Latest / Pediatrics Now: Cases Updates and Discussions for the Busy Pediatric Practitioner / Think Fungus, Part 1: Antifungal Resistance Every Pediatrician Should Know

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Think Fungus, Part 1: Antifungal Resistance Every Pediatrician Should Know · Pediatrics Now: Cases Updates and Discussions for the Busy Pediatric Practitioner

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I'm Holly Wehment, and this is Pediatrics Now, cases, updates,
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and discussions for the busy pediatric practitioner.
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Click on the link in this podcast for a free credit that may include CME,
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MOC, or ethics credit, depending on our topic or podcast.
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When we hear the words antimicrobial resistance, most of us immediately think
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about bacteria and antibiotics.
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But there's another threat receiving far less attention, fungi,
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that are becoming increasingly resistant to the medications we rely on to treat them.
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And for clinicians, that raises an important question. When should we think fungus?
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Today, I'm joined by Nathan Widerhold, PharmD, Professor of Pathology and Laboratory
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Medicine and Director of the Fungus Testing Laboratory at UT San Antonio and UT Health San Antonio.
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Dr. Widerhold is also a pharmacist and an internationally recognized expert in medical mycology,
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whose research focuses on antifungal resistance, emerging fungal pathogens,
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and the development and evaluation of new antifungal therapies.
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Dr. Widerhold, welcome to Pediatrics Now. Thank you for having me, and good afternoon.
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And thank you so much for being here in the podcast studio.
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Let's start really big. Why should pediatricians be paying more attention to
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fungal infections and antifungal resistance right now? What's changed?
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Well, we're starting to have an increased recognition of the problem of fungal
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infections and antifungal resistance.
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You know, fungi have been causing infections in humans and animals for millennia,
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and so they're not new, but our recognition of them being major clinical problems,
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has increased over the last two decades.
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And I think the recognition stems in part from the fact that we have more patients who are at risk.
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We have a lot of immunocompromised patients, a lot of very complicated patients
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in ICU settings, different patients with a lot of different risk factors that put them really in the,
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inside of fungi and having them become infected with these organisms.
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So you have a wonderfully simple phrase when you talk about this. Think fungus.
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What do you mean by that? When should fungus move higher on a pediatrician's differential?
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So we like to say think fungi because in some of these really ill patients,
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if they're not responding to therapy, most of the time clinicians are thinking
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either bacteria or viruses that might be causing the problems.
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But they need to keep in the back of their mind that fungi could also be involved.
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And so that needs to be in their differential diagnosis, especially in patients
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who might not be responding to therapies with antibiotic agents.
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And you recently had a big article published in Nature?
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So, yes. And so I was part of a group that wrote a commentary in Nature Medicine
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talking about antifungal resistance, the increasing threat, and then what else
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needs to be done to try to tackle this problem.
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We hear constantly about antibiotic resistance. How is antifungal resistance
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similar, Nathan, and how is it different?
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So it's similar in the fact that fungi can develop resistance when exposed to
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different antifungal drugs.
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So similar to antibiotic resistance, if a patient is receiving an antifungal,
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maybe be the wrong drug or the wrong dose, then those fungi can adapt in the
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patient and develop resistance.
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So that's something we are starting to think of more and more and something
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we're worried about with different groups of fungi.
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It's a little different than antibacterial resistance in that we have so few
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classes of antifungals that are available.
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And so if resistance does develop to one class and in some cases to multiple
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classes, then our treatment options are very limited. it.
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Antifungal resistance is not nearly as prevalent as antibacterial resistance.
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And so we worry about it, but the rates we see of resistance to certain antibiotics
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are so much higher than we see for, you know, for antifungal resistance.
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That being said, there are some new emerging pathogens, fungal pathogens,
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that we're starting to become increasingly concerned about that do have fairly
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high rates of resistance to certain commonly used drugs.
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Yes, I'm surprised how few classes of antifungal medications we actually have.
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Why is our antifungal toolbox so much smaller than our antibacterial toolbox?
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And what happens when a fungus becomes resistant?
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So the reason that I think we have so few antifungal drugs is,
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well, first and foremost, the development of any drug is a serious undertaking.
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It takes a long time and a lot of money for any drug, whether it be an antimicrobial agent or anything.
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Antifungals are particularly challenging because fungi, like us,
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are eukaryotes. And so there are a lot of similarities between fungal cells and R cells.
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And so when you develop an antifungal, you have to try to kind of walk a fine
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line, something that is going to have very broad and potent activity,
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but it's going to be specific for the fungus.
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And historically, that has been very, very difficult to do.
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And so a lot of the antifungals that we currently have available for use,
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have either a lot of adverse effects and toxicities or what we call drug-drug
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interactions because of their side effects or interactions with enzymes within our cells
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that are so similar to the enzymes within fungi. Hmm.
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Do you want to talk about that differential diagnosis and how much should that
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be on the radar? Would that still be considered, as we say in medicine, the zebra?
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The zebra? So, yeah. So, is a fungal infection a zebra is what you're asking? Yes.
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So, I think it needs to be on the differential diagnosis in patients who have
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a lot of different risk factors.
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So patients that we classically think of as being at risk for fungal infections
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are individuals who are highly immunocompromised.
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Think patients who have had solid organ transplants. Think patients who have
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had bone marrow transplants.
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Those who are receiving some type of cytotoxic chemotherapy for the treatment of a malignancy.
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Patients in intensive care units, those who have central lines or on ventilators.
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Anything that the fungus can develop a biofilm on, and then that can lead to infection.
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But there are also some other risk factors that we're starting to recognize more and more.
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Not necessarily in pediatric patients, but in more of the adults.
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For example, patients with COPD, those who have some type of underlying cavitary lung disease.
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Individuals like that were recognizing more and more being at risk for invasive fungal infections.
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So if a pediatrician suspects this, what would you advise? What's the next step?
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The next step probably is to start to order some laboratory tests that can help
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in the differential diagnosis and to either confirm or rule out a fungal infection.
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At the same time, if it's a highly immunocompromised individual or those with
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a lot of risk factors, it might be a good idea to consider also an ID consult.
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You know, here at the Health Science Center, we've been blessed in that we have
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had a lot of clinicians in the Department of Medicine Division of Infectious
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Diseases who have a lot of experience and expertise in dealing with fungal infections.
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And so they're a great resource in these types of patients.
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Let's talk about the fungus that has received so much attention lately, Candida aureus.
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What is it and what makes this particular organism so unusual?
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So Candida auris is a relatively new fungal pathogen.
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It wasn't described until 2009, I believe, and it was an incidental finding.
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It was some clinicians in Japan were doing some routine screening,
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and they were able to culture this out of the external ear canal of a patient.
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It wasn't causing a problem. It was just kind of a finding.
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Figured out it was a new species and published it in the literature.
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But then, for some reason, in between 2013 and 2016,
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simultaneously on multiple continents around the world, we start to have outbreaks
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of some pretty bad infections caused by Candida auris.
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And that's really when it started to capture the attention of the medical mycology community.
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We've since determined that, you
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know, some of the earliest clinical cases might have been back in 1996.
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But really, it didn't become recognized as a threat until 2013 to 2016.
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As I said, and we still don't know why, but it was a simultaneous emergence
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on multiple institutions on multiple continents around the world.
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At that time, it was recognized that it has some interesting antifungal resistance properties,
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but also in patients with invasive disease, it has a very high mortality rate,
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about just under 60% in some of the early studies that came out. Wow.
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We now know that that can vary depending on patient risk factors,
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but still the range that you see in the literature is a mortality rate between
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30% to 60% in patients with invasive disease.
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And it was found in someone's ear? Yes.
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That was the first finding? That was the first time it was kind of cultured
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and recognized to be a new species, yes. But again, it wasn't causing any type
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of problem to the patient. They had no signs or symptoms.
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It was an incidental finding. Wow.
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The headlines around candida auris can sound frightening. Who's actually at risk?
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And Dr. Widerhold, is this something a healthy child or family going about everyday
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life needs to worry about?
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This is not something that healthy individuals, a child or their family that
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are going about their daily activities, really needs to worry about.
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Candida R.S. really causes problems, invasive disease, in patients who have certain risk factors.
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What we've classically recognized as are patients who are in and out of healthcare settings.
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Usually, we think of skilled nursing facilities, long-term care facilities,
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patients who are on ventilators for a long time, they have central lines,
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they have other risk factors that put them in the site of Candida R.S.
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As having the opportunity for the organism to cause the infection.
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But in healthy individuals, this is not something we worried about.
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If the parent is immunocompromised or the child is, what advice would you have?
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I mean, this is advice I would give regardless if it was Candida auris or any type of infection.
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Hand hygiene is probably at the top of the list, making sure that you're washing
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your hands appropriately.
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We all learned how to wash our hands appropriately during COVID.
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Hopefully some of us still remember that. Yes, the sing happy birthday.
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That's right. That's right.
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I heard sing happy birthday or do the alphabet song. Yes, yes. So, yeah.
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So, that's probably the number one thing. So, Candida RS can be transmitted,
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but it's typically transmitted from person to person, not directly, but on surfaces.
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And so, that's where we really worry about it in the healthcare settings,
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is that patients can become colonized.
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And then if healthcare providers aren't taking the appropriate steps,
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like washing their hands before they go into the patient's room,
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using gloves, and then washing their hands after they leave,
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and the patient has gotten the candida auris on like the bed rails or a table
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or some mobile medical equipment,
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then the healthcare provider or even other patients in the room can pick that
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up on their hands or elsewhere and then take it to another location.
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And so hand hygiene is probably at the top of the list.
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Even in patients who might have become colonized or discharged home,
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then hand hygiene is still at the top of the list for family members and caregivers.
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Because there's not anything you could see to avoid. No, no.
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There's nothing that you can see to say, oh, this person is colonized.
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And once patients do become colonized, they can stay colonized for a very long
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time, months, if not years. Really? Yes.
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And so we all have different, what we call our microbiome.
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And so different flora, bacteria, yeast that are on our skin,
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within our respiratory tract, even in our gastrointestinal tract.
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And so it's something that we live with on a daily basis.
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Candida auris is typically not one of the normal flora that we see in patients
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or in healthy individuals.
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But Candida auris can colonize individuals and kind of take over certain niches
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on patients. Think under the arms and the ears, the nose, and the groin.
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And so those areas can become colonized.
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So the organism itself, the Candida auris, is not causing a problem, but it resides there.
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And then if you're not using proper hand hygiene or wearing gloves,
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if you're touching an individual who's colonized with Candida auris,
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then it can get on your hands.
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And if you're not washing your hands appropriately, then you can take it and
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spread it to another area, and then it can be picked up by other individuals.
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But can that person who's colonized, can you wash it off? It's no, no.
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It's very, very difficult to decolonize a patient once they become colonized.
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And so the CDC does not currently recommend any type of decolonization protocol.
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So what does that person do? Be isolated?
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So in healthcare settings, yes, they are put on contact precautions oftentimes,
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and the CDC recommends, if possible, that they be in a single-person room.
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If that's not possible, for example, in certain long-term care facilities,
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if that's not possible, then they recommend that patients who are colonized
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with Candida R's kind of be housed together and away from other individuals.
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What do you do on a day-to-day basis to wash your hands as a scientist,
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and what do you recommend we all do? I know we talked about what we learned
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in COVID, but how can we make sure that we're doing our best?
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Yeah, so our lab is a reference lab that deals specifically with fungi.
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And so I think one time I tried to count the number of times I washed my hands
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or used those alcohol rubs on a daily basis, because I lost count,
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because I'm doing it all the time going in and out of the lab.
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So really, what's recommended is the alcohol gels that are available,
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the alcohol disinfectants that you can put on your hands, those work really
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well against Candida auris, and that's what's recommended.
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If for some reason you have a healthcare provider or another individual that's
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been dealing with a patient that might be colonized, and their hands are visibly
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soiled or dirty in some way, then the recommendation is actually then to wash with soap and water.
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And so what I typically do and what I recommend our staff do is after working
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in the lab, wash your hands with soap and water.
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And then at the exit of each of our laboratories, we have those alcohol gel
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dispensers that are ready for them to use as well.
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So if you see, even if you've recently washed your hands, all of us in everyday
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life though, or the pediatrician as he or she is walking by in the clinic,
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go ahead and And use the alcohol dispenser when you can, too. Yes.
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I think that's important, not just for Candida auris, but just in general in
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health care settings. Just for that extra backup. Right.
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Anything else you want to say there in terms of prevention? It's a hard thing to prevent.
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We don't prophylax patients with antifungals for those who are at risk for Candida
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auris. That has not been shown to be effective. And we don't decolonize patients
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who we know are colonized.
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And so it becomes challenging. The other thing that in healthcare settings we've
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learned is that the normal cleaning agents, disinfectants that the janitorial
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staff might use in patient rooms,
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many of those are ineffective against Candida auris.
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So there are specific products that have to be used. And it's the FDA has what
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they call their LISP, and it's full of different agents, usually bleach-based
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or based with hydrogen peroxide.
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Those are effective in cleaning surfaces that might have been colonized with Candida auris.
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But a lot of the other types of cleaning products that are generally used in
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healthcare settings might be ineffective. So it's important to use the right
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types of cleaning products.
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Do you recommend that in clinics, pediatricians have these chemicals on hand?
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In clinics, we're typically not too worried about Candida auris.
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It's more really in hospital settings as well as in long-term care facilities.
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And so I think it's probably very important.
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In the clinic setting, patients aren't in there for a long period of time.
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And so in the clinic setting, I would prioritize proper handwashing above all else.
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So much comes back to handwashing. Yes, yes.
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It can be challenging to diagnose, though.
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It is, yes. The symptoms are a lot like a bacterial illness.
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Yes, and so the signs and symptoms, or the symptoms specifically of Candida
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auris, are not specific to Candida auris.
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In patients with invasive disease, they'll often have fevers or chills,
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just like you would see with some viral infections and bacterial infections.
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And so many times, Candida auris infections, as well as those caused by other
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fungi, don't get diagnosed until patients have not responded to antibiotic therapy
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or some type of other antimicrobial agent.
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Wow. So any advice there?
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I think, like what we mentioned before, think fungi. If you have patients who
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are at risk for fungal infections, including candida auris, maybe start to think
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about them earlier rather than later.
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We know that early diagnosis and start of appropriate therapy can improve mortality
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rates, not just for Candida RS, but all different types of fungal infections.
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And so if you have a patient who is really sick, has a lot of different risk
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factors for any type of fungal infection, trying to get that diagnosed early
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is probably one of the best things that can be done.
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Do you recommend people wash their hands before and after eating,
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before and after going to the bathroom, before going to a doctor's office?
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Definitely, I would wash your hands if you're going to a health care setting,
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whether it be a clinic, hospital room, washing your hands before and washing your hands after.
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That's one of the things the CDC does emphasize for health care providers going into patient rooms.
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Wash your hands before you enter the room and wash your hands as you're leaving
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the room. And so you're doing it twice really to try and prevent the spread
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of different types of microbes, not just Candidorus.
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You can't wash your hands too much or anything else you want to say there?
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I just think it's so interesting.
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While you're here, anything else you want to say? Your grandmother told you. Yes.
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And you wash your hands, though, for at least 15 seconds? At least, yes.
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So more is better, but at least 15 seconds. Yes, with good soap and water,
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yes. Not just, you know, don't just stick it under the water and take it out.
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Really lather up. Lather up and don't use antibacterial soap?
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I don't think it is adding any benefit, no. Okay, and maybe that's a different
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podcast. I think so, yes.
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What should pediatricians know about the children who are at increased risk?
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Are we primarily talking about children who are immunocompromised,
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medically complex, hospitalized, have central lines, and have had significant healthcare exposure?
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Yes, I would say all of the above there.
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Just like in adults, pediatric patients who are at risk or candidate RS are
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typically very complex.
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Where we have seen this reported is typically in those who may be immunocompromised
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or in the intensive care settings.
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Also those with central lines and in the unfortunate case where the child might be on a ventilator.
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And so these are very complex patients. It's not your typical healthy child
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that might be in school or daycare. Those aren't at risk.
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These are patients who have a lot of different things going on medically.
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You describe these as opportunistic infections. Can you explain what that means
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and why that distinction is important when we're talking to families?
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So many fungal infections, many fungi are opportunistic infections.
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The way I like to explain this is you have to give the organism,
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the fungus, the opportunity to cause disease.
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They're not going to cause disease or any types of problems in otherwise healthy individuals.
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And so you have to give it the opportunity to do so, whether the patient is
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on a ventilator, they have a central line, they're immunocompromised,
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they have some other type of condition that predisposes them to infection in
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general, including fungal infections.
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And so there are some fungi that we know can be problematic in otherwise healthy individuals.
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But for the most part, many of the fungi that we see causing disease in humans
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are opportunistic, meaning we have to give them the opportunity to cause disease.
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You know, the other thing that we can do in some of these at-risk patients is
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try to either improve their situation. And what I mean is that if a patient's
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immune status can be improved, their white cells can come back.
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We can take them off drugs like corticosteroids.
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We can remove the central lines when available, get them off ventilators.
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Anything that we can do to kind of improve the patient's overall health status
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will reduce the opportunity that the organism has to cause disease. Okay.
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It sounds really depressing and scary. Is part of your mission,
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though, to speak out about this and get ahead of it as much as possible?
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We like to try to get ahead of it.
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One of the things that the CDC, we work with the CDC on a regular basis,
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and one of the things that they've been trying to do over the last several years
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is to increase awareness of invasive fungal infections.
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So this week happens to be Fungal Infection Awareness Week. And so the CDC has
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been putting on different types of webinars all week. I'll be involved in one
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tomorrow talking about some of the testing that we do.
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And so in doing so, they're trying to educate not only clinicians,
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but also the general public about fungal infections and when they need to be
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concerned about them. And so they have a lot of good resources on their webpage.
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Those that are more general for the general public, and then also specific information for clinicians.
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And you mentioned it can take months and months once a patient has this, once a person does.
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Is that person on the medication the whole time, or how does that work?
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For some fungal infections, patients can be on antifungals for months,
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if not years, at a time. And this is not something that we typically say,
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okay, you're only on for seven to ten days and we take you off.
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Now, some fungal infections are like that, but many of these serious ones,
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the patients have to be on them for a prolonged period of time.
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Suppose a parent sees a headline about a drug-resistant superbug and asks their
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pediatrician, should I be worried
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about my child? What would you want the pediatrician to tell the parent?
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I think the pediatrician needs to be very reassuring to the parent.
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Most of these interactions are going to be with regard to a healthy child,
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where we're not worried about Candida auris or some other type of drug-resistant fungal pathogen.
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That being said, if this is in a child that has a lot of risk factors,
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is in and out of the hospital, then definitely the pediatrician needs to make
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sure the parent is aware that this could be a problem.
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But still, fungal infections are still quite rare compared to other type of
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infections caused by bacteria and viruses.
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And everyday life, school, restaurants, playgrounds, travel,
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otherwise healthy families, don't need to do anything different.
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But wash hands. Wash hands. And that goes not just for Candidars,
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but again, for everything. So, yes.
25:33
Click on the link in this podcast for free credit that may include CME,
25:37
MOC, or ethics credit, depending on our topic or podcast.
25:41
Nathan Widerhold, PharmD, Professor of Pathology and Laboratory Medicine and
25:46
Director of the Fungus Testing Laboratory at UT San Antonio and UT Health San
25:52
Antonio. Thank you for having me.