Intro: Welcome to UAB MedCast, a continuing education podcast for medical professionals, providing knowledge that is moving medicine forward. Here's Melanie Cole.

Melanie Cole, MS (Host): Welcome to UAB MedCast. I'm Melanie Cole. And today, we're highlighting non-tuberculous mycobacterial disease. Joining me in this panel is Dr. German Henostroza, he's a specialist in Infectious Disease and Travel Medicine and a professor at UAB Medicine; and Dr. Bryan Garcia; he's a specialist in Pulmonology and Critical Care Medicine, and he's an Assistant Professor at UAB Medicine. Doctors, thank you so much for joining us.

Dr. Henostroza, I'd like to start with you. Can you tell us about recent epidemiological trends and prevalence of NTM disease? What's changed over the years?

German Henostroza, MD: Thank you, Melanie. It's interesting. What we know so far about NTMs is that it's increasing, particularly in the United States where we have the most up-to-date data. It's very difficult to know the exact numbers, but it's estimated that around between 100,000 to 150,000 people in the United States are affected by non-tuberculous mycobacteria. There's multiple mycobacterias among those, but that's roughly the number in the United States. Now, worldwide that's a more difficult question to answer because nobody regularly cultures for it or identify them. We concentrate in what is called mycobacterial tuberculosis, but not in non-tuberculous mycobacteria. And these people that is affected in the United States is predominantly in the south of the United States where we find most of the cases.

Melanie Cole, MS: Well, thank you. And Dr. Garcia, what are some of the most significant updates or advancements in our understanding of NTM since you began practicing medicine? How has the understanding of the pathogenesis of this disease evolved in recent years?

Bryan Garcia, MD: That's a good question. And it's an area that needs ongoing future research because much of what we know now is still much of the same things that were taught to me a decade ago when I was doing my fellowship here at UAB even. And I think that that speaks to the need for ongoing research, because certainly there's more to the story with regards to the pathogenesis than we currently understand. For many of the individuals that we take care of, we suspect why these individuals have acquired these infections. But for most of them, we are left saying you're really the right host, and the exact reason why you and why at this time is really anybody's guess.

Going back to your first question about the epidemiology of the disease plays into the pathophysiology, it is definitely increasing and we certainly don't know the exact numbers as Dr. Henostroza pointed out in terms of how many people are affected by these infections. But here at UAB and other places I've practiced, there's a commonality that it is overwhelmingly this postmenopausal Caucasian female host or patient who acquires this infection later in life, typically in their 60s and 70s. Most of them have never smoked. But why it is that that unique cohort acquires the infections and they make up the bulk of our patients, that gets down to the pathophysiology and what's happening in their airway that they're so susceptible. And for most of these individuals, we really don't have a great understanding as to why that is.

Melanie Cole, MS: Isn't that interesting? So, what about diagnosis? Dr. Henostroza, have there been any notable developments in the diagnostic tools or techniques for identifying NTM infections? As somebody who is, as Dr. Garcia was just discussing, in that cohort of patients that would be most at risk, what are we looking for? Whether it's primary care or where, tell us what they're looking for.

German Henostroza, MD: It depends on where the disease is located, correct? So now, most of the non-tuberculous mycobacteria infections affect the lungs. And it's expressed as a pulmonary disease in different ways. Now if you think about the symptoms that it could have a patient with this infection, it will be cough, night sweats, fevers, fatigue, shortness of breath, sometimes chest pain, sometimes a lot of sputum, associated with other problems related to chronic lung diseases. But this is not specific of NTMs in the clinical environment. Many, many other infections could present like that. And therefore, it's important look at the risk factors that the patient has to develop NTM infections, which other comorbidities they have, because mycobacteria are environmental. Risk factors are things that we think are not tremendously risky. But for example, gardening for long periods of time and just inhaling dust without any mask protection, it could let the mycobacteria enter because these mycobacteria are in the environment, in the soil. So, that's one thing.

The other part is going to be, for example, if patients like to take hot showers for longer period of times or hot baths, it's also another way, because it's in the water, that vapor that comes out of that could come into your lungs. Now, once it's established in the lungs, which is the primary route of entry. It's just about diagnosing the patient is high index of suspicions of the physician that is looking at him or her. And then, doing the proper test.

Now, when it comes to testing of these mycobacterias, same diagnosis has been probably for the last 50 years, which is sputum examination under the microscope with something that is called acid-fast bacilli smear and a culture of the same sputum. There is novel techniques that allow us to rapidly identify things directly from a sputum. And it comes from things that are called novel methodologies that identify bacterias like MALDI-TOF, laser technologies, or molecular testing, but that usually comes when we have already the bacteria isolated in the cultures. So in terms of diagnosis is about the same culture of the sample of the sputum and then also examination under a microscope actually of the sputum itself. That's where we are in terms of diagnosis.

Bryan Garcia, MD: And I'll add to that two more things. One is that chest imaging is not diagnostic. But raises the level of suspicion. And so when a test radiologist reads CT scans, they will oftentimes see specific changes to the lungs that make them suspicious of the possibility of NTM infections. And chest radiologists over the past decade have become much better at stating, "I'm seeing these abnormalities. Consider that the possibility of an atypical infection, including NTM infections." They're doing a very good job of putting that into their impression of what they're looking at when they see a CT scan. And so, primary care doctors and pulmonologists, infectious disease doctors, when they're getting those CT scans, they're oftentimes having that suggestion given to them and that's, I think, helping patients get to their diagnosis a little bit sooner.

Like Dr. Henostroza pointed out, historically, diagnostics absolutely necessitates identification of the organism in the sputum or in a sample taken from the airway during a bronchoscopy as it relates to pulmonary NTM, absolutely must. As of present day, we're hopeful that there are some new labs being developed that are actually utilizing blood samples. And we're hopeful that some of these may prove to be successful. Some of the first trials have now been reported in the respiratory journals, for example. And the reason that that would be helpful is if we could make the diagnosis on blood samples and, again, this is not currently available, but in the future, if we had a way to make the diagnosis on a blood sample, that would really help with getting to the diagnosis faster for people who cannot provide a sputum sample, because not all patients with NTM infections will make sputum. And so when they don't make sputum, it means we got to go to a bronchoscopy, which is an invasive procedure. But if we could be able to skip that step and get the answer from blood work, that would be very helpful for those individuals. And we're hopeful that maybe in the next few years, we may be able to reach a point where a non-invasive sample, whether it's from the blood or actually even there's some testing being done looking at urine as it turns out, but finding not the infection, but the sign that that infection's occurring in those different types of patient samples. We think that that would be very helpful and we're hopeful that in the future we have those.

German Henostroza, MD: And let me add on to this, Bryan. It's important also to remember that while we're talking about pulmonary disease here and sputum samples for that, non-tuberculous mycobacteria also could affect any part in the body. We have seen infections in the brain. We have seen infections in the skin, which is related to a lot of cosmetic procedures, not only here in the United States, but outside of the United States; in the eye, in the joints. Prosthetic joint infections are growing with some concern for infections related to this non-tuberculous mycobacteria. So, not only is this sputum sample that is diagnostic, of course that's for pulmonary problems, but when it's extrapulmonary or it's outside of the lungs, then the test like Bryan was mentioning like a serological test or a blood test, it will be very helpful to determine other diagnosis that are not specifically in the lungs.

Bryan Garcia, MD: And I think that's a great point. And what I'll just add then too is something that makes our clinic very unique is that we do see people who have this. And the majority, it's they have pulmonary disease. And when they have pulmonary disease from NTM, it will stay in their lungs. And what Dr. Henostroza is talking about is we do also see people who have NTMs outside of the lungs. Most of these are, as he said, post-operative infections. An example, an alternative is I've seen an individual who dropped a clay pot with soil in it and caused a wound in their leg and they got the infection in their leg.

But that's something that makes our clinic very unique is we have so much experience in pulmonary disease management, experience with utilizing a lot of different antibiotics because the treatment for these is so tough. And parlaying that to be able to successfully care for these individuals who have extrapulmonary disease and being able to come to the table to them and say, "Hey, we have a lot of experience in understanding how we're going to use these antibiotics, how we're going to deal with side effects related to the antibiotics, and get you through this infection." And I think that that's something that our clinic is very unique and just wanted to comment on that.

Melanie Cole, MS: That's an excellent segue, Dr. Garcia. And this is such an interesting, enlightening discussion that we're having here today. Dr. Garcia, what updates can you provide regarding those treatment guidelines? Has anything changed?

Bryan Garcia, MD: The treatment guidelines for pulmonary disease NTM were updated, I believe it was in 2019, I think it was when it was. It was the first time it had been updated in probably about a decade. Most of the guidelines remained very, very similar or even the same. There was one new antimicrobial that came to market in the interim between the two guidelines. That antimicrobial is called amikacin liposomal inhaled suspension or ALIS, A-L-I-S. And the new guidelines kind of stated where in the treatment algorithm ALIS exists and should be utilized. It did recognize also that there is some ambiguity or, in certain instances, there's still an unknown, and whether or not the right thing to do is, for example, to use three antibiotics versus two in a certain scenario. And the guidelines were updated to reflect that there are these unknowns and that there are active trials to try to tackle these questions to better understand what does the appropriate treatment look like for each individual with NTM infection.

German Henostroza, MD: And I think, Bryan, also, it's important to address that most of what we know from non-tuberculous mycobacteria more and more are extrapolated from the classically non-mycobacterium tuberculosis, which is the disease that has basically taken over the world and in the United States was very common as well.

I guess, the understanding of non-tuberculous mycobacteria in general is that at least two antibiotics should be used in combination that are bactericidal. Now if three are needed or better, those are the trials that are needed the most just to say for how long? Usually, the treatment is going to be long. The expectation of a patient to be on treatment is going to be at least 12 months, if not more, in order to establish that the patient has been sterilized. And that's important to say because the goal of treatment is to prevent further damage in the lungs more than curing the patient.

We need to remember that cure as per se, the definition of cure is not always reachable with these treatments because most of these patients could relapse on the infection after two or three years being fine. So, the goal of treatment in all of these patients is going to be to prevent further damage in the lungs and just trying to have a standard or a quality of life standard actually over the next years.

Melanie Cole, MS: Dr. Henostroza, I have a question for you about infection control measures. But along those lines of what you were just discussing, side effects for the patients, how do you work with patients and possibly a multidisciplinary team to mitigate some of those side effects while you are, in a sense, sterilizing this patient?

German Henostroza, MD: That's a very important question. So, the first thing that we do in the clinic is just establish a rapport with the patients. They need to understand that the treatment is long. We also need to explain on any medication that we're going to give them, there's going to be side effects. There's no questions about it. And we are very thorough at explaining all the possible side effects that could come, the most common ones and the less common ones. And it's important as we have a multidisciplinary team, we have a nurse, we have nurse practitioners. Everyone should be involved because as a team, we manage the patient. The pharmacist is also involved, respiratory therapies are involved. So, we need to create this conscious in the patient that we're there to help, and understanding that sometimes these side effects are unavoidable.

If you ask me, for example, the most common side effect of a common medication that we use that is azithromycin is nausea. So, GI upset, gastrointestinal upset. So, we explained that to the patient. We said how she could prevent those things to happen, but it still could happen. And we tried to find the best way possible that the patient could adjust to that treatment since it's going to be for a long period of time. There's going to be some times that the patient cannot tolerate the treatment, and there will be the time that we need to decide, okay, so there's intolerance for sure and we need to change the medication. Because let's be honest, if you have a patient or someone who is sick that doesn't want to take the medicine or the medicine makes you more sick than the disease itself, why they are going to take it? So then, you don't achieve what the goal is of therapies to complete at least 12 months of treatment. So, it's very important communication here. Be attentive to, by phone, in the first visit, by phone telehealth visits. And then, always hearing what the patients need to say, and refer them properly to the appropriate level of care when they need to. I would say that's probably the most important part.

Bryan Garcia, MD: Yeah, I agree. I mean, we tell our patients, your journey will not be straight. We will not be giving you these antibiotics and expect that, you know, in 18 months of taking them, everything went perfect. Your journey will be filled with lots of pivots, and we're here to pivot with you. We encourage all of our patients to utilize our patient portal, message us. You know, we tell them there's no too much messaging. We want to know what's going on so we can help make those pivots for you. Timely and effectively based on what's going on, because every individual, when you give them these different antibiotics, there's the most common side effects, but then there's what is each individual experience and how do we mitigate those side effects, whether it's adjusting the time of day that we have them take the medicines, how they take them, are we giving them other medicines to help with their appetite or their nausea or their diarrhea, whatever it is, and then sometimes pivoting and saying, "This antibiotic doesn't seem like the right one for you. Let's try this one instead." But I think the key piece is what we are always telling them, which is there will be lots of pivots in this journey, and that's why our communication is going to be so important.

German Henostroza, MD: Yeah. And, Melanie, going back to what you mentioned that I think I missed to answer, infection control, one of the things that we tell our patients as well, which is a concern for them, the first question they ask is, "Can I transmit this to my loved ones or my family?" And the answer is no. This infection is not transmitted from person to person. As of now on what we know, yes, that's not possible. So then, therefore, it's important for them to be aware of that, that they are not going to pose a risk to anybody at home by having this infection, which is completely different from what we call tuberculosis produced by the mycobacterium tuberculosis.

Melanie Cole, MS: Thank you both. This is such a challenging disease and so interesting. So, I'd like to give you each a chance for a final thought. And Dr. Henostroza, as a specialist in infectious disease, what would you like primary care, Internal Medicine, other providers to take away from this discussion today? Any significant discoveries in genetics or molecular mechanisms that are underlying susceptibility or resistance to NTMs, anything that you'd like them to know?

German Henostroza, MD: Well, I think one of the important parts here is to understand that the use or indiscriminate use of antibiotics, it creates resistance in all bacteria, but also in non-tuberculous mycobacteria. So, one of the things that we need to be very conscious about is that when we prescribe an antibiotic, we need to be very sure of what we are treating. Otherwise, we will find surprises. By treating multiple times a urinary tract infection in a patient that potentially has a non-tuberculous mycobacteria, then it will create a problem for us when we see the patient in the clinic because has multiple times exposed this mycobacteria to this antibiotic. And that potentially could have caused some resistance on that patient.

So, number one is going to be to any physician or any provider who is treating infections to make sure that they know what they are treating. That's number one. And number two is going to be if they have any concern of this infection happening in their patients, but they don't have the expertise or the knowledge or are not sure, we're here to help. They could refer the patients to our clinic. They could call us, they could send a communication to us. Sometimes we answer questions directly. Sometimes we prefer the patient to be referred to us. It's either way that we could help them to achieve, which is the most important part is the wellbeing of the patient and appropriate treatment for these patients.

Melanie Cole, MS: Dr. Garcia, last word to you. How are you incorporating the recent updates you've discussed here today and advancements into your clinical practice? And what are the conditions under which you believe patients would benefit the most from your experience with NTMs?

Bryan Garcia, MD: Our clinic is unique for several reasons, some of which I've already mentioned, but having both perspectives, mine as a pulmonologist, as someone who has spent their career now focusing on the treatment of chronic lung infections, how that progressively affects your pulmonary function and your long-term lung outcomes. And having German's experience as really this tuberculosis guru and with his Infectious Disease background, I think allows patients to know that each time they're seen at our clinic, they're getting both perspectives. They might not see both of us that day. You'll probably just see one of us, but we're going to talk about you at before and after clinic. And we're going to make sure that we feel like we've done everything we can to optimize the antimicrobial regimen and the management of an individual's lung disease at the same time, so that we're really trying to mitigate and minimize any progressive loss of lung function.

And I think that creating this multidisciplinary clinic has allowed for that very unique opportunity for our patients who have an infection that most have never heard of, or they don't know anyone else with, allow them to come, get the education they need from us, to understand their health issues, and to feel confident that each time they leave, that they know that they've had folks with both of these really unique clinical backgrounds be able to come together and talk about their health to make sure that their long-term lung function outcomes, assuming it's pulmonary disease, is as optimized as it can possibly be. And, you know, we rely heavily on what are these current guidelines and incorporate them into our practice to make sure that we're from a multidisciplinary approach, appropriately attributing the guidelines to our patients.

Melanie Cole, MS: Thank you both so much for joining us today and sharing your incredible expertise for other providers. And for more information, please visit our website at uabmedicine.org/physician. That concludes this episode of UAB MedCast. I'm Melanie Cole. Thanks so much for joining us today.