Video Antimicrobial Decision-Making in MAC Lung Disease: Optimizing Treatment Outcomes and Microbial Conversion Play Pause Volume Quality 956P 684P 546P Fullscreen Captions Transcript Chapters Slides Antimicrobial Decision-Making in MAC Lung Disease: Optimizing Treatment Outcomes and Microbial Conversion Overview CLICK HERE FOR CME CREDIT Back to Symposium So thank you so much, uh, Professor Lang. Uh, thank you for inviting me to give this speech, uh, in this industry symposium at the ERS 2025 Congress. My name is uh Stefano Aliberti. I'm a full professor in respiratory medicine at Ummanitas University in Milan, and I'm the chief of the pulmonary department in the uh Humanitas Research Hospital. Uh, and I'm also chairing the Italian registry of pulmonary NTM and I will, uh, give a talk about, uh, uh, antimicrobial decision making in Mack lung disease with a focus on, uh, microbiology and, uh, uh, radiology. I would like to start first of all with a clinical case of an 80 year old female. Um, she just came to my, uh, to my clinic a few days ago. She's a retired, uh, uh philosophy teacher, former smoker, 36 years, and, uh, um, her past medical history is consistent for uh GERD, the gastroesophageal reflux disease, a cerebral cerebrovascular disease. She had a very bad glaucoma, a bilateral glaucoma, uh, with, uh, now a bilateral full blindness. She also suffered, uh, of mild hearing loss. This was induced by uh azithromycin. She took for two weeks at that time was uh given uh to her as an immunomodulatory. Uh, agent, uh, so one table, uh, one tablet 3 times per week, but after 2 weeks, um, She discontinued because of mild hearing loss. Actually, her husband uh is a physician, uh, he's a clinical microbiologist. So this uh mild hearing loss was, uh, uh, testified by the, by her husband, um, but she also has uh epilepsy on valproate. The story is a, is a two-year history of chronic cough and the reason why, and this is the reason why she underwent a CT scan. Uh, you can uh see the uh CT scan at the right, uh, top of my slide. The, the, this lady has uh multiple bilateral cylindrical bronchiectasis uh with some uh uh varicoid pattern at the right uh uh middle lobe. There is a lot of mucus plug and diffused stream bud pattern. As you can see from uh. The ongoing uh images here. The point is that she. Had two CT scans. One was in March 2024. These, um, I'm showing to you is the one done in September 2025 and there is a progressive evolution uh of the CT scan. Her pulmonary function test was done a few days ago. Uh, her FEV1 is uh uh 65% predicted uh after uh SAA. In terms of symptoms, as I mentioned, uh, she had a history of chronic cough from, for many years, but most of the physicians, uh, uh, told her this was, uh, to be attributed to gastroesophageal reflux disease. However, the situation over the past 12 months, uh, uh, got, uh, uh, worse with a daily cough with, uh, an impact on quality of life, marked, uh, a malaise. Uh, she, uh, had a weight loss of 7 kg in one year. The BMI is now 17, uh mild episodes uh of hemoptysis uh in 2025 and uh nocturnal cough also, uh, over the past few weeks. In terms of exacerbations, uh, the patient experienced for exacerbation from January to September in 2025, no hospitalizations, uh. And treatment with different antibiotics, uh, uh, gave her only a transient benefit. In terms of immune profile screening, uh, we found a relative TNB lymphocyte reduction uh with normal IgG subclassis. She underwent a bronchoscopy in June 2025 and in September, we received these results. Mycobacterium avium, uh smear positive with a time to culture positivity of one week. The pathogen was macrolite susceptible and the MIC for amiccain was 322. On the same bronchcal violavage, we found also rare colonies of Aspergillus species with a positive galactomanin and with Aspergillus PCR DNA detected. So this is the situation when I saw the uh the lady. Now I'm asking uh um What is driving the disease? Either mycobacterium or Aspergillus or both of them, or maybe some bacteria we were not able to find in the BL. Would you initiate treatment and especially what would you target? Aspergillus or mycobacterium? The case is a little bit difficult uh to me because The patient, uh, the patient, uh, is blind. With mild hearing loss, with a progressive CT and uh one year ago, the, the lady was able to walk and also to swim, but now she told me she can't leave the house because of malaise and cough. So, the disease is clinically relevant and the disease is also radiologically relevant. Now, let's focus on the mycobacterium me and let's review together what is the initial evaluation in terms of antimicrobial decision making. Usually, we consider 4 different pillars, host factors such as comorbidities, drug intolerance, the aim of uh treatment, and patient wishes. The diseases severity, both from a radiological point of view, from a microbiological point of view, from a clinical point of view. But also we tend to look at the case uh longitudinally because this usually gives us a lot of information in terms of treatment or watchful waiting. And finally, clinically relevance, especially if the patient has an immunosuppression and in terms of uh different NTM species that are isolated. Just to remind all of us, uh, the recommendation from the latest 2020, uh, international, uh, grade-based uh guidelines. Uh, inpatients who meet the diagnostic criteria for NTM pulmonary disease, uh, the expert, uh, suggests the initiation of treatment rather than watchful waiting, especially in the context of positive acid-fat basilized sputum smears, and or cavitary lung disease. So, microbiology and radiology should be evaluated uh uh in depth in order to decide to propose or not treatment to our patients. Let's start from a microbiological point of view. Um, first of all, one important question is about a systematic microbiological testing. These, uh, uh, there, there are no strong data in literature about screening for NTM in people with chronic lung disease, uh, um, but I think that first of all, we should uh have clear in mind the importance to have a direct talk maybe uh on a weekly basis with our lab because we want a precise species and subspecies identification. We want an appropriate and reliable DST in uh most of the case. And ideally, we also want to look at genotyping uh the same species isolate if the patient has a recurrent disease. In terms of, uh, in terms of, uh, screening, uh, a nice review paper has been published by Michael Lubinger in 2024 in the European Respiratory Journal Open Research. Uh, different risk factors, uh, have been evaluated. Uh, different, uh, immune system. Uh, immune system disease, um, have been suggested, uh, to be investigated for NTM, so not only bronchiect disease or patient with a previous tuberculosis or patient with a previous non-tuberculosis mycobacterial lung disease, but those with different degree and severity of immunosuppressions. Uh, people with, uh, specific clinical sign and symptoms and radiological patterns. For example, people with recurrent respiratory infection or amo disease or persistent cough or persistent sputum production. So 12 European experts uh uh through 3 round uh Delphi process, uh, uh, identified some clinical and radiological characteristics that might serve to better individualize a screening for NTM. We also know that not all the species uh uh have the same virulence and we also know about the importance of microlide resistance, uh, especially, uh, in the, uh, as, in terms of um response to treatment. Now, our patients uh was smear positive. The smear positivity is a clear risk factor for disease progression. I want just to mention these two papers. One on the left is published in 2017 and one on the right is published in 2019. As you can see in the multivariate analysis, the positive sputum smear is associated uh with disease progression with another ratio of 1.81. And on the right, a positive smear is associated with uh disease progression in non-cavitary nodular bronchistatic MACPD patients with an adjusted ratio of 2.04. So, this is the reason why we look at that and we make some decision according to the smear positivity. In fact, if you take a look at the Edwards uh paper published in the Annals of ATS in 2022, you see that uh a treatment initiation, an NTM disease was found, uh, was, uh, found in a cohort or of smear positive patients, uh, in a higher prevalence than in a cohort of smear negative patients. And finally, time to culture positivity. Uh, this is, uh, a very Intriguing and important data we need to ask to our uh lab, supported by these and other literature. These are the three papers I want to, uh, just, I want to suggest you to go through. The first one is uh the EWAS paper, uh, which is a retrospective cohort study of 125 patients followed at the Toronto NTM clinic uh between 2015 and 2019. Uh, this is the, uh, this is the frequency, uh, of the, uh, time to positivity with a median time to positivity of 12 with a range from 6 to 44. And uh the authors clearly uh show the, the time to culture positivity being associated with NTM disease, with the smear positivity, and with treatment initiation. Uh, sort of cutoff of 10 days, um, according to those data seems to be reliable, uh, in terms of disease activities, mere positivity, and treatment initiation. But there are also different study disease, uh, and, uh, and analysis from the converted data of about 71 patients published in the BNC infection disease a couple of years ago. As you can see, uh, there was, uh, a, a correlation between the time to positivity and uh the culture conversion either achieved or not achieved. And this data has been also confirmed by uh another paper published in just in 2022 by EAO and co-workers. Uh, you can see that the uh treatment time measured in months. Uh, was, has been plotted in the figure on the right, uh, with the, uh, time to culture positivity in days, and you can see, uh, patient, uh, who converted in red and patient who, who did not convert uh the culture in, in, in blue. And you can see that uh there is a, uh, a correlation between conversion and time to cultural positivity. The information, uh, the microbiological information are crucial not only at baseline but also longitudinally. So we need to look for different species also during treatment. We need also to have a DST of those species isolated during a period of watchful waiting or even during the period of treatment. But uh also smear is relevant to be looked at. Uh, during treatment or during watchful waiting because we might have an increase in the burden, in the microbiological burden or even a decrease or a negativity of the smear, but also time to positivity should be also looked at in case of an isolation of an NTN during the watchful waiting phase or during treatment. So these 4 important aspects of the microbiological domain should be also evaluated longitudinally. Now, moving to the radiological domain, we know that the fibro cavitary pattern as well as the number of lobes involved by the disease. are uh associated with uh progression in a patient with MAC PD and uh this is the classical fibro cavitary pattern on the left and the nodural broncstatic pattern on the right. We also have a, a score, the so-calledO score published uh uh in 2008 in patient with uh Mac PD looking at severity, extension, bronchialoltness, mucus plug, trim bud, cavity, emphysema, um, mosaic perfusion, uh. Uh, volume decrease, so a very complex, uh, uh, score, uh, but, uh, um, interesting, uh, because it was associated with lung function and lung function decline. Although now, uh, there might be uh very important literature, uh, to be considered, uh, especially, uh, in terms of AI, artificial intelligence, deep learning-based prediction models, uh, in people with NTMPD and the pet CT is extremely intriguing, uh, because, uh, there might be, this could be a marker of disease activity. Uh, could be some, some of us are using that. Uh, this is a case series we published a few years ago with the friends uh back in Turin in Italy. These were 20 patients, uh, uh, with, uh, mainly uh uh accidental finding of a non-tuberculose mycobacteria after a PET CT scan done. Because of lung cancer, suspicion, um, and we follow these patients longitudinally. So we think that uh ideally the, uh, the, the, the PET CT, uh, and the evaluation of the SUV max measurement uh could be part of, of a baseline assessment of patients with a newly diagnosed NTM lung disease. Um, and, uh, we might want uh brand new data in order to better understand the role of PET CT. In uh evaluating treatment response or during watchful waiting in people with uh NTM disease. Finally, I want to mention the um BC's score, uh that is uh a score published in the Blue Journal in 2021 including BMI age, cavitation, um erythrocyte sedimentation rate and sex as a prediction of 5 years mortality. So the estimated 5-year risk of mortality was 1.2% with people with score zero, up to 83% uh for those with score 5. So, so far, as far as I know, this is the strongest uh uh score to predict mortality in people with non-tuberculosis mycobacteria. When we start treatment, uh, uh, we also start looking at outcomes. Uh, this definition from the NTMNET, uh, uh, consensus, uh, group is extremely important, especially, uh, for those. Designing new randomized or clinical trials. Um, it's difficult, a little bit difficult to apply actually in, in the real world because the definition of all the different 12 outcomes uh in the majority of the cases are really precise. Uh, we try to look at those definitions in a real-life setting, uh, in this, uh, paper, in this, uh, abstract we submitted at the WBC in Dundee. Um, as you can see, the percentage uh of most of the outcomes are very low than the expected, mainly because in real life, The physicians tend not to do bronchoscopy, tend not to uh look for uh induced sputum, for example, in order to have the microbiological uh domain in the longitudinal evaluation. But if you take a look at the refractory disease definition, this was based on the 2020 guidelines among uh 762 MAC PD patients in the Italian registry, 40% uh reach a definition, a diagnosis of refractory disease. So, I, to conclude, uh, smear and time to positivity, in my opinion should be added uh in the microbiological report, uh, and to, and should be interpreted also longitudinally. In the next future, uh, I would love to have a strong AI and PET CT data to support the radiological evaluation and disease activity of people with NTM and MacPD. The multidisciplinary approach, uh, uh, is always uh suggested in order to manage comorbidities and have a clear impact in reducing disease activity of our patients. Um, in terms of standard operating procedures, we might need a larger consensus, uh, in terms of, uh, when to repeat a CT scan, when to repeat chest X-ray, uh, and, and several other aspects of disease management. And finally, I think that we need to have it published. Large consensus agreement on outcomes definition in real life. So let's go back to the clinical case. Now, we mentioned the microbiological domain, the clinical domain, and the radiological domain in a, in this lady uh with an isolation of Mac uh and Aspergillus. So the first question was, Mack lung disease, treat now or watch for waiting. There are some arguments to treat, I just want to sum up. There is a, a symptom burden with uh asthenia, weight loss, chronic cough, and there is a clear radiological progression with a smear positive and a short time to positivity. All these elements would support uh treatment uh because the disease is very active. There are some arguments in terms of putting the patient in watchful waiting because there are major tolerability barriers. Um, as I mentioned, there is a prior macro light associated hearing loss. Uh, there is blindness, uh, that might precludes the monitoring for, uh, uh, a tumbu optic toxicity. Of course, if we treat Macca, we should consider a malispiring combination with it with some clofazammine-based backbones therapy. And we should think also of inallamicaine maybe Alice because in Europe, uh, the patient has a clear. Limited treatment option indication of this drug because of the autotoxicity, uh, because of the macrolide resistance. If we treat the patient with a muasin, of course, autotoxicity and nephrotoxicity should uh Uh, deserve a precise monitoring plan? On the other hand, if we go for a watchful waiting strategy, a tight surveillance should be there. A second important question is, should we treat first or not to treat aspergillus? Well, we miss a complete Aspergillus workup in this patient, especially in terms of IgG, uh, for both Aspergillus species and Aspergillus fumigetus. If we want to treat aspergillu, it would be because the galactomanin is positive and there is a progression of a CT scan, so we think about uh a fungal disease, uh, maybe an early CPA. On the other hand, we want also to Do a watchful waiting because the colonies are rare because there is a single BL positivity and because we know that the patient is a good candidate, unfortunately for any pathotoxicity and for some drug to drug interaction. The final consideration is, uh, we should also think about non-pharmacological intervention. Air reclearance should be always optimized. Uh, we need to consider nasal irrigation. We should, uh, discuss with our nutritionist, uh, how to improve the nutritional support of these patients and of course, we should Uh, we should suggest vaccination, anti-pneumococcal vaccination, or maybe anti-ophilos influenza B is if appropriate. So with this, I would like to thank you all for listening and uh yeah, you might have my contact in case uh you might uh need any explanation or you might have any question about my presentation. Thank you so much. Published Created by Related Presenters Professor Stefano Aliberti, MD Professor in Respiratory MedicineHumanitas UniversityChief, Pulmonary DepartmentIRCCS Humanitas Research HospitalMilan, Italy
