ID:IOTS - Infectious Disease Insight Of Two Specialists
Join Callum and Jame, two infectious diseases doctors, as they discuss everything you need to know to diagnose and treat infections. Aimed at doctors and clinical staff working in the UK.
Episode notes here: https://t.ly/8DyqW
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ID:IOTS - Infectious Disease Insight Of Two Specialists
108. The yeasts: Candida part 1, overview and superficial candidiasis
In this episode there will be puns where you yeast expect them...
But more seriously, what does Candida albicans actually mean? What are yeasts anyway? How does this all relate to the Romans?
These questions, and more, will be answered as Alyssa and Callum continue the Fungal series with this, the first in a 3-parter on all things Candida!
In this episode we cover the Taxonomy (newly confusing), Epidemiology and Pathogenesis of Candida spp. before talking about superficial candidiasis.
Look out for upcoming episodes on invasive Candidiasis and C. auris!
Show notes for this episode here: https://idiots.notion.site/108-110-Yeasts-Candida-0eb5f9271f654312b59458d39f8de603?pvs=74
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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:Hello, Alyssa.
Alyssa:Hi Callum. How are you?
Callum:I'm good actually, I've been really healthy recently.
Alyssa:Oh, great.
Callum:Yeah, there's this new brand, I guess we talk about fish and how they have a lot of nutrients in them, omega and all that sort of stuff. So, there's this new brand called Owl, and they make this, super, healthy fish. Comes in a can.
Alyssa:Nice.
Callum:It's called, Super Fish Owl Candid.
Alyssa:Wow. Sounds amazing.
Callum:which is surprising because what are we talking about today?
Alyssa:Today we are going to talk about candida and focus on superficial candidiasis.
Callum:I don't know if I can continue the pod if, it's too bad if I'm just going to have to be fired from the show. Sorry, dear listeners, I might be a new low, but, anyway, yes, we're talking about superficial candidiasis, and Canada in general.
Alyssa:Yes. So this is the first of our, candida trilogy. So we are gonna run through, a bit about the background of Candida. some recent naming changes, talk about the epidemiology and pathogenesis. and then we're gonna focus on superficial candidiasis and, how it clinically presents how di Candidiasis is diagnosed and how superficial candidiasis is treated.
Callum:Yep, and then in the other parts of the trilogy, and everyone knows that the best things come in trilogies, we'll focus a little bit on invasive candidiasis with a special guest, and then we'll move on and talk a little bit about antifungal resistance in Canada. And The mechanisms of that and managing it with another special guest.
Alyssa:And we're also going to talk in that third episode, we're going to focus in on candida auris as well.
Callum:Yes, which, is obviously a huge problem. So should we just jump in?
Alyssa:yeah.
Callum:Do you know what Canada Alpacans mean?
Alyssa:Is it something to do, albicans, does that come from like albino meaning white?
Callum:Yeah. Do you know what Canada comes from?
Alyssa:tinned food that's canned? Ah, okay. Ah. Ah, so candida albicans.
Callum:of that terrible pun. Canada comes from the Latin word candidus, which means white. Which is where we get the word candidate from, because, Roman, if they were standing for public office, they had to wear a white toga, so that they were candidates because they wore white. Candida albicans means
Alyssa:White, white.
Callum:yeah, I love that, it is white, which, you know, I guess you can remember because it's called literally white, white.
Alyssa:White, white.
Callum:That's a stupid little fact to start us off with. So, what are candida? So we've, we did the fungal overview episode where we talked through the taxonomy. So hopefully you've listened to that. We won't explain it again, but essentially, single cellular fungi and candida are the sort of biggest group of yeasts, that's the yeast that we're going to see most commonly, it's hugely prevalent, and it predominantly affects women, which I guess is potentially one of the reasons why it's a little bit under, Why it's under research, isn't it? Like many things that are in women's health, how many people in, in a lifetime, how many women would expect to
Alyssa:Yes, I think about 70 percent of women experience one or more episodes of vulvae vaginal candidiasis in their lifetime. It does, account for a huge burden of infection.
Callum:I wouldn't be surprised if it was even hard. So this is a huge, hugely prevalent problem. and obviously there's a huge spectrum of disease from one end to the end. But, was it the most common human fungal infection?
Alyssa:Yes, so candidiasis, is the most common human fungal infection. So candida, candidiasis, you can think of it as either superficial infection, so cutaneous, and mucosal, such as oral candidiasis involved with vaginal candidiasis. but then it can also cause invasive disease. So the bloodstream infection or candidaemia, and also deep seated infection. so it's the most common cause of, invasive fungal infection in humans as well.
Callum:And candida albicans, you'll see reports, is 90 percent of human candida infections, are caused by candida albicans. and for candidemia it's about 40 50 percent of cases of candidemia. But what are the non candida
Alyssa:Yeah. So non candida albicans, species include candida glabrata, candida
Callum:Candida parasilosus, Candida tropicalis, Candida cruzii, Candida auris, Candida lusitanae, Candida guillermondii Candida dublanensis. I'm glad you took Gudrun mondii.
Alyssa:and I think one of the notable things is that Candida albicans really used to dominate, but there's been a rise in non albicans Candida's causing infection in recent years. So looking back at, data, in the UK, candida glabrata now accounts for 28 percent of candidemia and candida parasilosis for 12%.
Callum:So do need to know about these other candida as well. and we'll talk more about invasive candidiasis in a future episode. So everyone's favorite subject taxonomy. People love talking about it. And so we obviously did that fungal overview. So what specifically about candida taxonomy might be? Important to be aware of
Alyssa:So fungi were initially identified and grouped taxonomically based on examining how they appear morphologically and their phenotypic features. So they were then grouped based on sharing common features. but with molecular advances, fungi that were previously, grouped in the same genera have subsequently found to not be really at all related. So this has led to renaming of lots of, species. with new genera and species being created or them being assigned to different, genera.
Callum:I feel like fungal taxonomy and naming was already confusing and it's become more confusing because different fungi were named for different states. So they're telomorph or anamorphic states. In their sort of sexual reproductive cycle, and that's because they were morphologically quite different. One of the good news is, as I was reading about this again, and we've linked a paper, from Clinical Microbiology Reviews, which summarizes the taxonomical changes and the rationale for them, and in that they say that actually we shouldn't be using the anamorphic and telemorphic names anymore and just move because it's all genetic if it's the same species, the same species. So, yeah, we'll debate this on many episodes, I think, in terms of taxonomical changes, but I guess they have a good rationale for doing it. It's just clinically not that useful, but you probably do need to be at least aware of what they are. I think most laboratories, certainly locally, we are continuing to report, or if we do change Then we'll, give the new name and in brackets, same formerly known as X,
Alyssa:think that's really important because otherwise it can be quite confusing. Yeah,
Callum:life, isn't it? So, making reports clear. I think we gendered up a lot of things that you see that in bacteria as well. Like, for example, Gucci bacteria being renamed from propione bacteria. We still, report them as cutie bacteria but I think say to people like, it's like propionibacteria, people are like that as well. I've never heard of either of them, but it's not the best example. So yeah, so we should go through some of the renaming ones, just more so people are aware of them. I think this is particularly useful if you're ever going to a conference and, the idiots podcast hosting a quiz, because this might be something that's put in the quiz.
Alyssa:it might be something to put in a quiz. Yes. Yes.
Callum:the fizz if you were there. so Candida glabrata is now called, Nacosiomyces glabratus.
Alyssa:Cantidae cruzii is now called Pachyrhidriovetzii. Kudryazevii.
Callum:lusitania is now called Clavospora lusitaniae.
Alyssa:And candida guillemondii is now called Mayerizima guillemondii.
Callum:I did well out of that exchange there. I think the easy ones. I hardly recommend reading the review paper we put in there.'cause it is helpful and it's got a really nice table of all the changes. Also if you don't want to, don't bother because, that's not the most important part of today's episode. Okay. So epidemiology,
Alyssa:Yeah, so candida, and species previously in the genus candida, they're commensals, right? So they're found on human skin, in the GI tract, and they tend to cause opportunistic infection when people become immunocompromised or associated with, um, antibiotic usage, or essentially anything that promotes the growth of candida and then more invasive disease tends to occur in the context of a disruption of your cutaneous or GI barrier, such as having a central lining, having severe mucositis or GI surgery that allows those skin organisms or GI organisms to get into the bloodstream or into the peritoneal space.
Callum:often one of the commonest queries you get, I guess is we have sample site X and we've grown Canada. Is it significant?
Alyssa:Mm.
Callum:if you take a swab. of the genital area, you'll find candida. If you take a mouth swab, you'll find candida. If you take a gut sample, a stool sample, you'll find candida. These are a normal part of the microbiome. And actually recently I was reading a, there was a Nature Review article that I was reading in preparation for a talk on lung infections. And it was like, well, candida are a normal part of your lung microbiome.
Alyssa:Mm.
Callum:So they coexist with us. They are normally there. And, That's fine. And it's that balance between, when is it colonization? When is it infection? I think that's probably the major challenge. Like sometimes that's easy, like it's in the blood. Shouldn't be there really. So that's simple. But, and then it becomes more and more difficult. So as always with these things, it's like, how does it correlate clinically?
Alyssa:I think one important thing is that generally, if you're going to have candida infection, whether that's mycocutaneous, superficial or invasive, often you're colonized with candida first. So people who are colonized with candida, are then more likely to get candida infection. Mm.
Callum:If you do studies of the microbiome, and do sequencing of all sort of genetic material there, you're still going to find it, it's just maybe not enough to culture it, even if the culture is negative.
Alyssa:Yeah, no, that makes sense. Firstly, you need to be colonized. Then you need to have factors that promote overgrowth.
Callum:yeah,
Alyssa:such as like antibiotic usage, and that overgrowth might lead to superficial or mucocutaneous infection. And then if you have further factors that, impair your immune system, so either barrier immunity with a line or a breach of your GI tract, or impaired cellular immunity, then you're, at risk of invasive candidiasis. But sometimes because invasive candidiasis is hard to diagnose, All you might have on your positive cultures is that they've isolated candida from, a swab of their Traci site or from their sputum or in their urine or something. So you know that they're colonized and that is a prerequisite for subsequent infection by candidate. So it can be useful indication, that candida's around, but it has to be taken in context of their clinical presentation and their risk factors.
Callum:I think that's a really nice way explaining that sort of spectrum of disease. And just thinking of an example, when you were talking there, so in your mouth, if you're, got healthy, normal immune system, we will have candida in our mouth. it's normally there. Then say you get given antibiotics, you get oral candidiasis. You can see that, you might have a kind of white, coating the tongue or some other areas, you might get a bit of pain, redness. Again, if you're immune competent, that should just self resolve. Maybe we'll give some antifungals to get rid of that topically. But then if you've got an impaired immunity, say if you've got HIV, that can easily progress to a state where you get, esophageal candidiasis, and that actually makes you quite unwell. to swallow because of pain. so that sort of Continuous spectrum. And, whilst everybody has it in their mouth, obviously, not everybody's going to get that degree. So, most of this is colonization leading to infection, but you can get transmission. And we'll talk about this more when we talk about Candida auris, but there can be environmental toll. Okay. Contamination through fomites, et cetera, of candida.
Alyssa:Yeah. Mainly endogenous infection, isn't it?
Callum:Yeah. but other things could be exogenous.
Alyssa:Yeah. And I think that there are, evidence of there being some environmental niches for some of the other, non-albicans, candida species. And it's, unclear if some of those, can cause exogenous infections. But I think it, it's particularly true for Canada, a risk. We'll talk about that more in, episode three.
Callum:And I guess we've talked about non albicans infections. And as we talked about earlier on, the main non Albicans pathogens are Glabrata, Parasillosis, Tropicalis, and Cruzii, but Dublinensis and Lusitania are becoming more common. so we're talking there about that spectrum towards disease. What specific factors increase your risk of getting, Candida disease?
Alyssa:So you have to remember that candidiasis is an opportunistic infection and it's. occurs secondary to a combination of factors, as we've talked about. So the first one being use of antibacterial agents, which alters the colonizing flora to allow candida to proliferate, a degree of underlying immunosuppression, be that neutropenia or diabetes or steroid use, and then a breach of your, intestinal or cutaneous or mucosal barrier. that allows, the candida, to, invade and cause invasive infection.
Callum:Yeah, and I think the diabetes one is always the one that stands out in steroids as a sort of proxy to that as well. Diabetic patients and they very often, particularly when you get antibiotics, will be having problems with candidal infection, particularly if their blood sugars are uncontrolled, that sugary environment is a great culture media. another thing recently as a specific risk factor, to be aware of is that there's, these anti hyperglycemic agents for diabetic patients there are, SGL, SGL2 transcriptor blockers. So, SGL2 is a sodium glucose co transponder and basically by blocking it, more sugar leaves the body in the urine, but if you've got this nice sugary urine, then it's a great place for, bacteria or yeast or other organisms to grow. certainly locally, we've been seeing a couple of cases of of, people on these drugs that are getting candidal disease.
Alyssa:that like dopagoflozin, is it?
Callum:Yeah, Dapaglifosin. yeah, we had a case this week with someone who had, emphysematous pyelonephritis and, they had to candidise and they were just very unwell, with it. so be aware
Alyssa:turns your urine into a nice, rich culture media.
Callum:It does control your diabetes pretty well, and then in terms of virulence factors, just to run through that briefly, there's a graphic in the Alyssa's put there from one of the Nature Reviews, which is quite helpful just to visualize it. So can the albicans and some of the non albicans species also, the foreign hyphae so filamentous form that comes out from the E cell and it provokes an invasion. So the graphic in the notes shows that nicely. And it's also got something called Candidolysin, which is a cytolytic toxin. and that's secreted by the hyphal tip, so it allows it to worm its way in. tissue ahead of it so that it can, cause invasive disease. And they also have surface adherence molecules. So it allows them to adhere to surfaces and form biofilms. So thinking about things like, lines, mainly central lines, that tracheostomy site, even something like a stone in a urinary tract, you can stick onto that. So it doesn't necessarily need to be a synthetic thing, it could be something that's natural. Heart valves,
Alyssa:you get these lines and stones removed if you're going to clear the infection.
Callum:Okay, so that's the sort of pathogenesis and epidemiology. So we talk about clinical presentation of superficial candidiasis. So, Alyssa, what is the clinical presentation of superficial candidiasis?
Alyssa:Well, it really depends on the site. So you can divide it up as cutaneous, so it can cause intertrigo. So often that's where you get these, red areas, broken skin with some scaling that often occurs like under skin folds, like, under breasts or under an abdominal fold or in the armpits or groin, areas that are moist and sweaty. So I'd say that's, we see that fairly commonly in patients. another form of common cutaneous candidiasis is nappy rash or napkin dermatitis. So quite often babies who have nappy rash, Part of that's going to be, irritation from, the urine and feces in the nappy. but there can be an element of candidiasis contributing to that as well.
Callum:and then other sort of superficial, nail infections, which are very common. Onchomycosis. So most of these are caused by dematophytes, which are a type of mold, which we'll talk about in a future episode. About 75 percent of those are caused by dematophytes. 10 percent are caused by other molds, and the remainder, so 75 plus 10 is 85, so 15 percent are caused by yeasts and most commonly caused by candida albicans, which is one of the reasons why because all these different organisms have different antifungal treatments. So when patients have that, we'll often send samples off to the laboratory to try and figure out which of these it is. And then mucosal.
Alyssa:So mucosal candidiasis can affect the oral mucosa. So oral candidiasis, commonly called thrush. So you tend to get these white or creamy patches on the tongue and oral mucosa. And this is particularly associated with antibiotic use, use of inhaled steroids, underlying malignancy and HIV.
Callum:and then the second form of mucosal, so we mentioned this briefly earlier on, esophageal kind of diasis. So this is, more invasive, more rare, usually just got that diagnosed on endoscopy, but patients typically present with dysphagia, so different difficulty swallowing, or dynaphagia, pain on swallowing, or they may just have retrosternal chest pain, and most of the people that you'll see with this have got HIV. So if you ever do find somebody of esophageal candidiasis, make sure they've had an HIV test. or it might be if you're getting treatment for something like a malignant hematopoietic disease, severe immune suppression, patients. there's lots of other reasons why you might get it, but I have to say, well, I guess it probably reflects my practice, but all the people I've seen that have had esophageal candidiasis have been people living with HIV. And yes. very symptomatic and it's not just that, it might seem like, oh, it's just, esophagus, but like you can't eat or drink. So it makes people really, really sick.
Alyssa:and it's probably important to say here that, oral and esophageal candidiasis are, HIV clinical indicator conditions. So if you see these, phenomenon, it's just worth getting an HIV test, to exclude HIV and then vulvovaginal candidiasis, it's the most common cause of vaginitis. And as we've already said, it. affects a huge number of women's about 70 percent Have at least one episode of vulvovaginal candidiasis during their lifetime but some people seem to be particularly prone to it more than others and get repeated episodes and the main risk factors are again diabetes antimicrobial use or antibacterial use changes in your hormones. either due to an oral contraceptive pill or during pregnancy, or when women might start going through the menopause or using, hormone replacement therapy.
Callum:And the clinical picture of invasive candidiasis we'll come on to in a later episode. so we'll move on to talk a bit about lab diagnostics. So we'll talk about microscopy culture, how you identify them and. The antifungal susceptibility testing briefly. Firstly, microscopy. So, what is the microscopy picture?
Alyssa:So I think for, vulva, vagina or Mu Mucosal, candidiasis, generally Microscopies performed on a wet prep, so a swab from the vagina area or the oral area. and then looking at it under the microscope, you'll see oval shaped yeasts that bud, and. Majority of these, yeast species, the exception being Candida glabrata and Candida auris, will form either hyphae or pseudohyphae. so you might see presence of hyphae or pseudohyphae as well, microscopically. and that can help differentiate between this simply being, colonization and infection. Because if the yeasts are growing, hyphae or pseudohyphae, together with an inflammatory infiltrate, so presence of neutrophils, that's much more suggestive of this being infection rather than colonization.
Callum:Yeah, and I guess, a wet prep, just for those that aren't familiar, it's just, you just take your clinical specimen and you put it on a slide with a little bit of saline. There's no stain or anything else. so it's very cheap and easy to do. The other way they can do microscopy is a gram stain, so you're taking different counter stains and stains. And on that, the yeast, will stain dark and they're quite large, so in comparison to the bacteria we're looking for, they're big organisms. they're kind of unmistakable in blood culture, gram stain or something like that. and similarly you might see hyphae or pseudohyphae. So that's the microscopy. Culture, when would we do culture? I guess for superficial candidiasis, generally it's a clinical diagnosis and you treat empirically. again, you might do microscopy initially, but, culture is really useful less as a diagnostics, perspective from superficial, but more to, speciate. Because certain species have intrinsic resistance, anti fungals and also to do susceptibility testing. and they actually grow pretty well. So Canada will grow on, just a normal blood agar plate. They're not Nutritionally fastidious, so they don't need special care and attention. They'll grow on most things, but you can use selective agar, which we talked about in the fungal diagnostics episodes. You can go back and have a listen to that if you're really into and the fungal diagnostics point of view. But essentially Saburo with various added things, and or use a malt extract if you're looking to enrich it.
Alyssa:So quite often, yeah, we'll culture candida when we're not trying to culture it. So it'll just happen to grow on, on blood agar and, and then often it might, just be reported as candida species. as opposed to, being fully identified.
Callum:yeah. A lot of the time, as you say, it's just there. it's a normal part of the flora, so we won't speciate it, we won't do susceptibility testing on it. I guess if you did want to identify it, then, I'm going to talk to you about this briefly. So the germ tube test is, something that you may or may not have heard of probably if you're working in the lab, but on reports often it will say like germ tube positive yeast. That's certainly how we report things locally. So what is it? So it's a really quick and cheap test where essentially you take a bit of serum or another media, usually horse or rabbit serum. and you get your yeast cells that you've grown on a plate and you pop them in and then you leave them at 35 to 37 degrees for 2 to 3 hours. And then you look at them under the microscope and germ 2 positive, you'll see a short, non septate. There's no lines in it, cylindrical filaments originating from the yeast cell. And that's your sort of pseudohyphae, that kinds of albicans produce. And that'd be germ 2 positive. If there's no pseudohyphene, then it's germ tube negative and it's another candidate. There are also Dublinensis and Africana are also germ tube positive. So essentially when you're reporting it, if speciate it further, you just say germ tube positive yeast. And that basically means, if you're reading that, it means basically probably Candida albicans, but it could also be Dublinensis or Africana. and that's useful because it's really quick and it's really cheap And if it is one of those, then you can pretty much just say, use of the connoisseur, in most clinical situations of superficial disease. That's all you need to do. You just report it as that. And then I think we have a comment, which just says, germ tube positive candida albicans. This may be one of these organisms that generally susceptible to fluconazole. and that's it. You don't need, you can stop there. So from a laboratory workflow point of view, that's great because you don't have to go to sensitivities. area of the lab. You don't do any more work and it, there's so many samples with these, so you just want to get through them all, don't you? If it's germ tube negative, then what you would do is go on and speciate it further because, they're quite different organisms from each other and the susceptibility of them to antifungals is not as predictable. So how might we do that? So if you've got access to it, Molotov has become the, the mainstay of identification, for the speciation of Canada.
Alyssa:Yeah, I think, multi TOF is great for identification of yeasts in general. it's used pretty much as we use it for bacteria now for, reliably speciating different, yeasts, including candida. another way that you can identify, or that candida might be identified in the lab is using the candida chromogar plus. so this is, a selective and differential agar medium, that's chromogenic. so it's used for isolation and then presumptive identification for various candida species. It's a chromogenic agar, so it contains these different substrates that, depending on how they're metabolised, will result in a different colour change. and that colour change then allows you to identify the candida species. So it's particularly useful for screening for candida auris, because candida auris produces very characteristic, pinky purply colonies with a surrounding blue halo. Okay. So it's, it's useful for, rapidly screening for candida auris.
Callum:from a workflow position, if you can use a chromogenic agar, it just cuts lots of steps out, because I guess if you didn't have a Molotov and you wanted to speciate a germ tube negative Canada, then you're looking at doing biochemical tests might be one way of doing it and what they grow with. Which is essentially what the agar is doing, but it's just streamlined into just splitting up and then doing it automatically. And the other thing you can do is like other fungi, you put them on cornmeal agar and at a lower temperature and they have characteristic microscopic features that might aid their identification. So you use Morphological appearances to identify a different candidate and that's in that sort of, in these sort of textbooks you see all the different pictures, rarely done nowadays because obviously Moldatov sort of replaced that.
Alyssa:Yeah, although I think it's still done in the, mycology reference lab. Often the reference lab in Bristol, we use, multiple different, techniques to, identify pathogens.
Callum:It's that balance between, you can be really accurate with these things, but for a diagnostic lab, high throughput, the main thing is thinking about is what's the turnaround time? What's the cost per sample? that's the priorities to just get the samples out as quickly as possible. So they're clinically useful and as cheaply as possible. So we don't run out of money. Oh, wait, no, we already did run out of money. So, yeah. I never had any money. yeah, that's the sort of diagnostic side. I guess we could just touch the antifungal susceptibility testing here because, when you get your report back and, There has been susceptibility testing done, just to give you a bit of understanding how that's done. So like most things we talk about EUCAST. And then there's also, CSI in America and they both thankfully provide, break points, to determine susceptibility.
Alyssa:Yeah. And they also outline methodology that they use the antifungal susceptibility testing.
Callum:so I think it's mostly done by broth, Michael Dilution, and there's a link in the show notes to the EUCAST document outlining that, and they have the document on yeast break points and also there's one on where there is no break points, but I think most of the Canada h have break points, which makes it pretty straightforward. And essentially you just get your micro bro dilution. So there's lots of different, cells. Each'em got a different, concentration of antibiotic. so have like the conazole and you have five or six different dilution of fluconazole, and then which one that grows on will be a color change and tells you what the MIC is. That's pretty straightforward. I think the one we've got locally is Micronaut, which we all call the Merlin plate, but it's quite straightforward, I would say, actually, in susceptibility testing, Canada, thankfully, in terms of doing it.
Alyssa:okay. Yeah. I don't have, I don't have, much experience of doing BROS micro dilution with candida.
Callum:Other than the path for the biomedical scientists of making up all dilutions, pipetting out a multi channel pipette, I guess it's simple in terms of from the other things we talked about, that there are breakpoints and there's an established methodology. So, in terms of susceptibility testing, that's pretty straightforward, isn't it? Other than this feels like disk, that would be easier, wouldn't it?
Alyssa:the main thing to point out is that, so there are great points for candida albicans to. Amphotericin B, anidylifungin, mycofungin, fluconazole, itraconazole, posaconazole, and voraconazole. but then your casperfungin susceptibility is inferred from your anidylifungin and mycofungin results, so casperfungin isn't directly tested.
Callum:And you can infer sensitivities a lot of the time from the species. So that's for Candida albicans, there may be resistance, we'll talk about that in a future episode. something like Candida ala glabrata, so we know that Candida glabrata are susceptible to increased exposure to fluconazole. so you need to use higher doses, to treat it. and usually just in the urinary tract. like if it's a bloodstream infection, you probably wouldn't use fluconazole. And then another example is candida parasitosis has higher breakpoints for echinocandon. So again, you might be wary of doing that. so yeah, once you have the species name, you can make some guesses about, what agent you want to use empirically before you get susceptibility results. I think most laboratories will do that off to the reference lab, won't they, I think. we're quite lucky locally because we've got a sort of mycology specialist lab section and some really skilled biomedical scientists working there, which is fantastic. but if you don't and you may just send these off to the reference lab and then obviously takes a bit of time to get the results back.
Alyssa:Yeah, so locally, I know we perform fluconazole susceptibility testing, but that's all. For anything else, we send it to the reference lab, and I think we do that by e test. So, we use CCF CLSI methodology just because that's what they use in the Bristol Ology reference lab. So, that we are in line with them when we're interpreting breakpoints. and CLSI do have a protocol for antifungal susceptibility testing of yeasts using gradient diffusion strips. So e tests. So it's, less expensive, method of testing that could be used at a local laboratory level.
Callum:The next thing we've got is, this is tab tabalized table is tabalized.
Alyssa:Put in a table
Callum:Putting a table. This is putting a table, the key laboratory features of different Canada species, which actually is like a really helpful little summary, for exams. Tables never really translate well into, podcast form, like rule one, column one. Canada Alpaca. we're going to read it out, so let's just go have a look at it. is there anything that you want to draw from that table, that we haven't talked
Alyssa:Yeah, I think the main things that, candida albicans is yeast, but it's also filamentous fungus. It produces tree hyphy. and, that these are germ tube positive. It's not specific to candida, albicans say candida dubliniensis, it's also germatory positive and produced, true hyphae. Generally the other, non albicans candida species all produce pseudohyphae, with the exception of candida glabrata and candida auris. So these don't produce any hyphae or pseudohyphae, so these are just ovoid budding yeasts. and then the notable resistances say candida glabrata. All of these are intermediate or resistant to fluconazole. Candida re eye is an important one to, to know that they're all intrinsically resistant to fluconazole. Candida Parasitosis with mentioned tends to have higher mics to a kind of dens, and then Canida Lu is frequently AmBisome resistant. So important to get, your susceptibility testing for those.
Callum:As with many things, it's not just as simple. often when I speak to my non microbiology infectious diseases friends who work in specialties like A& E, you know, you are, although they don't listen, so they don't, and they're like, how hard can it be? Just give everyone meropenem, and I guess it'd be like, How hard can candidiasis be? Just give everyone amphotericin. Well, not if it's candida lissitaniae. Yeah, it is complicated. and then I guess we've talked before about BTD GUCAN, and, that is, is something that is positive in candida disease, so it could be a useful rule out test. We've got a negative BTD GUCAN, helpful to, to say they probably don't have invasive candida disease. and then we've also got candida mannin antimannin. What's that?
Alyssa:Yeah. So Candida Manan. So Manan is a cell wall component of Candida. So kind of like B 2D. Glucan is a cell wall component of lots of fungi. Manan is a specific cell wall component of candida. So when somebody has, a cancer. This will be circulating in the bloodstream in the same way that beta 2 glucan will when somebody's has another invasive fungal infection. And then anti manan are host antibodies that are formed against candida manan. So the candida manan anti manan test detects both manan and the anti manan antibodies. and it's more specific for, invasive candidiasis than B2D Glucan. I don't think we use it. I've never used it.
Callum:I've never heard of it before.
Alyssa:I know it's an option. It's out there, some places use it. but yeah, I've never used it personally.
Callum:You can also do PCR testing. so there's a trend towards, blood cultures and having rapid diagnostics on those, including multi panel, PCR testing which picks up. things quickly. So people might have something like biofire or, other things. And I think that one of the targets for that is yeasts. I guess that's becoming more of a well used option, because obviously a lot of time people have a severe infection unless you're already thinking about it. You might not have a SARTed empirical antifungal cover, so useful to know about these things quickly. So we've diagnosed this person with a superficial candidiasis. How do we treat it?
Alyssa:So there are several, go to guidelines. So for oral candidiasis and soft dual candidiasis. There are NICE guidelines. so generally, the recommendation is that for oral candidiasis mycotopical gel, like a myconazole oral gel for 14 days, or nystatin can be used as an alternative for 7 to 14 days. if individuals are immunocompromised or for more severe infection, then often oral fluconazole is used for 14 days and potentially extended to 21 days.
Callum:Yeah, it's interesting. I have to say it's such a common thing in the ward. he's got oral candidiasis and they're not compromised. They just had some antibiotics. Just give them some nice statin. I never actually prescribed my connoisseur oral gel,
Alyssa:No. Yeah, but that is actually listed in the NICE guidelines. But yeah, similarly, I've only ever, I've only ever used, Nystatin.
Callum:Okay, so that's oral, so how about vulvovaginal? This is a bit more complicated. There's BASH guidelines from 2019,
Alyssa:Yeah. So currently I follow the Bash guidelines from 2019. but it's worth saying at this point that the ECMM in co-operation with ISHAM and. and ASN, so the American Society of Mycology. Have recently developed, guidelines for diagnosis and management of cantidiasis, which are soon to be published in Lancet ID, I believe. They may already be out by the time this airs. so that's absolutely going to be a key guideline to, to go to for, management of, superficial cantidiasis and invasive cantidiasis. But for now, let's have a look at the BASH guidelines ones. so for acute, vulvovaginal candidiasis generally first line is, stapdosulfuconazole, with the clitrimazole, pessary, being second line. and this can be diagnosed clinically or on microscopy for recurrent vulvovaginal candidiasis. as we said earlier, it's important to get culture, and identify and speciate the candida and so on. Obtain susceptibility testing. so those that are fluconazole susceptible can be treated with fluconazole. and those that either respond poorly to fluconazole treatment or are fluconazole resistant. The main alternatives are, mys statin, pessaries, and boric acid pessaries. I know I have recommended. these alternatives before, and I think they can be quite hard to get hold of. but those are the main alternatives if for some reason fluconazole isn't effective, or the organism is fluconazole resistant.
Callum:Yeah. there's a flowchart that you've put in the notes, and it categorizes it by the resistance phenotype, I didn't even realize that boric acid pastries were a thing. I guess all I thought about boric acid was it's the preservative that we put in our urine culture tubes to stop getting, overgrowth. So I guess it's more of an antiseptic than antifungal in a way, isn't it? Yeah, and then the final point that they make is that, if you've got recurrent, What you think is vulvovaginal candidiasis and it's not responding to treatment. what's the, is there alternative diagnosis, is it ligand sclerosis? is it a pain syndrome? is there something else going on? but I guess that's the, the role of if you're culturing it repeatedly and it's resistant, then that might guide you one way or the other. So I guess culture is quite useful diagnostically there. So yeah, not as straightforward. And, um, I think the vast majority of these cases are. quite treatment responsive and, in associated risk factors, but when you get a recurrent and it's not responding well to treatment, it's, becomes quite tricky, quite difficult quickly.
Alyssa:And also another complicating factor is that pregnancy changes your hormones, and is a risk factor for vulvovaginal candidiasis. And your treatment options are further limited, in pregnancy and breastfeeding because, oral azoles should be avoided. And I think that there is some, association with, vaginal boric acid. being potentially teratogenic. So, generally, I think uncomplicated vulval vaginal candidiasis is seen in, primary care. and more complicated cases are often, referred to the gum clinic and managed by gum physicians. So I think it's something that We're not often consulted on, but it's worth being aware of these guidelines and knowing that if you need, some expert advice, it's probably the gun physicians that are most experienced with managing these.
Callum:Yeah, I think we put that on our report and just talking about pregnancy and breastfeeding. So episode 56, Jamie and I talked about pregnancy and, lactating antibiotics with, um. And in the show notes for that, there's a table. I don't think we talked about antifungals there, but in the show notes there, there's a table of antifungals. And I think the connoisseur anyway is, it's, you should avoid in the first trimester. But, from the resources we looked at there, it was generally okay in the rest of pregnancy and breastfeeding. and then clotrimazole is safe throughout, but, we'll come on to antifungal drugs in the future, so we'll need to go over that because I think it is important that, not an uncommon situation. and then finally, so we've talked about oral vulva, vagina, what about cutaneous, so skin?
Alyssa:so generally your options there are topicals, so, topical imidazole such as clitrimazole, myconazole, arequinazole can be used, um, for children and adults. so this is nice guidance that I'm summarizing here. other options are topical tobinifine or ketoconazole, but that's only recommended in adults, not in children. And then if the patient's immunocompromised or has particularly widespread, infection, oral fluconazole can be used for 14 days followed by a review.
Callum:What's e equo
Alyssa:I think it's just another topical imidazole. Yeah, I hadn't heard of that one either.
Callum:out. I've just never heard of that before. Okay, well that's treatment. Is that it?
Alyssa:I think we're done. Yeah. For this, the first of the trilogy.
Callum:Okay so that's the first part of the trilogy finished. for now our fellowship will be broken, but we will be reunited.
Alyssa:See you next time for invasive candidiasis.
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.
