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Invasive Candidiasis
115 Plays1 hour ago
In this, Dr. Sergio Zanotti discusses the management of invasive candidiasis in critically ill patients. Invasive candidiasis is frequent in critically ill patients and is associated with high mortality and morbidity. He is joined by Dr. Max Adelman, a practicing critical care and infectious disease physician at Houston Methodist Hospital. Dr. Adelman is an Assistant Professor of Medicine at Weill Cornell Medical College. Dr. Adelman’s clinical interests include bacteremia, hospital-acquired infections, immunocompromised hosts, multidrug-resistant organisms, and septic shock.
Additional Resources:
Books and Music mentioned in this episode:
Four Thousand Weeks: Time Management for Mortals. By Oliver Bukerman.
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Transcript
Introduction to the Podcast and Episode
00:00:06
Speaker
Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine. Sound provides comprehensive critical care programs to hospitals across the country.
00:00:19
Speaker
To learn more about our programs and career opportunities, visit www.soundphysicians.com. And now your host, Dr. Sergio Zanotti.
Understanding Invasive Candidiasis in ICU Patients
00:00:33
Speaker
In today's episode of Critical Matters, we will discuss the management of invasive candidiasis in critically ill patients. Invasive candidiasis is frequent in critically ill patients is associated with high mortality and morbidity. Our guest is Dr. Max Eidelman, a practicing critical care and infectious disease physician at Houston Methodist Hospital. Dr. Adelman is an assistant professor of medicine at Well Cornell Medical College, and his clinical interests include bacteremia, hospital-acquired infections, immunocompromised hosts, multidrug-resistant organisms, and septic shock.
00:01:04
Speaker
Max, welcome back to Critical Matters. Thanks so much, Sergio. Thanks a lot for for having me back. Well, it's been a while and we were commenting before we we started recording that we did ah an episode that I'll link in the show notes on C. diff back in the the height of the pandemic, but things have changed. You have moved. You're much closer to where I live now.
00:01:25
Speaker
But ah the topic of...
Significance and Types of Candida Infections
00:01:28
Speaker
Candida infections in the ICU, as somebody who wears two hats, the infectious disease and the critical care hat, I'm sure is very interesting and important for you. But why should our audience be interested in in this topic?
00:01:43
Speaker
Yeah, much like C. diff, candida is a really important infection for both ID and critical care docs alike. I think critical care ah practitioners and physicians really need to be up to speed on candidemia because it's a really prevalent infection in the ICU.
00:02:03
Speaker
Really a lot of our ICU interventions are specific risk factors for candidemia. So it's particularly prevalent in the ICU and it can cause serious morbidity and mortality among the patients who get it. And these folks are usually the folks who are already at really high risk of poor outcomes. So it's really prevalent It affects our most vulnerable patients in the ICU and it can cause really bad outcomes.
00:02:29
Speaker
Perfect. One of my observations with candida has been that when we talk about it, usually it's irrelevant. And when we're not talking about it, it's when it causes problems, right? People tend to overworry about things that are just colonization, but miss the real infections. What are the types of candida infection that we're going to talk about today that are relevant to the ICU? And could you provide an overview on the epidemiology of these infections in the ICU? Yeah.
00:02:56
Speaker
Yeah, absolutely. So that's an excellent point. um I think by talking about the times where we often see candida and it doesn't really matter, we know that candida can do what we call colonize the respiratory tract and the urine especially. And that means it just kind of lives there, but doesn't cause any clinical infection. So if you see a pop up in a urine culture or respiratory culture, you don't really have to worry about it and just know that it's not causing an infection in those sites. On the other hand, if you isolate Candida from what we call a sterile site, um then it is considered a clinical infection. So we can break down all of these Candida actual infections are what we call invasive candidiasis. And really we see this show up in two ways.
00:03:44
Speaker
The first is candidemia, which is a candida bloodstream infection, and the other is deep-seated candidiasis. And that's where we have candida isolated from a normally sterile place, usually the abdomen. um And this this form of invasive candidiasis called intra-abdominal candidiasis is really prevalent, especially in the um and the surgical ICU.
00:04:08
Speaker
You know, the incidence is a little bit hard to define. It certainly varies depending on the population. um But we know that the incidence and associated mortality of candidemia and invasive candidiasis are rising in the past few years.
00:04:24
Speaker
Candida might be the second most common cause of bloodstream infections in the ICU and probably makes up about 20% of ICU acquired bloodstream infections. um So it's it's pretty prevalent and it's something we all really need to to be thinking about and and you know, giving it sort of the respect it deserves because the severity of the infections it can cause.
Challenges with Candida in ICU Settings
00:04:48
Speaker
In terms of candida species today, could you give us a little bit more and also it talk about the importance of C. auris, which is, i think they changed the name I'm just going call it C. auris today, but that is really emerging as an important pathogen for us.
00:05:06
Speaker
Yeah, so, Sergio, we were talking a little bit about this before, but a lot of the names have changed. i don't want to get into all of the specifics, but if you see something that you're not sure if it's candida or not pop up in the microbiology report, just put it into Google and you can see if what it's one of the new names for candida. You know, the um ah microbiologists have gotten excited with renaming everything, but clinically it's vi The name changes have an effect how we clinically take care of these patients, except for probably adding a little more confusion.
00:05:36
Speaker
So Candida albicans has long been the most um prevalent species of Candida that we see, and it still is. This one is usually susceptible to the antifungals we use. On the other hand, there are other species such as Candida parapsilosis and Candida globrata that can be variably resistant to the first-line antifungals, and these have been probably increasing in prevalence over the past 10 or so years, and that's related to more antifungal use likely and more immunocompromised patients who are getting these infections.
00:06:12
Speaker
And then really the big one that we're all worried about is Candida auris. I'm sure everyone has heard about this one by now. It is but potentially multi-drug resistant and it's really worrisome because it really likes to colonize or stick to our medical devices. It's really difficult to clean, so even if you do your normal disinfection of a hospital room, it might stick around. And then it can just sort of get all over the patients and the nurses who are in the room.
00:06:43
Speaker
So it's a big issue for our kind of chronically hospitalized, potentially chronically critically ill patients because they're really at high risk for getting this infection with Candida auris. And then, as I mentioned, it can be multi-drug resistance. So that can make it more difficult to treat once folks do get it.
00:07:01
Speaker
What about the pathogenesis of invasive candidiasis? Obviously, there's ah a basic and characteristic of how candida becomes a problem and in and our ICU problem patients. Could you go over that?
00:07:15
Speaker
Yeah, absolutely. So a lot of candida species are common and live on all of us. So if let's just take candida albicans as an example. but Almost all of us sort of routinely carry candida albicans in our GI tract and even on our skin. And under normal conditions, this is really in check. Probably our gut bacteria do a good job of keeping candida in its little niche in the GI tract.
00:07:42
Speaker
um But then when we're in the ICU, and as I mentioned at the outset, really a lot of things that we do to patients in the ICU are specific risk factors for development of invasive candidiasis or severe candida infections.
00:07:56
Speaker
So, for example, all these patients get antibiotics, which in addition to killing The target bacteria can disrupt the microbiome and allow for candida to you know kind of expand in the GI tract. These patients are frequently immunocompromised, which um means that the candida won't be kept in check as well by the immune system. They have GI ah barrier dysfunction. So candida can, what we call translocate or move across the GI tract.
00:08:27
Speaker
So urinary catheters and central venous catheters allow Canada direct access into normally, we've kind of passed our normal mucosal barriers.
00:08:38
Speaker
So really all of the things that we're doing to ICU patients are putting them at higher risk. But usually it does take some actual disruption of a normal barrier. For example, a central line will allow the Canada that's colonizing the skin to crawl into the bloodstream through the central line. or if patients have had um GI surgery, then you know the disruption in the normal um GI tract can allow candida to leak from inside the lumen of the GI tract out into the abdomen where can cause an infection. So that's really how we see it most commonly. The other way patients can get candida infection is patients who are on chemotherapy or severely neutropenic. And they just have some gut barrier dysfunction and decreased immunity. And then the candida can again translocate across the GI tract.
00:09:29
Speaker
So really a severe defect in immunity in that last case or a disruption in the normal mucosal barriers in the case of GI surgery or central venous catheters are really kind of the the last step in leading to severe invasive candidiasis.
00:09:46
Speaker
And i should have mentioned it earlier in the introduction, but and Max, you recently published a wonderful review in chest and, uh, I overall enjoyed reading and learning from it. But one of the things that I really, really liked was your creative use of a figure to talk about risk factors.
00:10:07
Speaker
And usually that's just something people throw on a table, but you did it in a very creative way, I think, that really resonated with me because it really illustrated why our patients are such high risk for these infections. Can we talk about risk factors in critically patients for candida infections?
00:10:28
Speaker
Yeah, absolutely. Thank you so much. Yeah, this was ah a paper we were fortunate to work on and and led by a postdoc who works with me, Alejandra Perez, who's a fantastic ID doc who helped to put all this together.
00:10:41
Speaker
But really the big risk factors in ICU patients are those things that are going to let Candida get past the normal barriers. So these are things like Intravascular catheters, again, those central lines where provide candida direct access into the bloodstream. um Mechanical ventilators because candida can cling to the plastic tubing and be really hard to eradicate.
00:11:05
Speaker
Anything that's going into the bloodstream, so aside from IV catheters, ECMO is a big risk factor. Again, the antibiotics because they kill off the normal bloodstream. probably because it kills off the normal but gut bacteria and allows candida to overgrow. And then again, just being in the milieu of an ICU room where other people are coming in and potentially transmitting candida, especially candida auris from other patients who might be colonized. So really all of these things make the ICU unfortunately sort of ah a perfect um setup for candida infections. And then again, these these patients who are at really high risk and the patients who are at highest risk of getting it are the patients who are most likely to have bad outcomes from these infections.
Diagnosis and Treatment Strategies
00:11:53
Speaker
And one of the biggest challenges with managing candidate infection in the ICU is the diagnosis. We usually find out or confirm the diagnosis probably ah later than we would like to in terms of initiating aggressive and time-sensitive treatment.
00:12:12
Speaker
Could we go over the different buckets of and tools we have available as as clinicians to make a diagnosis of of a candida infection? And i think the risk factors is a great place to start because in these patients, we should be thinking, could a candida infection be part of what I'm seeing as the patients evolve? What are some of the clinical signs that we would be looking for for candida infection?
00:12:37
Speaker
Yeah, I think that's really a ah great point and a ah great segue. um Candida infections present exactly like sepsis from bacterial infections. So it can be really hard to know upfront with what you're dealing with.
00:12:53
Speaker
And as I mentioned at the outset, it's pretty common, but not common enough that we're going to be starting empiric antifungals on every patient with what looks like sepsis. Of course, you know every patient with sepsis is going to get um antibiotics to treat bacterial infection, but not every patient with sepsis. is going to get empiric antifungals to treat disseminated candid infection unless you're really thinking about it. So it can be really hard. um It can be really hard to treat appropriately before we get definitive diagnosis. And there are a lot of problems with definitive diagnosis that I'll get to in just a minute.
00:13:30
Speaker
So the symptoms are again essentially indistinguishable from um from disseminated or severe bacterial infection. So it can be really hard to distinguish just based on symptoms. I think kind of what I was taught in ID fellowship and kind of the classic teaching is that these are patients who might have high fevers after a few days of antibiotics. And that's certainly true.
00:13:55
Speaker
But patients with severe kidney infections can present just like severe bacterial infections in terms of septic shock, high fevers, looking really unwell at the outset. So this can present fulminantly right from the start and not just be kind of the thing that you're left thinking about after three or four days where you're not sure what's going on. so you need to be thinking about this more at the outset. I think the really the key thing that's going to help you think about this from the start is thinking about those risk factors we talked about up front.
00:14:24
Speaker
Again, if patients have been on already been on antibiotics for a while, if they've already been in the ICU for a while, if they have invasive lines and catheters, these are all risk factors. TPN, of course, I haven't mentioned yet, but that's a big risk factor for candidemia.
00:14:39
Speaker
Surgical patients with intra-abdominal abscesses, all of these things are things that should make you consider whether um A patient who looks pretty sick could have a disseminated candid infection.
00:14:52
Speaker
Unfortunately, we don't have any great ways to diagnose candidemia. early. So in the early phases of treatment, it really just relies on clinical gestalt to think ah about candidemia and think about whether we should be treating it before we get definitive diagnosis. But of course, as you're starting to treat, then you're also going to be sending your diagnostic tests.
00:15:13
Speaker
Still, the gold standard for diagnosing candida bloodstream infections are blood cultures. Sergio, as you mentioned, these can sometimes take a few days to result.
00:15:25
Speaker
Candida do grow on our standard bacterial blood cultures, you don't need to send the special fungal blood cultures, but they do grow a little bit slower. So it might take more like a day or two or three for Candida to show up on our routine blood cultures. So in that time, you really want to have been thinking about it so you're not waiting two or three days to be giving patients appropriate therapy.
00:15:47
Speaker
So blood cultures, again, are our kind of gold standard. The sensitivity of blood cultures might not be as high as we would like. I don't think there's a great, we kind of know the exact answer, but some studies have estimated that these might only be 50% sensitive for candidemia.
00:16:04
Speaker
So what else are we going to use? There are other um other markers of potential fungal infection, one of which is the beta-D glucan test, or the fungitel is the brand name. um This ah has been, you folks have tried to use this to diagnose candidemia early. It might be a reasonable adjunct test, but there are many false positives and even some false negatives. So it's not the perfect test.
00:16:31
Speaker
um Of course, if if a patient has an abscess or a focus of candida infection and they need source control, for example, they need IR drainage of an abscess, then you're going to want to send those cultures, of course, to see if there's candida growing in there.
00:16:46
Speaker
There was another test called the T2 candida panel that was pretty sensitive and specific for candida early, but unfortunately, this one is now off the market. It wasn't that widely adopted due to cost.
00:17:00
Speaker
um And then there are also some clinical risk scores for thinking about whether someone could have candida. um These were kind of developed around 20 years ago or so now. They have pretty high negative predictive value. So if someone doesn't score high on these tests, then they probably don't have invasive candidiasis. If they score high, it's hard to tell whether they do or don't. um These scores involve things that we're routinely thinking about, I think, such as TPN, dialysis, surgery, for example.
00:17:31
Speaker
so They just sort of back up your clinical gestalt as to whether a patient might have kinedemia or not. um so I guess just to summarize, these are hard to diagnose. They're common, but not so common that we're going to be treating patients empirically all of the time. so It's really important to think about these upfront. and consider starting empiric antifungals as we're sending off all these diagnostic tests.
00:17:55
Speaker
Excellent. I wanted to touch on two and aspects of the diagnosis and ask you if you could go a little bit deeper. So in terms of clinical signs, obviously, we are talking specifically about two categories of invasive candidiasis, which is candidemia associated most of the time in our patients with central line or other in and types of access and invasive intra-abdominal candidiasis.
00:18:26
Speaker
signs on physical exam that the intensivist or the critical care clinician should be looking when they examine their patients. I do believe that we can have a whole discussion on the value of the physical exam, but it's important for us to to look and touch our patients when they're in the unit. Yes, of course. Could you give us any any and any any insight of what sometimes you see and as ah and your ID hat lights up and you say, okay, this might be a problem?
00:18:53
Speaker
Yeah, it's a great question. i mean, i think the short answer is it's these are impossible, as far as I can tell, to distinguish up front from bacterial infection.
00:19:06
Speaker
So when you're doing... If you see someone who has septic shock and you're not sure why, I'd recommend doing the same things that everyone's going to be doing when they're considering septic shock for their bacterial infections. So if this patient already has a line, then you want to look at the line for any potential um signs of infection. Those would be things like erythema, pus coming out of the line, purulence around the line, fluctuance. um Of course, if the line has any of those things, then it's going to be highly concerning. But most of our CLABSIs aren't going to present with those signs or symptoms. So that can be really hard.
00:19:47
Speaker
You certainly want to get a good abdominal exam, especially in someone who is immunocompromised or someone who has just had an abdominal surgery. If there's any concern for intra-abdominal infection, then that would make you concerned for this.
00:20:04
Speaker
But In terms of distinguishing candida from bacteria, I don't think there's anything really on exam that's going to help you do that. So that's where kind of thinking about the patient and thinking about the risk factors is going to hopefully tip you off to thinking about candida and starting the appropriate antifungals. But I'll admit this is really hard. We don't really know empirically who should get antifungals and who shouldn't. um That's things we're you know hoping to work on. I think things like machine learning could potentially help us identify earlier who might need antifungals before we get those definitive diagnostics.
00:20:41
Speaker
um But just on our initial exam, it's really hard to know. And your exam should be similar for anyone with septic shock looking for potential sources of infection. And then if you do find a source, really thinking about early source control. So can you remove that line even before you know exactly what's going on? or do you need to have the patient go to IR or surgery to deal with the intra-abdominal abscess? So definitely a very, very tough problem. This is tough for bacterial sepsis. And I think candidosepsis just um adds another layer of complexity.
00:21:15
Speaker
Excellent. And the second question I had, you did mention, obviously, that the definitive treatment is blood cultures. Are there any, if we have a high suspicion for candida in one of your ICU patients, are there any tricks or any tips you could recommend to maybe enhance the probability that that culture would be positive?
00:21:35
Speaker
Yes. So, um, Blood cultures should be checked at the outset for anyone who you're thinking has um you know sepsis or disseminated bacterial or disseminated candidate infection.
00:21:48
Speaker
Standard blood culture practices are what we should be doing for any of these. And I think it's certainly helpful to ah remind the nurses or phlebotomists when they're drawing these, they you need to and get information.
00:22:03
Speaker
two sets of blood cultures. So each set has an anaerobic and anaerobic bottle, and you need to get, again, two different sets, each each with two bottles, and you need to fill them up to the appropriate amount. So ideally, this is someone who's going to have reasonable...
00:22:18
Speaker
venous access and you can get all of those bottles from different sites and you can fill them with the required amount of blood. And again, you know, I think this was confusing to me, honestly, for a long time, even as an ID fellow.
00:22:33
Speaker
Candida is a fungus. but you don't need to order the special fungal blood cultures to grow candida. So for almost all of our ICU patients, we should just be ordering routine blood cultures and you don't need those special fungal blood cultures and the routine blood cultures, candida will grow just fine on those.
00:22:53
Speaker
Excellent. Let's talk about treatment. And when we talk about antifungal therapy, I know that in your review paper and other places i've I've read, I mean, a framework that talks about prophylaxis, preemptive treatment, empirical treatment, and targeted treatment.
00:23:11
Speaker
Can we start with explaining those concepts?
Therapy Approaches for Candida Infections
00:23:15
Speaker
Yeah, absolutely. I'm glad to and you picked up on that in the review paper, and hopefully this will be helpful to folks. I think um this whole topic is a little bit confusing, so it's definitely good to spend a few minutes um going over this. So just to define terms, prophylaxis is what we use regularly.
00:23:34
Speaker
when someone is at risk for infection, but they don't yet have any signs, symptoms, or lab abnormalities that might suggest infection. So there are some patients who are going to be at high enough risk of candidate infection that they should be on prophylaxis. This is usually our patients with hematologic malignancy, chemotherapy, stem cell transplant, for example. So that's not our routine run-of-the-mill ICU patients.
00:23:59
Speaker
So if for all comers in the ICU, prophylaxis is not recommended. um This is what some of the risk scores that were developed 20 years ago, they tried to identify patients who might be at high enough risk of ah invasive candidate infections that they would benefit from prophylaxis. Unfortunately, we haven't really been able to identify groups of patients in the ICU at least who might benefit from prophylaxis. So that, again, is not recommended for all comers in the ICU.
00:24:27
Speaker
Preemptive therapy is giving patients antifungals if they have some lab test that is abnormal. For example, in our paper, we highlighted patients who have a positive glucan test, giving them preemptive therapy. i guess the thought here is that this is kind of prophylaxis or there's some subclinical infection. And by giving them antifungals, you can head that off.
00:24:52
Speaker
Again, there's no benefit here, so we don't recommend checking glucan levels to target your preemptive therapy. So then we're getting into really where most of us are spending all of our time, and that's thinking about empirical therapy. And as I've mentioned a few times, it's really hard to know which patients should give empirical therapy. And I guess just to be even more specific, empiric is when you're suspecting candidate infection, but you don't get have it diagnosed. So a common kind of scenario in the ICU is going to be someone comes in sick with septic shock.
00:25:28
Speaker
You have a few potential sources of infection that you're going to be looking for. um and you think they might have a candida infection and then you're going to start empiric therapy before you know exactly that it is candida or not.
00:25:43
Speaker
So as I mentioned, this is really tricky because candida infections in this setting will look just like bacterial infections. And again, we don't have great ways to predict whether a patient has candida infection. Hopefully things like machine learning will help us here. um to be able to identify patients who might benefit. There have been some large trials that have looked into this. The most well-known is the Empiricus trial published about 10 years ago or so now that looked at patients that were at particularly high risk for candidemia, whether adding empiric antifungals
00:26:18
Speaker
ah but before candida was diagnosed would help. And unfortunately, that didn't pan out in that trial. So there's still work to do to figure out exactly which patients are at high enough risk of candidemia that they should be given empiric antifungals before we know the diagnosis.
00:26:35
Speaker
And then the last category is targeted, and that's once you do have a definitive diagnosis, um treating patients at that stage. At that stage, things in some respects become a little bit easier. At least you know specifically which bug you're dealing with and you can really target your therapy to candida at that point.
00:26:57
Speaker
But again, a lot of us are gonna be spending our time in this empirical phase thinking about which patients need candidemia, how long to treat them for, when we can stop, and that's still a really difficult question.
00:27:09
Speaker
Excellent. And with the empirical therapy, like like you said, that's where most people spend their their brain power and their time. yeah It's also extremely important. In bacterial infections, we know that if you look at two patients, let's say with m MRSA, septic shock or so or or severe sepsis, and the one got empiric coverage,
00:27:31
Speaker
upfront and the other one got the coverage two days later when we had a positive blood culture, the outcomes could be quite different. yeah So picking the right patients, where and and our patients, we're talking about very sick patients, is extremely important and it can have an impact on on their on their mortality. And I was going to ask you, Max, from your perspective,
00:27:53
Speaker
I guess when I think of the mortality with candidemia, at least, it's high. It's 40% or north, I mean, based on what you read. is that My interpretation has always been it's probably driven first by...
00:28:08
Speaker
The protoplasma of the patients who get it are usually sicker patients, right? We don't see somebody come in from home with candidemia unless they have other risk factors, like we could see maybe a strep pneumon back and pneumonia and bacteremia in a young person, right? Yeah.
00:28:25
Speaker
So it's the people who get it. Also, there's always delays. And then that seems to be more of a driver than the actual virulence of the ah of of of the of the organism. Is that of ah the ah right way of thinking about this or doesn't really matter? Or or you think it's all three?
00:28:42
Speaker
Yeah, it's a great question. i think the easy answer is that it's probably all three. um but but certainly I think there are contributions of all. And I, my own kind of idea is that i certainly agree with you and I think most of it is driven by the protoplasm of the patients who get this, the you know, patients with cancer, with ESRD on dialysis, or patients with cirrhosis. And in the ICU it's more common among patients who have already
00:29:14
Speaker
had to be in the ICU for a few days, so certainly those aren't patients who are going to do well. There have also been at least retrospective studies that tried to look at what we call attributable mortality of candidemia itself, and some studies have put that in the area of maybe 20%, so perhaps you know some additional mortality just from getting candidemia on top of how sick these patients are before they develop candidemia.
00:29:39
Speaker
um And then the last part of that was delays in therapy. And again, the literature here i don't think is entirely clear. Empiricus trials suggested that it perhaps doesn't matter. There are retrospective studies that have shown that delays in therapy also lead to worse outcomes in patients with candidemia. So I think it's a little bit of all three, but I do agree with you that probably the biggest driver is the is the patients who are getting this. And then there is, um
00:30:11
Speaker
some contribution of virulence of the species. So you know ah for this audience, it probably doesn't matter so much, but some species are more vi virulent than others. Fortunately, it looks like although Aureus can be multi-drug resistant, it perhaps doesn't have the same virulence factors that lead to severe disease.
00:30:30
Speaker
So there's mostly about the patient, I would say, some about the bug as well, and then some about our delays in treating it appropriately. Excellent. I would like to go over some of a more specifics on a clinical types of candidate infection.
00:30:49
Speaker
And if you could expand on what would be your initial therapy when you suspect this? and What would be the the usual duration? And how do you think ah about source control in these patients?
00:31:03
Speaker
Yes, absolutely. So the usual therapy when we're suspecting our invasive candida infections, and again, just to go over the two types, that's most commonly candidemia, which means candida bloodstream infection, and invasive candidiasis, which is where... um It involves a organ, and most commonly that's intra-abdominal candidiasis.
00:31:31
Speaker
So the normal therapy when we're thinking about any of these, when we're giving empirical therapy, is going to be with a ah drug of the Echinocandon class. And those are mycofungin, caspafungin, and anadulafungin. They're all relatively interchangeable. They have some differences in dosing, but they all do the same thing. And ultimately, it depends on what's on your hospital formulary as to which one you're going to use. So for empirical therapy, we're almost always going to be using echinocandon
00:32:02
Speaker
when we um are suspecting any type of ah severe invasive candida infection. So we'll start there. And then I think once you've started therapy and got in your initial diagnostics rolling and at the same time, we need to be thinking about source control. So we know this with bacterial infections, and I think it's really the same thing with Canada infections.
00:32:26
Speaker
If you're suspecting line infection and the patient is very sick, I think we we know in Canada that failure to remove a line or intravascular device, if that's the source of infection, is associated with worse outcomes. And again, this is really tricky. know Our patients need these lines. They're in there for a reason. So the decision to remove them empirically is often really hard. It's somewhat easier if you have a positive blood culture a few days later. But if the patient's very sick up front and you're suspecting a line infection, you really need to be thinking about ah removing the line
00:33:01
Speaker
And, you know, best case scenario, I guess you're wrong and it was something else and you have to put in a different line. But but um if it is the line source and the patient might not get better until you remove that line. So that's certainly a ah really tough clinical decision to think about sort of empirically removing a line in a patient who might have a line infection. And then if they have an intra-abdominal source of infection, then talking to the surgeons and IR about getting that trained will be really important, just as in bacterial infection.
00:33:31
Speaker
And then once the patient has an infection, you need to, in addition to looking for the source, whether that's a line or intra-abdominal, if the patient has, excuse me, if the infection has spread to the bloodstream, then it can go other places in the body. So this is where you and your ID consultants are going to be looking for disseminated infection and sort of what other organs could this have gone to.
00:33:56
Speaker
and You also might need to consider source control for other organs as well. so For example, if it started with a line, but now it's in the patient's prosthetic knee, then they're not going to get better until they have that prosthetic knee drained or source control tapped. You need to be considering where else the infection could have gone.
00:34:17
Speaker
And then once you have all of those, and you can start to think about um duration of therapy, most commonly what we see in the medical ICU, at least, is if it's a line infection and it hasn't gone anywhere else, then we can treat for usually about two weeks.
00:34:33
Speaker
um If it's an intra-abdominal infection, then duration of therapy really depends on adequacy of source control. And it can be honestly really tricky to convince yourself that you have complete source control in these patients. So oftentimes we'll end up treating for a few weeks and then repeating imaging to make sure we have adequate source control before stopping therapy.
00:34:57
Speaker
If you're really convinced of source control off the bat, then from the STOP-IT trial, we know that just a few days of therapy after, um, after source control is adequate. And honestly, I'd have to look back to see if they included candida patients in the STOP-IT trial. But I think the same principle still holds. You probably don't need weeks and weeks of therapy if the patient has an intra-abdominal infection and has complete source control.
00:35:21
Speaker
Excellent. What about candida endocarditis?
00:35:26
Speaker
Yeah, this is a really, really tricky one. Candidate endocrinitis can make people really sick, and the patients who get it, you know, on top of our normal candidate infections, they probably also have um cardiac devices or prosthetic valves. So these are are patients who are really not well, um you know, not kind of set up to do well with these severe infections.
00:35:50
Speaker
So the therapy for these, once you've know define that it's a candida endocarditis, you can use an echinocandon for that. We often recommend increasing the dose. So for mycofungin, instead of our normal 100 milligrams, we go to 150, for example.
00:36:06
Speaker
oftentimes um Oftentimes, we'll use amphotericin for these patients, even if it's aceptible if it's a susceptible candida isolate. There's just more not great data, but potentially more data with infotericin and more clinical experience. So sometimes patients will require infotericin for candida endocarditis, and the treatment will be for six weeks. But really here, source control is going to be key. These patients are but pretty unlikely to get i' better with infotericin.
00:36:41
Speaker
with just the antifungals alone. So these are ones who really need to be talking to the surgeons about whether they can do source control procedures. And again, these are the patients who are least likely to be able to tolerate um a big open heart surgery, for example. So these are really tough clinical clinical questions. And actually, i'm I'm just thinking about a patient I had a few days ago um who had Candida auris tricuspid endocarditis, and she got um The cardiologists did the angiovac and thought they were, thought they debulked her tricuspid valve. And unfortunately, the vegetation just grew back. So these are really tricky ones, need to be thinking hard about source control. But even with that, they're often really difficult to manage and the treatment can be toxic and can last for several weeks.
Specific Treatment Considerations
00:37:30
Speaker
Max, any comments on intraocular candidiasis or central nervous system candidiasis that would be different than the approach you you have outlined for the other conditions? Yeah, that's actually a great question. And perhaps we didn't make this point quite clear enough in the review article. So thanks for mentioning it. One, this has honestly been a ah big point of debate between the ID and ophthalmology societies in the past few years. Once Canada has gotten into the bloodstream, one place we worry that it can go is the eyes.
00:38:01
Speaker
So for any patient with disseminated candidiasis, or excuse me, I should say, candida bloodstream infection or candidemia, you really need to be asking them about any ocular symptoms that could indicate whether it's gone to the eye. How often this happens is probably in the order of like one to five percent. But if it does happen, it can be a pretty severe complication.
00:38:22
Speaker
So check with your patients who have candida in the blood. If they have new eye symptoms, then you need to be concerned that it could have gone to their eye. And then that's, of course, when you would call your ophthalmologist for an optho exam. We used to recommend doing this routinely for all patients, at least the ID Society recommended an optho exam for all patients with candidemia, regardless even of eye symptoms. The ophthalmology society pushed back against that a little bit. So now I think most of us ask our patients about symptoms, and if they have symptoms, we'll recommend an optho exam. Of course, many of our patients won't be able to tell us about symptoms, so for those patients, I would still probably recommend an optho exam. um
00:39:04
Speaker
Again, if they have candida in the blood and they and they do have ocular symptoms or they can't tell you because Candida loves to go to the eye and can cause endophthalmitis. If they do have endophthalmitis, that is a very another very tricky condition to manage. The key here is that our first line therapy with echinocandins and again that's things like mycofungin casper function these drugs get into the bloodstream really well but they don't penetrate into tissues and especially protected sites like the eye and cns so if you have an eye or cns infection then you need to use other drugs for
00:39:49
Speaker
Ophthalmologic infections, we recommend often azoles. Those are things like fluconazole or voriconazole. For central nervous system, candida infections, amphotericin with flucytosine are the drugs of choice, so potentially pretty toxic regimens. But again, i think Probably the main takeaway um here for all ICU docs to know is just consider intraocular candidiasis for patients with candida in the blood and perhaps get your opthocolleagues to see them. And if you are concerned about this complication, talk to your ID docs about it because the a kind of candid drugs don't get well into these sites.
00:40:28
Speaker
Excellent. and Could you give us some therapeutic considerations for Candida auris? You did mention earlier it's a growing problem. It can be multidrug resistant.
00:40:41
Speaker
So we've heard, I mean, in some ICUs, a couple of cases. And what what what should we be thinking in these patients? Yes, absolutely. So I guess before we get there, I should mention that, um you know, again, the empiric therapy, we're going to be giving an Echinocandon, and then hopefully we find out that well, not for the patient, but for ease of treatment, once we find out that the patient does actually have a candida infection, the lab will tell you the species of candida, hopefully. And then most labs, I i think these days are doing...
00:41:19
Speaker
excuse me, antifungal susceptibility testing. so once you have that back, if the patient has a Candida species that's susceptible to something like fluconazole and they're otherwise doing well and can take PO,
00:41:34
Speaker
you can change them to fluconazole perhaps to complete the course of therapy. There are some issues with fluconazole. For example, it can prolong QTC. It can cause LFT abnormalities. But assuming things are going well and you know the bug is susceptible, then you can change from the echinocandon to fluconazole or another azole.
00:41:55
Speaker
Candida auris, as we mentioned, is a problem because it can... potentially be drug resistant. About 90% of Oris isolates are resistant to fluconazole, so you can't use azoles for them. um Probably about 30% or so are resistant to amfotericin,
00:42:17
Speaker
And then fortunately, the rates of resistance of resistance to echinocandons are still quite low on the order of probably about 10 to 20%. So fortunately, we're still usually able to use echinocandons for these. but But there are some places and some outbreaks where they've had multi-drug resistant Candida auris where they're resistant to all three of these sort of first, second and third line antifungals.
00:42:44
Speaker
So fortunately, there are a few new antifungals that are coming online. The one that we're all pretty excited about is called Phosmanagempix. That seems like still retains activity against Candida auris. There's also been some limited data about combination therapy for Candida auris. For example, adding flucytosine to another regimen could help. This would definitely be something to talk to your ID colleagues about early and be thinking about what else we might need to be ordering or looking into if we' we're worried that this patient has a very resistant Candida auris isolate.
00:43:20
Speaker
Fortunately, again, still relatively rare, and we're still able to use our first-line antifungal, which is an echinocandon, but ah potentially could be a growing problem. Are there any therapeutic drug monitoring considerations? and I presume it depends on the drug, but when do adjustments when are adjustments needed with renal, hepatic failure, or obesity? Yes.
00:43:44
Speaker
Yeah, it's a great question. I think a lot of us think that therapeutic drug monitoring, which is where you check drug levels of these things and potentially adjust the dosing or frequency, will be important. We don't have a lot of great clinical data to back this up right now for Candida infections at least, but hopefully this is something that we'll learn more about in the next ah five or 10 years or so, because I think it's certainly likely to be important. um For renal and hepatic failure, let me take renal failure first. Fortunately, the echinocandins are all dosed pretty similarly, so we don't have to worry too much about renal failure. um
00:44:27
Speaker
For hepatic failure, ah I think the main concern there is our azoles can contribute to hepatic failure. So that's definitely a time when you would want to think about switching the azoles.
00:44:40
Speaker
Obesity, some of us will increase the dose of echinocandins, especially for a resistant or potentially resistant candida isolate. So that's something to talk to your ICU pharmacists and ID colleagues and ID pharmacists about.
00:44:55
Speaker
So just keep this in mind that potentially we might need to think about targeting a little higher dose for our obese patients.
Considerations in Over-treatment and Prevention
00:45:03
Speaker
And again, hopefully we'll have more concrete data and evidence on this in the next little bit, because this could be a ah way we can optimize therapy for these patients, but I just don't think we know quite enough yet to recommend this routinely.
00:45:18
Speaker
Excellent. You talked about some of the new antifungals, ah but before we finish this and therapeutic section, could you comment on candida in the urine and in the respiratory secretions? We commonly see this in the ICU.
00:45:34
Speaker
I still think it's an area of confusion and over-treatment, and I just want to hear it from the expert. What should we be doing? Yes, so i this was another area that I'm glad you liked the review, and I wish we had focused on this a little bit more. So this is probably the most common time that we talk about candida in the ICU is when it's isolated from a urine culture or a sputum culture that we've sent working up infection.
00:46:06
Speaker
so again, candida lives... especially Candida auris lives on all of us in our GI tracts and potentially on our skin. And when we give antibiotics and patients have catheters, Candida can grow and it can grow into these sites like the lungs and the bladder potentially. So I'm sure it's there. Fortunately, Candida doesn't cause infections in these sites.
00:46:31
Speaker
um So you don't have to worry about treating it. So again, if you see candida in the urine or the sputum, you do not have to treat it. Just so no one you know gets mad at me. Of course, there's been a case report, I'm sure, of each, but let's just say 99.99% the time, you do not treat candida if you see it in a urine or respiratory secretion.
00:46:54
Speaker
That said, it does mean these patients are probably at higher risk of getting candida infections than patients who don't have this colonization. And we know this from the risk scores that I talked about a few sections ago.
00:47:09
Speaker
So having candida in these sites probably means that they have candida living on their skin, close to the catheter. It's probably more in their gut and you know just waiting to burst out of that surgical anastomosis when it unfortunately ruptures.
00:47:23
Speaker
So if you see candida in the urine or the sputum, don't worry about treating ah treating it. But if the patient does get sick in a few days and you're not sure what bug is causing their sepsis, this would be a patient who I would think pretty hard about starting empiric antifungals before we know exactly what's going on, because we know that having candida colonization at other sites is a risk factor for subsequent candida infection. Again, because these patients are at high risk of candida infections and they have candida essentially growing on their body, and from there it can crawl into the places we don't want it to get, such as their bloodstream.
00:48:04
Speaker
That's an important distinction. as ah As a risk factor, we should pay attention, but they don't usually indicate that we should be treating based on that finding alone. And my understanding, Max, is that a lot of the prediction scores include and this type colonization as risk factors or as gives you points for that, right?
00:48:24
Speaker
Yes, everything you just said, I i totally agree with. So as we close, Max, in terms in terms of a summary, could you share with us some pearls and pitfalls to avoid with candin infections in the ICU?
00:48:38
Speaker
Yes, of course. so I think one really important thing is the the thing we just mentioned that I won't belabor again, but just candida and the urine and respiratory secretion. So that's number one. Number two, I think is good standard sort of prevention of these infections. And that's the standard things we do to hopefully liberate our patients from the ICU. So take out the central line when you can, take out the urinary catheter when you can, um stop unnecessary antibiotics, all of these things that are just good standard ICU care are going to help prevent these infections.
00:49:14
Speaker
Number three, I think, is that ah the empiric therapy that we've spent a lot of time talking about. i really think this is ah a tricky thing. This is hard for docs like me who think about candida all the time. you know i i don't know how often I'm correct in predicting whether a patient has a candida infection, if it looks like they have sepsis, but I'm sure the number is quite low.
00:49:34
Speaker
So we need better tools here to think about who should and shouldn't get candida infections before you're able to definitively diagnose it, which can take some time. So hopefully there will be more and better tools coming online, such as potentially machine learning approaches that I mentioned that will help us at least kind of clue us in to who we might need to be thinking about candida infections before we know definitively.
00:49:58
Speaker
And then I think once patients, you know, once you think they have a candidate infection or you're more sure they do in kind of that definitive phase, think really hard about source control and where else this infection could have spread so that we can appropriately get source control everywhere it needs to be.
00:50:17
Speaker
And um then continuing antifungals, hopefully for no longer than they need to be continued. Excellent.
Personal Recommendations and Closing
00:50:25
Speaker
Well, Max, you' you've been on the podcast before, so you know how we end. We like to ask a couple of questions unrelated to the clinical topic. Would that be okay?
00:50:34
Speaker
Yeah, of course. So we talked about books last time, but it's been almost five more than five years. So I'm going to ask you, have any new books influenced you significantly? Or is there a new book that you might be gifting often to other people?
00:50:50
Speaker
Yeah, we were joking about this before, but last time was about a year into the pandemic and all of my books were um related to viral pandemic infections. I guess I was kind of into that theme back then. I'm into slightly more escapist books now. or i don't know if you want to call it that, but I've had a few close mentors um recommend a book called 4,000 Weeks about time management, and I've really, ah really liked that one. And it's probably more than time management, just about
00:51:22
Speaker
Sort of getting down to the things that are important and and trying to not focus too much on the other stuff. So I think that's been sort of a helpful book and hopefully a defining theme in this, you know, still early part of my career when I'm trying to figure out exactly what I want to focus on.
00:51:39
Speaker
Absolutely. And that's a wonderful book and we'll link it in the show notes. And way the way I would summarize that book and others that are similar is if you don't set your priorities, somebody will set them for you. yeah so Exactly. So be very intentional about knowing what's important for you and creating the space for that. Yes.
00:52:01
Speaker
What music album or playlist would you want with you in a prolonged isolation period? Deserted Island or like since we mentioned pandemics, if a pandemic were to isolate us again? Well, Sergio, we're both here in Texas, and I'm not a native Texan, but I but i do love Texas. And since I moved here a few years, we've been getting more into into country and sort of Americana music. So one artist that I've really liked is Charlie Crockett. He's from he's from South Texas. So sort of Americana folk, Charlie Crockett style country is is what I would take with me these days.
00:52:34
Speaker
Excellent. And I have to say that despite living in Texas, that is not my my my cup of tea and in music. i'm I'm really into jazz. But the reason why I ask these questions because I'm always interested in listening to new new things, reading new books. So I will definitely give Charlie Crockett a listen the next of days. I think he's...
00:52:55
Speaker
He's pretty approachable. you know, I still wouldn't say i love all types of country music, but I think he's really, um he's really excellent and worth a listen. Will do.
00:53:07
Speaker
Could you share with us something you changed your mind about over the last couple of years? Yeah, I guess on on that theme, you know, this is a great question, but I think living in Houston, um I've really changed my mind about, you know, i I wasn't sure what I would think about Houston when I moved here a few years ago, but I've really loved it. It's a fantastic place with all sorts of types of people and a lot of a lot of stuff to do. It's really sort of livable, approachable place. And The folks here are great. So i really, really like it here and I'm happy I'm here. Well, happy to hear that.
00:53:40
Speaker
And I can't call myself a native Houstonian, but ah they they say that you're not from where you're born, but where you love. And clearly, I love living in Houston. I have found a a lot of interesting things to to to do. a Very, very diverse and in many aspects.
00:54:01
Speaker
And I'm not very fond of of cold weather. So that has been an extra plus. Yes, I totally agree. And I have a slight variation on that.
00:54:13
Speaker
You know, you're not you're not from where you're born. I've i've heard you it's not where you were born, but it's where your wife's mother, um mother lives. So that's why I'm in Houston. Absolutely. That that always is ah is a big factor. Exactly. But I still I still like it. And it's been great being close to family. Awesome.
00:54:32
Speaker
So as we close, is there anything you would want every listener to know could be a quote or a closing thought? Yeah, thanks for asking this question. And I guess, you know, just coming off service, I think probably other folks know this, but guess this is mostly for me, you know, as much as anyone else, but just how...
00:54:52
Speaker
you know how rewarding it is to to talk to families of our patients i think it's easy to go through the day and and sort of check the boxes and deal with the medical stuff but um you know sometimes a few days into service i'm sort of just kind of going along and and doing that and then i talk to a few families and it really kind of gives me a little more energy so i hope i remember that the first or second day i'm on service every time and i'm sure everyone else knows that um but it's just always helpful for me to remind myself
00:55:23
Speaker
Absolutely. and And along those lines, and this is something I got right before we started the podcast. One of our our our team members from one of our programs outside of Texas shared that they had an event with family members and that the wife of one of our patients who had been in the ICU for a long time and gave a very eloquent speech. And at the end, she she looked at our team and I'm going to read what what she what what she wrote. or What she said was to the intensivist, when they are overwhelmed, you are steady. When they are afraid, you are calm.
00:56:01
Speaker
When they don't understand, you explain. When they are exhausted, you carry the weight with them. You don't just treat an infection or illness. You fight for his life and their future. You make impossible decisions with skill and compassion.
00:56:15
Speaker
You work long hours that may may never that they may never see. You stand in the gap between crisis and hope. I thought was beautiful and so powerful coming from a family member and just a reminder of the impact our work has on the life of others. So I'm happy you brought that up. This is something I was reading before we started, and I just felt, I mean, immediately, why not why not share? So Max, thank you so much for sharing your time and expertise with us.
00:56:44
Speaker
We definitely, and there's no two without a three, so we will definitely have you back soon to talk about critical care topics and especially those that interface with the world of of infectious disease. Thank you.
00:56:59
Speaker
Thanks so much for having me. And yeah, thanks for sharing that quote. That was really fantastic. And i certainly hope to live up to that. Thank you for listening to Critical Matters, a sound podcast. Make sure to subscribe to Critical Matters on Apple or Google Podcasts and share with your network.
00:57:14
Speaker
Sounds transforming the way critical care is provided in hospitals across the country. To learn more, visit www.soundphysicians.com.