Episode 118
118: Below the Belt
Drs. Morgan Hui, Jonathan Darby, Max Olenski, and Catriona Halliday join Febrile from Australia to share a unique case of a transplant recipient with a painless lump.
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Transcript
Hi everyone.
Speaker:Welcome to Febrile, a cultured podcast about all things infectious disease.
Speaker:We use consult questions to dive into ID clinical reasoning, diagnostics
Speaker:and antimicrobial management.
Speaker:I'm Sara Dong, your host and a Med Peds ID doc.
Speaker:Today's episode of Below the Belt is led by a team from Australia.
Speaker:First up, we have Dr. Morgan Hui.
Speaker:Morgan is a basic physician's trainee with an interest in infectious diseases.
Speaker:He is currently working as an ID registrar at Peninsula
Speaker:Health in Melbourne, Australia.
Speaker:Hi, it's Morgan.
Speaker:Very keen to be here today.
Speaker:Dr. Jonathan Darby is an infectious diseases and general medicine physician.
Speaker:He is the head of General Medicine at St. Vincent's Hospital, Melbourne,
Speaker:and an Associate Professor at the University of Melbourne.
Speaker:Hi.
Speaker:It's great to be here with you today.
Speaker:Dr. Max Olenski is an infectious diseases and general medicine physician with
Speaker:an interest in tropical medicine and infections in immunocompromised hosts.
Speaker:He is the current Perioperative Medicine Unit Clinical Lead at Peninsula
Speaker:Health and a Sessional Academic with Monash University in Melbourne.
Speaker:Hi, it's Max Olenski here.
Speaker:Thanks so much for having us today.
Speaker:Really excited for this podcast.
Speaker:Dr. Catriona Halliday is the Principal Hospital Scientist in charge of
Speaker:the Clinical Mycology Reference Lab at the University for Clinical
Speaker:Pathology and Medical Research and New South Wales Health Pathology
Speaker:based at Westmead Hospital in Sydney.
Speaker:She is actively involved in teaching both scientific and medical staff in
Speaker:medical mycology, and has a strong interest in culture independent tests to
Speaker:aid in the rapid diagnosis of invasive fungal infections and antifungal
Speaker:drug susceptibility surveillance.
Speaker:Hi, it's Catriona Halliday, and nice to be here too.
Speaker:Wonderful.
Speaker:Thank you guys so much for coming.
Speaker:We are just gonna quickly start by asking you to share a little piece
Speaker:of culture, because we call Febrile everyone's favorite cultured podcast.
Speaker:So really just sharing a little something non-medical that you like,
Speaker:whether that's pop culture or hobbies, um, or other interests that you have.
Speaker:So what have you guys been enjoying recently?
Speaker:I had the pleasure of going to see recently for International Women's
Speaker:Day, I went to see the RBG: Of Many, One, um, production about Ruth Bader
Speaker:Ginsburg's life, which was fantastic.
Speaker:It's one woman show, I think it's tour of the states, uh, and it's come back time
Speaker:and time again in, in, uh, Australia.
Speaker:That's cool.
Speaker:I haven't seen that.
Speaker:I was gonna say that in recent times, my daily routine has, uh,
Speaker:incorporated the New York Times puzzles.
Speaker:I, I sort of churn through them every morning while I'm
Speaker:having my morning coffee.
Speaker:And also I've been doing the cryptid crossword of late to try
Speaker:and get my creative juices flowing.
Speaker:Excellent.
Speaker:Love a good puzzle.
Speaker:Uh, Morgan.
Speaker:Uh, since Covid, I think I've been picking up golf after lockdown.
Speaker:Um, not that I play well, but it's enjoyable to get outdoors.
Speaker:And then in the same vein, uh, I've been watching a lot of golf, YouTube,
Speaker:especially being between studying.
Speaker:It's very easy watching.
Speaker:Um, and it's just something to turn my brain off at night, which is quite good.
Speaker:Yeah, the turning your brain off is usually a, a common
Speaker:theme on people's suggestions.
Speaker:Um, and rounding us out, Jonathan.
Speaker:Well, I saw you like travel and food.
Speaker:So yesterday at weekend Australian time, I said to my kids, I'm gonna cook dinner,
Speaker:and they requested bao buns, so I made bao buns yesterday, which was good fun.
Speaker:Labor of love takes most of the day,
Speaker:a lot of work.
Speaker:was very nice.
Speaker:Yeah, very nice.
Speaker:Amazing.
Speaker:I love it.
Speaker:Well, thank you guys for sharing.
Speaker:Um, all right, well, Morgan is in charge today and is gonna
Speaker:take us through the case.
Speaker:So I'll hand it over.
Speaker:Thank you.
Speaker:So today, our case involves a 49-year-old male who presents to the renal outpatient
Speaker:department with a four month history of a slow growing, painless right elbow lesion.
Speaker:He's adherent with his immunosuppression and a systems review is unrevealing.
Speaker:His past medical history includes a renal transplant in 2017 for primary
Speaker:focal segmental glomerular sclerosis.
Speaker:His pre-transplant assessment did not reveal any infections for
Speaker:which prophylaxis was afforded.
Speaker:His early post-transplant course was complicated by pulmonary aspergillosis
Speaker:and he was treated with a six month course of voriconazole with clinical,
Speaker:biochemical, and radiological resolution.
Speaker:At the time of seeing him, he has a stable allograft function, currently on low dose
Speaker:prednisolone, everolimus, and tacrolimus, and his comorbidities include well
Speaker:controlled hypertension, dyslipidemia, steroid induced osteoporosis, and GORD
Speaker:(gastro-oesophageal reflux disease).
Speaker:On examination his vitals were normal alongside a normal
Speaker:cardio respiratory exam.
Speaker:His abdominal examination revealed a non-tender right lower quadrant
Speaker:mass underlying a hockey stick scar, consistent with a renal allograft.
Speaker:He has a 1.5 centimeter non-tender mobile lump on the lateral aspect of his right
Speaker:elbow, not tethered to the underlying skin without notable discoloration, overlying
Speaker:skin changes, induration, nor sinus.
Speaker:There were no other masses on examination of his lymph node stations.
Speaker:At this point, is there anything else that you'd want to ask our
Speaker:patients and what differentials do you think that you'd entertain?
Speaker:Thanks Morgan.
Speaker:So just to summarize, this is a middle aged gentleman who's a renal
Speaker:allograft recipient with stable function on immunosuppression.
Speaker:His post-transplant course was complicated in the early stages, uh,
Speaker:with pulmonary aspergillosis, but he seems to have recovered from that with
Speaker:therapy, uh, and presents now with an incidental painless lump on his elbow.
Speaker:Some important questions that come to mind really are
Speaker:clarification surrounding exposures.
Speaker:Um, for instance, what he does for work, what sort of hobbies he has, um, has
Speaker:he had any animal contact, or, a little bit more about his sexual history.
Speaker:Uh, what else is important would be, um, whether there are
Speaker:other locoregional infections or constitutional symptoms of note.
Speaker:The differential diagnosis for a painless lump in a transplant recipient runs the
Speaker:gamut from a foreign body reaction to things like a lipoma or other soft tissue
Speaker:neoplasms, and this includes lymphoma.
Speaker:But considering this is through the lens of an infectious disease
Speaker:approach, I think it's important to entertain various sorts of infections.
Speaker:And likewise, we'd entertain things like run of the mill bacterial
Speaker:skin, soft tissue infections, like a furuncle or carbuncle.
Speaker:But syphilis and cat scratch disease also appear amongst the differentials.
Speaker:Considering a significant history, fungal etiologies need to be entertained,
Speaker:and this includes disseminated aspergillosis alongside sporotrichosis,
Speaker:and, um, more rare things like mucormycosis or rhizopus infection.
Speaker:Um, and then the fine print would be things like mycobacterial infection, viral
Speaker:or parasitic infections, things like TB or non tuberculous mycobacteria (NTM),
Speaker:um, or cysticercosis or trichinellosis but those sort of things would really
Speaker:come to, uh, the fore if his, um, exposure history was compatible.
Speaker:So taking our case a bit further, his social history revealed that the patient
Speaker:immigrated from the Philippines to Australia 18 years previously, where he
Speaker:returns to visit family and friends every six to 12 months, but not in recent times.
Speaker:He's in a long-term heterosexual, monogamous relationship and works in
Speaker:maintenance at an aged care facility.
Speaker:He's a sporadic gardener with no additional epidemiological
Speaker:exposures, and does not report any recent animal nor insect contact,
Speaker:nor recent locoregional infections.
Speaker:He consumes no alcohol nor smokes tobacco.
Speaker:On further history when pressed, he thinks that he might have had the onset following
Speaker:a seamlessly innocuous traumatic injury against a doorknob without skin breach,
Speaker:and no set associated systemic upset.
Speaker:His routine lab results were unremarkable with white cell count,
Speaker:LFTs, and inflammatory markers within normal limits, a stable renal function
Speaker:compared to previous, a non-reactive RPR and a negative QuantiFERON
Speaker:gold with a good mitogen response.
Speaker:Ultrasound sonography of the lesion revealed two small circumscribed
Speaker:ovoid masses suggestive of reactive lymphadenopathy.
Speaker:This was clinically corroborated upon surgical review and was resected
Speaker:en bloc with tissue set up for histopathological assessment alongside
Speaker:routine mycobacterial and fungal cultures.
Speaker:No organisms were seen from the Gram and Zeihl-Neelson stains, nor subsequently
Speaker:cultured . However, filamentous fungi were noted on fluorescent staining.
Speaker:Histopathological examination revealed multinucleated giant cells, and possible
Speaker:copper penny, aka Medlar bodies.
Speaker:In addition, there was a suggestion of a brown micro colony of hyphal elements
Speaker:with suspicion for an underlying deep mycosis, and the specimen was sent for
Speaker:further culture and identification.
Speaker:I guess, now, what do you think is meant by deep mycoses and
Speaker:how are they differentiated?
Speaker:Yeah.
Speaker:Thanks for that update, Morgan, on the case.
Speaker:Um, to, to just take a step back.
Speaker:This was a subcutaneous lesion and it, it didn't have any changes
Speaker:on the skin, which would make us think of an inoculation injury.
Speaker:But we were certainly taken by the history of his previous Aspergillus
Speaker:infection in the lung and wondered if this was a site of disseminated infection.
Speaker:And there is, as you've pointed out, Max, a broad differential in a immunosuppressed
Speaker:transplant patient with any lesion.
Speaker:But it was an unusual site.
Speaker:It was an unusual appearance with relatively few other additional
Speaker:symptoms, just that he brought this mass like lesion to our attention.
Speaker:And so to be honest, I hadn't really used the term deep mycosis
Speaker:in clinical practice before.
Speaker:Um, I know it's, uh, been raised here and has been talked about in, in
Speaker:some literature, but really when we think about these lesions, we have a
Speaker:broad differential from, from fungal to atypical mycobacteria to other
Speaker:organisms which may be indolent and slow growing in a transplant patient.
Speaker:But this suggestion here with the, the pigmented nature of the fungal elements
Speaker:certainly makes us concerned about a group of fungi, which we classify
Speaker:in the dematiaceous mould group.
Speaker:Um, this is an unusual finding, so this doesn't happen every day where
Speaker:you find this on a biopsy and sometimes has been found in further other
Speaker:organ sites such as brain or lung or subcutaneous skin and soft tissue.
Speaker:So the, the overarching term we would sort of use for this would
Speaker:be a phaeohyphomycosis, if it is related to a pigmented mold.
Speaker:Actually had to look up the word "phaeo", 'cause I've always
Speaker:wondered where that came from.
Speaker:And, and that's, uh, Greek word for dusky.
Speaker:So gray or, or black forming.
Speaker:And this is thought to be the melanin in this group of fungal
Speaker:infections' structure that causes that, that appearance.
Speaker:So there's a few terms we use here.
Speaker:And then the other term that we would consider is this term
Speaker:of chromoblastomycosis, where a chronic infection, usually due
Speaker:to inoculation but it could be dissemination in an appropriate host
Speaker:such as this with dissemination.
Speaker:Um, there is a well-known entity in the tropics where these patients have
Speaker:a crusted verrucous like lesion on the skin with chromoblastomycosis.
Speaker:And there's a range of specific species which are fairly geographically
Speaker:distinct depending on where a patient may have spent time.
Speaker:And so with this individual, whilst living in residential suburban
Speaker:Australia, we did note that his history is from the Philippines and
Speaker:traveling back and forth there fairly frequently with some sparse gardening.
Speaker:So we were concerned about this family of organisms from that basic
Speaker:microbiological description before we had a formal culture and identification
Speaker:from our mycology reference laboratory.
Speaker:The next step in his workup was the sterile tissue was sent to
Speaker:a diagnostic mycology laboratory for specialized fungal cultures.
Speaker:Uh, from here, Catriona will take us through exactly what happens
Speaker:in the lab to get our diagnosis.
Speaker:Thanks very much Morgan, and thank you Jon for that nice history and
Speaker:my, I've now learned what phaeo means in the phaeohyphomyosis.
Speaker:I've got a case at the moment, so that's good.
Speaker:Um, okay.
Speaker:So when the sample was sent to us for culture, we already knew that there were
Speaker:fungal elements seen histologically
Speaker:. When we receive samples in the fungal lab, it's really important that any
Speaker:tissue samples aren't actually ground up.
Speaker:We, we just make them into small pieces and put them onto the various agar and,
Speaker:um, we don't grind them up because if this fungus was likely to be, or we
Speaker:sometimes we don't even know if it will be, a mucormycete, this particular group
Speaker:of fungi are really, really fragile.
Speaker:Um, and grinding would destroy the hyphae and, and so the
Speaker:organism would be non-viable.
Speaker:So as a rule, no tissue samples are ground up in a mycology laboratory.
Speaker:So these, sterile pieces of tissue were put onto a variety of different media.
Speaker:We usually use a couple of different media, a very general purpose media
Speaker:with no antibiotics such as Sabouroud dextrose agar, and then we use more
Speaker:nutritious media such as a Sabouraud dextrose agar base, which might
Speaker:have something like brain, heart infusion and some antibiotics like
Speaker:chloramphenicol and gentamicin in them to suppress any bacterial growth.
Speaker:So following inoculation, we then use plates, but some labs do use slopes.
Speaker:The plates, we seal them with parafilm, and then we put them in an
Speaker:incubator at 30 degrees, rather than 35 degrees, which is what would be
Speaker:used for most of the bacterial growth.
Speaker:And 30 degrees, I think most fungi are environmental organisms and
Speaker:they just do better for growing at a slightly lower temperature.
Speaker:We keep these plates for four weeks and look at them every couple of days.
Speaker:And so the reason they're para filmed is, is both to, to keep the
Speaker:lids closed, but also prevents dehydration when they're put in the
Speaker:incubators for, for quite a long time.
Speaker:So that's the reason we use that lower temperature.
Speaker:And, in this particular case, after about 10 days, we noticed a small amount
Speaker:of growth of a, of a dark gray fungus growing directly out of that tissue.
Speaker:So as soon as we get positive culture, we would then always work
Speaker:in a biological safety cabinet.
Speaker:We would then put that organism and subculture it onto a general purpose
Speaker:Saboroud agar with no antibiotics in it.
Speaker:And we'll also prepare a slide culture by inoculating a potato dextrose agar plate.
Speaker:In order to identify fungi in the conventional way, you, you really
Speaker:need to see how those fungi are growing in their natural state.
Speaker:And so for that, you, you can use macroscopic appearance, but
Speaker:the macroscopic appearance can change depending on the media
Speaker:that you might be using, how much light there might be exposed, you
Speaker:know, to, and things like that.
Speaker:The macroscopic appearance can be a bit of a guide, but that microscopic appearance
Speaker:is what we need to identify something to the genus and ideally the species level.
Speaker:So you need to use a media such as potato dextrose agar
Speaker:to encourage that sporulation.
Speaker:Other media that could be used for microscopy to prepare slide cultures
Speaker:is cornmeal agar, which is probably a little bit less nutritious and
Speaker:more encouraging of sporulation.
Speaker:So in this particular case, again, we grew a very gray,
Speaker:velvety fungus with radial grooves.
Speaker:It changed and became a bit darker with age on the Sabourouds plate.
Speaker:And there was a bit of a dark, exudate or, droplets forming
Speaker:directly outta that colony.
Speaker:The reverse of the colony was also dark, so the fact that it was dark
Speaker:on the reverse as well as on the surface suggests that the organism
Speaker:does contain melanin, which fits with what we've seen histologically.
Speaker:Unfortunately the microscopic appearance of this fungus from the
Speaker:slide culture was not very helpful.
Speaker:We just got hyphae.
Speaker:We didn't see any conidia forming, and so if you don't see conidia
Speaker:forming out of that hyphae, we can't identify it using conventional methods.
Speaker:Fortunately, we have the ability to overcome this problem and
Speaker:perform DNA sequencing, which is, is actually now considered the gold
Speaker:standard for identification of fungi.
Speaker:There's a couple of different barcoding genes for fungal identification that
Speaker:we rely upon, the internal transcribed space region, as well as some organisms
Speaker:might identify better with something like the elongation factor gene.
Speaker:But for this particular case, we used DNA sequencing of the internal
Speaker:transcribed spacer region as well as the D1/D2 region of the 28S ribosomal DNA.
Speaker:We did two different PCRs.
Speaker:We sent that pCR product off the sequencing and ran the sequence
Speaker:results against gen bank data databases using a, a BLASTn algorithm.
Speaker:And I'd never had encountered the answer that we got.
Speaker:But the answer we did get from both the ITS sequencing was 99.4%
Speaker:identity to an organism called Falciformispora lignatalis.
Speaker:And I might have butchered that pronunciation, but I'm happy
Speaker:for someone else to correct it.
Speaker:Um, and then the next closest match was another species within that
Speaker:Falciformispora, uh, species, but it was further away at only 96% identity.
Speaker:So we were pretty confident that the organism we'd come
Speaker:across was this F.lignatalis.
Speaker:We did try and do antifungal susceptibility testing for this patient,
Speaker:but again, with antifungal susceptibility testing, you must have sporulation
Speaker:and, uh, we didn't manage to induce sporulation and therefore we weren't
Speaker:able to perform antifungal susceptibility testing in this particular case.
Speaker:Was it far enough away to call it catrionelis or not quite?
Speaker:It makes me feel better that you also doubt your pronunciation
Speaker:like,
Speaker:never come across this organism before and I'm yet, but I, and I haven't
Speaker:even come across that genus before.
Speaker:So,
Speaker:Thank you.
Speaker:Thank you so much.
Speaker:Uh, I guess what do we make of this and the significance of this organism?
Speaker:Would we call it a deep mycosis?
Speaker:Yeah.
Speaker:And is it how this syndrome typically manifests itself?
Speaker:Um, well, as we've said already, uh, this is an unusual organism
Speaker:and I think it's been implied as well that the world of mycology is
Speaker:forever changing and it is difficult to keep up with this kaleidoscopic
Speaker:landscape of fungal nomenclature.
Speaker:But this syndrome is indeed, um, consistent with what we call mycetoma.
Speaker:And whilst I am no budding mycologist, uh, I have done my research and we'll
Speaker:talk a little bit about mycetoma now.
Speaker:It is a chronic granulomatous subcutaneous infection caused
Speaker:by several species of fungi as well as soil inhabiting bacteria.
Speaker:Which is endemic within this so-called mycetoma belt, um, which spans
Speaker:from 15 degrees south to 30 degrees north of the equator and really
Speaker:within the tropics of the world.
Speaker:Sporadic cases have been reported worldwide, including in temperate regions,
Speaker:and it's really quite rare in Australia.
Speaker:And when it does occur, it occurs in the northern states and territories,
Speaker:which approach the tropics.
Speaker:We make a distinction between actinomycetoma and eumycetoma,
Speaker:the former being caused by soil inhabiting bacteria, and the latter
Speaker:from fungis, such as in this instance.
Speaker:And the typical presentation is usually with the triad of tumour, uh, sinus
Speaker:tracts, uh, and macroscopic grains, which are essentially colonies or
Speaker:aggregates of the infectious organism.
Speaker:Uh, it can extend to adjacent structures including bone, muscle, lymphatics.
Speaker:And the classic description from a long, long time ago was that of
Speaker:Madura foot, named after a region in India called Madura, where people
Speaker:would've stepped on this, these fungal organism, and it was quite disfiguring.
Speaker:Risk factors as you might gather are typically environmental or related to
Speaker:occupation, and thus it had previously been known or sometimes is known as
Speaker:an implantation mycosis, uh, and risk factors also included, such as in this
Speaker:instance, states of immunocompromised, whether they be inherited or acquired.
Speaker:The main age for this sort of syndrome is in the thirties and typically occurs
Speaker:in males with changing epidemiology based on an itinerant population
Speaker:in other regions around the world.
Speaker:It usually involves the, the feet, as an implantation mycosis where workers
Speaker:might be not wearing shoes and exposed to thorns and other things
Speaker:within the soil, and less likely to occur in parts of the torso, the
Speaker:arms and other parts of the body.
Speaker:Common organisms for mycetoma itself, or eumycetoma I should say.
Speaker:Madurella mycetomatis, which is the, the classic one, but it's worthwhile
Speaker:noting that eumycetoma itself is the minority of cases of mycetoma.
Speaker:It's 35% of cases of mycetoma across the board and within eumycetoma,
Speaker:Madurella mycetomatis, uh, accounts for 75% of eumycetoma.
Speaker:Followed by Falciforma species such as the other ones that Katrina had
Speaker:identified as being similar to the Falciforma lignatalis which
Speaker:was identified in this case.
Speaker:And they tend to differ by local epidemiology including
Speaker:climate, vegetation, rainfall, and, and different soil types.
Speaker:Little is known about the incubation period between inoculation and clinical
Speaker:manifestations, given that many patients do don't recall a specific predisposing
Speaker:injury, such as in this instance.
Speaker:It's worth noting that there are atypical presentations that typically affect
Speaker:immunocompromised hosts, whereby the classic triad might not be present.
Speaker:There are numerous case reports, uh, out there that highlight a link with
Speaker:the tropics in transplant recipients or those who are immunocompromised.
Speaker:For instance, patients who have migrated from their country of origin to a place
Speaker:that is not within the Mycetoma belt, and some 40 years later receiving a
Speaker:transplant and then having this fungus identified from various parts of the body.
Speaker:But there's yeah, um, really quite interesting cases out there.
Speaker:So beyond clinical suspicion, if someone came in with a similar presentation, how
Speaker:would you go about diagnosing mycetoma?
Speaker:Uh, it's hard not to have a talk like this without saying that clinical impression
Speaker:and an index of suspicion are paramount.
Speaker:Uh, and they are.
Speaker:Um, so the presence of that triad are certainly things that would give
Speaker:you an indication, but beyond that, in terms of clinching the diagnosis,
Speaker:it's a composite of growing the organism, and pursuing culture.
Speaker:Whether that be with a fine needle aspirate of the growth, wherever
Speaker:it may be on the body, uh, with subsequent inoculation under plates.
Speaker:I might ask you at this instance, Catriona, I know you mentioned that you
Speaker:would tend to culture these only at 30 degrees, but from my reading, sometimes
Speaker:these get inoculated at both 30 degrees and uh, 37 degrees for a number of
Speaker:weeks because different organisms within this eumycetoma syndrome tend to grow
Speaker:predominantly different, uh, temperatures.
Speaker:Is that fair to say?
Speaker:Or something you don't always do?
Speaker:Yeah, it is a fair enough question.
Speaker:I guess we're guided by standards for recommending what
Speaker:conditions we do grow fungi at.
Speaker:And certainly the guideline we used is the CLSI guideline, which the people in
Speaker:the states would be very well aware of and, and they make the suggestion that
Speaker:whilst you can put things at two different temperatures and some, some labs do put
Speaker:things at two different temperatures.
Speaker:Every time you put more and more plates out, you dilute how much
Speaker:sample you actually have to be able to try and, and grow things.
Speaker:So for fungal work, the general recommendation is you
Speaker:can just use 30 degrees.
Speaker:Uh, but, you've gotta remember, there's also plates that get set up
Speaker:for bacterial cultures, and there's no reason why many of these fungi
Speaker:wouldn't actually grow on some of the bacterial plates as well, and that is
Speaker:incubated at the higher temperature.
Speaker:So we have in my own lab times when we, we get something growing, but it's also
Speaker:growing on the bacterial plates as well.
Speaker:Great, thanks for that.
Speaker:So, beyond culture, the other things that are in establishing a diagnosis include
Speaker:histopathology with evidence of chronic granulomatous reaction, and possibly
Speaker:the presence of a grain, which given how rare it is, ought to be discussed directly
Speaker:with histopathology at your own lab.
Speaker:Um, given that this has not seen a great deal, and indeed when we returned
Speaker:to the histopathologist and asked them was that bunch of fungi you saw in a
Speaker:conglomerate consistent with a grain, and when they look through textbook,
Speaker:they confirm that indeed was the case.
Speaker:So, uh, good have good relationships with the various
Speaker:disciplines around the hospital.
Speaker:And imaging is used sometimes to determine extent of disease, whether
Speaker:it's invading in surrounding tissues, uh, but also to suggest whether
Speaker:or not, there may be improvements to help guide duration of therapy.
Speaker:I might ask Catriona, just lastly, is there anything in particular,
Speaker:you would say about sensitivities?
Speaker:Um, I know we weren't unable to achieve sporulation in this instance,
Speaker:but given this is , this was a rare fungus and something you hadn't quite
Speaker:encountered before, clinically, um, or at a lab level, if you were even
Speaker:able to achieve sporulation, would there be much to be gleaned from
Speaker:undertaking sensitivity testing?
Speaker:Yeah, so definitely.
Speaker:We would, uh, try and do susceptibility testing on any fungus that grew from a,
Speaker:um, and was deemed to be significant.
Speaker:In this particular case, we, because we couldn't get s sporulation, we
Speaker:couldn't do susceptibility testing.
Speaker:If we had been able to do susceptibility testing, all we would be able to give
Speaker:would be a value of, of what the, in minimal inhibitory concentration
Speaker:was for that particular isolate.
Speaker:Um, but that can often give clinicians some confidence that whatever drug
Speaker:they've decided to treat with, you know, is likely to be effective or not.
Speaker:There's certainly no break points available for any of these unusual fungi.
Speaker:We, we really only have break points available for one organism and one
Speaker:drug for Aspergillus fumigatus with voriconazole, but, and we don't really
Speaker:have breakpoint for anything else, so we are really only gonna be able to
Speaker:give you a number, which may give you confidence as to which drug can be used.
Speaker:Uh.
Speaker:From my experience with testing other dematiaceous fungi which grow
Speaker:in, you know, from cases like this, quite often itraconazole is actually
Speaker:really a, um, it suggests that it is quite an effective drug against
Speaker:these dark, slow growing molds.
Speaker:Uh, so.
Speaker:I'm not a clinician, but that is kind of my experience in the lab side of things.
Speaker:As you say, I think as clinicians we quite enjoy, uh, MICs that are low
Speaker:numbers, but appreciate that these are just environmental cutoffs and
Speaker:uh, it really comes down to trying to pick what you think is gonna
Speaker:be the most, um, effective agent.
Speaker:I think it'd be worth emphasizing that the biopsy is ideally an excisional
Speaker:biopsy because it's unusual to get either histological diagnosis or an
Speaker:effective culture on either an FNA.
Speaker:Um, sometimes a core biopsy, but in this instance, we were fortunate enough to
Speaker:have the surgical team perform a full excision, and I think that's really led
Speaker:to a, an expedited diagnosis in this case.
Speaker:I completely agree with that, Jon.
Speaker:And it's the same as if we'd have to go down the path of using, if we
Speaker:hadn't managed to grow it, if we'd gone down the path of having to
Speaker:use PCR directly from the specimen.
Speaker:Your, um, ability to get a, a positive meaningful result from a fine needle
Speaker:aspirate is, is quite, quite a lot lower than it would be if you get
Speaker:a nice, proper tissue specimen.
Speaker:Jon, how did you go on to choose your antifungal therapy in this instance?
Speaker:Yeah, so that was obviously a little bit complicated in the
Speaker:sense that we didn't have the full susceptibility data to guide us.
Speaker:And in these type of infections, there's no prospective randomized
Speaker:clinical trials to determine the most effective drug therapy.
Speaker:But we're used to dealing in these, let's call it gray zones, for the theme today.
Speaker:Um, in ID where we have to treat based on what's being reported to work
Speaker:and what we have familiarity with.
Speaker:I think the surgical adjunctive therapy is really important in these cases.
Speaker:If we can get local control with the surgical excision,
Speaker:then that should be emphasized.
Speaker:However, we still wanted to pursue some antimicrobial therapy in this case.
Speaker:Just recalling the case that it is a transplant patient
Speaker:on tacrolimus and everolimus.
Speaker:There are a lot of drug, drug drug interactions to consider and reviewing,
Speaker:you know, all of the literature in the past, a lot of the cases have been
Speaker:treated perhaps in more resource limited settings with ketoconazole, which we would
Speaker:rarely use in our setting currently.
Speaker:Um, and then itraconazole has certainly been used as Catriona alluded to.
Speaker:Many of the newer studies where there have been MICs reported, have reported
Speaker:low values to the newer triazole, such as voriconazole or posaconazole.
Speaker:We did have some experience with voriconazole in the past with this
Speaker:patient, but perhaps given that that was not that long ago, in a time interval,
Speaker:we considered a, a new agent perhaps being a better option to switch to.
Speaker:So we decided to use posaconazole.
Speaker:This certainly had some significant drug interactions and really reviewing this
Speaker:carefully with our nephrology colleagues and looking at the drug interactions.
Speaker:There's a significant interaction with the cytochrome P450 enzyme subset, 3A4.
Speaker:And so we had to look at that and the posaconazole was expected to significantly
Speaker:interact with tacrolimus so that the initial dose of the tacrolimus had
Speaker:to be about a third of the baseline dosing, and the everolimus had to
Speaker:be about 50% of the baseline dosing.
Speaker:So the treatment was certainly initiated in close consultation
Speaker:with the nephrology team.
Speaker:We did that at a time when they were ready and able to do drug levels
Speaker:quite frequently, and the tacrolimus actually had to come down further.
Speaker:So this particular patient was on 0.5 milligrams bd, which eventually
Speaker:went down to 0.05 milligrams BD in a step by sequential fashion,
Speaker:as the levels stayed very high.
Speaker:So whilst we look at reports of what is expected, it's a lesson that
Speaker:you always have to individualize these drug drug interactions.
Speaker:There was no ongoing imaging really for this particular site
Speaker:'cause we could clinically feel it and palpate it very nicely.
Speaker:I. Uh, we did review a cerebral image just for the completeness, uh, because
Speaker:some of these organisms have been known to disseminate to the central
Speaker:nervous system and that was normal.
Speaker:Uh, and we did repeat his pulmonary scan, which had the stable pulmonary
Speaker:nodules from his previous pulmonary aspergillosis with no change.
Speaker:So we elected to treat for six months.
Speaker:Uh, this was in the time where we had another worldwide epidemic going on
Speaker:with, with Covid, and so it was quite challenging in terms of monitoring
Speaker:and clinic visits, but we were able to get the patient in and ensure
Speaker:that he remained symptom free after successfully completing the treatment.
Speaker:Thanks to Morgan, John Max and Catriona for joining Febrile today.
Speaker:Don't forget to check out the website febrilepodcast.com, where
Speaker:you can find the Consult Notes, which are written supplements to the
Speaker:episodes with links to references, our library of ID infographics,
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Speaker:Febrile is produced with support from the Infectious Diseases Society of America.
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Speaker:wanna be more involved with Febrile.
Speaker:Thanks for listening.
Speaker:Stay safe and I'll see you next time.
