Drs. Tom Schmidt, George R Thompson, and Nate Bahr solve a pneumonia not responding to antimicrobials and discuss endemic fungal disease!

To learn more about the Mycoses Study Group Research and Education Consortium, check out the MSGERC page

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Febrile is produced with support from the Infectious Diseases Society of America (IDSA)

Hi everyone.

Welcome to Febrile, a cultured podcast about all things infectious disease.

We use consult questions to dive into ID clinical reasoning, diagnostics

and antimicrobial management.

I'm Sara Dong, your host and a Med-Peds ID doc.

I am looking forward to our episode today.

We have three guests that are joining us.

I will start with Dr. Tom Schmidt.

Tom is a second year ID fellow at the University of Minnesota.

He is interested in general ID, critical care, and the impact of a

changing climate on infectious diseases.

Hey, this is Tom.

Uh, happy to be here

Next I'll introduce Dr. Nate Bahr.

Nate is an Associate Professor in the Division of Infectious Diseases

at the University of Minnesota.

His areas of interest include histoplasmosis, the changing epidemiology

of fungal infections, drug pricing, and cryptococcal and TB meningitis.

Nate is a co-chair of the Education Committee of the Mycoses Study Group

Education and Research Consortium (MSGERC), along with Dr. Jessica Little.

Hey, this is Nate.

Excited to join.

And rounding out our crew today is Dr. George R. Thompson.

GR is a Professor of Medicine at the University of California Davis School of

Medicine, and he has a joint appointment in the Departments of Medical Microbiology

and Immunology and Internal Medicine in the Division of Infectious Diseases.

He specializes in the care of patients with invasive fungal infections and has

research interest in fungal diagnostics, clinical trials, novel antifungal

agents, and host immunogenetics.

Hey, I, I'm GR Thompson from UC Davis.

Thanks for having me.

Welcome.

So as everyone's favorite cultured podcast, we love to hear about a

little piece of culture, something that brings you happiness.

So I, I generally think, uh, and most folks I think know this about me,

one of the things that brings me the most joy besides my children is I

absolutely love birds and birdwatching.

My favorite birds are white breast and nut hatch, and the golden eagle.

I literally recorded something earlier this week that they also said birding.

Amazing.

What about you, GR?

Um, I, I spend most of my time chasing around my, my teenagers, trying to

figure out where they are in the world.

They've all picked up different sports that started during Covid, so I've

had to learn a lot about lacrosse and, and my son's sort of an avid golfer.

So by proxy, those are my three biggest interests right now.

My wife though, is an avid bird watcher, so the red wing black bird in

our backyard is frequently discussed.

Yeah, I didn't realize the Venn diagram of ID and birding was, uh, so overlapped.

Um, and then how about you, Nate?

Well, uh, those birds could have been made up for all I know.

So, I mess up your Venn diagram.

For me it tends to be about my kids, outside as well.

So, uh, I've had a lot of fun with them playing in the snow this winter

and now it's getting warm, so we're enjoying that transition and, so I'm

chasing them around and it's great.

Love it.

Yeah, spring is basically around the corner.

It's almost here.

Well, I wanted to start by just asking Nate to give folks a little introduction,

because you had reached out to me with Jessica Little from the Mycoses

Study Group, and I think that probably some of our listeners are involved or

have heard of some of the initiatives and and work that the group's done.

But I'd love it if you could orient people to that group and maybe let

them know if they're interested, how they could get involved.

So, Mycoses Study Group, um, it's actually the Mycoses Study Group Education and

Research Consortium, which just as you can tell, it's, it's very short and easy.

Um, but it does emphasize the correct things and, and those are

big things that we're interested in.

We wanna help further education around fungal disease.

And so, this is part of that effort.

We want to get information out that's important to, to clinicians

related to fungal disease.

We do that in a number of ways, but this is sort of an initiative to

try to make sure we're doing that in any way that can reach people, and,

and this reaches a lot of people.

In research, this group has been involved in a lot of very important research

studies over the years, and so, uh, a lot of the major figures that you're

reading their papers in, in fungal diseases, many of them are involved,

and often the Mycoses Study group has helped coordinate some of those studies.

So if people are interested, they can go to the website.

That's pretty easy to find.

That's a good place to start.

They can always email any of us as well, and we'll help send

them in the right direction.

But it's a group that, that, uh, is easy to become a part of and, and we're happy

to have new members and get them involved.

I realize what I should do is ask you if you ever abbreviate

M-S-G-E-R-C and say it any other way other than Mycoses Study Group.

I get confused, so no, I don't.

Love it.

Um, awesome.

Well, Tom is going to take us through a case today, so I'm gonna hand over to him.

Perfect.

So we have a 50-year-old man who presented to the ED in the midwest US

with a two week history of fatigue, low grade fevers, chills, and a new cough.

Cough has been non-productive.

No hemoptysis.

He was previously prescribed a short course of antibiotics from an urgent

care for pneumonia and given IDSA guidelines had done amoxicillin

monotherapy at that point, didn't really make much of a difference in symptoms.

And his history, mostly healthy.

Has a history of hypertension, well controlled, type two

diabetes, also well controlled.

On exam, he is afebrile with normal vitals.

O2 (oxygen) saturation on room air is 91%.

On exam, some bronchi on auscultation.

is otherwise unremarkable.

We do get a chest x-ray that does show an infiltrate in the right upper lobe.

So what do you guys think is going on?

What would be going through your mind at this point?

I think from my perspective, I guess as a fellow, certainly the things

I would be thinking about are, do we have the right, diagnosis?

In terms of if we're saying that this is a pneumonia, a bacterial pneumonia,

generally if they got outpatient treatment, it may just be things

like a monotherapy of amoxicillin.

Um, are we missing the organism there?

Is it something that's non bacterial?

Is it a fungal infection?

Uh, certainly I'd be less likely thinking of a viral infection, giving

the two week duration of symptoms, or thinking of other, uh, like

a parasite, something like that.

So overall I would be thinking of a bacterial infection that's not being

treated by what we prescribed or thinking of, uh, fungal infections

as well, given the chronic or the two week course of symptoms.

Yeah, I agree.

I mean, I, I think when you get to two weeks, you start

to question the diagnosis.

Did we give an antibiotic that that missed the pathogen?

Is this an atypical pneumonia?

You know, two weeks is a bit long, but we've had, you know, big Mycoplasma

outbreak over the last year.

You know, pertussis still increases in frequency.

Those patients, even with the right antibiotic, are gonna cough and

feel bad for weeks or even months.

I don't know much about the social history, but, you know, we talked

about our love of birds, but, uh, you know, chlamydial infections, right?

Maybe, you know, that have been missed with amoxicillin.

I think there's a lot of possibilities.

And we've brought up fungal disease and, um, you know, that's what I

love to talk about, so I just will.

But, you know, we've talked with the IDSA quite a bit about the pneumonia guidelines

because they're pretty silent on the endemic mycoses right now, and if you look

at the incidence, depending on where you practice in the United States, you know,

there's, there's one paper that shows in Houston, Histoplasma is maybe 8% of the

patients that come in with respiratory complaints in that particular study.

Central Valley of California, it's up to, you know, a quarter of all

CAP (community acquired pneumonia) is actually from coccidioidomycosis.

And then Nate, if you want to comment, I don't know how frequent

blasto is a cause of, of CAP, uh, up north, but probably not zero.

So, um, yeah, so, so, so the, the big endemics, you know, we, we

definitely consider and talk about.

Yeah, and I think you're getting to a good point there, GR, because

it, it, it matters where you are.

Of course, risk is different depending on where you are.

But we are starting to understand that our, notion of where you are with these

endemic mycoses maybe is a little off and they're not, in some cases as,

as restricted as we we once thought.

So, you know, knowing where you are, but also understanding the patient's

history a little better and, and if you haven't thought about them in a

while, maybe that's a good time to go find some updated maps and data.

They're out there.

You know, while we're on that topic, would, would you maybe comment a little

bit on some of the recent literature and, you know, knowledge about these

expanding maps for endemic mycoses.

So, for example, Nate, I've definitely shared the paper that you've worked on

called Redrawing the Maps for Endemic Mycoses, and I try to reinforce the

concept that we need to rethink these, you know, quote classic geographic

boundaries and not take something off the differential entirely based on location.

But I know there is also some thinking as well that for some of these papers, just

because someone is diagnosed in a certain place, that that doesn't mean that the

fungus is present in that environment.

Um, but I think that's balanced with the fact that we clearly have signals that

these fungi are an expanding locations.

So how do you, uh, sort through that and, and think about this sort

of spread of endemics as a whole.

Yeah, so I, it depends on the approach.

I think that's one thing to think about when you're looking at any

of these sort of papers, right?

So, our redrawing the maps for endemic fungi paper, that was all

based on published literature.

So that has an inherent limitation to it, right?

So there's definitely cases happening that, that are not included there.

There's also the, the very relevant point that simply having a case

somewhere doesn't mean it's in the soil nearby or things like that.

You need to know a lot more details, right.

Um, you need to know while it's, it's interesting if you, if you found some

cases of histo in Alaska, but did they, you know, just come from Kansas City?

Um, that's pretty relevant.

That's, that's all kind of important.

You know, there have been some interesting things like, you know, histo has been

found in soil in Antarctica, for instance.

Um, so there, there is some of this where our, our sort of traditional understanding

of this definitely has holes.

I think it's probably right to both at the same time think, there are

areas where the risk is much higher and there's also probably more areas at

risk than we traditionally thought of.

So I think one important take home would be if you're in an area where

you think to yourself, well, it can't be cocci, because of where I live, it

can't be histo because of where I live.

That alone shouldn't totally rule it out.

Um, it's part of the calculus, but you need to think of it a

little more than just ruling it out because of where you live.

That's my thought.

Yeah, thanks so much.

Well, Tom, can you update us on our patient.

So the patient is able to produce some sputum, uh, which

is ultimately sent for culture.

Due to progressive symptoms, he is ultimately admitted and placed on

broad IV antibiotic therapy with vancomycin and piperacillin-tazobactam

and then azithromycin as well.

He's noted to have a few intermittent fevers and ongoing cough.

Sputum culture grows typical respiratory flora.

A CT scan is obtained of the chest that shows a wedge-shaped

peripheral nodular focus in posterior area of the right upper lobe.

You get some additional history.

He lives in the upper Midwest with his wife and partner.

They have a dog and a guinea pig at home.

He works as an architect.

In the last year, he's traveled to Denmark for a vacation about six months ago.

He also traveled to Florida for a work meeting.

He has family in Arizona and most recently had a three week trip to

visit family and meet his new niece.

So you have some more social history.

What do you guys think now?

Yeah, so we talked a little bit about the differential diagnoses of these

patients with non-responding pneumonia, and this really shows that that approach

is essential because this patient, I mean, it's always hard to tell how ill

they are in a, in a text-based format or discussion, but they've gotten sick

enough to warrant admission with broad spectrum antibiotics, so presumably

they've gotten quite a bit worse and that really shows that just taking

a very detailed social history at times can avoid escalation symptoms.

And then, you know, this can be a very costly admission.

This is not stewardship savvy approach, right?

They're getting vanc, pip-tazo, and azithromycin, for what could very well

be an atypical or endemic pathogen.

Azithro is gonna cover most of the atypicals.

We don't hear uh, risk factors for pneumocystis or something like

HIV or transplant or et cetera.

So I think they're pretty well covered for, for most of the, the typical causes.

But, but the endemic mycoses really aren't, aren't covered as far as

their diagnostic approach or treatment.

And then, you know, what do you get from a dog?

Like, I don't know what kind of dog they have, you know, uh, kennel

cough or, you know, parapertussis, I guess is in the differential.

That doesn't seem like it usually warrants admission.

Guinea pig.

Nothing really comes to mind from respiratory causes of that.

Guinea pigs are very allergenic, um, but, but doesn't really warrant hospital

admission, then travel to Denmark.

That doesn't really raise any red flags.

Florida has a little bit of histoplasma, uh, down, you know, in the, I mean,

histo is ubiquitous across the globe.

Uh, you know, we, we commonly teach it in med school that it's just

in this sort of Mississippi River Valley, but that's really not correct.

But this history of travel to Arizona.

Again, where in Arizona, you know, if it's, if it's up in northern Arizona,

it's probably not any valley fever up there, but certainly Phoenix, you

know, Tucson, Scottsdale, the, the real hotspots for travel and vacation.

This three week timeframe certainly may have been exposed there.

I don't know what time has gone by since he's returned to the Midwest,

but that, you know, I'm gonna really wanna key in on that for, you know, some

more details of his travel certainly.

Uh, I got one thing to add related to the dog.

So, dogs actually can sometimes, unfortunately, give very

good clues for blastomycosis.

I've it's at least more than one hand.

Um, the amount of times that I've had patients tell me that their

dog was sick with blastomycosis coming in with respiratory failure.

So, they may not know they have it yet, but they know their dog

had it, and that can be actually a really helpful history clue.

Wow, that's so interesting.

Well, how would you approach sending diagnostics up, right?

Because we're talking about some of these fungal infections and have

kind of this undifferentiated case, which, which tests should we send off?

That's a great question and I think creates a lot of confusion,

particularly if you don't do this all the time because there's a number

of different tests available for coccidioidomycosis um, and you probably

can't determine which one you send.

It's probably just on the workflow of your particular institution.

So most hospitals will send an EIA test first for IgM and IgG

detection, and that's considered kind of a screening test.

The CDC published their endemic algorithm for diagnostics just

about six months ago or so.

And if either of those test IgM, IgG, or both are positive by EIA, then

you do additional testing with immuno diffusion and complement fixation.

And the reason you do that is the complement fixation titer, um, is

correlated with their symptoms, and also you can follow those

serially over time prognostically.

They, they do tend to correlate with the disease burden, so it can be really

helpful for some of the vague symptoms that you're not clear if they're

unrelated to their infection or not.

The last test I'd mentioned is the cocci antigen test.

For people who are immunocompetent, that's not a great test.

Um, we typically reserve that one for people who are

so highly immunocompromised.

They may not make antibodies, so, you know, very, uh, immunocompromised

states like solid organ transplant, bone marrow transplant, or,

um, HIV with very few T cells.

So that's really the group.

We reserve antigen testing from the blood or urine

In, in non-cocci diagnostics, I, I can add, with both Blasto and Histo,

we can send antigen testing out.

Blasto can often be caught with just a KOH prep on a respiratory sample.

So it, it isn't perfect by any means, but it's pretty quick so that's a good thing.

Um, particularly since many of these antigen tests we're sending out to get

done and, and they can take a while.

So those, those can be pretty useful, um, in, in this sort of patient too.

And, you know, the patient lives in the upper Midwest and so in addition to the

Arizona travel, I think that's important.

Like the sort of geo geographic stuff is pointing us in a

couple directions at this point.

So for this case, when you examine this patient, like let's say we were

talking through all these fungal infections, are there things that

you're looking for on the exam to help you with the differential?

I, I think definitely, you know, we've talked about the three major endemic

pathogens in the United States, you know, histoplasma in an immunocompetent

patient, they're really not gonna have oral lesions, some of those things.

Blasto probably could have some skin lesions.

Nate, feel free to jump in.

You know, much more common to have skin lesions in those, in

the immunocompetent patients.

And then for Cocci with primary pulmonary pneumonia, which is

what this seems likely to be.

You know, if there's a rash that's, that really pushes you in the direction

of coccidioides as the cause, or if you see an eosinophilia on their, uh,

differential with their CBC, that's also gonna sort of push you in that direction.

Um, so that's kind of the general approach to exam.

you know, we haven't confirmed this as coccidioides yet, but if we do, you know,

the next two things are to, to really check for risk factors for complicated

infection or check if they already have complications of the disease.

And so we do focus our, our exam on those findings as well.

And what's like a typical skin finding for blasto that folks might see?

Yeah, I, well, they can vary a bit, so I, I hate,

I put typical in quotations.

yeah, I don't know.

I'm not in, that's a little hard.

Um.

They vary a bit.

So the thing that should stick in your head is this sort of presentation plus

skin findings, in a area with risk factors, blasto should be on the radar.

Fair enough, so we do get labs and our diagnostics back.

We have a coccidioides EIA positive IgM 1.8.

Uh, IgG 4.0 and positive is greater than or equal to 1.5.

Coccidioides antibody by complement fixation is positive at 1:8.

Other testing is obtained.

Interferon gamma release assay, cryptococcal antigen, histo and

blasto antigen and serologies, all of which are negative.

So, yeah, thanks for those labs that, that's helpful.

I think that really does help firm up the diagnosis of primary

pulmonary coccidioidomycosis.

You've got a positive IgM and then you've already got a

complement fixation titer of 1:8.

So that really suggests exposure has been more than three or four weeks ago.

Um, so I guess that sort of fits with his, his trip to Arizona, and then so the

titer of one to eight, that's also sort of consistent broadly with someone that

might warrant admission to the hospital.

It can have a ref reflects a, a fairly significant burden of disease, but

titers are really most helpful to follow in a single patient longitudinally.

So a titer of 1:8 different patients may manifest quite differently.

So it's not quite as predictive.

We do know that titers above 1:16.

32 or higher, 50% of those patients are gonna have disseminated infection.

So that's a group really to focus on if they have high titers.

There's a tremendous difference in what lab runs your titers.

So labs that do a micro titers, so those would be the big reference

labs, ARUP, Quest, et cetera.

Those titers on in general run higher than the more specialized cocci tests.

So, um, you can't compare one lab's complement fixation

test to a different labs.

It needs to be done at the same, same location.

And then the general approach, this patient was uh, 50, so, you know,

um, uh, I'm almost 50, so that's just barely middle aged now, I guess.

That that's not really associated with, with risks for bad infection by age.

Uh, we know patients older than 65 have a rougher time, just like with almost every

infection, but this is a, a male patient, and we do know that males versus females

have a, about a six to one ratio of, of  coccidioidomycosis, uh, acquisition.

And the reasons for that are unclear.

We've, we've wondered if that's, you know, sociologic, just differences

in hobbies, occupations, et cetera.

But we've actually looked at our veterinary animals and a primate cohort

and saw the same thing across the board.

The male primates, male dogs all acquired, you know, cocci at a greater rate

than the female, uh, dogs or primates.

And then if, if the dogs were actually castrated, they're, they're

risk return to the same as females.

So we do think it's probably biologic.

And we know that cocci uses a number of different hormone receptors.

It can probably use those as either growth factors or carbon sources.

Um.

And so we think that's the major issue is just the testosterone.

Men, we hate to admit this, our immune systems are weaker.

That's why we get things like man flu.

Um, also that the sex hormones, you know, the second and third trimester of

pregnancy, when, when women have higher estrogen levels, that's also a risk

factor for bad infection with cocci.

We see people disseminate, uh, in their second and third trimester of pregnancy.

So all those are things we kind of consider.

This patient wasn't described as immunocompromised.

We do know that, that sadly not only has this sex predisposition for

bad disease, but there's certain, genomic ancestries, you know, those

from Oceana, like our Filipino patients, Marshall Islands, et cetera.

They, they have risks for, for worse outcomes with cocci as do our

patients of African genomic ancestry.

The genetics of that have been, uh, worked out a bit.

Uh, probably about 50% of the patients have been explained some really great

work done by the NIH, uh, Steve Holland and Amy Sue did a lot of that work with,

with sort of our patients in a group from Arizona, but there's still a lot to

learn, you know, how do we predict these?

And even all those risk factors we understand, we still examine

these patients really carefully.

Image anything that hurts, kind of approach 'em like Staph aureus, if it

hurts, look at it more closely, and, and just check for complications.

So that's kind of our big picture approach to these patients.

Well, maybe what we can do is also talk about treatment options and

general thoughts on, on therapy.

Yeah, I think, I think therapy in our, our view of treatment is, it depends who

you ask in the field of, of coccidioides.

So there's sort of two camps, you know, there, there's sort of

a group of physicians that say, well, most patients historically

did well even without treatment.

So if they have pretty mild symptoms, maybe don't treat 'em at all.

I think this patient's different.

They're clearly sick enough to be in the hospital, so they're

gonna need antifungal therapy.

Generally most patients start on fluconazole.

Um, in vitro that's probably the least effective drug, probably a mold active

azole, itra, posa, vori, isavuconazole.

All those are more effective in vitro. You know, we have only one comparative

study looking at fluconazole versus itra.

The itra patients generally did better, but our approach would be to

start this patient on fluconazole.

Generally a higher dose, more like 600 or 800 milligrams per

day if they're a 70 kilo person.

If they don't respond over just, you know, several weeks or a month, or if

they have side effects, which a lot of the patients do from fluconazole, alopecia,

cheilitis, xerosis, all that sounds benign until you've gotta deal with it

for a while, you know, we're pretty quick to put them on a drug that we think has

fewer side effects and more efficacy.

So, you know, itraconazole, this is a 50-year-old, you're not too worried

about heart failure yet, but, but that's definitely something to think about with

itraconazole, uh, as a negative inotrope.

Posaconazole, uh, looks at least in vitro, like it might be the most effective azole.

Does cause hypertension, and about a third of patients causes a

pseudo hyperaldosteronism syndrome.

Voriconazole, if you think about the regions that have cocci with, with Arizona

and California, there's a lot of sunshine.

So putting patients in those regions on vori as a photosensitizer can be

really difficult and in long-term use skin cancer, of course.

And then isavuconazole, we don't have as much data, but we've used a lot

of that, very effective and, and very benign, uh, doesn't tend to have a

lot of side effects with that drug.

So that's, that's our general approach.

I probably wouldn't give this person amphotericin B, I mean, again, it's

kind of hard to tell how sick they are you know, this, this format, but unless

they really are, are compromised from a respiratory standpoint, um, I'd probably

try to give them an azole and tell them, you know, over the next few weeks you

should start feeling better and improving.

And then I'd really look out for the development of erythema nodosum.

When they have that, that's a favorable prognostic sign.

It's a panniculitis, inflammation of the fat, typically on the shins.

We do see it on the forearms as well.

And that's not disseminated infection.

That's a sign that you've, you're starting to develop Th1 immunity to

the underlying, coccidioides species.

So, so those are all the things we approach in kind of that

first, you know, four week window.

So how do you decide on, uh, approaching CNS disease?

That's a great question.

'cause even uncomplicated pulmonary infection, they often have headache.

In the past if they had a high titer, everyone received a lumbar puncture

looking for disseminated disease.

One of our fellows wrote a paper about that a number of years ago and showed

if your headache is not changing in character, you know, more frequent

escalating in severity, timing, et cetera, and you have no other CNS symptoms, it's

not worthwhile to do a lumbar puncture.

You're just gonna get negative results.

And that was a multicenter study that, that sort of changed the

dogma associated with that practice.

We really need to find a good reason in adult immunocompetent

patient to do a lumbar puncture.

I mean, we think of those as fairly benign, but CSF

leaks are, are fairly common.

That's, that's sort of morbid for the patients.

That causes more headache, that definitely won't help them.

Um, so we, we try to only do that for people we really

feel like we're gonna help.

How about somebody that is more immune compromised?

Does that change your thoughts?

Definitely does.

If, if they're immunocompromised, we definitely have a much lower

threshold to do a lumbar puncture.

We still approach it generally the same.

They need to have a compelling reason, you know, some kind of a symptom

that's correlated with CNS infection.

We, we don't just do those on a routine basis like we do with cryptococcus, right?

Any crypto infection, they get a lumbar puncture for the most part, but

we don't tend to do that cocci, but I'd say we have a very low threshold.

GR knows my crypto background, so he knows that I'm lumbar puncture happy.

It's all right.

We love a good lumbar puncture, but we also try to avoid them

after we've caused some CSF leaks.

And I guess one other tangent that I'll ask is, let's say this patient

wasn't responding or you know, is running into issues down the road.

Is resistance common?

Is that something that we should be worried about?

So patients who don't respond to therapy are pretty interesting.

It's, it's fortunately, a fairly small group that doesn't

respond to a second triazole.

We mentioned we'd start with fluconazole probably, and then maybe a second

triazole later without a response.

But patients that don't respond to a second triazole are maybe

10 to 15% of those patients.

I think the field has always said resistance doesn't really occur in cocci.

To me, that seems sort of odd.

Why would cocci be such an outlier that there's no resistance?

Certainly clinical resistance occurs, you know, even if it's in vitro,

it's supposed to be susceptible.

The patient may not respond, but I think the good news is we have a number

of new drugs sort of on the way that are in phase two and three trials, and

so it'd be olorofim and fosmanogepix.

The bad part of that though, is some of the environmental antifungals that

are put down to deal with things like alternaria with almonds, uh, you know,

aspergillus on peanuts, et cetera.

So this other drug ipflufenoquin actually works just like olorofim

and uh, aminopyrifen works just like fosmanogepix, so if we put those down in

high concentrations in the environment, we may actually lose susceptibility

to these fungal pathogens before the patients have even seen the drugs.

And with that, we're really hopeful that some of these silos

of regulatory authorities can get on the same, same page.

And, and they really have.

The CDC has has led that with the EPA to try to break down some of

these barriers where, what's approved for the environment, you know,

the, the, the true One Health one world effects can be evaluated to

prevent, uh, spread of resistance.

And, and, you know, we've been very ahead of that game over the last,

you know, 20 years with antibiotics and chickens and those kind of

things, but we sort of neglected antifungals on our agricultural crops.

So this recent consortium is gonna hopefully solve that problem, but

it it still gets at the question, we're always gonna have resistance.

You know, we're in a constant battle with all these microbial pathogens.

We create a new drug, they figure it out over time.

You know, I'm always reminded of penicillin resistance was described in

the lab before a patient had ever seen penicillin during the advent of that.

So we, we, we need to really continue to search for new drugs because this

is gonna be an ongoing war forever.

Yeah.

So, you know, and that's, that's a great point because, of course many

of our new drugs come from, from very basic research at the beginning, right?

So new mechanisms are discovered, and they eventually lead to a drug discovery.

So, you know, this is a, a, great sort of segue to, to simply state

that we need definitely continued investment in, in mycotic diseases.

It's interesting when I started doing research as a fellow, I started working

in in crypto meningitis and I, I was sort of shocked at how relatively

little research was done compared to some other things that I knew about.

and then I started getting interest in TB meningitis and I thought,

wow, crypto has it really good.

I. And then I got into doing blasto and, and I've realized that there is somewhere

to go with less and less investment.

So, um, we need to learn a lot about this stuff and we need

continued investment in science.

Um, this is, this is the only way we're gonna continue to find out better

ways to treat things, better ways to diagnose things, who's at risk.

It's not time to, to stop.

We need to continue to invest.

Yeah, that is such an important point.

Tom, any other questions that you have?

. Thinking more generally, it's important for us to think about the intersection

of infection and climate change.

We'd love to hear from the both of you, uh, any insight you have into

how many of the recent wildfires might impact coccidiomycosis.

Yeah, that's a great question.

We really had, had thought a lot about wildfires, particularly during covid.

You know, we're cooped up in the house and then it starts

being smoky every everywhere.

And we affectionately called that "smovid" in, uh, California.

But during that time we started to really think about the amount of debris that

was being deposited by the wildfires.

You know, you could just walk out on the sidewalk and see

debris from, from the smoke.

And the particulate matter we had started to question, does this

actually carry living organisms?

And in conjunction with Leda Kobziar and her group who studies this,

she actually flies drones over wildfires to collect smoke samples.

Found that there is this living component of smoke and founded this new field

pyroaerobiology and you know, is published on that in Science a number of years ago.

You know, has found really a a who's who of opportunistic fungi with that, you

know, um, cryptococcus, cladosporium, mucorales, aspergillus, et cetera.

Has not found cocci in that, so that does create the question, you know,

uh, fire does create its own weather.

It sort of pulls smoke through the surrounding soil and vegetation

and can pull that up, you know, even into the upper atmosphere.

And, and maybe one of the ways pathogens travel very long distances.

But cocci requires drought as part of its lifecycle.

Fire obviously needs drought just to start large fires.

It does cause the question of these just true, true but unrelated.

And then the, the group at UCSF has published a nice paper just

a few years ago that did really show this correlation that.

They published that I think in Lancet Planetary Health using administrative

data from a number of hospitals and did show this very close correlation

between wildfire smoke and the number of coccidioides cases.

So we do think there's a close association.

We know firefighters get a lot of cocci.

Unfortunately a lot of the firefighter service is, is, you

know, California prisoners out here.

Um, and it's just hot.

They don't wanna wear protective gear.

It's too hot to, to keep that on.

They're, they're not actually out there putting out the fire, but they're

doing high risk activities like cutting fire breaks, you know, they're deep

down in the soil or, or digging up a lot of soil, potentially exposing

them to, spores in that environment.

so, so it's, it's a confluence of a number of factors, you know, we think, but an

area that's ripe for additional work.

Those papers are so cool.

I've, I've pulled some of them for, for puscast and, um, just

like found them so fascinating.

Oh Leda flying those drones over stuff.

It's cool.

Yeah.

That's very cool.

Yeah.

Nate, is there anything else that you wanna add?

Um, do I want to add something?

I mean, for cocci, I, I don't, I mean, I, you know,

I,, can only say cocci.

I can't say the whole thing, uh, without stumbling so

No one can.

It's impossible.

do you, do you wanna talk about hurricanes and mold or, uh,

tornadoes or any of that stuff?

Yeah.

Before I, I came back to Minnesota, I was in Kansas City and not long before

that, um, there had been a really big tornado in, in Joplin, Missouri.

And after that there was an amazing amount of, of sort of rare mold

infections, things that people weren't used to seeing very often, but were

seeing quite frequently after that.

So these, you know, these weather events, when they do things to soil,

they, they tend to carry mold with them.

And so it's, it's sort of an important point to think of if

something like that, you know, if, if some big weather happening in your

area, you're pretty likely to see more of that sort of thing happen.

Thanks so much to Tom, GR, and Nate for joining Febrile today.

Hopefully this got you excited to hear about fungal infections, so you can check

out the Mycoses Study Group Education and Research Consortium for more learning.

Their webpage is posted on the website as well as in the episode info.

I also encourage you to check out a recent webinar that had Dr. GR Thompson,

who is here with us on the episode, as well as Dr. Fariba Donovan, talking about

cocci in the aftermath of the wildfires.

So we will put a link to that webinar, which was, um, hosted just this past week.

You can check out the website febrile podcast.com to find the Consult Notes,

which are written supplements to the episodes with links to references,

our library of ID infographics, and a link term merch store.

Febrile is produced with support from the Infectious Diseases Society of America.

Please reach out if you have any suggestions for future shows or want

to be more involved with Febrile.

Thanks for listening.

Stay safe and I'll see you next time.