109. The yeasts: Candida part 2, Candidaemia and invasive disease

Yes we've done a Candida episode, but what about SECOND Candida episode?

This week in the second part of the Candida Trilogy Alyssa and Callum are joined by Professor Tihana Bicanic to discuss all things invasive Candidiasis.

Listen in to hear about treatment and diagnosis of this important condition, as well as some areas of current research and the most recent guidelines from ECMM-ISHAM. (Note this episode was recorded before they were released).

Show notes for this episode here: https://idiots.notion.site/108-110-Yeasts-Candida-0eb5f9271f654312b59458d39f8de603?pvs=74 

Transcript

0:00

Hi everyone, welcome to the Idiot's Podcast, that's infectious disease insights of these specialists. I'm Callum, and that's Alyssa, and we're going to tell you everything you need to know about fungal infection. Soon may the editing come to discontinue the tazos, son. One day when the CRP's done, we'll take our leave and go.

Callum: 0:22

Hello. We're in a quite, serious space, today. I was thinking, actually, we need to have quite a candid discussion about fungi in general,

Alyssa: 0:32

Yeah, I think we ought to have a, yeah, a really candid, discussion with a fungal. So,

Callum: 0:40

is because what are we talking about today? Well, we're gonna talk about, candida. And as we were planning this, episode, we were talking about we were gonna have a episode on Candida. And as we delved into this more and talked about what all the important issues are to talk about, we realize this isn't far more than one episode. We're going to be talking about lots of things, but I think really we need to introduce, our star guest. we're delighted to be joined by, Professor Tahana, Bichanik. who is a professor of infectious diseases and mycology at St. George's University, London. and as a clinical academic, she has an interest in invasive fungal infection, antifungal therapy and resistance, and her current work is primarily focused on candida, and she's currently running the Candi-RES Study, which investigates the development of resistance in Canada species and adult ICU patients, but is also heavily involved in lots of other important work relating to fungal disease. And I'm sure we'll hear about that more as we discuss. So, welcome. Thanks so much for giving up some of your afternoon to join us and put up with our terrible, terrible puns.

Tihana: 1:56

it's a pleasure. It's a pleasure. It's an important issue and we should be discussing it more broadly in the infection community in the UK.

Callum: 2:05

We'll do our best that the loyal listener goes out there and spreads the news. I'm not going to say good news because it's fungal infection. So there's not often good news, although maybe there is some. So we've talked about superficial candida. We've talked about this sort Taxonomy and some of the more basic stuff. So we thought we would focus, now a bit more on the, invasive side of candidiasis. And how we manage that, and then what we'll do later on is we'll talk about, resistance, and a certain candidate that some of you may have heard of that is particularly relevant at the moment. That's our topic. So in talking about invasive, candidal disease, why is, why do we worry, what's the sort of significance of this? why are we, why have we got a podcast, podcast episode on it? Why is it important?

Tihana: 2:55

Invasive candidiasis. So just to define what we, mean by that. So that bloodstream infection with candida species or yeast formally known as candida, as you'll learn in the taxonomy, or a deep seated infection, for example, most commonly in abdominal candidiasis or hepatosplenic candidiasis in hemat oncology patients. So this is the most common invasive. fungal infection, and certainly bloodstream infection in patients in hospitals worldwide, and certainly the most common invasive fungal infection we see in the UK. Why is it important? Because the sort of patients that get invasive candidiasis tend to be, in hospital, usually exposed to broad spectrum antibiotics, which, as Candida is a gut commensal, It's, selected for by antibiotic therapy. And also, these patients tend to have other risk factors for, such as being on ICU, having things like central lines, urinary catheters, sometimes prosthetic materials. being a surgical patient, particularly following abdominal surgery, and also the classic risk group that's at risk of all fungal infections, which is people immunosuppressed patients. So those on steroids or other immunosuppressants, either for management of disease or their acute infection. And despite therapies, because this is such a vulnerable population and roughly half of patients with invasive candidiasis are on the ICU, the mortality, even with modern antifungal treatment is in the order of 40 to 50%. That's the crude mortality because these are such sick patients and candida is really just a, if you like, marker of these patients.

Alyssa: 4:57

we touched on some of the main sites of infection there, so I guess bloodstream is the one that we see most. when should we be thinking about invasive candidiasis in these at risk patients?

Tihana: 5:09

Yeah, that's a good question because from a stewardship perspective and also diagnostics, this is an important group. So, I mentioned patients on ICU. So, ICU is the site where, there's the most empiric prescribing of antifungals, that is echinocandins, directed at suspected invasive candidiasis. So, there is something, called the candida risk score and different risk scoring systems have been developed and we certainly use that on our ICU. So the kind of patients that are at risk are those on ICU with sepsis and evidence of some sort of organ impairment, organ failures, such as shock requiring inotropes. Or one of the major organ failures like liver failure, renal failure. And then, having been on antibiotics broad spectrum and not responding to those. So it's not just those who have a fever, not responding to antibiotics. And then these patients also need to have one of the Candida risk factors that I mentioned. which can include diabetes, recent abdominal surgery, immunosuppression, use of TPN, also predisposes, and, also, a microbiological factor which is the presence of candida colonization at two or more sites. There's no validated Candida risk score that's widely recommended by guidelines, but at our own hospital, that is what we use. and we say the patient has to have been on antibiotics for five or more days and if they have a score of three or four, then we suggest that a beta D glucan is sent to the lab and we're lucky enough to now have this available on site. And an empiric echinocandin is started. So these are the patients? in whom we should be suspecting it. Obviously, when we see a yeast in a blood culture from the microbiology lab, and that is more than likely in the vast majority of cases to be candida, and that is a definitive proven diagnosis of invasive candidiasis.

Alyssa: 7:30

Okay, great. so we should be thinking about this in patients with, risk factors for candidiasis, which we've discussed, who have a febrile illness and are not responding to antibiotics. And there are risk scores available, albeit not, yet in, national guidelines that can help clinicians, evaluate the individual patient's risk. and I think B2G Glucan is, is a really valuable, adjunct for, that risk stratification. So would you say that the most valuable way that it's used is that if you have a negative B2D group and you can essentially rule out invasive candidiasis?

Tihana: 8:15

Yeah, essentially I mean, the negative predictive value is certainly in most studies above 95%, and when we've also did it also in our own practice, that's true. Unfortunately, though, the corollary of having a beta D glucan available, is it's useful if it's negative, but there are many things, that these patients are exposed to that can cause false positives. beta D glucan is, an antigen that's a constituent of the candida cell wall, but it's not just candida that Has it in its cell wall? So we also use it for pneumocystis diagnosis as you know and aspergillus so it's not neither specific to candida and also things like Haemodialysis, IVIG, there's a range of things And sometimes also abdominal surgery, recent surgery, that can cause, if you like, translocation of candida from the gut. So there can be false positives. So the positive predictive value is, often below 50 percent of a single beta D glucan at the standard threshold. If you look at the, the, EORTC criteria for diagnosis of invasive fungal infection, then, there have been some studies that have looked at using a higher cut off and certainly a cut off above 250 in the Fungitel assay may have a better positive predictive value, but at the current threshold of 80 in the Fungitel have It's recommended that a second sample is sent to improve the positive predictive value. The same is true, actually, of the candida risk score, unfortunately, in that we are using these, this risk scoring, thing to tell us when to actually start an echinocandon, but paradoxically, again, the risk score has a better negative than positive predictive value. So one of the things that I think we should be evaluating in our practice, and we're certainly planning to use it here, is What about the combinate, how does the combination of some sort of risk score and use of the beta D glucan? Some centers that are lucky but very few in the UK also have the candida PCR and they use both tests because if both tests are positive that improves the positive predictive value but if you're at a center like mine where you only have a beta D glucan available to you, then what I suggest is look at the value, look at the clinical context of the patient and repeat it and don't use one positive beta D glucan as a diagnostic marker for invasive candidiasis. Look at it in the round. If they've got intra abdominal candidiasis, see if there's evidence of candida being cultured from a sterile site such as a drain fluid or even better sample taken at laparotomy. that's a more definitive test but in an at risk patient with a compatible clinical picture and a positive beta D glucan then one has to treat them, presumptively for invasive candidiasis, even in the absence of proof.

Callum: 11:44

Yeah, I'm just thinking there about, not having btt gookah locally anymore. these tests are really useful when you have them. And, I guess the key thing is getting the result back quickly. you can send them off to the reference lab and ask them to do it. But, If the turnaround time for that is, four or five days, it becomes clinically not very useful. So I'm certainly going to go and have a look at this risk score.

Alyssa: 12:05

One thing that we ought to talk about is when to stop,

Tihana: 12:09

well, we've talked about when to start in ICU and we've talked about the high negative predictive value of beta D glucan, as we've said with the Candida risk score and the B 2D glucan, each of those have a high negative predictive value, much higher than positive predictive value. Once you get your B 2D glucan, on the ICU ward round, when you do your microbiology rounds on around day three to five, you should review the patient clinically and in light of. How they've responded to your presumably empiric echinocandon that you've injected. Is there another bacterial cause or non infectious cause? And if not, if the beta D glucan is negative and the patient's clinically improved, then at that point you stop your empiric echinocandins. It's positive at a low level, again you look at the clinical picture, consider false positives, send a repeat test. The other thing to say that if it is positive, don't keep repeating the test. Which I see happening here in practice because it will stay positive for quite a long time, maybe weeks to months we're finding, so it's not useful to monitor in a patient with invasive candidiasis response to treatment and telling you when you can safely stop therapy.

Alyssa: 13:41

I know, galactomannan is often used to monitor. Treatment response, um but not so much BC flu can, flu

Tihana: 13:50

The other thing diagnostically that I would say to all of you is ask your lab. In the past, it was difficult for labs with small turnaround of tests to consider, implementing the Fungitel. because the tests are done, there were large plates, it's an enzyme immunoassay, as I understand. But now, there's something called Fungitelstat, and there are other assays where you can buy just a certain number of smaller sort of individual single use tests. So this can make it more cost effective for labs to do it. My, my lab uses a test, made by a company called, I think, Fujifilm or, and there's also Waco, but I know that Fungitel does now a so called Fungitel stat. So I do think it is useful. We'll come to talk about antifungal resistance, but really one of the most challenging things is you alluded to with invasive candidiasis is knowing when to suspect it. And once you start empiric therapy because of the risk of resistance, knowing whether you should continue how long for and when to stop. So having these tests in house is, I think, a really valuable adjunct to give you the confidence to be able to advise the clinical teams that it's okay to stop.

Alyssa: 15:21

yeah.

Callum: 15:22

I think if three in the morning, the person's really sick and they've got that risk, nobody's going to be saying you can't start an antifungal because we need that early treatment, but being able to narrow down in that stewardship angle is so important.

Alyssa: 15:35

Yeah. so I guess it's easy if you isolate candida in blood culture. My understanding is that even though these are commensals, they should never be considered, a contaminant, a skin contaminant, for example. It should always be treated as significant due to the severity of the disease. If we don't have candida in blood cultures, are there, cultures that can be useful? You mentioned about screening patients for colonization and if they were positive in two sites. So do you use like a five point candida screen approach in your center do you actively screen these patients or is it, if you've opportunistically picked it up

Tihana: 16:14

Well, you're absolutely right. no is the answer and of course the whole colonization index concept depends on you having sent samples. one of the challenges when we come also to talk about candidate resistance later on is that the diagnostic guidelines do recommend that all high risk area patients, including patients on ICU and immunocompromised patients, have their candida species, particularly from respiratory sites and urine, are speciated. where as when you're reporting from the microbiology labs, these are often just, reported as colonizers, what other sites, are useful? Clearly, if the patient has candida in a catheter specimen of urine, its significance depends on whether they've got a raised white cell count, whether it's a mixed infection with bacteria, is the patient unwell or not? that sort of thing. So it's all a clinical interpretation, like it is for any microbiology urine result. If a candidate has grown from a urine of a patient who's got, either renal obstruction or some sort of foreign body like a stone or a stent, then that is potentially, could be significant and could be an invasive focus. and we often see, I see in my clinical practice, for example, people with stones causing obstruction and then require neprostomy and then the neprostomy urine, for example, grows candida again. These patients have often been exposed to antibiotics previously and maybe even had. bacterial UTIs and then the candida is eventually a selected for. But in these cases, growing a candida from a urine is significant. as we know, candida is an avid biofilm form and likes to stick to stones and stents. And in that setting, it's often difficult to treat the infection, partly because of urinary penetration for example, the echinocondyns don't get into the urinary tract, the fluconazole gets in much better, but also the fact that actually nothing penetrates in the biofilm and until there's source control, then we can't effectively treat this infection. Where else do we see candida? We see it also in neonatal meningitis. So this is a group at risk of CNS disease. So again, in these cases, again, having an antifungal that penetrates into the site. is important. So I believe paediatricians tend to use amphotericin B based preparations in these instances, certainly in any adult or neurosurgical patient, for example, with a shunt infection. Again, you would probably not be using an echinocandon because that doesn't penetrate into the CNS. You would use amphotericin B. The other things of course to look out for in any instance of Candidemia bloodstream infection is a, bit like Staph aureus if you like. Candida likes to form metastatic pockets of infection. And where it particularly likes sticking to is, Heart valves and it can see to the back of the eye as well causing fungal balls or even endophthalmitis So that this is why? Microbiology registrars always recommend and I would As you say, recommend that any patient with candidemia, a bit like a patient with staph aureus bacteremia, does need an in person clinical review, not just a phone call, for the team and an assessment of whether they've got any visual symptoms. Sometimes you will get pushback from the ophthalmology team. Their guidelines don't necessarily recommend an eye exam. in all patients with candidemia, whereas most infectious diseases society guidelines do. I think the incidence is only in the order of three or four percent. However, of course, it can be devastating if it's not caught early and whilst conscious patients can report floaters. Which I think appear a bit later on subsequent to the candidemia, like in the second week. Patients on ICU of course can't, report any visual symptoms. So again, if there's evidence of endocarditis, then that has clinical implications because candida tends to cause very large vegetations and often the management needs to be surgical as well as medical. And again, if there's a prosthetic valve, there's the biofilm issue. And of course the issue with knowing that there's endophthalmitis is if the patient's on an echinocandin, that is not going to penetrate into the endophthalmitis. vitreous fluid or aqueous fluid, and therefore you need to adjust the regimen according, obviously suited to the organism. But again, agents such as fluconazole, together with flucitazine both have excellent brain penetration. And so we need to know this. We also need to know, of course, if there is, deep seated or metastatic infection because that may then, cause us to prolong the duration of therapy. at the moment for uncomplicated candidemia, that is candidemia in the absence of deep seated or metastatic sites is just two weeks from the first negative blood culture. So the guidelines recommend we take daily blood cultures And then you continue a kynokandin therapy, and from about day five onwards, when hopefully you will have sent the candida or your lab will have in house susceptibility testing, which again, most, a lot of labs don't have. But if you find that you have an azole susceptible species and the patient is stable, you can then deescalate them. to Fluconazole. But if you do have, any kind of, deep sight, then of course you need to consider prolonging, the course of therapy.

Alyssa: 22:54

So lots of parallels with the Staph aureus bacteremia that, never considered a contaminant in the blood culture, require clinical assessment for the source of infection and for evidence of deep organ involvement, TTE to look for, endocarditis. of some sort of evaluation of eye involvement, whether that be by an ophthalmologist or at least questioning regarding symptoms. And then we want daily blood cultures, staph aureus, bacteremia, we don't do them that frequently. And then generally a 14 day course of treatment from the date of the first negative.

Callum: 23:38

Yeah, just reflecting what you were saying there. And I think locally are most of our candidemia. All right. I think we have more candidia from urology than we do from intensive care. And I don't know if that's because we're doing well in intensive care or badly in urology, but it's a very common thing that we were thinking about in starting empirical antifungals in that situation. And I guess we'll come on to treatment. But, it's really tricky. Thank you. to think about. And, I guess the most common reason we're getting consulted about this is, these patients where they are colonized and that abilities to tell which patient is colonized, which patient is infected is really challenging. you're getting a Deep respiratory sample with candida on it, is that important? Probably not. But I guess the good thing about blood, the good thing about this is that you can get on a blood culture as opposed to quite a few of the invasive fungal disease we're talking about, which are, you don't have that sort of definitive, test.

Tihana: 24:33

Yeah, although the sensitivity of blood cultures is quite low. Again, it depends whether you take the full volume and both bottles. Very rarely, maybe some reference centers have special fungal blood culture bottles, but most of us, including, I don't know about your centers, but my center just uses aerobic blood culture single bottle. They've stopped doing anaerobic blood cultures. so, serial aerobic, especially if under filled, but the sensitivity is fairly low again, a bit similar to bacteremia. So the median colony forming units per mil of blood in series where this has been looked CFU per mil. So it's a low organism burden, intermittent shedding into blood. So it's great if the blood culture is positive, obviously the specificity is high, but if the blood culture is negative and clinically, it seems to be like it could be an intra abdominal, candidiasis, or you do imaging in a hemato oncology patient. Although I have to say I've very rarely seen it in the clinical context, but you see hepato splenic abscesses, then, that's, sufficient radiological, proof. And then say you get a candidate from an abdominal drain and a patient with collections on CT. I think that is sufficient evidence to treat these patients on a clinical basis without a positive blood culture.

Alyssa: 26:10

And I think that it really highlights the importance of having a high degree of clinical suspicion in at risk patients, and not relying on one single diagnostic modality, but thinking about, screening for colonization, taking well filled blood cultures, regularly if they're persistently febrile, thinking about, non culture based diagnostics. and, doing that in a timely manner such that if they do have invasive candidiasis, you're not going to be picking it up too late. Ha,

Callum: 26:48

Yeah, the importance of blood cultures and taking them correct. I think sometimes, especially as a very junior clinician, you're given a long list of tasks and you feel like you just need to get through it and you don't maybe realize the importance of getting, oh, it's gone red. I've done enough. Aim and I had a bit of a deep dive into blood cultures in episode five of the podcast Back to Bacteremia so if you're interested in, if you've not listened to that you can go have a listen to it. I also have a book that I got which is called The Dark Art of Blood Cultures. which has a lot of really interesting insights into, when you should take blood cultures, et cetera, so, we've talked about the different clinical presentations there. we've talked about candidaemia, endocarditis, ocular infection. urinary tract, and then we mentioned metasplenic abscesses as well. And we've gone into the diagnostics in there, talking about B2D, Glucan and blood cultures. so say we've got our patients, we've identified, they've got candidemia, we're looking for different sources. what would you suggest? We would recommend as an approach and where we would be looking for guidance on this, because certainly I've been using the IDSA guidance, but they're quite old.

Tihana: 27:57

That's right. the IDSA guideline I think is from 2016. but the good news is that there is a new global guideline that's accepted for publication at Lancet Infectious Diseases. It's by two societies, a European one called ECMM, European Confederation of Medical Mycology and an international one called ISHAM, International Society for Human and Animal Mycology. So This is multiple experts reviewing the literature, grading, there is a shorter guideline and then there's a supplement with the full guideline with lots of helpful figures and algorithms. But, In summary, the treatment, the first line treatment has not changed from what it was in IDSA and also the old ESCMID candida guideline, which is with an echinocandin. the options have expanded now. so we used to have just three daily echinocandins as an option, capofungin, anigilifungin, and mycofungin. Which ones do you use in your hospital?

Callum: 29:04

Well, I think we used to have Castle Fungan first line, but then we moved to Nidjiva Fungan. I think it was to do with interactions if I remember correctly, or Cost.

Tihana: 29:16

I think it's the liver, it's the one that's not hepatically metabolized. So if you have liver pain, that's an attractive one. Plus, when we moved to it, it was the cheapest

Alyssa: 29:28

funkin at the moment, but I think it does vary depending on

Tihana: 29:32

yeah. So, there is a new kid on the block amongst the kynacandins, and that's actually made it into this guideline. It's called Rezafungin., I don't know if you've heard of it, but Rezafungin is a new Echinocandin. It's structurally most related to Nidulofungin. Again, it benefits from the good safety profile of, the other Echinocandins. There's no drug interactions really to particularly worry about. No dose adjustments in the elderly, obesity, renal or liver failure. So it's very attractive in that perspective. So that can also be used, but it's given once a week, so it has a very long half life. So a bit like, dalbovansin, it's an option, particularly in those you might be able to discharge early or, that need OPAT. So the echinocandins still remain the preferred, strongest recommended first line option. antifungal. Why is that? Because in the clinical trials, they've been shown to have essentially superior activity, both in terms of clinical improvement, and also psychological clearance. So time to clearance of blood cultures, compared to Fluconazole. So in the seminal study comparing with Fluconazole, fluconazole to 400 milligram a day, I believe. two days median time to blood culture conversion in the anegyla fungal arm and five days in fluconazole. So fluconazole, especially if using lower doses, is much slower to kill yeasts. So basically, you should start with an echinocandin always, except under the circumstances that we talked about earlier. If you have a CNS focus, then you might consider amphotericin B. If you have a urinary focus, you could consider amphotericin C. Maybe fluconazole with or without flu or amphotericin. B doxy coline, which penetrate well into urine. But if you have a straightforward bloodstream infection, you should use an kinin upfront. And then around day five, when hopefully you have your susceptibility profile back, or at least you know the species of candida. Then you can consider in a patient that's improved and of course you've pulled the line if they're on ICU You've changed the catheter etc. Depending on the context and they don't have endocarditis You can then consider de escalating usually to fluconazole at a dose of 400 to 800 milligrams a day. there are certain species if you, like our lab, is still evaluating in house candidate testing. Again, this is another thing that I would encourage you, if you're a bigger center, to try to, in addition to the beta d glucan, encourage your lab to consider in house testing at the very least for gluconazole and candida because that will give you a guide as to whether to de escalate. One of the challenges of that is That fluconazole, testing is an e test, which of course depends on training of the staff, because it's definitely operator dependent. there are also commercial, susceptibility, testing things for candida, such as a yeast 1 sensitizer, which I know our lab are evaluating. So providing that you have the susceptibility back, or if you don't, you can look at whether the patient has been previously had been exposed to gluconazole. If they have, and they've had a candidemia, I probably wouldn't deescalate

Alyssa: 33:37

Hmm. Yeah.

Tihana: 33:38

because it's possible they have a resistant species. In terms of using species as a guide, you will know that pandida glabrata is, Though not intrinsically resistant. is intrinsically less susceptible. So usually, regardless of the MIC, the lab will only report a candida glabrata as either intermediate or resistant, never sensitive to fluconazole. So the intermediate is often reported as susceptible dose dependent. So they may say, okay, try to treat with doses of 800 or even 1, 200 milligrams a day. My personal view is that if somebody has invasive disease, I would prefer to use an echinocandon for a glabrata because you can select for the resistant subpopulations on fluconazole therapy. Again, there are certain species like cruzii, which is rare in the UK in bloodstream infection, but it's intrinsically resistant. So if you see that in blood, you'll know not to de escalate. There's also candida parasilosis, which has variable rates of gluconazole susceptibility, tropicalis, etc. So sometimes you can guess, for some species and obviously albicans in a patient who's not had gluconazole before, chances are they may well be susceptible if you haven't got the results back from your lab. I would not take my chances with a glabrata, Unless you either have an M. I. C. but even then, in a serious infection, I would treat with a kind of Candence.

Alyssa: 35:29

Yeah, no, that's fascinating. And I hadn't realised actually the benefit of the kinocandidins over fluconazole for clearing candidemia. I thought that the rationale for starting with a kinocandidin for empirical therapy was purely because until you have the ID and the susceptibilities, you don't know if it's going to be a candida glabrata or a cruzii, or an ourus, as we'll talk about later. So, so start with something that, will cover all.

Tihana: 35:58

you're right. so the spectrum of cover is also important and I should have mentioned that. So, spectrum is important as is the rapidity of killing and lowering the infection burden and the PK of the drug, so penetration of the site. All these things are important when considering the choice. So guidelines are guidelines by definition, but there's no getting away from looking at the clinical context. just to say, so amphotericin B again is very broad spectrum, but obviously is more toxic, And is also fungicidal against candida. There's actually no clinical trial that's done a head to head of liposomal amphotericin B against the kind of candida. It's the only trial compared deoxycholate, which of course was more toxic. when I reviewed it the other day, I was looking at that, the literature on this. and then the most recent trial of Rezafungin compared weekly to daily Casparfungin, and found weekly to be non inferior. So, we use Echinocandins because of their spectrum, because of their sidality, and because they're safe with few drug interactions. So you're right, all those three things are why they are first line.

Alyssa: 37:17

Yeah. and I guess with candidemia, apart from the treatment, important treatment aspects is removing that source of infection. So, if that's a line or, if that's prosthetic material in the urinary tract, you're going to struggle to clear your candidinia or your urinary tract infection if you don't

Tihana: 37:39

yeah. I'm draining you of that pus, getting radiology or the surgeons to drain in and drain that abdominal collection that no antifungal, no matter how fungicidal, is going to penetrate or antibiotic.

Alyssa: 37:56

And do you ever prophylax patients against, you know, who are high risk of, invasive candidiasis, who would you start on fluconazole prophylaxis?

Tihana: 38:07

is a, this is a controversial issue I'll tell you who we start broflaxis. So, anyone with an abdominal perforation,, especially upper GI, esophageal, We use fluconazole prophylaxis to prevent because mediastinitis with candida can be life threatening, and also with lower GI perforation, but the guideline which I've got open here. this is the global guideline in high risk adult ICU patients including those who have undergone abdominal surgery and are at risk of invasive candidiasis. Fluconazole, marginally recommended. But not defined what high risk means. Those undergoing abdominal surgery, they say recent abdominal surgery and recurrent gastrointestinal perforations or anastomotic leakage. I don't know what is meant by recurrent perforations. My view would be the ones we do clinically at the moment is not the top one. ones. Some people say that duodenal surgery is particularly high risk. So anything upper GI I gather is higher risk. Things like, I don't know, duodenal bypasses and surgery there. But I think, If patients have a perforation or ongoing leak then they probably, until that perforation is sealed or they have an esophageal perforation, they should get fluconazole as prophylaxis. Again, you've got to look at the epidemiology of your centre. If your centre is dominated, as some centres are now in southern Europe, by azole resistant candida, which we'll talk about then probably using fluconazole prophylaxis in this patient is not a good idea. If anything, I will just select out. And that's one of the arguments against universal prophylaxis. is that you're selecting out. However, I would also argue that we shouldn't be starting these patients on echinocandensis praphylaxis, because that's our class that we keep in reserve for when they become septic. So I think we have to just, look at the guidelines, that are going to come out and then review our local context and decide and try to really define. a group in our clinical context, a high risk group, where we recommend prophylaxis.

Callum: 40:52

to what we do as well as transplant. liver transplant patients that we're looking after, I think get routine fluconazole prophylaxis, just I guess, cause you're messing around if you're, biliary tree and anastomotic leaks. certainly I think that's in the transplant guidelines, although correct me if I'm wrong.

Tihana: 41:07

I thought, or at least at King's in london, that in liver transplant they often use, certainly in the liver failures, they use a lot of echinocandins because of the interactions of gluconazole with tacrolimus. And also, if you have liver failure, the concern about giving azoles. in liver failure, but, certainly I know Kings use a lot of Echinocandin, Brachylaxis.

Callum: 41:33

I think we decided to stick with fluconazole, but it would be expected. Because it's normally they are able to adjust the tacro dosing based on that.

Tihana: 41:40

Excellent. Well, that's again good if you've got on site therapeutic drug

Callum: 41:45

yeah, we're lucky to have that. yeah, One of the

Tihana: 41:48

Yeah, another thing that if you're going to tweak things, especially with the azoles, of course, fluconazole, we don't recommend TDM, but any of the mold active azoles or things like azoles interacting with other important drugs, you can only do that if you've got on site TDM and you can make dose changes in, in either drug in real time.

Callum: 42:14

So just to summarize, we've talked about invasive, candidiasis. How that's defined, what sites of infection. candidemia, and then the sort of potential secondary sites such as endocarditis and ocular infection. And other invasive foci, so urinary tract invasive disease, and then rare complications such as, hepatocystic abscesses. we've talked about when to suspect, this, what, how to risk stratify, which patients. to be, treating empirically for candidemia and when to do your diagnostics. who to prophylax, which, is still uncertain. And then once you've established that the person has invasive candida, how we'd approach treatment. So, looking at guidelines, and looking forward to the new guidelines, which are going to be published in 2025 and LUNS ID. and the relative, weighing up of what treatment, but certainly looking at akin canons as our first line empiric therapy, unless there's things like urinary tract involvement. and, we've touched on some other topics, around sort of resistance and the impact of the different species have. But we'll come back and we're gonna talk about specific Canadas and the, the big bad, Canada that everyone's worried about. so, thanks very much, for joining us both and, that was our part of our candid series of discussions.

Alyssa: 43:38

Thank you so much. It's lovely to have you join us.

Tihana: 43:42

You're most welcome. It's a pleasure.

Alyssa: 43:45

See you soon.

43:51

Thank you for listening to The Idiot's Podcast, the UK's premier infectious disease podcast. Questions, comments, suggestions, why don't you send them in to idiotspodcasting at gmail. com. Have a five star review in your pocket? Calum and I would love to have it. Please drop it in your podcast player of choice. We tweet at idiots underscore pod. And if you want to donate to support the show, there's a link to do so in the description. But until next time, I'm Jay. I'm Calum. See you then. Now that the episode's done, we hope you learned and had lots of fun. So go forth and treat people with some of what you now know. Now that the episode's done, we hope you learned and had lots of fun. So go forth and treat people with some of what you now know.