All right, everybody. Welcome to today's webinar, hosted by the webinar vet. My name is Doctor Stephanie Morley.
I'm a veterinarian and the president of Vetin, your sponsor for today's webinar. We are very pleased to bring to you Doctor Jennifer Granick to speak to you about optimising antibiotics, tips for choosing the best drug, dose, route, and duration. I'd like to thank all of you for joining and spending this hour with us, and I'd also like to thank Dr.
Granick in advance for sharing her time and expertise with us. Briefly, I'd like to explain why Vetin is sponsoring this outstanding speaker on this important topic. We have recently launched a new product called the Vetin Pouch.
It's a local drug delivery device that allows for sustained daily antibiotic dosing directly at the site of infection. It can be redosed daily with the correct antibiotic for up to 30 days and is removed similar to a drain. Dosing locally is the most effective method for treating biofil-related infections while minimising systemic exposure.
So please check us out at www.vetlin.com to learn more.
A few housekeeping items to mention. If anyone has any questions for our speaker, please put them in the Q&A box. And for comments or other queries, use the chat box.
And now allow me to introduce Doctor Jennifer Granick. Doctor Granick is an associate professor of small animal internal medicine at the University of Minnesota College of Veterinary Medicine. She received her DBM from the University of Wisconsin, completed a small animal internal medicine residency and master's of Veterinary Medicine at the University of Minnesota, and a PhD in Comparative pathology from the University of California.
She co-chairs the Wassava's Therapeutics Committee and is a member of the AVMA's Committee on Antimicrobials, and co-directs the University of Minnesota's Antimicrobial resistance and Stewardship Initiative. Her research focuses on antimicrobial use and companion animals. Thanks so much, Doctor Morley for that introduction.
And I'm gonna turn off my video. I'll turn it on again so I can see you all at the end for questions. Thanks for joining today.
So I have no relevant disclosures for this talk, and the goal of this hour is to talk about antimicrobial resistance, discuss empiric antibiotic prescribing, how we can use cytology to aid in our decision making, talking about antibiotic susceptibility tests, how we interpret them and use them to make antimicrobial selections, and then we'll talk about the impacts of dose, duration, and route of administration. And particularly how that might relate to, Pet owner compliance. So first, antimicrobial resistance.
So antimicrobial resistance or AMR is the ability of microorganisms to remain viable and multiply in the presence of antimicrobials to which they used to be susceptible, and we call this acquired AMR, . In truth, antimicrobial resistance is as old as microbial organisms. It's an evolutionary and natural process, basically survival of the fittest, but when we use antimicrobial drugs, we accelerate this process.
And, and that, accelerates the development of antimicrobial resistant organisms. So, This, this ability of of microorganisms to develop antimicrobial resistance is an adaption to environmental pressures, and that includes the pressures that prescribers put on these organisms when we make a prescription for antimicrobials, and it occurs in a few different ways, genetic mutations as well as sharing of genetic material. This is just an example of that.
So antibiotic stresses on bacteria can lead to mutations, and mutations that are helpful for those bacteria to survive in the face of antimicrobials then are perpetuated, due to bacterial replication. And so that's, I think what a lot of folks think of when they, think about antimicrobial resistance and the use of antibiotics. But probably what happens.
More commonly, that we also need to worry about as prescribers is the ability of bacteria to share resistance genes. So once resistance develops and it's encoded in genetic elements, those genetic elements can be transferred to other bacteria, and that can be other bacteria of the same or different species and as a way for resistance to . To spread throughout an environment.
So with that in mind, if we have. Two patients, one receiving antibiotics and one not receiving antibiotics. This illustration shows you how antibiotics can increase the spread of antimicrobial resistant organisms in the environment.
So if two individuals have the same mix of both susceptible and non-susceptible bacteria in their microbiome, for example, and one of those individuals is given an antibiotic, we know that bacteria are shed continually by people and animals into the environment, all the time. And in a patient that's given an antibiotic, the ratio of resistant bacteria to susceptible bacteria that are shed into the environment goes up. And this is what makes infection prevention control efforts really, really important, but also is a window into how antimicrobial resistance can be spread just in in households, for example.
So antibiotic resistance is a category of antimicrobial resistance, and that's what the rest of this talk is going to be focused on. So we know antibiotics are critical for both human and animal health, and antibiotics use can lead to the development of antibiotic resistant organisms, as I just illustrated. So that means for us as prescribers that judicious or really careful use is required to slow the emergence of antibiotic resistance and maintain the efficacy of these antibiotics that we need in order to treat our patients.
So in comes antimicrobial stewardship. This is a way or a framework that we can use to improve the way we prescribe antibiotics and to preserve the efficacy of these drugs. And the American Veterinary Medical Association Committee on Antimicrobials, has provided a definition of antimicrobial stewardship that's specific for veterinarians, and they say that stewardship is the actions veterinarians take individually and as a profession.
To preserve the effectiveness and availability of antimicrobial drugs through conscientious oversight and responsible medical decision making while safeguarding animal, public, and environmental health. So really this definition incorporates a one health approach to this big problem. And to guide excuse me, to guide veterinarians on this antimicrobial stewardship effort, the AVMA has defined five core principles of antimicrobial stewardship.
Those include committing to stewardship, so basically just caring about it, advocating for a system of care to prevent common diseases. I think this is one thing veterinarians already do very well. So every time we see a patient for vaccinations and other preventative care, we are, we are doing antimicrobial stewardship.
The other piece of preventing common diseases, of course, is infection prevention and control measures. That's something that I think as a profession, we can, we can do more, and, and potentially, could, could benefit from more resources for. Selecting and using antimicrobial drugs judiciously, again, because use of these drugs drives antimicrobial resistance is is something that every prescriber needs to pay attention to.
Evaluating antimicrobial drug use practises. So, you know, what are the outcomes when we use these drugs? How much are we using?
What types of drugs are we using? These are all things that we can do some monitoring of and determine if there's areas that we can improve our own practise. And then obviously educating and building expertise.
So your presence here today at this talk is is a way to to get continuing education and that means congratulations, you, you are practising antimicrobial stewardship. So let's focus in on number 3, select and use antimicrobial drugs judiciously. So we're gonna talk first about empiric antibiotic prescribing because this is what most of the prescribing that we do is when we're talking about antibiotics.
There are a lot of reasons for this. One of the big drivers of empiric prescribing is simply the costs associated with diagnostic workups and the fact that most of our patients don't have insurance. So, That can sometimes lead to uncertainty in terms of the diagnosis, or, sometimes just the clinical presentation makes it quite obvious that we know what we're treating.
We're gonna talk about all those things. But empiric prescribing is certainly an appropriate, An appropriate practise, it, it, it means that we don't have bacterial susceptibility testing to base our decisions on, but we can get a lot of information from our physical exam, from our history taking, and from other diagnostic tests, including point of care tests like cytology that we'll talk about in a little bit. So why do we prescribe empirically?
Well, sometimes we prescribe empirically because we have life-threatening infections in our patients and we just can't wait for antimicrobial susceptibility results back, or we have an infection that will cause significant morbidity if we wait. As I already mentioned, owner financial limitations are a major reason why veterinarians need to prescribe antibiotics empirically, because maybe we can't do the full diagnostic workup. And so, we're making a little bit of a guess.
We think that, a patient has, say, a urinary tract infection. We know that many urinary tract infections are caused by E. Coli, so we empirically prescribe an antibiotic that will cover that.
There are situations where getting a sample for antimicrobial susceptibility testing, for example, is difficult or potentially puts the patient in danger. So examples of that might be a patient that has pneumonia that is already oxygen dependent, for example, there may be other things that you're thinking of that you see commonly in your practise. There may be times where we just don't need to culture.
It's not something that we need to spend the owners, . Money on at this juncture. So, common infections that respond quickly to common antibiotics, don't necessarily need antimicrobial susceptibility testing, particularly if in your region you don't see a high rate of antimicrobial resistance.
So, this can be really geographically dependent, so depending where you live, you may, you may find that even for common infections, you do want to do cultures. So let's talk about a couple of examples of where and prescribing is appropriate and and and when it's not a good idea. So first we have Maddie.
She's a 10 year old female spayed Labrador retriever. She's presenting, for frequently needing to go outside to urinate. She's straining to urinate.
She's had a small accident by the door, and the owner noticed that the urine was blood tinged. Otherwise, Maddie's acting normally, she's got a normal appetite, and her, activity level seems normal. When she comes into the clinic, we are able to get a urine analysis, and when we look at the urine under the microscope, we see that there are a lot of white blood cells, 15 to 25 per high-powered field, and there are two numerous to count rods.
So, the, the, Veterinarian in this situation prescribes amoxicillin, which is a recommended first line agent for urinary tract infections in dogs for 3 days. And we are fortunate that Maddie responds. Within 2 days, all her clinical signs are resolved and she has a really good outcome.
So in this case, empiric prescribing is appropriate. She comes in with really classic clinical signs of a urinary tract infection. We have cytologic evidence that she has a bacterial infection, and we, we are treating her with a first line antimicrobial agent.
And her infection clinically resolves. So let's contrast Maddie's case with Gertie. Gertie is also a 10 year old female spayed dog.
She's a German Shepherd. She also presents initially to her veterinary clinic with lower urinary tract signs. Gertie, however, has fear aggression and she really needs to be sedated for any exams and any sampling.
Or handling at all. She's, seen at a practise that's a multi, veterinarian practise. At the time of this first visit, her owner declined sedation, so no sampling is done.
She's empirically prescribed, Clavamox for 5 days, as this is her first time having, evidence of a urinary tract infection. And again, even though we didn't get to look at the urinary sample in her particular case, it seems reasonable to provide her with empiric antimicrobials because given her age and signalment and her clinical signs, she really does fit the clinical picture of an older female dog with a urinary tract infection. So that seems fine, but this is when things go awry.
Two weeks later, she returns with clinical signs, so same clinical signs that are indicated lower urinary tract infection. She sees a different provider this time and is prescribed Clavamox again, but for a longer course of 15 days. So she has some relief of clinical signs on the antibiotic and then the clinical signs return off of antibiotics.
Over the next 4 months, she comes into the same clinic she's seen by many different veterinarians. Every single time the owner declines sedation, so there is no urine sample taken at any of these visits. And so she gets again, empiric prescribing of various antibiotics, including ceffavesin, and refloxacin, and cephalexin at various different doses.
So, in the end, Gertie finally sees a veterinarian that puts their foot down and says, look, we really, really need to do more diagnostics. We have to sedate, Gertie because we are not being successful in eliminating her clinical signs. So they are able to sedate her, get a urine sample, they submit that for bacterial culture and susceptibility testing.
As you can see here, she's got a staph infection that is resistant to basically every antibiotic on our panel, except for Rifampin. And when they do additional diagnostic testing, including abdominal radiographs, she's got really huge bladder stones. They're likely strew bit stones, which are common with staph, pseud intermediate infections in the in the bladder of dogs.
So, this is an example where empiric selection was not appropriate, after that first visit because with recurrent or persistent infections, we really need to do more diagnostics, and that includes bacterial culture and susceptibility testing to see if we have a multi-drug resistant infection, which Gertie had. So the outcome for poor Gertie was not as good as for Maddie. She was taken to surgery to remove these stones because there was a fear of putting her on a drug like rifampin for the time it would take to dissolve these stones.
When the veterinarians got into surgery and tried to sew the incision into her bladder back up. The infection had been so chronic that the bladder mucosa was friable and was unable to hold a suture, and so she had to be euthanized on the surgery table. So, certainly there are, there are times and places where empiric prescribing is acceptable and needed, and there, and there are times when it's not and recurrent infections is certainly one where we really wanna push for doing additional diagnostics.
If we are going to prescribe an antibiotic, how do we choose wisely if we don't have, all of the diagnostics that we would like? Well, we should be basing selection on what the likely organism is at the site of infection. So I mentioned already, you know, E.
Coli is a really commonly found organism that causes urinary tract infections. And so, especially if we have evidence on a urine sample that we have rods, then we should be, likely targeting E. Coli or other gram-negative rods with our selection.
We need to think about the expected efficacy of an antibiotic against the bacteria that we think might be there, and the ability of the drug to reach the site of infection at the appropriate concentration. And this is really important because there are some drugs that, can reach high concentrations in the serum, and others that, can reach even higher concentrations in the urine because they are excreted by, the kidneys. And so I, you know, no veterinarian needs to walk around, memorising all those things, but if you consult a good, formulary, there should be some information in the formulary about how these drugs are handled in the body.
So if you are trying to treat a urinary tract infection, for example, you wanna look for a drug that's ideally renally excreted because it's gonna get to the concentrations you need in the urine. A really nice example of this is the drug amoxicillin. So amoxicillin is a recommended drug for treating urinary tract infections in the bladder.
It's renally excreted, it, has a good spectrum of activity and will treat gram-negative rods including E. Coli. However, it doesn't reach a plasma concentration that is high enough to treat E.
Coli in the tissue. So if instead of a lower urinary tract infection, instead we were concerned about a potential tissue infection like in the kidney, then amoxicillin probably wouldn't be the drug of choice because it's unlikely to reach the concentrations that we need. So another factor that as prescribers, we need to think about when choosing empiric antimicrobial drugs is to consider first line agents first.
And there are all sorts of resources out there that can tell you what what you should consider as first line agents. I have an example here, from our own teaching hospital where we have, Decided what we consider to be agents that are OK for empiric prescribing, and those are in green. Our second line agents, we, we recommend that culture and susceptibility testing is, is performed, and then for anything in the orange are generally drugs that are not used in our hospital.
If there were a particular situation where they would need to be used, then we would expect several things to be true, like, the, the use of the drug needs to be supported by culture and susceptibility testing. There needs to be no other option. There needs to be a reasonable chance for a cure, so we're not treating, chronic conditions that have no chance for a cure.
And then usually there's a, a quite a consultation process that goes on in our hospital. But the EMA, for example, has . Guidelines on tiered prescribing for infections in animals.
You can consult the WHO list as well, and so, you know, you may have your veterinary Medical Association, that can provide this type of information. If you are wanting to look at this particular chart, or a version of it, you can see our website here at the University of Minnesota at ARSI.Un.edu.
So what makes a first line agent, a first line agent? Why do we say certain drugs are OK to reach for first and other drugs should be reserved? Well, really this is based on how those drugs are used in human healthcare.
So are they critical for human health care? If they are, they shouldn't be a first line agent. How likely use of those drugs are to result in significant antimicrobial resistance?
How likely those drugs are to cause adverse reactions in our patient. And then, are these drugs generally affected for common conditions, and if they are, then that that would be a good choice for a first line agent as well. So first line agents often include antibiotics like amoxicillin, as I already mentioned.
Some practises may not carry amoxicillin and only carry amoxicillin in combination with a beta lactammase inhibitor, and in that case, that might be something you need to reach for empirically. First generation cephalosporins like cephalexin and cefazolin are considered first line agents, and then trimethoprine sulfas also can be considered first line agents. Second line agents again are drugs that have an increased risk of causing development of antimicrobial resistance, and those include drugs that are commonly used in veterinary medicine, but should be used with care and only when needed, and those include things like 3rd generation cephalosporins.
So some of the common ones that you may see used in practise are drugs like ceffavecin, labelled as convenia, cefpodoxime, labelled as syloceph. And fluoroquinolones, including drugs like enrofloxacin in the United States, that's labelled as Betrol, ciprofloxacin is a drug that we really shouldn't be using orally in our veterinary patients because it has really poor bioavail availability, that could potentially be something used injectably. So first line agents, again, are used for empiric prescribing, usually, For guidelines that are available for particular conditions, consensus guidelines will tell you which empiric drugs should be used for those conditions.
And so, we, in our own hospital consulted a lot of the available prescribing guidelines for small animal infections to develop our first line agent or prescribing list of drugs. Second line agents again. Should be supported by culture and susceptibility and third line agents, again, should be used only as a last resort.
There should be a reasonable chance that the infection can be cured. So wouldn't it be appropriate, for example, in a patient with a an incurable, non-resectable transitional cell carcinoma that had recurrent infections, of the urine because we're never going to be able to resolve that patient's urinary tract infection, and they should be supported by culture and susceptibility. So I mentioned guidelines and there are several prescribing guidelines out there.
They're extremely. Useful. They're all available online and free of charge, so they're all open access.
Some of the guidelines that you may or may not have heard about come from the International Society for Companion Animal Infectious Diseases, and those include a current guideline for canine superficial bacterial folliculitis. There will be updated guidelines coming out, hopefully this year on Pyoderma. There are guidelines for canine and feline urinary tract infections, as well as canine and feline respiratory diseases, and these are available online and you can find them all at Iscade's website, ISAID.org.
Additionally, the European Network for optimisation of Veterinary Antimicrobial Treatment has produced guidelines last year on canine acute diarrhoea, and I expect this year, surgical antimicrobial prophylaxis guidelines will be coming out too. So as these, as these guidelines come out, I recommend everybody consult them and then, use them to make practise decisions in your own practise. Some of these guideline resources have been distilled into really easily accessible sources.
So, for example, the AVMA has looked at the available prescribing guidelines and distilled this information into a one sheet table for easy reference, for those. Practitioners that are present today that are AVMA members, you can log in to the AVMA website and find this. AVMA has other, guidelines or other resources as well, including, pet owner educational pieces.
So informing pet owners when their pet needs to be treated with an antibiotic and when they don't need. To be treated with an antibiotic. There's some guidance for antimicrobial susceptibility testing, and they have a lot of species-specific resources.
So if you're in a country other than the United States, your veterinary Medical Association may have additional resources. The British Small Animal Veterinary Association has fantastic resources for prescribers as well. At the University of Minnesota, we've done something similar, so we, distilled some of these prescribing guidelines into a half page sheet, both sides.
We print them out and laminate them for the clinicians and the students, the veterinary students in our hospital, but this, PDF is available on our website. Other resources include American Animal Hospital Association, its microbial stewardship guidelines, I mentioned the British Small Animal Veterinary Association Protect me resources, the Canadian Veterinary Medical Association has a fabulous first line app, so it's got all of these guidelines essentially at the tip of your fingertips on your phone in an app. So all of those resources can be really helpful when we're trying to make empiric prescribing decisions.
Additionally, I mentioned diagnostic testing and sometimes diagnostic testing being a a limitation for veterinarians, but cytology is our best friend. So we should all love cytology. It's, it's inexpensive.
Many veterinary clinics can do cytology in clinic if they have a microscope and some, some quick stain. We use diff quick stain here in our hospital. It's can be performed as a point of care test relatively quickly.
I always love looking at things under the microscope cause it's all purple and pink, and I think that's really pretty, and it can be very satisfying, to, to do this sort of diagnostic testing and make a diagnosis yourself. So cytology can be critically important for us to just verify the presence of bacteria. If we suspect that there's a bacterial infection and we are able to get a sample, then we can prove to ourselves that there's bacteria there.
And if there's not, then we need to think of an alternative diagnosis because if there's no bacteria present, then we're not treating a bacterial infection and antibiotics are not going to help our patient. If we do see bacteria, then cytology can be really useful because it can determine the morphology of that bacteria. So are we seeing rods, are we seeing cocci?
Our empiric choices may change if we need to target gram-negative versus gram-positive bacteria. So gramme staining can be useful too, but many rods are gramme negative, many coxi are gramme positive. If there are bacteria in our sample that can confirm the need to do antimicrobial susceptibility testing, so we certainly don't want to send off samples if we don't have a bacterial infection present because that can be a really expensive test for pet owners.
And I always recommend that if antimicrobial susceptibility testing is sent to the laboratory for culture, then we really do need to do cytology alongside of that. It's really important for us to interpret antimicrobial susceptibility testing. Because we might see, for example, a mixed population of organisms on cytology, and when we send our sample to the lab, it's possible that only one of those organisms grows.
And so, that might change the way we select antibiotics because if the, if we know we have a mixed population, then we probably need to have a broader spectrum in our antimicrobial selection. Sometimes, cytology can reveal the presence of bacteria that are not easy to culture. So, for example, if we send off an, an aerobic culture, it's possible that we could see anaerobes on our cytology, and sometimes they have kind of classic morphology.
They tend to be a little bit more filamentous looking in some cases. There may be bacteria that are hard to grow, and that we wouldn't necessarily culture in routine, bacterial culture, methodology, but we could potentially see on our cytology and we could alert the lab that we suspect something different. And I already mentioned mixed in infections.
The other thing that's really important when we look at cytology in addition to Seeing the bacteria is, is correlating the bacteria with the degree of inflammation that we see. If we're looking at, say, a skin sample, we know there's bacteria on the surface of the skin all the time, so we really want to correlate what we see with our cytology to help us determine whether there's a true infection. So are we seeing intracellular bacteria?
Are we seeing a a significant white cell response, for example? So here's an example. We've got Barb, she's a seven year old female spade shih-tzu.
She has a history of seasonal allergies. Her owner, did not yet get her in for her cytopoint injection. The owner gave her Benadryl at home and also gave her some leftover cephalexin that she had at home.
She's got really itchy red skin between her toes and it's not improving with the cephalexin that the owner gave her. She's licking a lot. So, you know, next steps, well, we need more information, right?
She's not responding to therapy as expected. So there might be something else going on. And when she presented to the veterinarian, they did cytology of the skin between her toes and found that she had a whole bunch of yeast.
So the antibiotics were not helpful in this situation and what she really needed was an anti-fungal therapy. Another example is Martina, 14 year old female spayed domestic short hair. She had non-healing draining wounds on her ventral abdomen.
Cytology revealed piogranulomatous inflammation, but the culture that was submitted to the lab was negative after 3 days. Because of the significant inflammation. The veterinarian asked the lab for additional staining, including acid fast stain, which revealed that in fact there were acid fast positive rods, and this cat in fact had a mycobacterium infection, which mycobacterium can be really hard to grow in the lab and takes a long time.
So, informing the lab that was doing the culture that they suspected mycobacterium, allowed for the lab to culture long enough to be able to grow up this bacteria and speciate it for them. OK, so antimicrobial susceptibility testing, is, is really helpful, particularly when we have a history of antibiotic use or other reasons why antimicrobial susceptibility testing is imperative. Remember that this test is for selection of systemic antibiotics.
So, so it's not gonna predict the efficacy of antibiotics that are used topically. And it can be really important for detection of multi-drug resistant organisms. We know patients are at risk for multi-drug resistant infections when they have a recent history of antibiotic use, particularly in the last 3 to 6 months, and again, that's due to that selection pressure.
In humans, we know that Humans given antibiotics in emergency departments develop about 6% of them go on to develop multi-drug resistant infections within about 30 days. And this is just an example from, a veterinary hospital showing that animals that receive antibiotics in hospital do tend to carry, at least for several months, multi-drug resistant bacteria, including, Enterobacteralis that are resistant to 3rd generation cephalosporins, and some of these animals even had carbapenem resistant organisms, even though none of these animals received those drugs. So we should be doing ASTs when we have patients that have a history of recurrence or excuse me, history of antibiotic use, history of hospitalisation.
Certainly history of recurrent infections like in the situation that we talked about with Gertie, if they have no or poor response to empiric antibiotic treatment, if they have life-threatening infections, culture is ideal because if they're not responding to our empiric therapy, we are already behind the eight ball, right? And we need to have the culture pending so that we know what to treat with. And then there's also the potential risk of spreading of multi-drug resistant organisms between animals or people that have those infections in the household.
So if animals come from a household with someone else in it that has a history of a multi-drug resistant infection, we should probably culture those. If we're gonna culture, we want to provide the lab with good samples. And so that would ideally be a cystocentesis sample for urine to avoid contamination of bacteria in the, in, in the urethra.
If, if that's not possible, a clean midstream urine catch is reliable, but it's reliable if it's, it's collected by someone in the clinic. We only need a small amount, 5 mLs is all we need, so that's like a tablespoon. We don't want to have owners collect urine at home, have it sit on the counter for hours, and then have them bring it in.
Because there may be contamination in those samples, and so if we know how we collected it, we know that we can rely on that sample. Samples should be refrigerated until submitted to the lab, and ideally they're submitted promptly so they can be plated within 24 hours of collection. When we're talking about wound samples, there's some controversy in veterinary medicine about whether or not wounds should be cleaned and debrided before sampling.
But in human healthcare, it's generally recommended that wounds are cleaned and debrided before we sample. And that makes sense, right? Cause we don't want to culture what ends up in the trash.
We want to culture what remains in the wound. So, Ideally, we would be swabbing cleaned tissue so that we can target what what bacteria remain in the wound. It's unclear whether swabs or doing a biopsy of the wound is better, and both at this point seem to be acceptable at least for the data we have in vetMed.
When you do submit a sample, in addition to getting you know, a, a good quality sample, you want to provide the lab with information that they can use to provide an appropriate interpretation for you. So you want to tell them the patient's signalment, species is important. There are different breakpoints for determining whether bacteria is susceptible or not to an antibiotic depending on the, the species that we're gonna apply the antibiotics to.
You want to provide medical history. Tell the lab where the sample came from, and also, what you, what you think, the infection, where the infection is. So, for example, if you just submit urine, the lab's gonna assume that that's that you're interested in, lower urinary tract break break points.
But if you have a patient that you suspect has a kidney infection, then the lab would apply different breakpoints and you need to tell them that you suspect a kidney infection. So when we are interpreting our results, there are a few things that we just need to remember. So antimicrobial susceptibility testing, is based upon how much drug is available at the site of an infection, compared to how much drug is needed to inhibit growth of the bacteria.
And so the minimum inhibitory concentration is the amount that, that inhibits growth of bacteria at a concentration that's expected to be achieved in the tissues. The break point is the concentration used to determine whether or not the isolate that you send in from your patient, is susceptible or resistant to the drug. So, the, there are lab standards that determine what these breakpoints are, and they base that upon a a bacteria that has no acquired resistance to the antimicrobials that are being tested.
And they make these determinations based upon in vitro sceptibility of the bacteria to the drug, the expected concentration of the drug at the site of infection, and then again the specific animal species, because animals may have different, they may handle drugs differently in terms of absorption and secretion of those drugs. When we get these samples, the, or the results back from the lab, they tell us whether we have our organism is susceptible or not susceptible to particular antibiotics, and they do this by comparing the MIC, or the, the concentration of antibiotic that inhibits the growth of the bacteria that we've sent to them to the standard breakpoint. And if the MIC is below the break point, then that is considered susceptible, and that would be a drug that would potentially be efficacious to use in our patient.
The way these reports look vary between labs, but usually they tell us about the organism that was grown. So what type of organism, in this case, the sample here was an E. Coli, tells us about the amount of growth.
So in this case, it was a urine sample. It was collected by a cystocentesis, and there were greater than 10,000 colony forming units per mL. They, the lab will report, The, the susceptibilities, if there is a mismatch, so there's no available breakpoint for your species of patient and for that bacteria and drug combination, then they may report that is not not applicable.
So you can see from this, we have the MICs, that minimum inhibitory concentration. We have the lab's interpretation, and what's confusing, I think, for some veterinarians is what's missing is the break point. So we don't see the number that the lab compares the MIC to.
They're doing that internally. So really what you need to pay attention to is this interpretation, the susceptible resistant or potentially intermediate. So once you have this information, again, you want to choose a first-line agent.
If there is a first-line agent that your bacteria, from your patient is susceptible to. If there are no first-line agents that you can use, based upon the results of your AST panel, then you would choose a second line agent. Other considerations include patient comorbidities, so if they have kidney disease, you might need to be careful about what drugs you use if there's potential toxicity associated with that drug.
And then consider whether the drug will reach a good concentration at the site of your infection. One caveat when you're looking at these results is that you don't want to compare MICs between antibiotics, because we use different concentrations of these drugs, when we are dosing them, it makes sense there will be different concentrations, that would be, inhibiting bacteria in a, in a dish, in, in these, . AST dishes and so we can't compare drugs, we can only look at are they susceptible or or resistant.
These breakpoints are always changing. An example is that the, Clinical and Laboratory Standards Institute, changed a bunch of break points last year and updated break points for Staphylococcus. It can take some time for labs to catch up with these changes, so you might want to call your lab or check out available information on the website of the standards organisation that your laboratory uses.
There's really great information on the worms and germs blog. Scott Weis does this at the University of Guelph, and so if you're interested in this, I, I urge you to check out that blog. So in the last few minutes, we've got, let's talk about route of administration.
This really matters. Route of administration affects the bioavailability of the drug, as well as the drug concentration. So, Topical drugs are going to reach much higher concentrations than we can reach when we give a drug orally and and look for concentrations in the serum.
So we can't use antimicrobial susceptibility testing to predict whether a topical drug is going to be effective because, again, the concentrations are really different and antimicrobial susceptibility testing is based upon the concentration in the serum. Whether drugs are given orally or IV is going to affect how bio bioavailable the drug is, there can be differences in drugs getting into tissues if they're lipophilic or hydrophilic. So generally drugs with a high volume of distribution reach really good concentrations in tissues, and those that are hydrophilic and have a low volume of distribution, maybe not.
So I mentioned topical antibiotics reach a really high concentration, and sometimes can overcome when we see non-susceptibility at at tissue concentrations, on our AST panels, so don't let that dissuade you from trying those drugs. We can use topical drugs for things like external ear canal infections, cutaneous infections, wound infections, and topical therapy topical therapy alone can be beneficial for surface and superficial pyodermas, and sometimes they don't even need antibiotic therapy, but just antiseptics. Focal infections can be easily treated with topical therapy.
And when we have really highly multi-drug resistant infections, it may be that we have no other choice, but topical therapy. So this is an example of a case. Marley, a 2 year old female spayed lab.
She was hit by a car. She had lots of wounds that needed to be closed slowly over time, healing by second intention, and she had multi-drug resistant, infections in these wounds. So the only choice that we had was teach treating her with topical therapies, and they were just as effective as, systemic therapy in her case, so just remember that topical therapies are not just adjunctive therapy, and they can really be life saving like they were in this case.
There may be species differences in oral bioavailability of drugs, so just keep that in mind. Ciprofloxacin is a is a fluoroquinolone that is a human drug. It's really inexpensive compared to some of our veterinary fluoroquinolones, but we shouldn't be going for it because it just has really poor bioavailability in dogs.
So in this case, we're spending the owner's money on an ineffective drug that may be resulting in antimicrobial resistance because we're giving ineffective doses. And then, client compliance is important when we're providing antimicrobials, pet owners really just want to be part of the decision making process, and, and pet owners are aware of antimicrobial resistance, . They, they want to be communicated with and we need to make sure before prescribing that we communicate with them about a formulation of drug that would be appropriate for them and for their pet.
So that might be, you know, discussing the option for chewable drugs, liquids, or flavoured options. And duration of therapy can have a really big impact on compliance. Duration of therapy, for most of the things that we treat now are much shorter than they used to be, and so that can make it easier for pet owners to give drugs.
This is just an example. If you haven't checked this out on YouTube, I encourage you to do it. Harvard Medical School created this huge, like table size auger plate.
They put E. Coli on the plate, and in the very edges of the plate, there's no antibiotics, but as you move from the edges of the plate into the centre of the plate, there's increasing concentrations of antibiotics, and they show that the bacteria develop all of these mutations in order to be able to grow into the auger with the increasing concentration of antibiotic. And this happened over a period of 11 days.
So that's, for me, that was a really clear illustration that the longer that we treat bacteria with antibiotics, the more at risk they are of developing antimicrobial resistant mutations. And so this leads to some myth busting. We don't need to treat past c clinical resolution of infection.
So if a patient is clinically responded, we don't need to keep going. It, patients don't need to finish the entire prescribed course of the antibiotic in order to prevent resistance, because resistance is more likely the longer we treat with an antibiotic. So again, we're after a resolution of clinical signs.
And this is just an example in human healthcare about how human healthcare has changed the approach to duration of treatment for many common infections. You can see they're treating pneumonias for 3 to 5 days, kidney infections for 5 to 7 days, and so on. And I think this is the way that we'll be going in veterinary medicine, as we develop more data that shows us that we can treat for shorter periods of time.
But already, we have evidence that shows that in bacterial pneumonia in dogs, about 10 days is all we need for treatments and that taking X-rays or radiographs is not useful in determining clinical resolution, and that we should be basing this upon how the patient's doing clinically. And then we have great data and these are in the current Escade urinary tract infection guidelines that we only need to treat most lower urinary tract infections for 3 days. And I'm just gonna skip this for time so we can have time for questions, but we have some good data in animals if they have comorbid conditions like kidney disease that we might need to make some dose adjustments.
So in patients with kidney disease, penicillins, we really don't need to change, doses. For cephalosporins in animals that have really later stage, kidney disease, we might need to decrease the Frequency. So for example, go from 8 every 8 hours to every 12 hours.
For trimethoprim sulfonamide, again, in patients with late stage kidney disease, we might want a dose reduced to a, avoid adverse reactions. And for fluoroquinolones in cats with chronic kidney disease, we might not want to either increase the interval or use, a fluoroquinolone that's less renotoxic, like something like marbofloxacin. So thanks for your attention.
I think we have some time for questions. And we have several. We have one, bacteria and refugia.
Any evidence that the target populations will revert to susceptibility when antibiotic is removed. So, yeah, that's a, a really great, great question. I think when we're talking about reverting to susceptibility, we shouldn't be thinking of it in terms of like an individual bacteria, but like the population.
So if we, if we take antibiotic pressure off a population of bacteria, then Those bacteria that were that had the advantage when the antibiotic was present, because all of the other bacteria that were susceptible to the antibiotic were killed. Will potentially lose that advantage when the antibiotic is removed. And so we might get a population where the proportion of susceptible bacteria are again, the majority, but I, I, you know, it would be hard to say whether or not we'd actually lose the bacteria that have the resistance genes.
It really depends on what other things that they have that makes them fit to sort of compete in that situation. OK, what is a good empiric drug for pyometra that is going to need to wait overnight or a day or two to go to surgery while the client raises funds? Yeah, that's a, a good question.
I am, I'm an internist, so I don't do emergency surgeries, but I, I, I think, you know, you probably want something that has got Like a gramme negative spectrum, it's, you know, you're probably looking at things that are going to be kind of waking up from the the . You know, the potentially contaminants from the GI tract and the lower urinary tract, so you know Clavamox might be a really good choice in in the innerim while you're waiting. OK.
Can you give an estimate as to the percentage of risk of K Zika with TMS use? Yeah, that's a great question. I don't know that I can tell you a percentage, but I can tell you.
You know, off the top of my head, but I can, can tell you that most of the, the, adverse effects of using trimethroprine sulfas occur after 5 days of use. So if you're using a drug like TMS to treat a lower urinary tract infection, for example, you only need to treat for 3 days, and so the risk is probably pretty low, . But I, I can't tell you off the top of my head what the percent of, of that adverse reaction is.
There are certainly animals that we shouldn't be using the TMS in, so if they already have KCS, you might want to avoid it. And then Dobermans and some other breeds, are genetically predisposed to have adverse effects. So, so you just wanna double check that before you use a drug like that.
But for most of our patients, short courses of TMS is perfectly safe. And the nice thing about it is that a lot of veterinarians don't use that drug, at least here in the US and so oftentimes the bacteria is susceptible to TMS when it might not be susceptible, say, to amoxicillin. All right.
Culture and sensitivity always is always problematic. Is anyone developing a quick cheap PCR for bacterial resistance or sensitivity markers, irrespective of what bug is there. Yes, that it's, that's a really loaded question.
So there are, several companies that are developing quick tests for identification of bacteria, like non non-culture tests, as well as the presence of, resistance genes. I think, we probably need to wait and see how those are validated, because the presence of a resistance gene or the presence of a bacteria that we can detect molecularly might not be the whole story of whether that's causing a clinical problem. Especially if there's a mix of bacteria.
So, I, I think those, I think more rapid tests are on the horizon. It's certainly something that, I, I, I know it's in the works and, but I, I can't tell you right now that there's anything right now that you should go out and get. But, stay tuned.
I think, I think we'll see some on the market, but I think we really wanna make sure that we look at, hopefully they'll they'll produce some peer reviewed studies that that increase our, Our, our comfort in using those tests. Great. Can you refer to the antibiotics categories that cannot be combined when giving double antibiotics, for example, due to antagonism?
Oh, so that's a great question, and I. I think sometimes. The, the, this antagonism is more theoretical than proven.
So I definitely hear things that say, OK, you don't wanna give a bactericidal drug alongside a bacteriostatic drug. So for example, using a fluoroquitalone and doxycycline, but the, it gets a little bit fuzzy because Some drugs are bacteriostatic and bacterial or bactericidal, depending on the dose, and we know in certain infections, those drugs that you wouldn't think would be synergistic might be synergistic. So, you know, for example, Bartonella infections, the recommendation is to treat with the doxycycline and a fluoroquinolone, .
I think probably most infections don't need multimodal therapy. I, I would say the ones that do are things like aspiration pneumonia, where you really do need broad spectrum. And so when you're trying to combine drugs, those guidelines already tell us what to do, right?
So we can use an aminoglycoside and, or a fluoroquinolone and something like a, a penicillin or amino penicillin, . So, yes, I, I, I, I, I am aware of concerns about using some combinations of drugs together, but they're they're, I think that's more theoretical than proven. It may maybe we just need to do the studies and it'll be proven, but Right now I, I wouldn't worry too much about it.
All right, when using viteryin and honey, what order do you use them in? How doesvitericin penetrate honey, and how often per day? Oh, great question.
I think you would need to use the veterin first, and then apply the honey, cause the, the honey, like, so we would use, medi honey. You can get medical grade honey that's like within bandages, so you can you can keep those on for a couple of days. It's just how long you keep honey impregnated bandage on is gonna depend on like how effusive a wound is, for example, .
But if you're just using honey and you're applying your own bandage, then you probably need to apply that at least once a day, . Again, not a surgeon, but that would be my recommendation, . So, and the better and I think you would, you know, want to do that anytime you cleaned or rebandaged.
All right, a couple more. Can you comment on the efficacy of injected antibiotics versus oral equivalents in relation to time taken to reaching make and benefit? Yeah, that's another great question.
So in, in, . In a situation where you're using like an IV injection of antibiotic, you're gonna have a likely a quicker time to peak concentration than you would if you gave the drug orally, but there's not gonna be enough, like they'll eventually be the same, so I, I don't think If you're in a situation where, say, an owner can't hospitalise an animal, I don't think there's, I don't think there's a reason not to use an oral antibiotic. I, you know, it will get to the same concentration because the doses that are recommended for oral administration take into account what the oral bioavailability is in that particular species and what that the expected serum concentration is.
You're going to reach that concentration faster if you're giving it directly into the blood. All right, I'm gonna get one more out here cause we're, we're at time. But there is a general saying that antibiotics should be administered for almost 5 to 7 days.
Should we restrict administration if signs resolve, even before the 5 to 7 days? Because you said AMR is more about how long we treat with antibiotics. Yeah, so I would say, yes, I mean, when I went to that school, we treated lower urinary tract infections for 14 days, and we have a couple of studies, peer reviewed papers now, out there that say that we can treat for 3 days.
So, I think if a, there, there are many situations where if the patient has completely clinically resolved their, infection, then we probably can stop treatment. There, there may be some other surrogate tests that we can do. So I mentioned with pneumonia, that radiographs are not the test that we should be doing to determine when we stop treatment.
However, the papers that looked at duration of therapy for pneumonia off, a couple of them anyway, looked at C-reactive protein. And they showed normalisation of C-reactive protein at about that 10 or 11 days. And so if you're a little bit concerned about cutting your duration of therapy short, And you, and I just told you can't rely on radiographs, then you could potentially run a different diagnostic test like a C reactive protein.
But for most things, if the patient's clinically improved, I think we can stop the, the, the antibiotics even if we traditionally thought we needed to treat for 10 days because the truth is those durations are largely not evidence-based. And so hopefully, we will get more and more evidence that tell us what we really should be treating in terms of duration for common infections, and we don't have that for everything yet. But for example, in our practise, we usually are treating pyelonephritis for 7 days, whereas when I went to, when I did my residency, we were treating those for weeks on end, and so, and that has not resulted in any poorer outcomes for our patients.
And in fact, in patients that have. The potential to have recurrent infections, the shorter the duration that we can improve their clinical signs the better because of that risk of creating a population of resistant organisms in their microbiome that's gonna cause that next infection that's gonna be harder to treat. Awesome.
We have a lot more questions. I'm sorry we can't get to all of them. This is wonderful.
So thank you again, Doctor Granick, for your time and your expertise. This is a lot of wonderful information. Thanks to Vetlin, the makers of the Veteran pouch for sponsoring, and most importantly, thank you to all of you for attending.
The recording of the webinar and CE certificates will be available in 24 hours' time. So thank you, everybody. Thanks for having me.
Thanks for attending, everyone.
