Several outbreaks of a relatively new, resistant fungal infection - candida auris - have been reported in the Pacific Northwest. It is highly contagious and its mortality has approached 60%. Listen in as we discuss what to watch for and how to prepare if this reaches your geography.
THE GAMECHANGER:
Candida auris is resistant to most antifungals, has high plasticity, and its mortality approaches 60%.
Geoff Wall, PharmD, BCPS, FCCP, BCGP
Professor of Pharmacy Practice, Drake University
Internal Medicine/Critical Care, UnityPoint Health
Reference
Cristina ML, Spagnolo AM, Sartini M, Carbone A, Oliva M, Schinca E, Boni S, Pontali E. An Overview on Candida auris in Healthcare Settings. J Fungi (Basel). 2023 Sep 8;9(9):913. doi: 10.3390/jof9090913. PMID: 37755021; PMCID: PMC10532978.
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Not a member? Get a Pharmacist Membership & earn CE for GameChangers Podcast episodes! (30 mins/episode)
CPE Information
Learning Objectives
Upon successful completion of this knowledge-based activity, participants should be able to:
1. Discuss characteristics of C. auris infections that make it difficult to avoid outbreaks 2. Describe issues surrounding treatment of serious infections with C. auris
0.05 CEU/0.5 Hr
UAN: 0107-0000-24-058-H01-P
Initial release date: 2/26/2024
Expiration date: 2/26/2025
Additional CPE details can be found here.
Several outbreaks of a relatively new, resistant fungal infection - candida auris - have been reported in the Pacific Northwest. It is highly contagious and its mortality has approached 60%. Listen in as we discuss what to watch for and how to prepare if this reaches your geography.
THE GAMECHANGER:
Candida auris is resistant to most antifungals, has high plasticity, and its mortality approaches 60%.
Geoff Wall, PharmD, BCPS, FCCP, BCGP
Professor of Pharmacy Practice, Drake University
Internal Medicine/Critical Care, UnityPoint Health
Reference
Cristina ML, Spagnolo AM, Sartini M, Carbone A, Oliva M, Schinca E, Boni S, Pontali E. An Overview on Candida auris in Healthcare Settings. J Fungi (Basel). 2023 Sep 8;9(9):913. doi: 10.3390/jof9090913. PMID: 37755021; PMCID: PMC10532978.
Pharmacist Members, REDEEM YOUR CPE HERE!
Not a member? Get a Pharmacist Membership & earn CE for GameChangers Podcast episodes! (30 mins/episode)
CPE Information
Learning Objectives
Upon successful completion of this knowledge-based activity, participants should be able to:
1. Discuss characteristics of C. auris infections that make it difficult to avoid outbreaks 2. Describe issues surrounding treatment of serious infections with C. auris
0.05 CEU/0.5 Hr
UAN: 0107-0000-24-058-H01-P
Initial release date: 2/26/2024
Expiration date: 2/26/2025
Additional CPE details can be found here.
Hey, ce plan members from CE Impact. This is Game Changers. I'm Jen Moulton, and this week we're talking about a topic that you may have seen in the news and if you live in the Washington State area, you probably know about it all too well. There's a new outbreak of the multi-resistant fungus Canada oris, and with us today is Jeff Wall. Thanks for being with us today.
Speaker 2:Bye, bigger, jen.
Speaker 1:Yeah, welcome. Everybody knows you well, so I think the intros aren't necessary.
Speaker 2:No, I don't think so either. We can definitely dive into this and I appreciate the introduction. This is important because I have to honestly that this fungus has kind of been no pun intended in the periphery of my vision. Don't take that for a joke. I'm starting to see where we're starting to get more and more outbreaks, and I think the CDC is taking this very seriously and I honestly hadn't heard much about it simply because there had been an outbreak in my neck of the woods. But it has definitely hit the lay media and this is a bad organism, and so I thought this would be a good topic and so, working with CEI, we kind of put our heads together and thought, yeah, this is something that's big and it's something that I'm sorry to say that many of my listeners and listeners of the podcast have a fortunate good shot of seeing as the numbers of this bug arise and are going up all across the world, including the United States. So it's currently being defined by the CDC as an emergent, rapid progressing global infectious disease threat. So hopefully that means we're going to start getting a lot more money thrown at after you know what to do.
Speaker 2:But what really piqued my interest in what Jen had talked about is there's a lot of lay media press talking about a big outbreak in Washington state and fortunately nobody died from this outbreak, which, from what I've read, is pretty unusual. But it was like in the first big outbreak in the Pacific Northwest done in Seattle and King County. So far there have been five cases that have been confirmed. All of them were pretty sick but none of them ended up actually passing away from it. That's a good thing. The reason they found this was because one of the hospitals in this kindred hospital in Seattle and again, this is all public knowledge, so I don't see why I can't use their name it's a long-term acute care hospital and they actually have a pilot program where there are screening all their patients who come in for this, canada aris. So this is not staff arias. I've already heard a couple people you know. Is that related to staff arias? No, it's nothing, it's just spelled similarly right. So Canada aris, they are screening everybody for it and they found it. And then patients, you know they were kind of sick to begin with. They found down the road they were actually much sicker, and so that I think, because this has had so much lay media presence, I think people are going to get questions about it and I think from the practitioner perspective, what makes me nervous, scared about this bug, is it's incredibly high level of resistance, especially for a fungal organism, and we'll get into that in just a second.
Speaker 2:The bug itself, canada aris, was first identified in Japan in 2009. By 2016, the CDC had had enough overseas reports of being reported in Asia and Europe that they actually directed US laboratories that when they saw they needed to report it to the CDC. And when they did that, then they did kind of went backwards in a lot of these areas that's an epidemiological studies and found that again there had been reports of. They have found Canada aris backwards way back to 2013, so it's been circulating around in the United States for about 10 years here. But the problem is it was kind of a low level threat. Yes, it was a bad bug, but most of the time people didn't run into it, so it wasn't any big deal. And then COVID hit and up. There is a high level of correlation between recent COVID infection and the development of severe Canada RS infections. As I've read, the reason for that connection is largely unknown at this point. So why exactly a viral infection would lead down the road to a serious fungal infection is currently being investigated. But they've done several retrospective studies and have found that if you had a recent COVID-19 infection, that that was a high risk factor for going on to develop Canada RS.
Speaker 2:And, as of the kind of immediate post-pandemic period, we've seen a spike of about 50%, relatively, of numbers of Canada Aureus infections being reported. Now, again, a lot of that is some bias because prior to 2016 in the United States we weren't even testing for it, so if you don't test for it you're not going to find it. But certainly they've seen a reported spike in the cases in the intervening years since the pandemic started. And again, I was personally completely unaware of this. So doing the research for this podcast, it really did. All of this really kind of surprised me because I just hadn't heard or seen of that and I think it speaks to the fact that this, like a lot of localized infectious diseases, if you run into it personally or you see it in your health system, you kind of become vigilant of it, but if you don't, it's just something kind of on the periphery of something you read and you're like, oh well, I hope I never run into that I think. Unfortunately, given what we've got, I think you are probably going to run to that here in the next several years.
Speaker 2:It is an opportunistic pathogen. It has a high level of hospital outbreaks and mortality approach is 50% in bloodstream infections and people have Canada Aureus. Mortality is obviously much less in other types of infections, but that is significantly higher than even Canada albicans blood infections, which have a pretty high mortality associated with them as well. Candidemias are not good things and people don't tend to do well with them, but that mortality quote is significantly higher than what we have with other cannibal subspecies and the reason for that is that it is unbelievably resistant. Most cannibal species are very susceptible to the azol class and antifungals Like Canada albicans is at least in my neck of the woods usually susceptible to plain old fluconazole and it works pretty decently and it even relatively resistant organisms like Canada glabrada.
Speaker 2:Ok, we may not be able to use fluconazole, but the other more potent azoline fungals like voriconazole work quite well against them. That is not the case with Canada auris, where almost azoline fungals are resistant to it and, unbelievably, even other antifungals, including apheteris and B, have a high incidence of resistance and that's pretty amazing. So that is, I think, one of the big reasons why this has been so challenging is if somebody does develop a serious infection with it by the time you figure out it is Canada auris the patient has already probably been sick for a few days, and can you catch them before they pass the point of no return and find something that's actually going to work against them. And there's some strikes we have going on there as well that we're going to talk about in just a second. So the other big problem that's associated with Canada-R-S is that it is an unbelievably hardy strain of fungus.
Speaker 2:It has an incredibly high level of plasticity, which means in English that it lives on just about every surface and it lives for a long, long time. So it survives on a range of surface types, including dry sites, wet site, plastic surfaces, stainless steel surfaces. It's actually viable for up to 14 days on plastic, which is incredible, and it is highly tolerant to both level of salinity or how much salt and heat. Now, why is this? It is because, again, it has this phenotypic plasticity, which really means is that, like most yeast organisms, it can change its shape, basically of will, and in this case it can switch shapes between the typical yeast form that you probably remember seeing back in microbiology. Then it can switch to other types of yeast forms, including filamentation yeasts and other types of yeast forms that basically make it. If it finds itself in an unfriendly atmosphere, it can actually alter its shape to adapt to that atmosphere, which is just unbelievable.
Speaker 2:And so epidemiologic studies and this is pretty disheartening epidemiologic studies have been done in hospitals that have had outbreaks of Canada-R-S and they have in patients who have had this. They've looked at, they've done epidemiologic detection and surveillance in the rooms of these patients and they found that Canada-R-S was detected on the mattresses, the bedside tables, the bedrails, the chairs, the windowsills in patients, and here's the kicker up to three months after the patient had been discharged. Just absolutely incredible. And so this is an incredibly hearty organism and probably beyond the scope and purview of this pod is what strategies can we use to disinfect rooms? Are we going to have to burn a hospital room to the ground when someone comes in, because that's about all that's left to treat this? That's just incredible and that's far more a sturdiness associated with an organism, except for things like maybe C diff that are able to form a spore around them. It's absolutely incredible what we've seen with this organism and then again. So the one-two punch of this is a difficult bug to disinfect, in both people and in rooms.
Speaker 2:And again we go back to the resistance. The surveillance studies from Asia, where it's been around the longest, found that 93% of these isolates are resistant to fluconazole, 85% are resistant to all other azole antifungals, 35% are resistant to amphitericin B and I don't believe I've ever heard of any fungus with that level of resistance to amphib. Amphib is only always kind of been the hydrogen bomb of antifungals and the only reason we don't use it more often is that it has all these weird side effects and light-threading side effects, which is why old men like me call it antiterrable. It's an amphitericin, but it's just one of those things where I really can't think of too many times in my career where we said, well, we can't use amphitericin because it's resistant. It's like, really, you know, I didn't think there was resistance to amphetamine. Well, there is.
Speaker 2:The good news is that the kind of candins are less resistant. It's still high, but it's more like 10% to 12%. So there I and the guidelines currently recommend that as first line treatment If you have a, especially a bloodstream, a septic infection with canardaris but it does there are still pockets where that that resistance goes up. So it is entirely possible that you can run into a strain of canardaris that is resistant to basically all known antifungals that are on the market and in fact some of these epidemiologic studies that have been done have found that, again, up to 10 to 12% of some of the strains that they've they've been collecting and doing susceptibility studies on are resistant to all three classes of antifungals currently routinely used in the US.
Speaker 2:Again, amphetamines and B, the azoles and the kind of candin. So just just absolutely unbelievable. I won't. This isn't a microbiology pod, so I won't dive too much into why. Just suffice it to say that that nearly all the antifungals that we have on the market work in some way, shape or form to break up or gastro, which is our gastro, is basically the, the main component in the fungal cell membrane and basically almost almost all the antifungals we have buying to that and break it apart at some point, and that causes cell death. And so again, there's some genes that that, that that potentially, that apparently canardaris, because it's able to to alter its shape, can basically alter the binding sites of all these antifungals to this ergosteral cell wall and once that happens it essentially is is linked to resistance. So just absolutely incredible.
Speaker 2:As far as infection is concerned, you don't want to push the panic button if, just because the patient grows out candida aris, like all candida subspecies, it is entirely possible that it's a commensule in a patient and in fact, like MRSA, once apparently you are colonized with candida aris, it's you pretty much can't get rid of it. It's going to be with you forever, apparently, and so it is. You know, if someone you know, for example, is relatively healthy, things are going fine, they maybe have a urinary tract infection and the, the UA, shows yeast and you grow up. Candida aris, you know, but they also grows on our E coli or something. I would not panic and go, oh my goodness, we're going to have to try and figure out some weird antifungal combination to treat this. You know, like most candida species, you know it is entirely possible, it's just a commensule. However, if it is in a sterile body site, such as blood, csf, pericardial fluid, then unfortunately that probably means you have a systemic infection with it and things are not going to be so great.
Speaker 2:Other testing, again traditional culturing, is done. You can use a serum, beta-glucan I think that was to have our time pronounced on that one. It has a negative result, it has a low probability. So it's a fairly sensitive test but it's not specific. So if you weren't exactly sure, that might be something you could do, unfortunately.
Speaker 2:Then let's say you do find Canada. It's important to remember that a lot of small hospitals don't even speciate. They just say you've got East and we have Canada and we just don't know which one it is. And even in hospitals that do speciate. East standard culturing techniques often have a hard time telling Canada ours from other cannibal subspecies, and so you probably will need some high-tech stuff like Moldy Toff or something else that will help actually identify this Canada subspecies as ours. So just kind of keep that in mind, yeah, that you might get this. This is a Canada species. We can't seem to identify which one it is. We know it isn't albicans, we know it isn't glabrada or the stinnier and these others. They just haven't ID'd it. It might well be Canada ours, and you might well have to direct your microbiology lab, if they have the ability to use some PCR technology, to really try and figure out what you're dealing with here.
Speaker 2:Susceptibility testing gets really tricky as well because, as of the recording of this podcast, there are no breakpoints that are approved by CDC and FDA for susceptibility and resistance, so that's going to make things kind of challenging. There's been a couple of retrospective studies that have tried to get at that and tried to take a look at what an MIC 90 might be. But as of now, if you get a culture back, you're probably not going to get this susceptibility panel back unless you specifically ask the microbiology lab to do special testing to figure out what the MIC of various and sundry antifungals are against this bug. So again it sounds like a lot of bad news, unfortunately which I guess it kind of is If you were to run into a patient with a serious again in a sterile site, canada ours infection. As I said before, unfortunately you're probably not going to be able to use any A's on antifungals because they have a high level of resistance and so that's probably not something you're going to want to use. That really kind of leaves you in the realm of amphitarris B or the kind of Candens.
Speaker 2:Current recommendations are that I kind of Candens are reasonable, but if the patient is super duper sick it might be reasonable to switch to life of some of the amphitarris B if they're not perking up. But right now the current guidelines say either Caspa fungion or MIC fungion are recommended as first line therapy in adults and children over age two and then just basically following their clinical course. Because the way this bug is set up you may well not get identification of the organism or susceptibility testing that you can use. So basically your only real barometer of how the patients, if you've got the right bug drug combo, is to see how the patient's doing. If you have some signs of symptoms of infection for more than two days, the current recommendation is to switch life of some of the amphitarris B, again noting that there's a high level of resistance there as well. So that's the current recommendation Start with a kind of Canden and go to life of some of the amphitarris B if the patient isn't improving.
Speaker 2:As far as synergy dosing and now we're kind of getting off into the weeds here Apparently there's a couple of in vitro studies that suggest that the combination of boric connoisseur and MICA fungion may have a strong synergy against Canden RS. And again, that's that kind of in the test tube and we don't know what's going on here. Are there any other drugs that are available, or on the market or heading to market, that might help us with this very, very resistant and apparently becoming more common organism? And the answer is yes. There are several cousins of a kind of Candins that are in phase two and phase three studies that are being looked at, not just for this bug but a wide variety of other yeast forums as well. But there actually is a drug that's currently on the market, that's been studied, and we actually talked about this drug a year or two ago when it first hit the market and that's a Brexifungerb I get, this is a huge, long name.
Speaker 2:A Brexifungerb is actually FDA approved in the United States for vaginal yeast infections and it is a first in class tripeninoid antifungal agent and it has a target targets the same sites on the gestural cell wall as a kind of Candins. It does it at a slightly different area so it doesn't have the same resistance pattern as a kind of Candins do, but again it works the same way. It basically blows the cell wall apart and that allows the at least the cell death of the fungus. It is FDA approved again in the United States for vaginal yeast infections. I have not seen it just because we usually don't need to use anything that powerful for vaginal yeast infections. That we can usually use to the connoisseur and that works pretty decent in most people. And this is of course a much more, you know, a much more expensive drug.
Speaker 2:So there are some thought that if you had a serious infection with a multi-dark resistant version of Candida RS that you could try this medication. It's the least available in the United States and relatively easy to get. The $64. Question is what dose, how long? I mean all that would be up in the air. So if you were faced and had your back against the wall with you know, a multi-dark, resistant version of this, I think it might be reasonable to try, but you would really be out on a limb as far as dosing and amount and all this other stuff Plus.
Speaker 2:Unfortunately, it only comes orally and so you know again, if someone was super duper sick, septic shock, in the ICU, you may not be able to get access for them to get the drug as well. So a not very good news, sort of of a game-changers, because, yeah, this is a bad bug. It's rapidly being spread across the country, so resistance is super high, like all Canada infections that are serious, not, you know. Not, you know surface infections, but you know infections like Candidemia. It has a high mortality associated with it and once you've got it doesn't seem like you can get rid of it. And I think we're really going to have to rethink infection control techniques in these patients if they can literally find this bug months after the fact in somebody's room. So fascinating and semi-terrifying organism that I think we're going to have to keep an eye on as time goes on. So not good news, jen, but no, no.
Speaker 1:Thanks, Jeff, for that.
Speaker 2:You think, thanks, I think Not a great way to start our Monday. I know.
Speaker 1:One question I had. So you talked about, you know, the discovery of this. You know they were actually screening for it, like proactively. So are you seen or do you foresee, I guess, that hospitals will start to screen for this? I mean, given the fact that you know, once they're in your hospital, it's hard to get rid of it, right? I mean have you seen that yet, or do you anticipate that in the near future?
Speaker 2:I do anticipate it in the near future. My health system does not do that and I have the sneaking suspicion is this is one of those. It's going to happen to the other guy until it happens to me, right? You know, the Pacific Northwest, unfortunately, has been ground zero in many ways for COVID, and so it is really all that surprising because of the relationship between COVID infection and Canada Are that they have now seen a big spike of that, I suspect, as this bug finds pockets throughout the country once your health system gets hit with it, right, once you have an outbreak, you're going to be doing that at least for a while, and I think that's yeah, I do think that that's what's going to happen is, as soon as hospitals have an outbreak or area hospitals have an outbreak you know a hospital two miles from you as an outbreak of this stuff. Given it's you know it's unbelievable heartiness, I think that's what a lot of places will do.
Speaker 1:The problem is it's going to be pretty pricey, you know because that's what I was going to ask, yeah, and because, yeah, I mean you'd think that you would want to do that proactively before you actually get it, and then you're, you know, being in reactive mode. But what's the cost of that, right? What considering they're going to?
Speaker 2:have to do again the, you know the, the PCR technology. Now my hospital, of course, we, you know, most large hospitals have, you know, this equipment. I'm sure they're going to have to get the special equipment that they need to actually look for this bug. Our current blood culture, pcr identification, the film array, basically looking for individual bugs, does not look for this. It looks for Canada albicans, and it looks for Canada glabrada, and that's it. And so will they have to. You know, they will have to do a special test.
Speaker 2:Will the companies that do these PCR technology add that test as standard to their, their blood culture a panel? Those are all great questions. But you know, in a bug like this, you know, it's kind of like you know MRSA in the old days or COVID, really, that you know, once you have a serious outbreak, I think you're kind of forced by infection control dictates to really take a look at it. You know again, just to prevent somebody walking in who may not even have a sunny symptoms but they're colonized with it and then they roll around the bed, yeah well, and that's what the study talks about is people didn't even have symptoms, so you?
Speaker 2:wouldn't have exactly not screened. Exactly. And then the next person who comes in there is an immunocompromised patient, and then we're in real trouble.
Speaker 1:So yeah, yeah, well, definitely a game changer.
Speaker 2:Yes, indeed, not all game changers are good, unfortunately.
Speaker 1:No, that's right, not all game changers are good. Well, definitely something to keep an eye on and I appreciate you digging into it. It isn't a great way to start our Monday, but definitely knowledge is power, so we have to be ready for it, I guess, when it comes. So appreciate you digging into it.
Speaker 2:No problem, thanks, jeff.
Speaker 1:Yeah, thanks for being with us today. If you're a CE plan member, be sure to claim your CE credit for this episode. And, as always, thanks again, dr Wal. Have a great week and keep learning.