Hello, my name is Louise Southwood, and I am an emergency surgeon at New Bolton centre. I first became interested in the topics of antimicrobial use in equine medicine, back when I was a surgery resident, when I was a 2nd year surgery resident, our hospital was closed due to a salmonella outbreak which had a devastating impact on. Our training programme on our hospital and most importantly on our patients with an extremely high morbidity or fortunately a low mortality.
So that experience really made me think or rethink how I use antimicrobials in my patients. And having been taught like a lot of us, oh, you know, treat them with antimicrobials because they might need it or just keep them on for a little bit longer because they might need it it's how I was taught and having gone through that experience, during my residency, I started to look into the literature and really reconsider. How, how I am using, these antimicrobials.
You know, they're safe, they're generally very effective, and for the most part, they're fairly economical, to use. And so, you know, should we be concerned about our antimicrobial use? Should be, revisiting, what we do with these drugs?
So, in the first part of this talk, I'm gonna answer those questions, that question should we be concerned? And one of the things that I've noticed as I've got more experience, as a clinician is we really need to be fiscally responsible when taking care of our patients. If we increase the cost of treatment, people aren't gonna be able to afford to treat.
Animals and so being fiscally responsible about the drugs we administer including antimicrobials is important and obviously there's some numbers there on the screen antimicrobials, potassium penicillin in our hospital could be quite expensive so if we can decrease the duration of treatment, we can decrease our cost. Any microbial associated complications, are also an important consideration. You've got, acute kidney injury with your aminoglycosides, you've got the occasional procaine reaction with procaine penicillin G.
But probably one of the most serious complications that we see is antimicrobial associated diarrhoea, and I already alluded to, the association between antimicrobials and salmonellosis and so I'm gonna talk a little bit more about that, in the next few slides. Bigger issue even to the complications is antimicrobial resistance and I am gonna go in depth with that not just in human medicine we hear about any microbial resistance in human patients but also on the impact that it's had in equine medicine. And then obviously as veterinarians, we really want to optimise our patient care and so appropriate use of antimicrobials is absolutely critical to actually be effectively treating our patients.
And then I'm gonna also introduce the concept of antimicrobial stewardship, which is basically the responsible use of antimicrobials. So antimicrobial associated diarrhoea, it's relatively low incidence, and this study was actually done at several private practises in Kentucky, and they actually showed that that the true incidence is less than 1%. However, while that incidence is low, I'm gonna show you some data that suggests the mortality is quite high and it can be expensive to treat these horses as well if they do develop any microbial associated colitis.
So, this was a study, this is some older data out of the University of California Davis, and they actually showed that parenteral antimicrobials increase the risk of salmonolysis about sixfold if you add in parenteral and enteral 40-fold, and then horses with gastrointestinal tract disease are particularly predisposed to salinalosis. So there's definitely a strong association between antimicrobial use and salinalosis. It's not just salmonella, you know C.
Diff or Clostridium difficile, is also associated with antimicrobial associated colitis, definitely in humans but also in veterinary medicine, and you can see here in this study, the mortality was 40%, so 10 of 25 horses died, from a C. Diff associated antimicrobial associated diarrhoea. So the mortality, so this can be a serious disease.
This is another study, this is, this is somewhat of an older study. I'm just looking at diarrhoea in general in horses, and they actually found that any microbial associated diarrhoea had a worse prognosis than the other types of acute diarrhoea. And finally back to the study I described in the beginning where they actually had a low incidence of antimicrobial associated diarrhoea, the mortality in that study was almost 20%, and they found that 4 of those, 4 of the 6 horses, actually 4 of the horses that had antimicrobial associated diarrhoea, had C.
Difficile, and 2 of those animals died, and salmonellosis was identified in 3 of the horses. So I've mentioned, so the mortality, even though the incidence is low, the mortality, can be extremely high and as an emergency clinician, I see a lot of these cases and it can be a devastating, it can be a devastating disease when it occurs to the individual horse but also to the hos hospital as well and these are several studies that have been published. And there are actually more in the literature that actually have described the impact of a salmonella outbreak in a hospital and this can have a long lasting effects for even years after the outbreak on the case load and then just the perception of clients on the hospital so it's it's a very, very serious issue.
So that's, if that's not enough to convince you to be careful about your animicrobial drug use, any microbial resistance is that it is a huge issue, and this was a statement by the European centre for Disease Prevention and Control, that basically stated that animicrobial drug resistance is gonna be one of the biggest issues that we face going. Forward, and this statement was published in 2007, increasing infection due to mouldy drug resistant bacteria, bacteria that are totally or almost totally resistant to currently available antimicrobials. So this, this is a problem.
In our hospital, you know, you can, you can read this, you know, things that are happening in human medicine and you know they talk about antimicrobial drug resistance. This is, this is an example, this sensitivity pattern is an example of an E. Coli and an innerobacter cloakia which are two of our most common surgical sites infections post ciliotomy, and this is a typical resistance pattern and you can see the The intro intro inerococcus is resistant to everything except for immipene, which is not an antimicrobial that we use routinely, period, and definitely don't use routinely in adult horses.
And so for example, these types of infections, I often don't treat them with antimicrobials because they're typically the organisms that are typically fairly resistant and even the E. Coli is multi-drug resistant. So resistant organisms in veterinary medicine, like I said, you know, we definitely see quite a bit of resistance in our hospital, there's been multiple reports in the literature looking at methicillin resistant Staph aureus or multi-drug resistant Staph aureus.
And these are just a couple of the papers looking at this, and you can see this paper here had 11% of animals from nasal samples, 11% of horses from nasal samples had a methicillin resistant talococcus aureus isolated. So actually in our hospital, we don't have a high incident of MRSA and we definitely see it, but we don't see it with a lot of infection, but it's definitely, it's definitely a problem in some hospitals. It's not just MRSA, a lot of bacteria are resistant.
This is an example of a paper out of Kentucky, that showing, Microlide and rifampin resistance to Rhotococcus equia, we definitely, some of the farms in our area, we also see these types of organisms. And this, this problem actually emerged because of farms treating subclinical infections of Rhotococcus with antimicrobials. So these are animals not showing clinical signs.
But with abscesses identified radiographically or ultrasonographically, they treat them with these antimicrobials and you can see here a pre-treatment, 24% had resistance organisms, and post-treatment 62%, and that was based on a transtracheal wash sample. Similar, this study down here look at was looking at vancomycin and multi-drug resistance in Eococcus, and I already showed you the data from our hospital, on that organism, and, 80% of Eococci tested were resistant to vancomycin and almost 100% to multiple drugs, and that tends to be a fairly resistant organism just, just naturally. So how does this resistance occurs and there's been quite a few studies, a lot of them out of the UK and some like this one out of Colorado, looking at patterns of how resistance develops, antimicrobial use and resistance, is there particular antimicrobials that drive the resistance?
And so in the next couple of slides, I'm gonna show you the results of some of those studies. And this first one out of Colorado shows you that both hospitalisation and antimicrobial drug administration was associated with multi-drug resistant in E. Coli.
And so it's, so even the animals that were just in the hospital and not treated with antimicrobial still developed more resistant organisms. And this one was just surveying. So multi-drug resistant E.
Colien almost 50% of samples, 50% of faecal samples, I had resistance, and I'm going to introduce the concept here of the extended spectrum beta lactase producing E. Coli and just over a quarter of the samples, had that, and I'm gonna talk a little bit more about that later because that's an emerging issue in the literature. So high levels of Maori drug resistance here.
This study, also out of the UK out of the University of Liverpool showed that 7 of 8 resistance to 7 of the 8 antimicrobials are studied in multi drug resistance to at least 3 antimicrobial drug classes, classes up to 7 days of hospitalisation. And this is the definition of a multi-drug resistance when they're resistant to at least 3 classes of antimicrobials. Once again, this is out of the UK but a different hospital, resistant E.
Coli and 60% of samples, they actually found it wasn't resist different between hospitalised and non-hospitalized horses. What they did find though is this resistance was transient, which is encouraging, and it lasted for about 2 weeks in the non-hospitalized horses and for 2 months, in the horses that were, hospitalised. So in the beginning I discussed MRSA.
This is a study looking at MRSA, MRSA was isolated from 40% of animals, and all sample sites tested positive on one occasion, and I believe most of the positive samples were from, the nasal cavity. So I mentioned before this this concept of extended spectrum betylactamase producing E. Coli, and I'll say in a couple of slides exactly what that is but that's something that has been observed, and this is basically increases resistance and increases pathogenicity and so this was a study that looked at.
Of courses presenting for colic and also with open wounds, they swab the nostrils, the faeces and, and the wounds of the horses that actually had an open wound, and their conclusion from their study that there's an alarm alarming carriage rate of gram-negative multidrug resistant pathogens, and 11% of faecal samples had these extended spectrum beta lactamies producing E. Coli, and 3% of nostril. Nostril swabs.
So, these organisms are out there, and this is another study that also showed basically these extended spectrum betylactammates producing E. Coli, a high incidence of that. And the reason I put this study in is their conclusion, you know, they say these results highlight the importance of any microbial stewardship and infection control practises in equine medicine.
It's not just the hospitals, this is a study that found these resistant organisms also in, writing centre and there's been other studies that have shown resist MRSA and resistant organisms just out, in the population. So even though hospitalisation and any microbial use definitely, definitely it can exacerbate this and increase, you know, the percentage of, . Samples, containing these organisms, these resistant organisms, it's out in the population as well.
So what are these extended spectrum beta lactammase producing E. Coli and, and I had to look this up, as the name implies, they produce an extended spectrum of beta lactammase and if you remember the the penicillins, the cephalosporins, they're the. Beta lactam, any microbials, they have the beta lactam ring, and basically these organisms produced an enzyme that break down that ring, so the antimicrobials rendered ineffective.
So this is a plasmid. It's transmitted horizontally, so not just vertically from generations, but it's, transmitted horizontally. It spreads rapidly, these resistant dreams spread rapidly.
And they're also associated with increased pathogenicity. So they can hydrolyze all penicillin, cephalosporins, monobactrims, and there's also some cross resistance to trimethoprim and your fluoroquinolones as well. So these, an important, you know, this is an important resistant organism that's emerging in the literature.
How else do they transmit resistance this is another study that I found that relatively recent cauliflages and if you remember cauliflages are viruses that infect bacteria and they can also transmit resistant genes, and this is a study in an equine clinic that shows that these cauliflages were on almost all, about 3/4 of the surface sampling sites. They were even present after cleaning and disinfection, and this is important, and about a third of them transferred antimicrobial drug resistance. So this is something that's not a tonne of this in the literature, at least I haven't found it, but it's something that we need to be mindful of, and keep an eye out for on going, going forward.
So, so what, so we've got all these resistant organisms out there and I think an important concept is resistance doesn't always mean an increase in pathogenicity. So, so some of these organisms are just resistant. However, it does delay appropriate treatment and I think that is definitely an impact that we see and this is a study out of a human hospital.
And they actually showed that inadequate antimicrobial treatment, so you picked the wrong antibiotic, increase in mortality was 42% when patients were started on an inadequate antimicrobial initially, this is only 18%, I shouldn't say only 18%, still 18%, still quite high, when patients were treated with the appropriate antimicrobial. And they also found that prior antimicrobial treatment drove the use of the initial use of inadequate antimicrobial, it increased the risk by over threefold. So not only sometimes there's an increase in pathogenicity, but not always, but the big impact on patient care is that we're gonna with increased resistance, we're going to select the wrong antimicrobial or in some cases, maybe we won't be able to select an appropriate antimicrobial at all.
So, I liked this paper critical shortage of new antibiotics and development against multidrug resistant bacteria. Time to react is now, and I'm usually I said at the beginning of this talk, you know, I'm not gonna tell you necessarily all the answers, I know I'm not necessarily gonna change your how you practise and how you use any micro. Peoples in this one talk, but my goal is to encourage you to react and just encourage you to really think about how you're using antimicrobials.
Does this animal really need antimicrobials? Can I decrease the duration of treatment and still effectively take care of the animals? So I just, my goal is to encourage you to react and to really think about your antimicrobial drug use.
So if I haven't convinced you so far, we've talked about antimicrobial complications, primarily antimicrobial associated diarrhoea and horses, we've talked about resistance, which is an ongoing emerging problem. The other thing is we've got to optimise our patient care. We want to really take care of our patients and use these antimicrobials so they're effective.
So one thing we got to keep in mind, increased utilisation drives resistance. The more pressure, the more those organisms are going to evolve and develop resistance. So, we've got to optimise our dosing regimens, and that's both for prophylactic, which I'm going to talk about quite a bit and a little more challenging therapeutic antimicrobial drug use.
So we're going to talk about prophylactic first and then therapeutic. So, one of the most common times that we use antimicrobials is for surgery. One of really, really important thing is antimicrobial drug use should not replace a traumatic and aseptic surgery.
Halstead's principles of surgery have to be followed. You want to minimise haemorrhage, you wanna minimise trauma. You wanna use the correct instrumentation, the appropriate size and appropriate type of suture material and implants.
You want to eradicate dead space. To bride any dead tissue. So following those principles are absolutely critical to prevent infection, and we should never just use any microbials, to, to compensate for poor surgical technique.
So not all surgeries need antimicrobials. Generally, as a guideline, if your infection rate is less than 5%, you should not need antimicrobial, less than 5% without the use of antimicrobials, you should not need to use any microbials. So clean surgical procedures should not need antimicrobials, and the definitions are there.
Where you do need any Microbials is you clean contaminated and you contaminate procedures clean contaminated is when a gastrointestinal tract, urogenital tract is open, but any contamination is, is, is controlled, it's contained and contaminated is when you have more extensive uncontrolled contamination. So your traumatic wounds, gross contamination from the gastrointestinal tract, and then your dirty and infected procedures, you're not using antimicrobials prophylactically in those cases, you're actually using them therapeutically and so that's a completely different type of use. So prophylactic antimicrobial use, like I said, I'm gonna focus on surgery.
Where, where do we go wrong with this? And the three areas I'm gonna talk, talk about, and we do, there's scientific evidence to back up, appropriate use in this setting. First of all, as inappropriate timing of antimicrobial administration.
And then excessive duration of prophylaxis is the other area where I think a lot of us make mistakes and then inappropriate selection of many antimicrobial drugs, and I'm gonna talk about that briefly. So timing of perioperative antimicrobials, it's absolutely critical that the serum and tissue drug levels exceed MIC for the most common organisms, during surgery. So you want your peak concentrations during surgery and you want to maintain them, so you need to repeat the dose during surgery if necessary.
And you do not want to be giving your antimicrobial drugs at the completion of surgery, it's too late there, and we've known since actually 1961 that giving antimicrobials at the completion of surgery has the same infection rate as not using any microbials. So we want to give them right before surgery, right before we make our incision. So as some guidelines, and they should be administered within 30 to 60 minutes of beginning surgery.
And if the duration of surgery exceeds to half-lifes, you should repeat doses. So for example, if you're using a penicillin and gentamicin regimen, you wanna get them on board as close as possible, as close as reasonable, to. When you're beginning surgery and a lot of times if the surgery extends beyond 2 hours, you probably want to repeat your potassium penicillin.minoglycosides are concentration dependent antimicrobials and do not need to repeat the dose and we'll talk about that.
Any microbial prophylaxis beyond skin closure is unnecessary and there is plenty of data and I'm gonna go through in the next couple of slides of data supporting that. There is absolutely no data to support prophylactic antimicrobial administration beyond 24 hours and even really beyond the immediate surgical procedure. So timing, I mentioned this, I mentioned that we've known since 1961, that, and it was Burke who published that data that, any microbials have to be on board before surgery, and this is some, older data out of the New England Journal of Medicine.
That actually demonstrate infection rates in surgical procedures depending on when antimicrobials were used. And so here, this is when the infection rate was less than 1% when antimicrobials were administered immediately before surgery or within 2 hours. This bar here on the left shows when they were administered too early, so you missed that peak, having that peak concentration during surgery, and here's the infection rate when it was missed post, when it was administered post infection.
So clearly they need to be on board during surgery. Configuration, and there's been some work published looking at duration of antimicrobials for colic surgery, that's, you know, always a fairly hot topic and one study showed that, you know, there was no difference between having an infection rate between having antimicrobials, post-op antimicrobials for 5 days versus 3 days. Well, they don't even really need them for 3 days.
And there's been a lot of work, done in the human field with this, and this study showed that single dose as effective as a Multi-dose regimen for, for antimicrobial prophylaxis. Similarly, this study, and this is, this is abdominal surgery, this is not, you know, clean elective procedures, which basically shouldn't need any microbials. This is abdominal surgery, it's clean contaminated surgery.
And this study showed that single dose prophylaxis is effective as a triple dose. Prophylaxis in elective abdominal surgery, there was no difference in infection rate. So really they need the antimicrobials just at the time of surgery and not beyond surgery.
So this is emergency abdominal surgery in humans, so obviously a lot of contamination, and they concluded similarly, you don't need prolonged antimicrobials and some of the take home messages from this study is that contamination is different from infection. Contamination does not require therapy, and therapy is continuing antimicrobials beyond that immediate perioperative period. Generalised peritonitis, so if you've got actually an infection, localised abscesses require at least 5 to 7 days of therapy.
And that post-op pyrexia is not, is not an indication for any microbials. I'm gonna talk about that briefly when we talk about therapy. This is another study, human patients undergoing colon surgery, that anti microbials for less than 24 hours.
So just, so just confining them to that immediate perioperative period is effective in preventing surgical site infection. Now granted, in a lot of human surgery they do quite a bit of prep, you know, they prep. Skin 24 hours in advance, you know, for their colon surgeries, you know, they do procedures to decontaminate your colon, not completely, but at least decrease the bacterial load, but still, they've actually demonstrated multiple studies that antimicrobials beyond surgery has no benefit.
So not only does it have no benefit, it can also be detrimental. And this study looked at appropriate use of any microbial prophylaxis. So what was appropriate, what was defined as appropriate in this study is not for clean surgical procedures.
Limited to high-risk patients, or if they had a foreign body, a single dose pre-op, so no antimicrobials for clean procedures, a single dose preoperatively in most patients, and you could they were allowed to extend them for 24 hours in high-risk patients, and they had to select appropriate antimicrobials. 65% of human patients received inappropriate prophylaxis with extended duration of prophylaxis being the most common reason. And what they actually found the nosochromal infection rate was higher when prophylaxis was inappropriate than when it was appropriate.
And the wound infection rates when it was inappropriate was 15% and 5% for appropriate use. This is another study, in human paediatric patients, basically the increased duration of surgery, contamination surgery. And here's something we haven't investigated a lot in veterinary medicine but an inexperienced surgeon increased wound infection rates.
And you can see there are several variables that were not associated with wound infection, and one of those that was the use of perioperative antimicrobials. Wounds are a challenge for us. What do we do with them?
Is it prophylactic? Is it, is it therapeutic? And there's one study this was in, from humans, they found no benefit to antimicrobial for simple soft tissue wounds, and I think this is one area where in in medicine, we can do a little bit better.
So for example, if a horse has a laceration in the upper body. It doesn't involve, you know, it just involves a soft tissue. It doesn't involve any synovial structures or bone.
Does that animal really need any microbials if we do adequate debridement and keep the wound clean? And I will say probably not that any microbials are probably not going to change whether that wound dehises or becomes infected. Meticulous surgical debridement is absolutely critical.
And then if you're going to use antimicrobials for these wounds, and I'm talking about acute wounds, not chronic wounds that are already infected because that comes under therapeutic use. This is acute traumatic wound. You want to get your antimicrobials on pre-bridement.
I know some people want a culture, you know, synovial. Structure, I usually don't bother with that anymore because quite frankly, if it's open, and those cultural results aren't going to be particularly useful, but I do make sure I've got my antimicrobials on board, preoperatively and a lot of the distal limb wounds, and we've got to think more about using local antimicrobials rather than systemic. But I do think these are a challenge with antimicrobial use.
So which antimicrobials to use? I think, I'm not gonna say a lot about this, you need to take into consideration, you know, potential confounding issues, comorbidity, such as, if you've already got some renal issues, you probably don't want to use an aminoglycoside, etc. But I will encourage you to stick for prophylaxis to stick to your first line antimicro.
And and avoid using some of the 2nd and 3rd line antimicrobials, so avoid using nrafloxacin, use penicillin, gentamicin, trimethoprine sulfa. Even try to avoid using a 3rd, 4th generation cephalosporins without, if you, unless you have a culture and sensitivity to back up its use. So that's kind of segues into the therapeutic antimicrobial drug use, and I think the way I approach this is if I have a patient often with a fever, the first thing I think of is does this animal?
Require antimicrobials and even before I start putting them on antimicrobials, I try and find the source of infection and try and get a sample. Now granted, I work in a tertiary care facility and so I'm not seeing primary care, primary care, infections. However, that's the way I approach it.
Does this animal need antimicrobials? Is it gonna be life-threatening if I wait, and work out where the infection is, and if, and if I can make my decision of any microbial drug use based on culture and sensitivity. So then you got to look, where is the infection coming from?
A lot of times we see it coming from a colitis. So, and a lot of times if it's semiosis or a Clostridia or just a just a dysbiosis, we do not start these on any microbials, one exception being in our area, we see a lot of atomic horse fever, and so we will start them on oxy tetracycline, but that's very seasonal. But in general, if they've got a colitis, especially if they've got a history of antimicrobial use, and now they've developed colitis, we usually do not treat them with antimicrobials.
Is it a have they, if it's a post-op patient, do we treat them with, you know, is it a surgical site? Probably the most common source of fever, post-op I mentioned before, I usually don't treat these animals with antimicrobials. I'll definitely clean it, prep the wound.
A sample for culture and sensitivity testing so I know what organisms are causing our infections in our hospital, but I usually don't start these animals on antimicrobials unless the infection is severe or unless it's causing some pretty marked clinical signs. Does the animal have pneumonia? I scold the chest.
I'm going to talk, in my next lecture a little bit about, you know, the use of ultrasound to diagnose pneumonia. Is it, is it the chest? Is it the incision?
Is it the gastrointestinal tract? And we'll talk about obtaining, if you are concerned about pneumonia, diagnosing that and also obtaining a sample before you start antimicrobial use using transtracheal wash. So identifying the source of a fever, and that includes post-op fever, and we have some data that suggests that just an animal, for example, after colic surgery, if an animal has a fever, it doesn't necessarily mean they have an infection.
Sometimes it can be inflammation. If I'm dealing with an animal that has a post-op fever, what do I do? I usually check a white count, and often if they're leukopenic, I'm going to be thinking more some sort of colitis.
And like I said, we usually don't start those animals on antimicrobials. And so I look for leukopenia. Depending on the case of the type of surgery, I'll look, peritoneal fluid analysis.
Not particularly useful in the immediate post-op period. However, you know, a week or so later, it can be diagnostic and especially if you're looking for intracellular bacteria, it can be helpful. Is it the surgical site, whether it's post-ileotomy or, or some other surgical procedure, is it a superficial or a deep surgical site infection, and so you want to investigate the surgical site.
Is it catheter related? If the animal has an intravenous catheter, we actually see a decent amount of these, and you can examine the catheter site, but I've had the occasional animal that hasn't had obvious signs of a catheter associated infection, and I've removed the catheter and the fever is resolved. So if you're not finding another source of the infection, go ahead and and replace the, the jugular vein catheter.
And then obviously the thorax, the chest, does the animal have pneumonia or pleural pneumonia? And you can address this by auscultation, you know, doing a rebreathing examination with rebreathing bag over the horse's nose, and now with the ready availability of point of care ultrasound, you can. An ultrasound probe on the chest to examine any pathology.
So the take home message of this is rule out any, try and investigate where is this fever coming from, what is going on with this animal, and if possible, get a sample before you start any microbials. So what type, what type to pick, this is just some really basic information. You've got your time dependent and your concentration dependent antimicrobials, and this is important, your time-dependent antimicrobials, you want to be above the MIC of the either infecting or most likely infecting pathogen, and you want it to be above the MIC for as long as possible of the dosing interval.
So these, these antimicrobials need to have therapeutic concentrations for as long a time as possible. As opposed to concentration-dependent antimicrobials, you want to get that really high peak of 10 times the MIC, 10 to 12 times the MIC, and you want to get a nice low trough. And this, and the, the importance of the trough is it's actually the trough that prevents renal toxicity and acute kidney injury.
And using this regimen so will actually decrease resistance, improve your clinical response with that really high peak and decrease toxicity with the, with the trough. And so keep that in mind, like these antimicrobials are used, used differently. And a lot of times if we're treating, you know, a patient, you can measure peak and trough concentrations of these antimicrobials, especially your Amicain and your gentamicin.
You know, with regard to, you know, animicrobial drug use, I, I found when I was when I was looking, doing a literature search for this, I found this paper out of the Australian Veterinary Journal, and one of the challenges we have not so much in equine, I think it's more of an issue, you know, in our farm animals is, you know, you've got on label use. Does not necessarily comply with with a proper antimicrobial, good antimicrobial stewardship, essentially, and an example of that, at least in the US is safety of fur, it's required to be a administered at 2.2 milligrammes.
Per kilogramme every 24 hours, which for a time-dependent antimicrobial is inadequate and so that's going to drive resistance and that's a problem that you, that you know, you're required to use it as such, and it is a threat to antimicrobial stewardship, some of these labelling requirements. So one of the big issues is how long do we keep them therapeutic antimicrobial drug use, how long do we keep them on antimicrobials, and I think everybody struggles with this, but I will challenge you, to try and be more critical about deciding when to stop imicrobials, and there's been a lot of information in the human literature about this, and I'm just gonna touch on a few Studies, ventilator associated pneumonia is a big problem in critically ill human patients. And this study actually showed that 8 days was the equivalent to 15 days of antimicrobial administration, and they found that the survival, the relapse, and the recurrence was all of similar, a similar percentage of similar incidents if they treated the patients with 8 days versus 15.
But they had, these patients had more antimicrobial-free days and they found they had decreased multi drug resistant pathogens. So essentially these patients, they could keep them on antimicrobials for a shorter duration and still have the same effect. And remember I said in the beginning animicrorobial drug use drives resistance, so the less we can administer, the, the less resistance.
But once again, we've got to take care of our patients. And this is a study you're, you'll, if you investigate this in the literature, they talk about discontinuation policies and so that's criteria that have been put in place to try and determine when can I stop imicrobials and some larger human hospitals will actually have criteria, computer, you know, they have a computer programme that tells them when they can discontinue it and some of the things they've looked at is patient temperature, leukocyte count, radiographic findings. Our absence of pros in the sputum and then the PA inspired to arterial oxygen.
Ratio. So these, they use these criteria and once patients meet certain criteria, they can stop the antimicrobials. I'm just reviewing the literature more recently, one of the things that was, seemed to be a hot topic out there was using procalcitonin, to measuring that to determine when, they can actually safely stop antimicrobials when they're using them therapeutically in some of these patients.
The acute phase protein that we probably use most commonly is fibrinogen. I know different, different countries have different acute phase markers, but maybe that is one thing that we can, we can kind of use and develop some data on to try and decrease our antimicrobial use and more objectively decide when to discontinue our antimicrobials when it comes to therapeutic use. So, like I said, I think we've got pretty good guidelines for prophylactic, especially surgical prophylactic antimicrobial drug use.
There's a lot of data out there, we need to have peak concentrations during surgery. And avoid treating them beyond that beyond definitely beyond 24 hours, but really even beyond that initial perioperative period. Therapeutic antimicrobial drug use, I, I think the take home message for that is based it on if you can base it on culture sensitivity testing and we really need to come up with criteria and equine medicine to decide when can we stop these antimicrobials.
What else can we do? What else can we do? And there's been quite a bit of, you know, work in human hospitals looking at this, simple things, improve hand hygiene, wear gloves, use contact precautions.
This is an example of one of our stalls. Our stalls have gloves outside. If we've got a patient that has some, you know, sort of some infection, we will use a gown, foot bars, hand sanitizer when you're coming out of the stall.
We're required to clean our horse's feet before they walk around the hospital. All. Active surveillance cos know, for example, we do active surveillance for salmonellosis, if we get a surgical site infection, we usually, culture and do a sensitivity so we can actually keep track of what organisms we have, educate the staff, enhance environmental cleaning.
I think that's obviously a challenge in equine medicine as well. So there's other things that we can do to try and decrease infection rate and antimicrobial. And any microbial use.
The, so the next couple of studies that I'm going to talk about are, larger human hospitals have developed animicrobial guidelines to, basically to optimise optimise antimicrobial use, antimicrobial stewardships in their hospital, and the guidelines are obviously based on data, in the literature. So this was a study that looked at optimising antimicrobial drug use in surgery, it was out of the Netherlands, and they actually found when they implemented these guidelines, they decreased prophylactic antimicrobial consumption, and they decreased the duration of antimicrobial use beyond that 24 hour prophylaxis. There was more patients that received 24 hour prophylaxis, cost savings of 57%, they decreased hospital stay, and they actually decreased their nosocomial infection rate.
And I can keep this in mind because I mean we're all hesitant, you know, to change our antimicrobial, usage, you know, we're, we've all got habits, and, but I think stepping out, some of these studies show that stepping out and decreasing use is actually a benefit to the patient. This was another study, Antimicrobial practise guidelines, and they had a computer assisted, decision support and that decreased expense, decreased antimicrobial drug use, improved just the perian animicrobial prophylaxis, and they decreased the average number of prophylactic antimicrobial doses per patient. Once again this is another one a little bit more recent looking at the impact of antimicrobial stewardship in critical care.
Once again they were able to decrease the antimicrobial drug use, decrease cost of patients which I mentioned in the beginning, should be an important driving factor for us to decrease cost of patients, decrease their. There was less inappropriate use and over a six month period of time, they decreased the antimicrobial drug resistance. They did not see an increased infection rate.
They did not see an increased length of stay of their patients and they did not observe an increase in mortality and this is in critical, critical care, critically ill patients. So, so there's quite a bit in the literature of these you know, discontinuation policies of hospital policies for both prophylactic and therapeutic antimicrobial drug use and you saw from the last papers I presented a lot of those are from the 90s and the early 2000s and it was interesting to review the literature again with the more recent literature and what they've actually found is that. Those having put those protocols in use, they've re-evaluated and actually come back to the doctors and said, Look, this is the data we've got.
And so that's actually increased compliance and these studies are actually looking at effectiveness and sustainability of these stewardship antimicrobial stewardship programmes, and they've actually shown they're very, very effective and very sustainable. And this one down here has a plan to study Act framework. Where you plan the guidelines you do you put them in, you study that results and then that feedbacks in and you give, you know, feedback into the system to actually improve it and and these programmes actually work.
And like I said in the beginning, most of us don't work in these massive human hospitals, but I think one of the important things is for us is to once again think about does the animal Need antimicrobials, am I using them appropriately and then monitor our infection rate as we decrease our antimicrobial drug use. So I hope this has been helpful. Like I said in the beginning, I haven't got all the answers at this point, but my goal is to just have you think about how you're using your antimicrobials and see if as a group of veterinarians we can all do better.
Thank you.