Episode 122
122: StAR: Protect the Macrolide! NTM Pulmonary Disease
This StAR episode features the CID State-of-the-Art Review on Nontuberculous Mycobacterial Pulmonary Disease: Patients, Principles, and Prospects.
Our guest stars this episode are:
Minh-Vu Nguyen (UC Davis Health)
Charles Daley (National Jewish Health, University of Colorado, Icahn School of Medicine at Mt Sinai)
Reeti Khare (National Jewish Health)
Journal article link: Nguyen MH, Haas MK, Kasperbauer SH, et al. Nontuberculous Mycobacterial Pulmonary Disease: Patients, Principles, and Prospects. Clin Infect Dis. 2024;79(4):e27-e47. doi:10.1093/cid/ciae421
Journal companion article - Executive summary link: https://academic.oup.com/cid/article-abstract/79/4/805/7823163
From Clinical Infectious Diseases
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Febrile is produced with support from the Infectious Diseases Society of America (IDSA)
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 we are getting back to one of our StAR episodes.
Speaker:These are based on the Clinical Infectious Disease journal,
Speaker:CID, State-of-the-art Reviews.
Speaker:Today our topic is going to be Nontuberculous Mycobacterial
Speaker:Pulmonary Disease or NTM.
Speaker:So I'll introduce our guest stars.
Speaker:First up is Dr. Minh Vu Nguyen.
Speaker:Minh Vu, or simply Vu, is a recent former mycobacterial research
Speaker:fellow at National Jewish Health.
Speaker:He is now a new Assistant Professor of Medicine in the Division of
Speaker:Infectious Diseases at UC Davis Health in Sacramento, California.
Speaker:There, he and his pulmonary colleagues have started building a
Speaker:multidisciplinary NTM Care Center.
Speaker:Hi, this is Vu from UC Davis.
Speaker:Pleasure to be here.
Speaker:Next we have Dr. Charles Daley.
Speaker:Chuck is a Professor of Medicine at National Jewish Health, University
Speaker:of Colorado, and the Icahn School of Medicine at Mount Sinai.
Speaker:He is the Chief of the Division of Mycobacterial and Respiratory
Speaker:Infections at National Jewish Health and Chief Research Officer at the new
Speaker:Bronchiectasis and NTM Association.
Speaker:Hey, this is Chuck.
Speaker:I'm very excited to be here and glad that you're joining us today.
Speaker:And closing out our group of guest stars today is Dr. Reeti Khare.
Speaker:Reeti is an Associate Professor and Infectious Disease Laboratory
Speaker:Director at National Jewish Health.
Speaker:Thanks so much for having us.
Speaker:I'm excited to be here.
Speaker:My name is Reeti.
Speaker:So before we jump in, as everyone's favorite cultured podcast, we like to
Speaker:ask our guests to share a little piece of culture, basically just something
Speaker:that you enjoy or brings you happiness.
Speaker:So what have you guys, um, had in mind for today?
Speaker:I love anything chocolate on chocolate, that's, that would
Speaker:be my favorite thing to do.
Speaker:Like anything that's disgustingly chocolate, like
Speaker:molten lava chocolate cake.
Speaker:Excellent, excellent.
Speaker:Um, for me, I don't know if this is considered culture, but I just
Speaker:adopted two cats while on consults.
Speaker:So, um, it's been hectic, but they're nice.
Speaker:Are they small cats or like adult cats?
Speaker:They are adolescent cats.
Speaker:So they're, I got 'em when they were nine months and they act exactly
Speaker:like adolescents and, um, in fact, I, they've been banging the door for
Speaker:the last hour, but maybe now they're calming down 'cause I hear other voices.
Speaker:Well we'll see if they make an appearance.
Speaker:They, they will try.
Speaker:What about you, Chuck?
Speaker:Yeah.
Speaker:You know, one of the things I really enjoy is Forrest Gump.
Speaker:We have a lot in common, and I always watch the movie if I run across it.
Speaker:Excellent.
Speaker:That's kind of surprising no one's said Forrest Gump before.
Speaker:Love it.
Speaker:Um, well thank you guys so much for being here and also for creating this
Speaker:article that we're gonna talk about today.
Speaker:We're talking about your state of the art review, nontuberculous
Speaker:mycobacterial pulmonary disease: patients, principles and prospects.
Speaker:NTM, which I'm gonna say for short, is a huge topic and we know that NTM
Speaker:pulmonary disease is an increasing problem and something that I feel
Speaker:like we all encounter at least a little bit of in ID clinic.
Speaker:I thought maybe we would just start by a quick kind of background on
Speaker:these organisms and maybe a little bit about how humans can be infected.
Speaker:Okay.
Speaker:Yeah, of course.
Speaker:Well, actually, we can begin by asking you a question, Sara.
Speaker:Um, how do you think the name mycobacteria got its name?
Speaker:I.
Speaker:Oh, I have no idea.
Speaker:I didn't prepare.
Speaker:Well, I didn't know this until this morning either, but, uh,
Speaker:Chuck, maybe you can tell us.
Speaker:Yeah.
Speaker:Well, yeah.
Speaker:So when, uh, mycobacteria were first, uh, discovered in their growth on, uh,
Speaker:on the culture media looked like a mold.
Speaker:So it was thought they may be a fungus.
Speaker:So the word myco was used.
Speaker:I mean, certainly if they were discovered today, they would have a different name.
Speaker:Love it.
Speaker:Yeah.
Speaker:Um, so yeah, so mycobacteria, the most famous one is obviously tuberculosis.
Speaker:And you guys probably heard of the new book that just came
Speaker:out, Everything's Tuberculosis.
Speaker:But I, if he's gonna write a second book, everything else would be non
Speaker:tuberculosis mycobacteria, and it includes over 190 species of soil and water
Speaker:inhabitant, uh, mycobacteria, excluding obviously M tuberculosis and M.leprae.
Speaker:And again, they live in the soil.
Speaker:They're all around us.
Speaker:Plumbing, dust, natural and municipal water.
Speaker:And most patients who get it, they get it from either inhalation
Speaker:of these mycobacterial laden soil, water, and dust aerosols.
Speaker:Or they ingest fluid or dirt or whatever into their GI tract and then aspirate
Speaker:'em into the lungs by a two step route.
Speaker:Now since we are all kind of inhaling or ingesting mycobacteria, not all
Speaker:of us actually get disease, right?
Speaker:So who gets disease?
Speaker:And it's only very susceptible hosts.
Speaker:Patients, particularly with, um, local or pulmonary anatomical
Speaker:structural abnormalities and local immune dysfunction,
Speaker:particularly chiefly bronchiectasis.
Speaker:And then we can talk about, there's two big categories of NTM and
Speaker:Reeti, do you want to jump in?
Speaker:Sure.
Speaker:Yeah.
Speaker:It's sort of helpful to think of these nontuberculous mycobacteria as
Speaker:being divided into two major groups.
Speaker:Those that grow on solid media from subculture within seven days.
Speaker:Those are the rapid growers.
Speaker:And then those that grow after seven days, those are the slow growers, and that's
Speaker:important because they have different diagnosis, different treatment, and
Speaker:they look different in the laboratory.
Speaker:And Reeti, do you know anything special?
Speaker:What makes Mycobacteria special in terms of their cell wall or, or capsule
Speaker:compared to, let's say your typical gram-positive or gram-negative bacteria?
Speaker:Yeah, mycobacteria are special because they have this unique cell wall.
Speaker:Their outer cell wall is kind of, um, embedded with these mycolic acids that
Speaker:make them very resistant t o things going into the cell and things coming
Speaker:out, which means that all of a sudden they become impermeable to things like
Speaker:plasmin, so they can't mutate that way.
Speaker:They become impermeable to antibiotics, and so that has a lot of
Speaker:implications on how we manage them.
Speaker:Oh, awesome.
Speaker:Chuck, do you have anything to add to that?
Speaker:Well, the only thing I would say is that even though we have, uh, so many species,
Speaker:uh, fortunately most of them don't harm us, I. Um, this'll come back when we
Speaker:talk about the laboratory and why it's so important to know which species has
Speaker:been isolated from, uh, your patient.
Speaker:Sara, do you have any other questions?
Speaker:Is that a good intro?
Speaker:Yeah.
Speaker:I'm gonna bring you into clinic with me today and tell you
Speaker:about someone who's shown up.
Speaker:Um, so we're in clinic.
Speaker:We have a 70-year-old woman who's been referred for possible NTM infection.
Speaker:So to give you a little background, she had been seen in the emergency room
Speaker:actually for some urinary symptoms, got a CT of her abdomen pelvis to rule
Speaker:out kidney stones, hydro nephrosis and they notice that, in some of those cuts
Speaker:towards the base of the lungs that there's some scattered tree and bud nodularity.
Speaker:And so she has a follow-up CT chest that shows some subacute versus
Speaker:chronic changes that are consistent with bronchiectasis, more of those
Speaker:tree and bud nodularities, and then a couple scattered pulmonary nodules,
Speaker:all pretty small, under a centimeter.
Speaker:And so when you talking to her, she kind of reflects back and says, you know,
Speaker:I guess I always did have bronchitis.
Speaker:Every time I had a cold, it progressed to this chest cold.
Speaker:It happens probably three to four times a year.
Speaker:And in between she has some rare intermittent cough, um, usually
Speaker:non-productive and has a little bit of chest pressure, thinks her
Speaker:weight has been mostly stable.
Speaker:She kind of feels like she hasn't been paying attention to it.
Speaker:Um, she, herself is a lifetime non-smoker, but notes that both of
Speaker:her parents smoked heavily in the home until she became 18 and moved out.
Speaker:And she spends most of her time in Florida, travels
Speaker:frequently around various places.
Speaker:But she's just in general a pretty active person.
Speaker:She kayaks, she hikes, she runs and she's just noticed that her activity
Speaker:recently has gone down and she blamed it mostly on just getting older.
Speaker:She does have a hot tub as well as an outdoor salt water pool at her home
Speaker:in Florida, and so we're not even gonna get to micro results right away.
Speaker:I'm gonna pause here and just ask what you're thinking
Speaker:about for this patient so far.
Speaker:You know, does this story fit with NTM pulmonary disease?
Speaker:What other information are you gonna be trying to gather to
Speaker:help put this all together?
Speaker:Yeah, I'll, I'll, I'll speak to this first.
Speaker:Um, you know, I think I saw this same patient, uh, multiple times last
Speaker:week since she must be moving around.
Speaker:Um, so, you know, this is pretty classic for us, right?
Speaker:This, this postmenopausal woman who comes in with a cough, maybe some
Speaker:declining, uh, exercise tolerance.
Speaker:And it's not unusual these days to have these incidental diagnoses
Speaker:made where they often get a CT of the abdomen and they see the base
Speaker:of the lungs and they, they see the bronchiectasis and or the tree and bud.
Speaker:And that's really good, right?
Speaker:Because this is usually an early diagnosis earlier than if we'd
Speaker:waited for them to come in because of their cough, which could have
Speaker:possibly been years from that time.
Speaker:Uh, so, you know, cough.
Speaker:And fatigue the most common.
Speaker:She didn't mention fatigue, but cough and fatigue.
Speaker:About 80% of patients with pulmonary NTM present with that,
Speaker:um, some shortness of breath.
Speaker:It's usually a productive cough.
Speaker:It's like this case, if you catch 'em early, it's often a dry cough.
Speaker:Um, and, and that doesn't trigger people that you know, that, uh,
Speaker:it's, when it becomes productive and they're failing antibiotics,
Speaker:then sometimes they'll order the CT.
Speaker:Uh, so she was lucky that this was found earlier.
Speaker:Radiologic findings, we always talk about kind of two different types, which
Speaker:is the, uh, what is called the classic.
Speaker:And by classic it means, it was what was described many years ago, which
Speaker:is fibro cavitary, upper lobe cavitary with volume loss looks like TB.
Speaker:They often enter the healthcare system and a TB clinic, and then they
Speaker:don't grow TB. They grow MAC and then they, they come back out to, to us.
Speaker:And the other, which now I would say is kind of the classic, the more
Speaker:common is the nodular bronchiectatic disease, which it sounds like
Speaker:the she has with bronchiectasis and some tree and bud nodularity.
Speaker:All of these things should make the clinicians suspect pulmonary NTM.
Speaker:Um, and that should lead to getting a culture, a respiratory
Speaker:culture to try to confirm that.
Speaker:And unlike TB, I mean, as you know, um, we don't make a diagnosis
Speaker:just because someone grew an NTM because Vu said earlier, these
Speaker:things are found everywhere.
Speaker:We all were showering in them, drinking them, swimming in them.
Speaker:We're we're surrounded by them.
Speaker:So we, we came up with these diagnostic criteria back in 2007.
Speaker:But let me just tell you now, in 2025, no one has validated these criteria,
Speaker:so they should be used as a guideline, you know, there, and, and that is
Speaker:that we look for symptoms consistent with NTM radiographic findings.
Speaker:And then we confirm that with, uh, the laboratory, uh, which
Speaker:is a critical component of this, uh, diagnostic algorithm.
Speaker:So we take a peek at her records.
Speaker:We find that she has one expectorated sputum culture from about six months ago
Speaker:that had Mycobacterium chimera and she had a second sputum culture that was drawn a
Speaker:couple months later that has M abscessus.
Speaker:And so we make a plan now to gather more information, get multiple sputa, and so,
Speaker:you know, why does testing take so long?
Speaker:You know, why can't we develop a rapid test to detect NTM like we have for TB?
Speaker:Yeah, testing does take a long time, right?
Speaker:Culture is six to eight weeks, and that's just really because we are waiting for
Speaker:mycobacteria to grow to detectable levels and they only double once every 24 hours.
Speaker:And then of course, once we get a positive, there's more
Speaker:time needed to identify it.
Speaker:And then once we identify it, it takes at least two to four weeks
Speaker:to grow up enough biomass and actually do susceptibility testings.
Speaker:So molecular testing is definitely a question I get quite often
Speaker:about doing that directly from a specimen so we can try to speed
Speaker:up results for an NTM diagnosis.
Speaker:I mean, we do this for TB and it works, but it's a little bit more
Speaker:nuanced for NTM because unlike TB, NTM are not always considered pathogens.
Speaker:Just detecting an NTM from a sputum could be a contaminant, it could be a dead bug,
Speaker:it could be DNA from a previous exposure.
Speaker:And so a positive result doesn't necessarily mean anything.
Speaker:And then the flip side is true as well.
Speaker:A negative result doesn't necessarily mean anything either.
Speaker:A PCR could be falsely negative because our assay is too broad, it's not
Speaker:sensitive enough or it's too narrow.
Speaker:We've just focused on a few NTM and miss the other NTM
Speaker:that's actually in our sample.
Speaker:So molecular testing has the ability to speed up testing.
Speaker:It can do more than ID, it can look for drug resistance markers, so it
Speaker:has a lot of, a lot of opportunity.
Speaker:We just need the right test designed optimally that will
Speaker:actually give us enough information to change our management.
Speaker:We're not quite there yet.
Speaker:Maybe I can ask a question, Reeti, how, how often do you
Speaker:see a mixed infection like this?
Speaker:Mixed infections are actually fairly frequent in our samples.
Speaker:About two to 12% will have at least two mycobacteria, but I don't know
Speaker:what that looks like from a patient.
Speaker:Um, number of patients.
Speaker:How often do you see co-infections?
Speaker:Yeah, it's more, it's, I would say more common.
Speaker:You know, we published a number of years ago our experience with
Speaker:abscessus and, uh, 55% of our patients with pulmonary abscessus
Speaker:had concurrent or previously had MAC.
Speaker:So it that, you know, it's pretty common to see mixed infections.
Speaker:And one reason why people hearing this might see the discrepancies is that
Speaker:from a lab point of view, Reeti is comparing in a single sample, two to
Speaker:12 or two to x, y, z percent is growing two different NTM in the same sample.
Speaker:Whereas Chuck is talking about from a whole patient who has
Speaker:cough with multiple samples.
Speaker:So multiple samples, you're more likely to have a mix of different NTM over
Speaker:several samples, so that's why you might see the discrepancy in the percentage.
Speaker:Yeah.
Speaker:And you know, your paper has this really nice focus on, you know,
Speaker:patient-centered care and how we can walk through these discussions with
Speaker:our patients, which is really hard.
Speaker:Before we talk anything about antibiotics, I thought we could pit stop there and,
Speaker:um, have you share some of that about how you approach these cases, how
Speaker:you talk about the goals of treatment and, and set expectations with them.
Speaker:And I, I think part of that of course is counseling on sort of risks.
Speaker:And, and management of comorbidities.
Speaker:But for such a huge nebulous topic, especially in the early stages when
Speaker:you don't have micro, I think, um, many of us very much welcome resources
Speaker:like this that help set the stage, but I'd love to hear your insight.
Speaker:Yeah, of course.
Speaker:Well, I can start us out.
Speaker:I know that like you said, it is nebulous.
Speaker:Um, but you know, you alluded to something.
Speaker:Uh, really important that you said.
Speaker:A lot of times we're still waiting on micro, right?
Speaker:And I think the non nebulous part is in the beginning is that let's get
Speaker:the diagnosis correct first, let's make sure they truly, truly have NTM
Speaker:pulmonary disease rather than just colonization or something else going on.
Speaker:But maybe they accidentally grew an NTM from one sputum, uh, culture.
Speaker:So, you know.
Speaker:Kind of reiterating what Chuck said in, in the 2020 guidelines, and that started
Speaker:from the 2007, the general guidelines, you need to meet three criteria in order to
Speaker:be diagnosed with NTM pulmonary disease.
Speaker:That is one, the microbiologic criteria on where you have to have repeated
Speaker:growth of the same species or subspecies.
Speaker:Radiologic criteria.
Speaker:So imaging, particularly chest CT, consistent with NTM pulmonary disease.
Speaker:Could be cavitary, could be nodular bronchiectatic.
Speaker:And then finally, symptoms compatible with NTM pulmonary disease
Speaker:while excluding other diagnosis.
Speaker:Now, this is a big caveat because you probably know yourself, some patients will
Speaker:deny symptoms or they do have symptoms, but they just don't recognize it.
Speaker:So that itself is a little nebulous.
Speaker:But during the first meeting, especially if they only have one or maybe just
Speaker:two sputums, and you don't have a convincing picture, getting to the
Speaker:right diagnosis first is the first important step of patient-centered care.
Speaker:Yeah, I mean, you know, one of the first, uh, PICO questions that we
Speaker:addressed in the 2020 guidelines was, uh, should you start treatment?
Speaker:So, you know, you weigh what Vu said, the whole picture, uh, symptoms,
Speaker:microbiology and radiology to try to make a decision if you're going to treat.
Speaker:If you decide to treat, it is a very important at the very beginning, uh,
Speaker:to go through the goals of treatment.
Speaker:And, and this is where the discussion between the patient and the physician
Speaker:or provider is critical because, um, we're not gonna make that decision.
Speaker:Uh, the patient ultimately will make that decision and we need
Speaker:to make sure that we're providing them with realistic expectations.
Speaker:And unlike TB, it's, the discussion is always the same, uh, because we expect to
Speaker:cure our patients with drug susceptible TB and most even our drug resistant here.
Speaker:That is not always the case.
Speaker:So that discussion takes some kind of a different flavor, depending if they
Speaker:have mycobacterium kansasii where we can treat and cure 95% of the time.
Speaker:Uh, MAC, where it's more like 70 to 80%.
Speaker:And then the discussion with Mycobacterium abscessus is that, you know, cure
Speaker:really is difficult to achieve.
Speaker:And Vu knows that when people come here, I tell them we don't
Speaker:use the cure word with abscessus.
Speaker:Uh, we use the control word first, and if we get to cure, that's fantastic,
Speaker:but that's not realistic discussion, and, uh, a lot of patients who
Speaker:come to us are failing treatment.
Speaker:They're not culture converting, and, and they're frustrated because they
Speaker:were told they would be cured and, and it was not a realistic expectation.
Speaker:So when we do get NTM that grows in culture, you mentioned we need to identify
Speaker:it, of course, and your paper talks a bit about how those kind of imprecise or
Speaker:challenging components of identification.
Speaker:So why as like for ID learners on here that are listening, why
Speaker:does it matter for them to know the identification beyond just the
Speaker:complex level for these mycobacteria?
Speaker:One of the biggest reasons for a full and accurate identification is because
Speaker:of differences in treatment patterns.
Speaker:We know that slow growers and rapid growers have different treatment patterns,
Speaker:but even within these groups, even within closely related organisms like
Speaker:the abscessus subspecies, they can carry resistance genes at different rates.
Speaker:So for example, the erm gene.
Speaker:Erm genes cause inducible resistance to macrolides and some abscessus
Speaker:subspecies have them, some don't.
Speaker:Same thing with the fortuitum complex.
Speaker:Some of those species carry an erm gene and some don't.
Speaker:Knowing which mycobacteria you are actually dealing with will help you
Speaker:pick the right drug, especially the important drugs like the macrolides.
Speaker:There's a few other reasons too, I think.
Speaker:Vu, do you wanna speak to those?
Speaker:Of course, so, you know, Reeti said it best.
Speaker:Uh, treatment patterns will, will change based on the species and subspecies.
Speaker:But another thing too is kind of going back to diagnosis.
Speaker:It helps us determine whether a species or subspecies is likely
Speaker:causing disease versus not.
Speaker:So again, part of the diagnostic criterion for microbiology is repeated
Speaker:growth of the same species and subspecies, and it convinces that that
Speaker:is more likely to be disease causing.
Speaker:When different species subspecies grow kind of sporadically,
Speaker:which we often see too, and none of them has grown repeatedly.
Speaker:It suggests that these cultures are more likely, I'm not saying absolutely, but
Speaker:just more likely to be colonization.
Speaker:And in the case of identification of MAC, the most lab would call it simply
Speaker:M.avium complex, or I've seen M.avium- intracellulare group, various renditions
Speaker:of that, but basically, remember a complex, and Chuck will always tell
Speaker:you this, A complex is a collection of different species and subspecies.
Speaker:And knowing that just a complex doesn't help us decipher whether this
Speaker:is the same species or subspecies growing and therefore likely causing
Speaker:disease or versus just colonization.
Speaker:It also helps providers try to sort out if somebody is responding to
Speaker:treatment or if they are just getting re-exposed to another very similar bug
Speaker:that we haven't differentiated out.
Speaker:Um, and we can also, by knowing exactly what we have, we can start
Speaker:identifying organisms that could potentially be causing outbreaks.
Speaker:And that's actually happened a few times.
Speaker:We know that M. intracellular subspecies chimaera can be associated
Speaker:with outbreaks in heart surgeries with these heater cooler units.
Speaker:We have recently found an outbreak, um, of M.abscessus subspecies
Speaker:masiliense in stem cells.
Speaker:Um, so that's another reason why we wanna do that.
Speaker:And so reaching out to your laboratory and requesting that full identification
Speaker:as well as any potential drug markers that may be associated with the bugs
Speaker:may be really important for you to know.
Speaker:But something I'd like to point out is that it's not always possible
Speaker:for your lab to be able to do it.
Speaker:Um, there are actually dozens of tests available for NTM testing,
Speaker:but only like one or two of them are available in the US.
Speaker:Um, so access is a real problem.
Speaker:Even our laboratory, we get our tests from Europe and they get
Speaker:stuck in customs every single time.
Speaker:Um, validating these tests is difficult, especially when you
Speaker:don't see a lot of these organisms.
Speaker:So a lot of providers may have to rely on reference labs to
Speaker:get the results that they need.
Speaker:Yeah, I might, uh, add to this.
Speaker:Mycobacterium avium complex, I like to say is probably more
Speaker:complex than you recognize.
Speaker:So we used to have the MAI, right?
Speaker:That's when we knew there were two species, avium and intracellular.
Speaker:But now there are 10 species and, uh, two of them avium.
Speaker:It has four subspecies, and intracellulare has three subspecies.
Speaker:Chimaera,
Speaker:which used to be a species, and yongonense, which used to be a species,
Speaker:they're now subspecies and therefore many labs will just stop at the
Speaker:intracellulare and you won't know.
Speaker:So for example, I mean this was a real life example during the heater
Speaker:cooler unit, uh, outbreak years ago, unfortunately, believe it or not,
Speaker:still happening, but uh, at its height.
Speaker:Um, I know of a hospital that they ran their clinical micro
Speaker:logs and they grew no chimaera.
Speaker:They were so excited.
Speaker:They had no chimaera cases until they figured out their
Speaker:lab didn't identify chimaera.
Speaker:They just stopped at intracellulare.
Speaker:So, uh, ultimately they did have cases, so first outbreak investigation.
Speaker:But the, the other is of those 10 species, I bet you most, uh, uh, providers
Speaker:don't know all of those names because they don't get it reported to them.
Speaker:So they don't even know they exist.
Speaker:But let me give you an example.
Speaker:You have a patient, some tree and bud Nodularity.
Speaker:Um, if they grew M.avium three times, you, particularly if they were symptomatic,
Speaker:you'd, you'd consider treating them.
Speaker:But what if they grew vulneris?
Speaker:Well, that's MAC, that's one of those MAC species.
Speaker:I probably wouldn't treat that.
Speaker:I'd probably just go right to airway clearance and see if I
Speaker:could clear that without, because this clearly not as pathogenic.
Speaker:The other, um, ones, um, that are within Mac, you, they're just not as
Speaker:pathogenic as avium and intracellular.
Speaker:So, most providers in the US don't know what actually is growing in their
Speaker:patients, uh, respiratory specimen.
Speaker:Many people who listen probably know that there are these available
Speaker:guidelines and consensus articles for when we do wanna treat our
Speaker:patients with NTM pulmonary disease.
Speaker:And certainly your paper is focused on kind of giving a more, I'd say
Speaker:broad approach and framework for people to start thinking about this
Speaker:when they're selecting antibiotics.
Speaker:And I'm gonna highlight Figure five from, from your paper that hopefully
Speaker:folks have pulled up and can look at.
Speaker:What, what things should we know?
Speaker:After you implement step one and you decide to start antibiotics, then
Speaker:in step two you must start with the macrolide if the target NTM in a
Speaker:specific isolate from the patient is macrolide susceptible, your whole
Speaker:regimen will build around this macrolide.
Speaker:This is because the macrolide and aminoglycoside are the two most
Speaker:important classes of antibiotics against NTM that are susceptible to them.
Speaker:With the amino glycoside reserved for severe or treatment limited
Speaker:disease because of toxicity.
Speaker:Something that we'll touch on later.
Speaker:In MAC pulmonary disease, sputum conversion rate goes from 70 to 95%
Speaker:when the MAC is macrolide susceptible down to five to 36% when is not.
Speaker:We see the same pattern in M abscessus from 72 to 88% in macrolide susceptible
Speaker:down to 25 to 35% in macrolide resistance.
Speaker:This leads us to step three.
Speaker:If you have an SGM or a slowly growing mycobacteria like Mac, you need to add
Speaker:ethambutol to protect the macrolide, to prevent the isolate from developing,
Speaker:acquired macrolide resistance, irrespective of the ethambutol MIC.
Speaker:This is why NJH does not report ethambutol MICs anymore in their MIC
Speaker:panels for SGM because many providers were incorrectly dropping ethambutol
Speaker:when they saw an elevated ethambutol MIC.
Speaker:And I think this is a nice lead in, uh, into step four, which will heavily involve
Speaker:the whole discussion about interpreting MICs in NTM disease in general.
Speaker:How do we use our susceptibility results?
Speaker:You know, we send our sample to National Jewish, we get it back.
Speaker:How do we understand those?
Speaker:Are they reliable?
Speaker:I, I'll start with the testing and then you guys can take it
Speaker:Okay.
Speaker:Alright.
Speaker:As much as I love lab testing, the thing to know about NTM susceptibility testing
Speaker:is that it just doesn't correlate with clinical response as well as we'd like.
Speaker:Um, we know that AST results are fairly reliable for some drugs like amikacin and
Speaker:macrolides and rifampin for M.kansasii, but the others maybe not so much.
Speaker:Um, but why, why is it like that?
Speaker:And I think there's a few technical reasons.
Speaker:A big one is the way we do testing.
Speaker:We use broth micro dilution, which is very routinely used in bacterial testing.
Speaker:We borrowed the method from routine bacteria, and it works very well for
Speaker:routine bacteria, but the premise of the technique is to test one bug
Speaker:against another drug independently.
Speaker:So one bug, one drug independently.
Speaker:But that's not how NTM treatment works.
Speaker:We need to treat NTM with three, four more drugs, and sometimes those
Speaker:drugs work synergistically, sometimes antagonistically, but we're not
Speaker:testing them that way because we just don't have the methods yet to do it.
Speaker:Another possibility is that we're not accounting for
Speaker:heterogeneity of NTM infection.
Speaker:We know that mycobacterium tuberculosis is heterogeneous.
Speaker:That's why we test it with a completely different method.
Speaker:We use the proportion method, but for NTM, again, we use broth micro dilution.
Speaker:We pick one colony and we test it against all these drugs, and this ignores the
Speaker:probability that all the bugs from the patient are not going to be the same.
Speaker:And then there's the sheer length of time it takes.
Speaker:We have to incubate these mycobacteria with the various drugs for days,
Speaker:sometimes up to two weeks just to get enough growth to read.
Speaker:And by then the drugs themselves might be breaking down.
Speaker:Yeah.
Speaker:Yep.
Speaker:Pretty much.
Speaker:And, um, I mean, to add on to the complexity or, so that's just the testing
Speaker:part, but let's say hypothetically for whatever antibiotics and bug that
Speaker:you have, the test is fairly accurate.
Speaker:Why do some combinations don't have quote unquote, uh, in
Speaker:vitro and in vivo correlation?
Speaker:And most of the time it's actually because of a lack of data.
Speaker:There's so many bugs, there's so many antibiotics, there's just no.
Speaker:No one did enough to do studies to say confirming that the this MIC at this break
Speaker:point will lead to this good outcome.
Speaker:Um, there are a few bugs and antibiotics combination that has
Speaker:been looked at with some decent data that show there is no correlation.
Speaker:That's like rifampin and ethambutol in MAC or INH in M.kansasii, but that's
Speaker:only a few where there's actually some decent, maybe trials slash observational
Speaker:clinical data saying that, okay, we looked at it and there actually is
Speaker:no, uh, correlation, at least at this breakpoint, but to further add complexity.
Speaker:Maybe one other reason is because clinical outcomes also depends on the
Speaker:host, not just purely killing the bug.
Speaker:You can kill the bugs all you want, but if you have a airway that is
Speaker:malformed from bronchiectasis.
Speaker:They're just gonna be stuck there, and you're not gonna get somewhat equivalent
Speaker:to maybe source control inside the lungs.
Speaker:Let's look at it and a different analogy.
Speaker:Let's look at, let's say, MSSA, you know, Staph aureus.
Speaker:So we know MIC matters in Staph aureus.
Speaker:That's why there's MSSA, MRSA, but the MSSA, no matter how much
Speaker:nafcillin or cefazolin you give them, if they have an undrained abscess.
Speaker:Patient's not gonna get better.
Speaker:And as ID doctors for us, that's a no brainer.
Speaker:So are you gonna say nafcillin and cefazolin MICs don't matter in MSSA?
Speaker:No.
Speaker:'cause we know it's a source control issue.
Speaker:Almost the same.
Speaker:Not perfectly analogous.
Speaker:Maybe it's the same thing in N TM pulmonary disease with
Speaker:these bronchiectatic airways that the NTM just gets stuck.
Speaker:Or even if you get 'em out with airway clearance.
Speaker:The patients might inhale them back, so therefore they don't get, quote, the
Speaker:clinical outcomes you would expect purely from a bug killing MIC point of view.
Speaker:The only thing I would add is there are two drugs for which we do
Speaker:believe the MIC determinations, and that's the macrolides and amikacin.
Speaker:So I do want, I do want the listeners to, to believe those MICs and that those
Speaker:cut points that determine susceptibility from resistance, and those are based
Speaker:on trials, uh, data that show that there is worse outcomes when, uh,
Speaker:we're above those MIC breakpoints.
Speaker:But then that's it.
Speaker:You know, the rest, uh, are laboratory derived cut points.
Speaker:That doesn't mean they're not useful, it just means they're
Speaker:not as definitive of a cut point.
Speaker:And so, you know, when I have to build a regimen for Mycobacterium
Speaker:abscessus, um, I. You know, I'm gonna look down that list.
Speaker:And there are some, I believe, more like imipenem was mentioned by Reeti.
Speaker:It's an unstable compound by the time we read the rapid
Speaker:grower at three to five days.
Speaker:I don't know what the concentration is, so I, I don't pay attention to that one.
Speaker:Uh, but other drugs that are more stable that I do tend to
Speaker:pay a little bit more attention.
Speaker:But even if they cross that magic resistant cut point, that
Speaker:doesn't mean I'm not going to use them as I build that regimen.
Speaker:Uh, because we know, we see people respond to treatment even when drugs
Speaker:are in the regimen that don't look that active, but it's all we have.
Speaker:Exactly.
Speaker:Exactly.
Speaker:I think a lot as Id doctors, we love that, right?
Speaker:We love antibiotics, we love MICs.
Speaker:What's the lowest MIC and what's the best antibiotic?
Speaker:But, uh, at National Jewish, uh, I learned the importance of treating the underlying
Speaker:disease, whether it's bronchiectasis, COPD, acid reflux, et cetera.
Speaker:Optimizing nutrition.
Speaker:And finally, if they have bronchiectasis airway clearance therapy, airway clearance
Speaker:therapy, airway clearance therapy.
Speaker:So that's why in figure five at the very top, the number one is do those three
Speaker:things, then think antibiotics after.
Speaker:And that's gonna be a big lesson for a lot of, uh, purely ID folks out there
Speaker:who are not familiar with air clearance.
Speaker:They just deal with the antibiotics part, but I want them to understand
Speaker:the importance of air airway clearance.
Speaker:Yeah, and I feel like that's a big part of it, is finding a good
Speaker:pulmonologist to partner with if, if you're not, if you need help
Speaker:thinking about those and managing the, especially the airway clearance.
Speaker:Yeah, I, I have run into a number of ID docs in the past few years that
Speaker:they start the airway clearance because the pulmonary docs are not doing it.
Speaker:Mm-hmm.
Speaker:And, uh, and I applaud them because, uh, they're watching
Speaker:videos and trying to learn, you know, more about airway clearance.
Speaker:'cause at the end of the day the patient in front of us is who we're trying to
Speaker:help, and we sometimes have to do things that we, we may not have been trained in.
Speaker:But if we don't have that available around us, then let's do it.
Speaker:Perfect.
Speaker:So, I made this patient up and.
Speaker:I kind of gave a background saying that they've had a
Speaker:culture that's had MAC in it.
Speaker:There's been one with M.abscessus, and you know, I'm gonna leave this broad and just
Speaker:say we repeated cultures and there there could be a variety of things that happen.
Speaker:You know, maybe we have a couple cultures that subsequently have MAC,
Speaker:that maybe we confirm M.abscessus.
Speaker:Maybe it's a mixture.
Speaker:And rather than just picking one and focusing on that, I thought maybe you
Speaker:could kind of compare and contrast the types of possibilities and the context of
Speaker:that treatment framework that you gave, like how you make decisions more than us
Speaker:focusing on kind of one specific example.
Speaker:So, I mean, this is a tough question, right?
Speaker:So let's say they're growing multiple organism over a series of, uh, sputa.
Speaker:So they're growing, let's say M.abscessus same subspecies or MAC, MAC.. And
Speaker:then they, they're intermingled.
Speaker:So.
Speaker:You have to find the one that grows the most and that's likely the one
Speaker:that's driving, that's the primary one.
Speaker:So let's say, you know, it is M.abscessus masiliense, um, growing four different
Speaker:times and you get two other cultures that's also MAC, that and maybe M
Speaker:subspecies something, something.
Speaker:So you know, you're going want to treat M.abscessus (assuming they
Speaker:meet the diagnostic criteria).
Speaker:Should you ignore the MAC?
Speaker:That's the question.
Speaker:Right?
Speaker:Um, and that's a tough one.
Speaker:And we see this is where a lot of nuance come into play.
Speaker:And it comes down to the macrolide, the macrolide, and protecting the macrolide.
Speaker:So if we are treating the M abscessus with a macrolide therapy, which we likely are,
Speaker:'cause it's massiliense and we wanna use a macrolide when we can, and I'm assuming
Speaker:that the Mac is also macrolide resistant.
Speaker:If you're just treating the M abscessus without any other MAC drug,
Speaker:you're basically subjecting that MAC to evolutionary pressure with just
Speaker:purely monotherapy with azithromycin.
Speaker:So even in this case, even if we don't think the MAC is driving the disease and
Speaker:it's only secondary slash colonization.
Speaker:We don't want it to become macrolide resistant.
Speaker:So in this case, we might throw on ethambutol in addition to the M abscessus
Speaker:regimen, broadening it to cover both organism, understanding that we're
Speaker:trying to treat only the M abscessus, but we're also preventing macrolide
Speaker:resistant development in the MAC.
Speaker:How did I do, Chuck?
Speaker:Well, you learned, you learned well, Vu, um, protect the macrolide.
Speaker:That's the mantra.
Speaker:Um, and these, these are often very complex decisions and, and sometimes
Speaker:we can't define a dominant one to go after and we have to treat both.
Speaker:But you can do that.
Speaker:We have to do it.
Speaker:Uh, that's usually gonna take about five drugs to do that.
Speaker:So it's not easy.
Speaker:Um, and I would just say this is when I would consider calling a friend.
Speaker:Uh, trying to get some encouragement with the, uh, the best way to approach this.
Speaker:Uh, because unfortunately we do see people referred here who
Speaker:developed macrolide resistance because one of the two was treated.
Speaker:And, uh, one drug was exposed to basically monotherapy and
Speaker:they're now macrolide resistant.
Speaker:And whether that's abscessus or macrolide resistant, uh, Mac, you know, you've taken
Speaker:someone who's likely to be cured now to someone who's likely not to be cured.
Speaker:I think one other sort of branch that I thought we could just touch on is how
Speaker:you adjust your approach if patients have severe or treatment limited disease.
Speaker:And maybe actually just starting by saying how you explain what is considered
Speaker:severe or treatment limited disease.
Speaker:Okay, I'll, I'll talk about this.
Speaker:So severe is a little more easy.
Speaker:Like usually when I, for the sake of this paper, only severe was
Speaker:referring to cavitary disease.
Speaker:So any form of cavitary disease, or even if they have nodular bronchiectatic,
Speaker:but very profound, like multiple lobes, a lot of involvement of nodule
Speaker:bronchiectatic and the patient's really sick, and a BMI of 15 or something.
Speaker:I would consider that severe even without cavity.
Speaker:Treatment Limited is a term we designed just for this paper, and
Speaker:it's not well established as standard terminology in the NTM world.
Speaker:Because we're basically combining for the sake of word count limitation
Speaker:and meeting it, we just basically squeeze in treatment refractory meaning
Speaker:NTM disease that got treated with guideline based therapy and by six
Speaker:months still haven't culture converted.
Speaker:Um, that's based on MAC, but we are extrapolating it to other NTM.
Speaker:But basically that's the MAC term for treatment refractory MAC.
Speaker:But we're also adding in NTM where their primary best drug is resistant to.
Speaker:So for example, macrolide resistant, uh, MAC will be.
Speaker:I will squeeze it into treatment limited disease
Speaker:'cause you can't use a macrolide.
Speaker:So for the sake of the paper, I squeeze those two two in simply
Speaker:because I think the next step would be something that a lot of ID doctors
Speaker:or most doctors are afraid of, and that is adding on IV amikacin.
Speaker:Chuck, do you have anything else to add?
Speaker:Yeah, I mean, I think now the, the other option is ALIS, um, amikacin liposome,
Speaker:um, installation suspension, which, you know, in the 2020 guidelines was frankly
Speaker:one of the few novel recommendations.
Speaker:Um, and it was one of only four strong recommendations in the whole guideline.
Speaker:And it's because we had phase two and phase three randomized data showing, um,
Speaker:that in people with treatment refractory MAC, that if you added ALIS to guideline
Speaker:based therapy, culture conversion was 30% by four months versus only about 9%.
Speaker:And people who didn't get it.
Speaker:And so that, so that, you know, did make it into the guidelines.
Speaker:Of course it was FDA approved.
Speaker:Um, also, so I still think though, that if it's cavitary disease that
Speaker:you're looking at and you haven't already given them IV amikacin.
Speaker:I would probably give IV Amikacin in that setting and then transition
Speaker:them after a couple of months.
Speaker:Now, this is not in the guidelines, this is that art of medicine.
Speaker:Um, but it's some, it's something to, uh, I think consider, but I,
Speaker:but I do think it gives us, ALIS gives us another tool, uh, to use.
Speaker:Do you guys wanna talk about surgery at all?
Speaker:Yeah, I mean, I, I figured, since these episode, we obviously can't
Speaker:cover such a huge topic in, in one.
Speaker:So I, that's why I thought we'd focus on the framework and maybe spend the rest
Speaker:of the time thinking about how we monitor these patients, what are other therapies?
Speaker:And that actually was gonna be one of my questions of what, when
Speaker:and how you identify patients to refer for surgical resection.
Speaker:Um, and, and how you think about that.
Speaker:So for surgery, you know, we do it a lot at NJH 'cause we have a surgeon
Speaker:who is a well-known expert in it, but usually they should be referred for
Speaker:evaluation for lung surgery if they have very uncontrolled, severe symptoms,
Speaker:most commonly is, uh, hemoptysis, that doesn't improve on any treatment,
Speaker:particularly if they have focal disease.
Speaker:Uh, doesn't mean you have to be perfectly focal and unifocal.
Speaker:It could be I. You know, it could be widespread, but mainly the disease,
Speaker:the biggest disease side is in a single segment or lobe of a lung.
Speaker:And if we think they're unlikely to achieve response
Speaker:by antibiotic therapy alone.
Speaker:So in this case, a lot of times we refer to patients with macrolide resistant MAC
Speaker:that maybe have a severely bronchiectatic right middle lobe to get that right middle
Speaker:lobe removed, and that's our most common, um, surgical referral at National Jewish.
Speaker:Yeah, we, we, you know, we, we do a lot of surgery.
Speaker:It's done at the University of Colorado by Dr. John, uh, Mitchell, who's basically
Speaker:done all our surgeries for over 20 years.
Speaker:He's probably done about a thousand patients by this time, and he has
Speaker:almost all of it, uh, uh, robotically.
Speaker:Um, so he's pretty amazing.
Speaker:It's still a very small minority of the number of patients we
Speaker:see that actually go to surgery.
Speaker:And, uh, to Vu's point, they're, you know, they often have resistant
Speaker:organisms, may have already been failing therapy, uh, have focal disease,
Speaker:probably cavitary disease is the most common reason people go, uh, to
Speaker:surgery, but they do well afterwards.
Speaker:Um.
Speaker:Um, he's, he's published with a robotic approach, you know, a 7% complication
Speaker:rate, which is very low, zero mortality in 20 years, at the time of surgery.
Speaker:Um, and culture conversion rates of 80 plus percent.
Speaker:In fact, if you look at 15 studies, we did a systematic
Speaker:review part of the guidelines.
Speaker:Um.
Speaker:The culture conversion rate was 80 to a hundred percent.
Speaker:So at least on the micro biologics how you are, you are now getting control.
Speaker:We always say it may not lead to cure, but it will help us get control.
Speaker:Yeah.
Speaker:And you know, from, you're experience seeing a lot of these patients, I
Speaker:thought maybe I would just ask if you have any big take homes or pearls
Speaker:for us to consider for those who are on therapy, either monitoring their
Speaker:response or monitoring for adverse effects of the uh, antimicrobials.
Speaker:Yeah, I would say, you know, you kind of need to have pretty frequent follow up.
Speaker:Uh, but more importantly, the thing that we see lacking the most among
Speaker:a lot of referring providers is that they, they don't get surveillance
Speaker:cultures frequently enough.
Speaker:And ideally, we want, once they start therapy.
Speaker:We do want, uh, repeat sputum every one to two month as possible.
Speaker:And this is helpful because it determines, um, length, total length
Speaker:of treatment and help monitor, um, disease treatment progress.
Speaker:You know, we have to balance the treatment response that we're
Speaker:evaluating with the adverse, uh, events.
Speaker:And, and unfortunately we know those are common.
Speaker:Um, and, and it's just part of, of the, in the management of these patients.
Speaker:Um, so the things that we're looking at are, you know, usually a complete blood
Speaker:count, comprehensive metabolic panel.
Speaker:Uh, that's kind of goes without saying, but I think the thing to
Speaker:remember is that ethambutol can produce optic neuritis and although it's
Speaker:not common, it can be catastrophic.
Speaker:So we really want those, uh, uh, those patients receiving ethambutol
Speaker:to have, uh, visual acuity monitoring, red, green color discrimination.
Speaker:No one has ever studied the optimal frequency in which that should be done.
Speaker:And we really kind of get, get into details and the guidelines on this.
Speaker:Um.
Speaker:But, but I, I think that, uh, it's a very important, uh, thing to do.
Speaker:What we tell patients is, um, read the same font every day, you know,
Speaker:because don't wait till your next, uh, ophthalmology appointment.
Speaker:Uh, but just every day, same font.
Speaker:If you feel like you're seeing some visual decrement, then you stop the drug.
Speaker:We empower the patient to feel you stop the drug and you inform us.
Speaker:And then we'll go from there.
Speaker:Mm-hmm.
Speaker:Um, and so I think that's important.
Speaker:And the other is amikacin ototoxicity is unfortunately a common adverse event.
Speaker:So we wanna monitor audiograms for that.
Speaker:We usually do baseline if they're getting iv, we, we
Speaker:typically do monthly audiograms.
Speaker:But one thing we're seeing is people with, um, ALIS are not getting audiograms, but
Speaker:it's still possible, much less common with than with iv, but it is possible.
Speaker:So same thing we do baseline audiogram on someone beginning ALIS, and, and
Speaker:then we, we check much less frequency anywhere between three and six months,
Speaker:probably three months if someone who we see already has a little hearing
Speaker:loss, maybe six and someone who doesn't.
Speaker:Um, but I think both should be monitored.
Speaker:Excellent.
Speaker:To start closing us out, I'm gonna change gears and just ask
Speaker:you guys what is on the horizon?
Speaker:Like, what are you excited to learn more about, understand better,
Speaker:maybe studies that are in process.
Speaker:What should we all get excited to, to learn about in the coming years about NTM?
Speaker:Well, I'll, I'll probably take this one.
Speaker:Um.
Speaker:There are a number of clinical trials that are occurring and number of drugs
Speaker:in the pipeline that, uh, have not quite made it, uh, to the clinical trial arena.
Speaker:But I hopefully will.
Speaker:Some of the things that I think we're very excited, exciting is, um, and things
Speaker:that we're interested in here at National Jewish, some of the new drugs, for
Speaker:example, ALIS is in, uh, has, uh, enrolled into a trial for treatment naive Mac.
Speaker:Uh, not waiting till they get refractory.
Speaker:And there were two trials, and the first has been resulted and, uh, it was a
Speaker:very positive trial in, uh, pretty much every way, both primary and secondary.
Speaker:And so it's in now a larger trial.
Speaker:That was a six month trial.
Speaker:This is, we're waiting for the results of a 52, uh, wk
Speaker:trial and that ends in October.
Speaker:So we we're gonna know, hopefully later this year, the results of that.
Speaker:Uh, omadacycline, uh, completed a phase two trial.
Speaker:Also very positive trial.
Speaker:This was in, this was a monotherapy trial in people with mycobacterium abscessus,
Speaker:and again, primary and secondary.
Speaker:Uh, very positive.
Speaker:And we look forward to see that drug and we're using it now, but we would
Speaker:like to see evidence to, uh, help us.
Speaker:Uh, inhaled clofazamine is a trial that is beginning now and is already enrolling,
Speaker:and so that's a very interesting approach of giving very intermittent inhalational
Speaker:treatments because of the long half-life.
Speaker:Um, uh, mycobacteriophage, uh, this is, you know, also not,
Speaker:not just with mycobacteria, but with bacteria in general.
Speaker:It's a very interesting area, uh, of investigation.
Speaker:Uh, there are trials for pseudomonas, but there are no NTM trials now, but there are
Speaker:cohorts, uh, that are being, uh, studied.
Speaker:So that's pretty cool.
Speaker:I, I will end, uh, I think with, um, uh, something called orc.
Speaker:ORC is a compound.
Speaker:That an aurine model was basically a hundred percent protective against
Speaker:ototoxicity from an amino glycoside.
Speaker:That trial is beginning now several sites under the leadership of
Speaker:Kevin Winthrop at, uh, Oregon.
Speaker:Uh, but we're very excited to see, you know, can we take an active drug
Speaker:like the aminoglycosides and make them safe or safer than they are now?
Speaker:But anyway, I, I think a lot of things that are very exciting are happening.
Speaker:We could, we'd have to do a whole nother podcast to talk about them.
Speaker:That's great.
Speaker:Um, very exciting to hear all those.
Speaker:And I guess I'll just open it up, you know, for any closing
Speaker:thoughts you guys have.
Speaker:Anything else that we didn't cover so far?
Speaker:I guess I'll just reinforce the unofficial title of this talk, which is protect the
Speaker:macrolide, protect the macrolide, protect the macrolide, but uh, in addition, um,
Speaker:do airway clearance therapy if they have bronchiectasis and for slowly growing
Speaker:mycobacteria, particularly MAC, do not drop ethambutol because ethambutol,
Speaker:guess what protects the macrolide.
Speaker:So please do not drop ethambutol from your MAC regimen unless
Speaker:the patient is, uh, going blind.
Speaker:Yeah.
Speaker:And, and also don't treat him only with a macrolide and a rifamycin because the
Speaker:rifamycin does not protect the macrolide.
Speaker:Correct.
Speaker:And I guess the other thing we should do, we should thank the authors.
Speaker:We're not the only authors.
Speaker:And uh, and there was a cat theme here, so Vu, he adopted two cats, but to get this
Speaker:thing written, he had to herd the cats.
Speaker:And he did an incredible job of that.
Speaker:Yeah.
Speaker:Oh, thank you.
Speaker:Yeah, the authors were amazing.
Speaker:Like all, I think 12 of them.
Speaker:Um, I remember getting the, the bits and pieces of everyone, and I know,
Speaker:um, CID said 5,000 words and then I put it all together and it was 9,000
Speaker:words and I was like, wow, that's, this is gonna be, this is gonna be fun.
Speaker:It is like telling your cats to like stop eating, but they keep eating
Speaker:kind of equivalent, you know, it's like, okay, how do you stop 'em?
Speaker:But yeah, they were, I mean the authors were amazing.
Speaker:Obviously Reeti and Chuck, but the others particularly, I'm gonna give a shout
Speaker:out to the very, one of the very middle author who doesn't get enough credit.
Speaker:His name is Vinicius, he wears multiple hats.
Speaker:He's like a microbiologist and data analyst and research all at the same time.
Speaker:But he's the one who actually kind of designed these figures, like
Speaker:particularly that, that fancy figure one with that giant mycobacterium.
Speaker:Yeah.
Speaker:He drew that.
Speaker:I drafted a really ugly version of that, um, pen and paper, and he made
Speaker:it like not ugly, which is great.
Speaker:Oh, and Chuck has it right there.
Speaker:Wow.
Speaker:I love a good graphic.
Speaker:This is place to give a shoutout for that.
Speaker:Yeah.
Speaker:Awesome.
Speaker:Um, well I am just, again, very, very grateful that you
Speaker:guys took the time to do this.
Speaker:Yeah, it was a pleasure.
Speaker:Thanks for
Speaker:Thanks.
Speaker:Thanks.
Speaker:Yeah.
Speaker:Appreciate
Speaker:thanks again to our guests for joining Febrile Today.
Speaker:Make sure to check out their State of the Art Review in CID entitled
Speaker:Nontuberculous Mycobacterial Pulmonary Disease Patients Principles and Prospects.
Speaker:Check out the website Febrile podcast.com where you'll find the Consult Notes,
Speaker:which are written supplements of the episodes of links to references,
Speaker:our library of ID infographics, and a link to the merch store.
Speaker:Febrile is produced with support from the Infectious Diseases Society of America.
Speaker:Please reach out if you have any suggestions for future shows or
Speaker:wanna be more involved with Febrile.
Speaker:Thanks for listening.
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