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COVID-Associated Fungal Pneumonia · The SHEA Podcast

• 0:08
  SPEAKER_00: Welcome to the Rapid Response Podcast brought to you by the Society for Healthcare Epidemiology of America, Shay, promoting the prevention of healthcare associated infections and antibiotic resistance and seeking to advance the field of healthcare epidemiology and antibiotic stewardship.
• 0:23
  SPEAKER_00: I am Dr.
• 0:24
  SPEAKER_00: Christopher Sarnage, Chief of Medicine and Hospital Epidemiologist at the Madison VA Hospital and Associate Professor of Medicine at the University of Wisconsin School of Medicine and Public Health.
• 0:34
  SPEAKER_00: I will serve as today's podcast moderator.
• 0:37
  SPEAKER_00: Discussion on the podcast does not reflect Shay's perspective, but facilitates communication of multiple perspectives and experiences as we go through this challenging time together.
• 0:46
  SPEAKER_00: Shay is excited to launch this episode of the podcast.
• 0:49
  SPEAKER_00: COVID-19 updates what we know now.
• 0:52
  SPEAKER_00: Today's discussion will focus on COVID-associated fungal pneumonia.
• 0:56
  SPEAKER_00: COVID-19 has presented so many challenges to those of us on infectious diseases and infection control, and keeping up with all the new information has been a particular challenge.
• 1:05
  SPEAKER_00: Fungal pneumonia associated with COVID-19 infection has been one of those topic areas that I know that has been difficult for me to stay on top of.
• 1:13
  SPEAKER_00: And we are therefore very fortunate to have somebody with us today with expertise in this important clinical area.
• 1:19
  SPEAKER_00: Dr.
• 1:19
  SPEAKER_00: Martin Honegal is an associate professor of medicine at the Division of Infectious Diseases at the University of California, San Diego, and the Section of Infectious Diseases and Division of Pulmonology at the Medical University of Graz, Austria.
• 1:33
  SPEAKER_00: You know, there's a published a number of recent articles on this topic.
• 1:36
  SPEAKER_00: I'm very much looking forward to our conversation today.
• 1:40
  SPEAKER_00: Martin, thank you for joining us today.
• 1:42
  SPEAKER_00: If you don't mind, let's go ahead and jump right into the discussion.
• 1:46
  SPEAKER_00: So my first question is: can you provide our audience with a general overview of how the association between COVID-19 and fungal pneumonia came to be recognized?
• 1:57
  SPEAKER_01: Thank you so much, Chris, for having me and for the nice introduction.
• 2:00
  SPEAKER_01: So it's indeed my pleasure to be here today and talk with you about COVID-associated fungal infections, which indeed have increasingly become a focus of our attention over the last one and a half years.
• 2:13
  SPEAKER_01: So at the high-level summoner, I think it's really interesting that actually the first association may have really started with Canada, right?
• 2:21
  SPEAKER_01: Because many ICU physicians reported mostly local colonization, local infection, tracheitis.
• 2:27
  SPEAKER_01: And that was initially mostly the point where they ended the exploration, right?
• 2:31
  SPEAKER_01: So they got a lot of thracheal secretion.
• 2:33
  SPEAKER_01: And there they saw basically tracheitis, and that's what described.
• 2:36
  SPEAKER_01: But they did not really have an indication of invasive infections.
• 2:40
  SPEAKER_01: I think, but that's what was first described, and I remember back in March, April 2020, which I heard from ICU decisions.
• 2:46
  SPEAKER_01: And then I think things moved along, and there was increasingly a spagillus found first in draftal secretion, because in many ICUs, people were reluctant to do bronchoscopies due to the fear of transmission of the virus.
• 2:58
  SPEAKER_01: So it was mostly druccal secretion, and there was always the question mark you know, is this only colonization?
• 3:03
  SPEAKER_01: Is this a sign of infection or not?
• 3:05
  SPEAKER_01: So it was still flying under the radar.
• 3:08
  SPEAKER_01: As time advanced and people got more secure with feeling with the virus, there was more and more bronchoscopies performed.
• 3:16
  SPEAKER_01: And we did then also at some point have some autopsy proof that actually some of these patients developed COVID-associated pulmonary aspergillosis.
• 3:23
  SPEAKER_01: And we also found more aspergillos, of course, in BL fluid, and we found out that you know this is growing at least airway invasive, so tissue invasive, although it takes really a time until it becomes angular invasive and disseminated.
• 3:36
  SPEAKER_01: But nevertheless, I think this increased the awareness, and there was some discussion, you know, whether this is colonization or infection and what stage, but I think the awareness was already really starting, at least among ID physicians and people who LSEU physicians, with people who deal dealt with the patient.
• 3:50
  SPEAKER_01: And I think the big change then was coming with basically the third major infection.
• 3:56
  SPEAKER_01: And the rumor started, I think, back in December 2020 until January, February 2021.
• 4:04
  SPEAKER_01: And I remember that I got contacted by some news outlets because they read these reports from Indian newspapers that there was a ton of COVID-associated muco mycosis, mostly renocerebole infections happening in India.
• 4:16
  SPEAKER_01: And I got interviewed, and some of these outlets didn't publish it because they were not sure if these resources were reliable.
• 4:23
  SPEAKER_01: At the end, many of these stories did not get published until finally there was enough evidence.
• 4:27
  SPEAKER_01: And then I think starting May, there was just this huge media outcry of about the black fungus, how they called it, the problem in India and the mucomycosis, the COVID-associated mucoma mycosis outbreaks in India, which of course affected very many who got diagnosed with it.
• 4:42
  SPEAKER_01: And I'll come to that potentially later.
• 4:44
  SPEAKER_01: I guess even more did not have the renocere, but other mucomycosis infections to potentially never get diagnosed.
• 4:50
  SPEAKER_01: So, but I think really that was the big game changer in terms of media awareness, at least and general awareness in the population, was the like fungus COVID-associated mucomycosis reporting and the huge numbers we saw in media.
• 5:03
  SPEAKER_00: That's very interesting.
• 5:05
  SPEAKER_00: So it sounds like there's pretty decent consensus at this point that clearly patients with severe COVID-19 pneumonia can develop COVID-associated invasive fungal infections.
• 5:21
  SPEAKER_00: I guess one of the big questions, you know, that's been rattling around in my brain as I think about this has been to what extent are these COVID-associated invasive fungal infections being driven by host factors or the virus itself versus what we're doing to these patients from a therapeutic perspective, and in particular, kind of thinking about things like steroids and the cytokine inhibitor therapies, and to what extent are those potentially playing a contributing factor here?
• 5:53
  SPEAKER_01: Thanks.
• 5:53
  SPEAKER_01: I think this is a very good question.
• 5:55
  SPEAKER_01: And I really have begun to dissect this question into different fungal pathogens because obviously they're very different, and the groups of buttogens and also the immunological mechanisms that may play a role are very different.
• 6:06
  SPEAKER_01: So, first of all, when we just start off with Canada, I really think that there is at least no strong immunological pathway that predisposes specifically COVID infected patients who develop candidate infections.
• 6:19
  SPEAKER_01: But of course, as you said, there are all the clinical risk factors, right?
• 6:22
  SPEAKER_01: And it starts off with treatment of COVID, steroid treatment, doxy doxilithum up treatment, but also patients being long-term in the ICU.
• 6:30
  SPEAKER_01: Patients have, of course, all the other classical risk factors for developing candidate infections.
• 6:35
  SPEAKER_01: Rose spectrum antibiotics, potentially prescribed to our all these classical risk factors come into play.
• 6:41
  SPEAKER_01: And that's why for now my working hypothesis is really now we have a lot of pre-COVID patients in ICUs, and of course, we continue to see candidate infections in ICUs.
• 6:49
  SPEAKER_01: So that's my association there.
• 6:51
  SPEAKER_01: And also when you think about candid RS outbreaks, they have also continued, of course, now when with COVID, but I have not seen this exponentially increase or so with COVID that we have much, much more candid RS outbreaks, more than usually we, of course, we expect this to increase from year to year a bit, right?
• 7:06
  SPEAKER_01: But we have not seen this exponentially.
• 7:08
  SPEAKER_01: I think the story becomes different, and I would say, in my opinion, more interesting when we come to Aspergillos, because there are some important immunologic pathways, specifically due to COVID infection, that may predispose these patients.
• 7:23
  SPEAKER_01: There's some hypothesis about the release of danger-associated molecular patterns that are increasingly released during severe COVID ARDS.
• 7:31
  SPEAKER_01: And of course, they cause lung injury, pulmonary epidemic damage that also may help aspergillos to grow there and bate the tissue, the lung tissue there.
• 7:40
  SPEAKER_01: But then there are also some collateral effects or post-recognition pathways that are necessary for patients to fight COVID.
• 7:48
  SPEAKER_01: But that then at the same time, for example, the hyperactivation of the interlocking one pathway may predispose these patients or leave the niche for fungal pathogens, aspergillos specifically here to grow.
• 7:59
  SPEAKER_01: And at the same time, of course, the other risk factor are the clinical risk factors.
• 8:03
  SPEAKER_01: Again, long dose, high dose, um dexamethasone, gotsilitzome up, and other classical risk factors we have in this patient.
• 8:11
  SPEAKER_01: And then last but not least, of course, when you think about mucomycosis, again it's a mixture.
• 8:15
  SPEAKER_01: I do think for mucomycosis specifically, the treatment may also play a big role because I do think one of the reasons why we found so many cases in India, much more than anywhere else, is the fact that there was dexametasonis that was available there over the counter and they did not have a lot of oxygen supplies.
• 8:33
  SPEAKER_01: So they had done a dexametasone overuse, going much more than what we use in the US or what's used in Europe.
• 8:40
  SPEAKER_01: And that may have triggered, in addition, to a high rate of undiagnosed diabetes that's present in India and the COVID-associated mucomycosis outbreaks.
• 8:50
  SPEAKER_01: But of course, even for mucomycosis, there are also important immunological mechanisms in terms of free iron that's increased, also in part due to COVID.
• 8:59
  SPEAKER_01: So there are also immunological mechanisms that come into play for mucomicosis.
• 9:03
  SPEAKER_00: So extending off of kind of what you were describing in India, there has been at least one large study, although it did not reach statistical significance showing that higher dose dexomethasone might be associated with some improved outcomes in patients with severe COVID-19.
• 9:24
  SPEAKER_00: Do you have any concerns that if clinicians kind of move in that direction, at least in the United States, that may kind of contribute to promoting more invasive fungal infections?
• 9:35
  SPEAKER_00: Or do you feel like those concerns are overblown?
• 9:39
  SPEAKER_01: Generally, yes, of course.
• 9:40
  SPEAKER_01: I mean, we are always traditionally, even before COVID, we saw these two types of aspergulosis infection, invasive asperpulmonary aspergulosis, right?
• 9:48
  SPEAKER_01: We saw this infection we are seeing in neutropenic patients where it quickly goes angianinvasive.
• 9:53
  SPEAKER_01: And then we were always seeing these typical infections that appear in patients on long-term corticosteroids, which are usually airway invasive.
• 10:00
  SPEAKER_01: And you can say that they're much more similar to what we're seeing in COVID patients.
• 10:03
  SPEAKER_01: And of course, I do think there is it's more complex than just corticosteroids, but once we get to higher dose and longer corticosteroids, this would definitely, in my opinion, likely um further increase the risk.
• 10:15
  SPEAKER_01: So at the end, it's the same now for you know the 10-day dexamethasone that we are currently using.
• 10:20
  SPEAKER_01: It's always a question now what's the benefit?
• 10:22
  SPEAKER_01: And if does the benefit outweigh the risk?
• 10:24
  SPEAKER_01: Currently don't have evidence that, you know, for example, stopping dexamethasone early in patients where it's indicated is justified because potentially the benefit of receiving it is higher than the risk of developing a fungal infection.
• 10:36
  SPEAKER_01: But of course, I think once it gets to lower evidence, longer term, higher dose corticosteroids, this benefit-risk ratio may change.
• 10:44
  SPEAKER_01: And at one point it may be equal, and at one point the risk may even be too high.
• 10:48
  SPEAKER_01: So I think that's very important to keep that in mind and focus on multiple outcomes in such studies and not just on the pure COVID recovery.
• 10:56
  SPEAKER_01: Great.
• 10:56
  SPEAKER_00: So our audience is largely focused on hospital epidemiology and infection prevention.
• 11:02
  SPEAKER_00: And, you know, one of the questions I have, although maybe it's not as big of a concern given the way that at least patients with severe COVID pneumonia are kind of have kept it from a negative pressure perspective.
• 11:17
  SPEAKER_00: But is there any concern or reason to be concerned that the hospital or healthcare environment may be contributing to fungal infections?
• 11:25
  SPEAKER_00: Or is this more of a function of patients coming in to the hospital with severe COVID and already have these pathogens kind of colonizing their respiratory tract?
• 11:34
  SPEAKER_00: Or is it possible that they're acquiring these organisms during the course of their hospitalization?
• 11:40
  SPEAKER_00: And again, that might depend on the type of fungus that we're talking about here, but just want to kind of get your perspective on that.
• 11:46
  SPEAKER_01: I think both are important.
• 11:48
  SPEAKER_01: And as you have rightly said, Chris, I mean, it's really a question which fungus we're talking about.
• 11:52
  SPEAKER_01: I do think for us Bagellas and also for MUCOR, of course there can be hospital outbreaks, right?
• 11:57
  SPEAKER_01: And it was also very much theorized and hypothesized in the beginning of the pandemic that those centers who had a lot of cases, there was potentially, you know, much more construction work.
• 12:06
  SPEAKER_01: That's what we know, construction work, building bigger ICUs, building additional ICUs, etc., provisional ICUs that may have contributed to locally high levels.
• 12:15
  SPEAKER_01: And that's always something we have to take into account also for us for killers and also for MOOCO, for example.
• 12:21
  SPEAKER_01: MOOCOR, there is a great study that showed that MOOCOR is pretty much everywhere in India, including in the hospitals, right?
• 12:27
  SPEAKER_01: But it's also outside the hospital.
• 12:28
  SPEAKER_01: So the question is how many patients do it only get in the hospitals versus how many patients bring it with them in the microbiome.
• 12:34
  SPEAKER_01: And then, you know, it just grows when it has the opportunity.
• 12:37
  SPEAKER_01: So I think generally for more infections, it's more that people bring it with them because we have not seen these huge outbreaks with the defined hospital source.
• 12:46
  SPEAKER_01: But that said, nevertheless, we should always keep our eye open, especially if we have really high rates, whether there is a source in the hospital, whether there is a reason of building or buildings need built or et cetera, that may contribute to the high rates we're seeing.
• 13:01
  SPEAKER_01: For Canada, obviously, and specifically Canada RS, it's a very different story because Canada RS is a classical pathogen that gets transmitted not so much from patient to patient in the ISU, but from patient to caregivers and to another patient.
• 13:13
  SPEAKER_01: So there definitely the hospital plays a role.
• 13:16
  SPEAKER_01: But at the same time, we had Canada RS cases recently at UCST as well.
• 13:20
  SPEAKER_01: And it's so hard, these patients are colonized everywhere, and it's really hard to contain these outbreaks.
• 13:25
  SPEAKER_01: We were lucky and we were able, but it's really a ton of work for our hospital hygiene and hospital epidemiologists to really keep this, contain these outbreaks because they are very contagious and it's nearly impossible to get rid of candidaris in a patient who is colonized everywhere, basically.
• 13:41
  SPEAKER_01: So okay.
• 13:43
  SPEAKER_00: So when we kind of look at a patient, we're at least thinking about the possibility of a COVID-19 associated invasive fungal infection, what kind of factors should elevate that concern and you know move us closer to initiating treatment either empirically or definitively, or you know, what should we do next once we have those concerns?
• 14:06
  SPEAKER_00: So can you talk a little bit about you know how you approach this clinically?
• 14:10
  SPEAKER_00: And for those of us who are thinking about how we should approach this with our patients, can you kind of walk us through that thought process so we kind of understand that a little bit better?
• 14:20
  SPEAKER_01: Yeah.
• 14:21
  SPEAKER_01: So I think first of all, we need to have a patient who's not doing good, right?
• 14:25
  SPEAKER_01: So I would really focus your diagnostic effort specifically on the ICU because many of these fungal infections really happen in the ICU setting.
• 14:33
  SPEAKER_01: And I'm taking out, I mean, muco mycos in India, this is sometimes, but it's a different health system.
• 14:38
  SPEAKER_01: But I think for the United States, we really need to focus on the ICU primarily.
• 14:41
  SPEAKER_01: We'll eventually see somebody out of the ICU, but most of our patients with COVID-associated fungal infections will be in the ICU.
• 14:47
  SPEAKER_01: And then, of course, the other question that has to be taken into account is that the patient is doing worse.
• 14:52
  SPEAKER_01: Usually, when patients get admitted to the ICU, at this point they're already doing worse.
• 14:56
  SPEAKER_01: So that's why I would really emphasize here the importance of potentially doing an early bronchoscopy, because these patients come to the ICU for a reason, not because they're doing better.
• 15:05
  SPEAKER_01: If this is not feasible, of course, you could also have them in ICU, but as soon as the patient is doing worse, I think the only way to really be able to diagnose it, and specifically now for aspergulosis, is to do a bronchoscopy because, and not just the trechel secretion, because it's harder to interpret the evidence, but do a bronchoscopy and test this for culture and also do a BL galactomanon.
• 15:25
  SPEAKER_01: This is very important, and there is a lot of discussion about that.
• 15:28
  SPEAKER_01: You know, what does it mean if I have aspergulosis culture positive from BL and what does a positive BL galactomanon mean?
• 15:34
  SPEAKER_01: Could this be a false positive?
• 15:36
  SPEAKER_01: I don't like the term false positive here because I'm always thinking of aspergulosis as a spectrum of disease, right?
• 15:42
  SPEAKER_01: And even what's now maybe colonizing or just a little bit growing on the airways, and maybe just a little bit growing into the tissue, they continue to grow in the tissue, and four or five days later it grows deeper, and eight days later, that was shown in the models for corticorticeroid patients, um, it becomes ango-invasive.
• 16:00
  SPEAKER_01: And I think this concept is really good.
• 16:01
  SPEAKER_01: And obviously, it doesn't mean that everyone where we isolate an aspergillos and BL fluid or have a positive BL galacumon would develop invasive ango-invasive disease and die of it.
• 16:11
  SPEAKER_01: I mean, definitely not.
• 16:12
  SPEAKER_01: That's not something I propose.
• 16:13
  SPEAKER_01: But at the same time, when we look into recent studies, and I think these have really been intriguing, they've looked into prognostic factors in patients with COVID-associated pulmonary aspergillosis.
• 16:24
  SPEAKER_01: The one thing they found, and one of these studies has recently been accepted at the Journal of Clinic and Microbiology, and I think Sarah Delier is the first offer, it's from a beam from France with Alexandre Alan, the last offer.
• 16:35
  SPEAKER_01: They found once our zero markers for aspergillos, meaning serum galactomanan, becomes positive, or even blood PCR, 100% of patients die, no matter if you treat, right?
• 16:47
  SPEAKER_01: So this is the point where it's definitely too late to diagnose.
• 16:50
  SPEAKER_01: And of course, you would still probably prescribe treatment, but we definitely want to be earlier in the pathogenesis where diagnosed is, for example, aspergillos here.
• 16:58
  SPEAKER_01: I'm talking specifically about aspergillosis, and also treat earlier.
• 17:01
  SPEAKER_01: And I think this is now pretty much consensus.
• 17:03
  SPEAKER_01: And we can discuss, you know, whether it's over treatment, potentially it's over-treatment, but this is the time to start treatment, and we can't differentiate otherwise.
• 17:09
  SPEAKER_01: I would just emphasize, you know, please, if anyhow possible, do a bronchoscopy and get a BL, because once you get into the upper respiratory tract or a secretion only, or even split, and the over-treatment may increase and you may really start treating more patients than you need to treat.
• 17:25
  SPEAKER_01: So I think that's the key issue.
• 17:26
  SPEAKER_01: Patient is getting worse.
• 17:28
  SPEAKER_01: None of these patients who is getting worse and comes with COVID to the ICU has a beautiful imaging results, right?
• 17:34
  SPEAKER_01: If you do a chest CD or Stex Ray, they all many are white, they are not looking good, obviously, um, due to the ERDS.
• 17:40
  SPEAKER_01: So it's hard to differentiate radiologically whether this is COVID or whether there's a fungal infection somewhere as well.
• 17:45
  SPEAKER_01: Um, so this is not helping so much, it's mostly clinical the patients doing worse.
• 17:49
  SPEAKER_01: Sometimes you see some typical signs, you know, with some cavernous lesions, that's something you can keep an eye out.
• 17:55
  SPEAKER_01: But if you don't see it, you can't rule it out, especially if the lung is not here, of course, which it never is in these patients.
• 18:01
  SPEAKER_01: So, yeah, I think that's the key.
• 18:03
  SPEAKER_01: And then it's bronchoscopy, vasperculosis, and also for muco mycosis.
• 18:07
  SPEAKER_01: I think it's very important to have a culture because potentially you can find mucor in a BL culture, and this will help you.
• 18:14
  SPEAKER_01: There's also some development towards mucoralis BCR, which I hope is, you know, we had some recent studies on that that really look good and it's getting commercialized.
• 18:23
  SPEAKER_01: So we're getting to a stage with mucoralis BCR, also from BL and also from blood, actually.
• 18:28
  SPEAKER_01: This gets ready for prime time, I think.
• 18:30
  SPEAKER_01: So this will also help us in the future to better diagnose these infections.
• 18:35
  SPEAKER_01: And then Canada, of course, a key thing here for Canada is culture, blood cultures, obviously for candidemia.
• 18:42
  SPEAKER_01: This is always something we're concerned of.
• 18:44
  SPEAKER_01: And any other cultures, if we have some abscesses or something, of course, some other sterile sites where we suspect candidate infections, cultures.
• 18:52
  SPEAKER_01: But of course, BL culture for Canada, and probably to get back into that later, won't help a lot because we mostly will find Canada BL because it's a colonizer there.
• 19:01
  SPEAKER_01: So it depends again on the fungus, I would say.
• 19:04
  SPEAKER_00: Very helpful.
• 19:04
  SPEAKER_00: So if I can summarize, clinical trajectory is probably your most useful trigger tool for considering a fungal pneumonia.
• 19:15
  SPEAKER_00: Atypical imaging findings with cavitation would also potentially be another situation.
• 19:21
  SPEAKER_00: But again, that would need to be factored with the patient's clinical trajectory and simple recovery of an organism from a respiratory specimen, particularly an upper respiratory tract specimen in a patient whose clinical trajectory is actually trending in a positive direction, wouldn't necessarily dictate a need for a bronchoscopy.
• 19:39
  SPEAKER_00: But obviously, if somebody's clinical trajectory was not improving or trending in the wrong direction and you had that upper respiratory tract specimen or that imaging finding, your recommendation would be really push for a bronchoscopy or a lower respiratory tract specimen if possible.
• 19:56
  SPEAKER_00: And then in those situations, if recovery is identified, certainly would justify impaired antifungal therapy.
• 20:04
  SPEAKER_00: And if I'm hearing you correctly, doing trending of serum biomarkers doesn't have a whole lot of utility in this population.
• 20:13
  SPEAKER_00: Is yeah, am I interpreting that correctly?
• 20:16
  SPEAKER_01: I would absolutely agree with that.
• 20:18
  SPEAKER_01: I think you know for serum galacnoman, it comes it becomes positive too late in the disease.
• 20:23
  SPEAKER_01: So it doesn't help us a lot.
• 20:24
  SPEAKER_01: We can still easily do it, of course, but it won't help us a lot.
• 20:27
  SPEAKER_01: And serum beta D glucan is specifically complicated to interpret in the ICU in these patients because we know there are so many factors.
• 20:34
  SPEAKER_01: It can be a marker of leaky gut.
• 20:36
  SPEAKER_01: I mean, as soon as a patient gets septic, of course, the gut becomes leaky.
• 20:39
  SPEAKER_01: There may be translocation of some fungal cell wall components, although this doesn't mean that there's the whole canada translocated.
• 20:45
  SPEAKER_01: So it's really also correlating well with some of our SEU scores.
• 20:49
  SPEAKER_01: So there's studies that show a very clear correlation between serum beta lecle and sofa scores in SEU patients, independent of any fungal infection.
• 20:56
  SPEAKER_01: So I think zero markers don't help us at dawn, obviously, here.
• 21:00
  SPEAKER_01: So we really need to go um to the BL, unfortunately.
• 21:04
  SPEAKER_00: Okay.
• 21:04
  SPEAKER_00: I want to kind of circle back on the Canada piece a little bit.
• 21:08
  SPEAKER_00: So, you know, I think you've alluded to the fact that we have seen what appears to be an increase in the number of bloodstream infections with Canada, in particular, Canada aurus has been very problematic in institutions that have had that.
• 21:23
  SPEAKER_00: And you alluded to the fact that there's been potentially some tracheitis on ID Twitter.
• 21:29
  SPEAKER_00: There's been some comments about is it possible that we're seeing, you know, actually COVID pneumonia, which I don't think I've yet seen in my clinical career.
• 21:38
  SPEAKER_00: And I still kind of keep it an exceedingly rare complication.
• 21:42
  SPEAKER_00: Is there any evidence that I need to be reevaluating my position on Canada causing pneumonia?
• 21:48
  SPEAKER_00: And how does recovery from Canada and the respiratory tract kind of influence your decision for the initiation of antifungal therapy?
• 21:55
  SPEAKER_00: So that's you know a double-barreled question, which I should never ask, but maybe I'll I'll with the first any evidence that Canada is actually causing COVID pneumonia or pneumonia in COVID patients at this point that you're aware of?
• 22:09
  SPEAKER_01: Thanks.
• 22:09
  SPEAKER_01: It's again a good question.
• 22:10
  SPEAKER_01: I think I've also seen some evidence, but it's mostly coming from isolated case reports, right?
• 22:15
  SPEAKER_01: So that's what I've seen isolated studies or other larger studies that are not as much I was not a reviewer on because when I read when reading them, I see some issues there, also mostly in lower rank journals where they've published where they report a lot of cannabis infections.
• 22:29
  SPEAKER_01: And but they are only they are based on some evidence that doesn't convince me mostly.
• 22:34
  SPEAKER_01: But I have not seen strong evidence.
• 22:36
  SPEAKER_01: I mean obviously I think when you think about the whole field of candidac pneumonia, I think we've been first we thought it's frequent I think like 20 30 years ago then we came to the point where we had these autopsy studies where we said this does never occur basically.
• 22:50
  SPEAKER_01: And now we're back to the point where we say it's very rarely occurring.
• 22:54
  SPEAKER_01: It can occur very rarely but it's still super rare.
• 22:57
  SPEAKER_01: And cannidaisolation for example in respiratory drugs is definitely not an indicator of a fungal infection of the lung because otherwise everybody would have it and we know from autopsy studies that it's super super rare.
• 23:08
  SPEAKER_01: At the same time with COVID when just thinking about the pathogenesis of course in these ARDS patients with epithelial damage, etc, you could potentially think of course if you have candidate that potentially and everybody has candid that in some patients it can cause you know some lung tissue infection.
• 23:25
  SPEAKER_01: So I would not rule it out completely.
• 23:27
  SPEAKER_01: The one problem I'm having with it is that I have not seen I heard rumors but I haven't seen this large scale evidence that this is really occurring often.
• 23:35
  SPEAKER_01: And therefore for now I'm still kind of like seeing and looking literature and looking for more evidence because I'm yet not convinced that this is really a larger issue.
• 23:44
  SPEAKER_01: I definitely think it can occur rarely so it's not something we can completely rule out but I think it's pretty rare.
• 23:52
  SPEAKER_01: At least from our ICUs I can say you know UCSD also what I heard from colleagues in Europe from other places in the US I haven't heard that it was a big problem there.
• 24:02
  SPEAKER_01: It was mostly superficial candida infections upper respiratory tract that's what I heard but these pulmonary candida infections not really that I heard that this was an issue and we also have not seen in the meantime we have a good number of autopsies as well right so we do have autopsies and was also not described in these larger autopsy studies that this is really occurring frequently so I would just take a sit back and really wait for more evidence to emerge on that before giving too much attention in this direction.
• 24:30
  SPEAKER_00: Okay so strong recommendation not to routinely treat a respiratory specimen where Canada is recovered and and really should be a high threshold for pushing you towards considering treatment for a Canada isolate.
• 24:44
  SPEAKER_01: Okay.
• 24:44
  SPEAKER_01: Well it's it's very important because otherwise pretty much all ICUs would end up getting treatment right because it's so frequent that you isolate in the respiratory tract in most patients in the vast vast majority of patients this doesn't mean anything.
• 24:57
  SPEAKER_01: So that's a very important I think a very important point to summarize that yeah.
• 25:01
  SPEAKER_00: Fair enough.
• 25:02
  SPEAKER_00: I'd like to finish up with what to do during the empiric phase obviously once a decision to get a bronchoscopy has been made I think depending on where you practice that may take a while to get that bronchoscopy done.
• 25:17
  SPEAKER_00: And so the question you know I have is what in your mind is a sufficient threshold to kind of initiate empiric antifungal therapy do you always wait until you have the bronch or just trying to kind of tease that out and assuming that you've met that threshold what's your standard antifungal regimen that you recommend in in patients and I realize that that might depend on the the scenario that's in front of you but just wanted to pick your brain a little bit on that.
• 25:48
  SPEAKER_01: I think that's very important and also important to emphasize on that.
• 25:51
  SPEAKER_01: So of course I'm in a very lucky position here at UCSD that we do at Donov bronchoscopies and also our pulmonologists as you physicians do a lot of bronchoscopies.
• 26:00
  SPEAKER_01: So it's not a big issue there and they do it even often very frequently when patients get our admitted COVID 19 patients we are there.
• 26:07
  SPEAKER_01: So but of course it's not everywhere the same and it really varies from institution to institution within the US within the same nations within the same states right and that's always something you have to be taking into account right if you're in institution where just bronchoscopies are really rarely performed or very late performed or you wait very long for example for your galactomanan test result.
• 26:26
  SPEAKER_01: I mean that's also something when you wait may not help you so much right so I think in this scenario where it's just hard to get bronchoscopies of course you would get as deep as possible into the respiratory tract what's still feasible right so you would have to use draft secretion evidence in these patients if it's just not possible to get a bronchoscopy and react on that.
• 26:46
  SPEAKER_01: Obviously again clinical factors would definitely need to come into play I would argue against screening all drag everybody in your ICUs with Drachal secretions and treating everybody with positive I would rather have a diagnostic driven approach where you screen those who are doing already worse and where you suspect there could be something.
• 27:05
  SPEAKER_01: But then of course if you only get a traffic L aspiration of course and this is growing aspergillos you would potentially need to react on that if you don't get anything else and don't wait for your serum collectomanantopy positive because this would be delayed.
• 27:17
  SPEAKER_01: So in such a setting you would need to react on what you have available and just be critical and look into the patient, look into the clinics whether all of this makes sense.
• 27:26
  SPEAKER_01: In terms of what to use I mean I think that there's guidelines now what we should use for COVID associated pulmonary aspiculosis and this goes back to what's recommended primarily in ICU patients and this is also of course going back where we have literature for right primarily these guidelines recommend either boriconosol or isabuconosol as treatment but I've read a study a while ago and it was probably not a super high ranked study but it was an interesting approach because ICU physicians were were asked about the drugs they hate most and boriconosol as an antifungal which is you know not in the top importance of course and frequently subscribed treatments made the top five there.
• 28:04
  SPEAKER_01: And the reason is it's not because there's anything bad about it.
• 28:08
  SPEAKER_01: It was a huge game changer in the mycology field in 20 years ago and it really was the first drug that really led to improvement of survival of aspergulosis.
• 28:17
  SPEAKER_01: So it was a game change and it's a fantastic drug that really changed our field.
• 28:21
  SPEAKER_01: But at the same time it's difficult to use specifically ICU because it has so many drug-drug interactions with so many other treatments that these patients are getting.
• 28:29
  SPEAKER_01: And this can result in of course first of all levels going up and down which is a problem by itself because we know if it's too low it's not effective and if the levels are too high there are some toxicities, hepatotoxicities, neurotoxicities so we're dealing with that problem that there's a small therapeutic range for woriconosol.
• 28:49
  SPEAKER_01: But for ICU physicians even more threatening they are also changing the levels of many of the other treatments that are also metabolized over the same super and other systems of the liver.
• 28:59
  SPEAKER_01: And that's of course something that's really threatening the whole treatment approach in this patient sometimes.
• 29:04
  SPEAKER_01: So that's why many ICU physicians are reluctant to use so much boriconosol.
• 29:08
  SPEAKER_01: Some don't use it at all in their ICUs because of peace.
• 29:11
  SPEAKER_01: Isovuconosol is a new version a new triazole which has a little bit of broader spectrum and also contains a little bit of mucoralis at least in contrast to boriconosole but it's also the primary choice of course for aspergulosis it's now also recommended as alternative first line.
• 29:27
  SPEAKER_01: The reason is that it the intract drug interactions are a little bit on the lighter side but they're still there.
• 29:33
  SPEAKER_01: It's still important to consider them and also the other thing is that there's no therapeutic drug monitoring usually necessary except in some ECMO patients.
• 29:40
  SPEAKER_01: In some special circumstances you should think about that but usually you don't need to do therapeutic drug monitoring.
• 29:45
  SPEAKER_01: So you don't need to be as concerned as much about isobucanosol levels.
• 29:49
  SPEAKER_01: Although isobuconosol can still change a little bit the levels of some of your other drugs.
• 29:53
  SPEAKER_01: And then of course this results in many ICU physicians that want to go away from that route to use the second line treatment which in the guidelines at least secondline treatment which is liposomal amphothers B, which by itself of course in terms of drug truck directions it's much preferable.
• 30:10
  SPEAKER_01: The one thing always to take into account of course specifically in COVID patients is the potential of nephrotoxicity specifically because there's some COVID association to the kidneys, right?
• 30:20
  SPEAKER_01: So we know that COVID can cause kidney damage itself and then you add a drug that also causes toxicity that's the concern there.
• 30:28
  SPEAKER_01: But nevertheless I think many ICUs and Dr Different many ICU physicians are highly valued in their expertise use a lot of liposomal amphodericin B also as firstline treatment in their COVID patients.
• 30:42
  SPEAKER_01: When we go away from aspergillus obviously and go to MOCOR then it's a very clear cut recommendation for MOCOR liposomal amphodericin B is the first choice that's very clear cut and very much in all the guidelines they all agree on that.
• 30:57
  SPEAKER_01: For candidate infections luckily we have drugs that are in terms of their pharmacokinetics very much preferable echnocandines that we can use that don't really have a problem with drug drug inductions.
• 31:08
  SPEAKER_01: We can really use them well in the hospital setting and yeah so this is much easier to treat obviously it becomes more complicated once we have to discharge patients and they need oral follow-up therapy because then we need to change to for example fluconosol because we don't have oral echnocandes currently yet available although this may also change within the next year or two hopefully well this has been an amazing conversation Martin I really appreciate you taking the time to jump on with us today.
• 31:35
  SPEAKER_00: Before we leave I guess I want to ask you do you have any final thoughts or comments that you want to leave us with that we didn't address with our other questions?
• 31:44
  SPEAKER_01: I think we pretty much went through the most important parts of this I mean maybe just an outlook at the end because I think we agree that COVID will stay with us of course for much longer and we'll see how it stays with us but we'll stay with us at one point or the other and I think we will continue to see some patients in our ICUs also with COVID as we move along.
• 32:04
  SPEAKER_01: And I think the one thing is just to emphasize in terms of the future we are still currently pretty much limited in terms of antifungal drugs we have available because we only have three classes for antifungals but there is definitely some hope on the horizon because finally after 20 years where no other new antifungal drug class was approved, we now have um new antifungals that are currently in phase three evaluation and hopefully become available for us clinicians.
• 32:29
  SPEAKER_01: And this will really help because first of all in terms of their tolerability and drug truck interaction profile but also in terms of for example candidaris we haven't talked so much about candidaris but this is really a threat due to truck resistance and we need urgently new trucks that are better active against candidaris and some of these new trucks are.
• 32:48
  SPEAKER_01: So I think the future lies ahead of us with new challenges but luckily in our field currently there are also some new solutions inside so yeah I think it will continue to be interesting and it will continue to keep us busy over the next years.
• 33:02
  SPEAKER_00: Thank you so much we really appreciate you sharing your perspective and experience in this important area.
• 33:07
  SPEAKER_00: This podcast can be accessed on Shay's online education center learning CE under the Rapid Response program where you also find resources such as the SHA COVID 19 town halls interested in becoming a SHA member take$20 off of any membership type using the coupon code learning CE2022 at checkout this concludes today's episode of the Rapid Response podcast thank you for tuning in