achievable dosing regimen. As part of the antimicrobial toolkit, beaver have also produced some helpful material to help with antimicrobial selection.

This information is technically designed as an example of what a practise might put together as part of their own antimicrobial guidelines. It's not a firm set of recommendations. A first line choice and alternative are listed for a variety of scenarios, but one limitation of these examples is that no guidance is included as to when the alternatives might be acceptable.

What concurrent measures are required, or indeed when antimicrobials might actually be necessary. For example, penicillin existed against the use. Is listing its use in the presence of chondroids.

But the fact that chondroids acquire local management, not just penicillin treatment is not noted. There are also some controversial examples such as penicillin being listed as prophylaxis against strangles of what practise widely now considered inappropriate from an antimicrobial stewardship perspective. So this toolkit is designed to be of assistance, but not to give sort of firm set of guidelines.

Dose. We need to avoid underdosing. In an Australian study, approximately 30% of antimicrobial doses given to horses perioperatively were insufficient to reach effective tissue levels for common equine pathogens.

And it's known that all antimicrobial usage can select for antimicrobial resistance, but exposure to sublethal levels may increase the rate of the development of antimicrobial resistance. And what dosage we should be using is a contentious issue for some of the antimicrobials used in equine practise. Should we be using data sheet doses?

Whether or not that's permitted to use dosages that differ from the data sheet is different in different parts of the world. In the UK, the VMD issued a statement confirming their position on a number of factors such as this. My interpretation of this is that vets in the UK are permitted to use off-label doses when there's evidence that those doses would either be more efficacious or contribute less negatively to the development of antimicrobial resistance.

A common example here is trimethopram sulphur, where there's evidence to support higher and more frequent dosing than is often recommended on data sheets. And we also use antimicrobials that are not licenced for equine use, for example, doxycycline or metronidazole. What dosage should we be giving these at?

We could use examples given in the beef toolkit. Many of these are different data sheet recommendations based on scientific literature. However, they're not clear-cut black and white correct answers, in part because these just don't exist for all of the antimicrobials.

I think that the listed doses for metronidazole and gentamicin, in particular, just want to mention. As I already mentioned in the UK. There is not a licenced equine metronize or product, meaning therefore, that there's not a specific licence dosage to go along with it.

In the beaver tool kits and also in the recent review by Hardefel and colleagues, a twice daily metronidazole dose is listed. There are a number of papers which have not found twice daily dosing to be adequate for metronidazole and adult horses. And I've not been able to find adequate support for this dosing regimen, but I would personally feel comfortable with it.

Metroido plays a key role in the management of clostridial infections across the species in bacteria, where there are few antimicrobial options. Potentially under dosing is not what we want. So my personal stance on this is to continue to use 3 times daily dosing until a point where more convincing support is available for twice daily dosing.

There've been a number of recent papers looking at higher doses of gentamicin in horses. For example, 10 mg per kg rather than 6.6 mg per kg IV.

These papers drew attention to the fact that 6.6 Migs per k did not lead to desired plasma concentrations for killing target bacteria in a significant proportion of cases. And for reasons that we've discussed, this is a concern.

However, both studies also demonstrated that increasing the dose to 10 megs per kg was unlikely to make a significant difference, with only a 2% increase in the number of isolates adequately targeted in Angelica Schster's study. There's no yet published safety data at this dosage. So the current dosage listed in the Beaver Toolkit is 10 milligrammes per kilogramme.

But I think we need to weigh up the potential pros and cons prior to using this off-label dosage. Duration of treatment. The old adage, you must finish the course has led to some misunderstanding about the use of antimicrobials.

The course in veterinary medicine is the duration determined by the vets. To be required to achieve clinical resolution of the infection. Provided that no adverse events occurring, completing this recommended therapy continues to be advisable for clients.

However, preordained treatment duration does not need to be completed. For example, when prescribing post-surgical antimicrobials, there's no logic to 5 days versus 24 hours without specific indication for 5 days in order just to simply complete a course. Duration should be restricted to the shortest effective duration.

Although evidence is minimal in horses. The duration of therapy required to resolve many infections in people is actually far shorter than was traditionally thought. In people, there's now extensive evidence that longer courses do not improve outcomes in a variety of clinical scenarios.

And there are also some examples demonstrated in veterinary species. For example, for dogs with uncomplicated urinary tract infections, there's evidence that 3 days is as effective as 10 days of therapy. So, I take home messages.

Firstly, reduced antimicrobial exposure can reduce the development of antimicrobial resistant resistance. Decreasing the development of disease requiring antimicrobial therapy can be achieved by. Minimising contagion of conditions which may require antimicrobial therapy.

Addressing predisposing factors for bacterial infection and decreasing iatrogenic complications through good clinical hygiene. Secondly, when considering the use of antimicrobials in prophylaxis and disease, we should ask ourselves, is there a bacterial infection or a high likelihood of a bacterial infection? If so, can the current infection be managed without systemic antimicrobials?

And if antimicrobials are required, are there supportive treatments that could decrease the time to resolution? And thirdly, optimising treatment efficacy can reduce the duration of antimicrobial exposure. The number of antimicrobial classes used and subtherapeutic antimicrobial exposure.

Reducing the development of antimicrobial resistance. Antimicrobial usage can be optimised by appropriate antimicrobial selection. Using optimal doses and durations of therapy and appropriate care of medications.

There are a number of resources that I've drawn on for this talk, which are listed here. Thank you very much for listening. And if you do have any questions, please don't hesitate to get in touch.