1 00:00:07,613 --> 00:00:08,513 Hi everyone. 2 00:00:08,513 --> 00:00:12,833 Welcome to Febrile, a cultured podcast about all things infectious disease. 3 00:00:12,863 --> 00:00:16,523 We use consult questions to dive into ID clinical reasoning, diagnostics 4 00:00:16,523 --> 00:00:17,963 and antimicrobial management. 5 00:00:17,993 --> 00:00:21,143 I'm Sara Dong, your host and a Med Peds ID doc. 6 00:00:21,272 --> 00:00:24,542 Today we are getting back to one of our StAR episodes. 7 00:00:24,782 --> 00:00:27,812 These are based on the Clinical Infectious Disease journal, 8 00:00:27,812 --> 00:00:29,852 CID, State-of-the-art Reviews. 9 00:00:30,508 --> 00:00:33,788 Today our topic is going to be Nontuberculous Mycobacterial 10 00:00:33,788 --> 00:00:35,588 Pulmonary Disease or NTM. 11 00:00:35,965 --> 00:00:37,855 So I'll introduce our guest stars. 12 00:00:38,084 --> 00:00:40,134 First up is Dr. Minh Vu Nguyen. 13 00:00:40,304 --> 00:00:44,324 Minh Vu, or simply Vu, is a recent former mycobacterial research 14 00:00:44,324 --> 00:00:46,090 fellow at National Jewish Health. 15 00:00:46,096 --> 00:00:49,666 He is now a new Assistant Professor of Medicine in the Division of 16 00:00:49,666 --> 00:00:52,996 Infectious Diseases at UC Davis Health in Sacramento, California. 17 00:00:53,150 --> 00:00:55,850 There, he and his pulmonary colleagues have started building a 18 00:00:55,850 --> 00:00:57,920 multidisciplinary NTM Care Center. 19 00:00:58,017 --> 00:00:59,997 Hi, this is Vu from UC Davis. 20 00:01:00,087 --> 00:01:00,807 Pleasure to be here. 21 00:01:01,637 --> 00:01:03,677 Next we have Dr. Charles Daley. 22 00:01:03,804 --> 00:01:07,987 Chuck is a Professor of Medicine at National Jewish Health, University 23 00:01:07,987 --> 00:01:11,290 of Colorado, and the Icahn School of Medicine at Mount Sinai. 24 00:01:11,504 --> 00:01:14,384 He is the Chief of the Division of Mycobacterial and Respiratory 25 00:01:14,384 --> 00:01:18,234 Infections at National Jewish Health and Chief Research Officer at the new 26 00:01:18,234 --> 00:01:20,590 Bronchiectasis and NTM Association. 27 00:01:20,716 --> 00:01:21,976 Hey, this is Chuck. 28 00:01:22,036 --> 00:01:25,011 I'm very excited to be here and glad that you're joining us today. 29 00:01:25,475 --> 00:01:29,155 And closing out our group of guest stars today is Dr. Reeti Khare. 30 00:01:29,278 --> 00:01:32,508 Reeti is an Associate Professor and Infectious Disease Laboratory 31 00:01:32,508 --> 00:01:34,518 Director at National Jewish Health. 32 00:01:34,803 --> 00:01:36,036 Thanks so much for having us. 33 00:01:36,036 --> 00:01:37,026 I'm excited to be here. 34 00:01:37,026 --> 00:01:37,886 My name is Reeti. 35 00:01:38,203 --> 00:01:44,323 So before we jump in, as everyone's favorite cultured podcast, we like to 36 00:01:44,323 --> 00:01:48,213 ask our guests to share a little piece of culture, basically just something 37 00:01:48,213 --> 00:01:51,028 that you enjoy or brings you happiness. 38 00:01:51,118 --> 00:01:54,328 So what have you guys, um, had in mind for today? 39 00:01:54,531 --> 00:01:57,831 I love anything chocolate on chocolate, that's, that would 40 00:01:57,831 --> 00:01:59,721 be my favorite thing to do. 41 00:01:59,961 --> 00:02:02,131 Like anything that's disgustingly chocolate, like 42 00:02:02,521 --> 00:02:04,881 molten lava chocolate cake. 43 00:02:05,007 --> 00:02:06,327 Excellent, excellent. 44 00:02:06,907 --> 00:02:09,757 Um, for me, I don't know if this is considered culture, but I just 45 00:02:09,757 --> 00:02:12,457 adopted two cats while on consults. 46 00:02:12,577 --> 00:02:17,187 So, um, it's been hectic, but they're nice. 47 00:02:17,257 --> 00:02:19,892 Are they small cats or like adult cats? 48 00:02:20,287 --> 00:02:22,897 They are adolescent cats. 49 00:02:22,897 --> 00:02:26,497 So they're, I got 'em when they were nine months and they act exactly 50 00:02:26,497 --> 00:02:31,297 like adolescents and, um, in fact, I, they've been banging the door for 51 00:02:31,297 --> 00:02:36,187 the last hour, but maybe now they're calming down 'cause I hear other voices. 52 00:02:36,294 --> 00:02:37,914 Well we'll see if they make an appearance. 53 00:02:38,244 --> 00:02:39,864 They, they will try. 54 00:02:42,279 --> 00:02:43,059 What about you, Chuck? 55 00:02:44,169 --> 00:02:44,409 Yeah. 56 00:02:44,409 --> 00:02:47,679 You know, one of the things I really enjoy is Forrest Gump. 57 00:02:47,776 --> 00:02:51,616 We have a lot in common, and I always watch the movie if I run across it. 58 00:02:52,771 --> 00:02:53,521 Excellent. 59 00:02:53,851 --> 00:02:56,761 That's kind of surprising no one's said Forrest Gump before. 60 00:02:56,761 --> 00:02:57,211 Love it. 61 00:02:59,041 --> 00:03:04,301 Um, well thank you guys so much for being here and also for creating this 62 00:03:04,301 --> 00:03:06,191 article that we're gonna talk about today. 63 00:03:06,651 --> 00:03:09,471 We're talking about your state of the art review, nontuberculous 64 00:03:09,501 --> 00:03:14,361 mycobacterial pulmonary disease: patients, principles and prospects. 65 00:03:14,441 --> 00:03:20,456 NTM, which I'm gonna say for short, is a huge topic and we know that NTM 66 00:03:20,456 --> 00:03:23,426 pulmonary disease is an increasing problem and something that I feel 67 00:03:23,426 --> 00:03:26,612 like we all encounter at least a little bit of in ID clinic. 68 00:03:26,926 --> 00:03:31,336 I thought maybe we would just start by a quick kind of background on 69 00:03:31,336 --> 00:03:36,106 these organisms and maybe a little bit about how humans can be infected. 70 00:03:36,214 --> 00:03:36,504 Okay. 71 00:03:36,809 --> 00:03:37,529 Yeah, of course. 72 00:03:37,529 --> 00:03:40,989 Well, actually, we can begin by asking you a question, Sara. 73 00:03:41,159 --> 00:03:45,599 Um, how do you think the name mycobacteria got its name? 74 00:03:45,854 --> 00:03:45,974 I. 75 00:03:47,044 --> 00:03:47,884 Oh, I have no idea. 76 00:03:49,879 --> 00:03:50,599 I didn't prepare. 77 00:03:51,934 --> 00:03:55,144 Well, I didn't know this until this morning either, but, uh, 78 00:03:55,174 --> 00:03:57,184 Chuck, maybe you can tell us. 79 00:03:57,394 --> 00:03:57,634 Yeah. 80 00:03:58,054 --> 00:03:59,164 Well, yeah. 81 00:03:59,164 --> 00:04:05,704 So when, uh, mycobacteria were first, uh, discovered in their growth on, uh, 82 00:04:05,794 --> 00:04:08,984 on the culture media looked like a mold. 83 00:04:09,704 --> 00:04:11,984 So it was thought they may be a fungus. 84 00:04:11,984 --> 00:04:14,204 So the word myco was used. 85 00:04:14,234 --> 00:04:17,414 I mean, certainly if they were discovered today, they would have a different name. 86 00:04:17,641 --> 00:04:18,061 Love it. 87 00:04:19,156 --> 00:04:19,636 Yeah. 88 00:04:19,786 --> 00:04:25,876 Um, so yeah, so mycobacteria, the most famous one is obviously tuberculosis. 89 00:04:26,236 --> 00:04:28,696 And you guys probably heard of the new book that just came 90 00:04:28,696 --> 00:04:30,616 out, Everything's Tuberculosis. 91 00:04:31,036 --> 00:04:35,526 But I, if he's gonna write a second book, everything else would be non 92 00:04:35,556 --> 00:04:42,879 tuberculosis mycobacteria, and it includes over 190 species of soil and water 93 00:04:42,879 --> 00:04:48,869 inhabitant, uh, mycobacteria, excluding obviously M tuberculosis and M.leprae. 94 00:04:49,359 --> 00:04:51,159 And again, they live in the soil. 95 00:04:51,159 --> 00:04:52,029 They're all around us. 96 00:04:52,029 --> 00:04:55,629 Plumbing, dust, natural and municipal water. 97 00:04:55,989 --> 00:04:59,739 And most patients who get it, they get it from either inhalation 98 00:05:00,069 --> 00:05:04,119 of these mycobacterial laden soil, water, and dust aerosols. 99 00:05:04,864 --> 00:05:11,554 Or they ingest fluid or dirt or whatever into their GI tract and then aspirate 100 00:05:11,554 --> 00:05:14,404 'em into the lungs by a two step route. 101 00:05:14,537 --> 00:05:21,047 Now since we are all kind of inhaling or ingesting mycobacteria, not all 102 00:05:21,047 --> 00:05:23,537 of us actually get disease, right? 103 00:05:23,537 --> 00:05:25,727 So who gets disease? 104 00:05:25,727 --> 00:05:27,537 And it's only very susceptible hosts. 105 00:05:27,557 --> 00:05:34,397 Patients, particularly with, um, local or pulmonary anatomical 106 00:05:34,397 --> 00:05:38,447 structural abnormalities and local immune dysfunction, 107 00:05:38,567 --> 00:05:41,387 particularly chiefly bronchiectasis. 108 00:05:42,167 --> 00:05:47,537 And then we can talk about, there's two big categories of NTM and 109 00:05:47,797 --> 00:05:48,722 Reeti, do you want to jump in? 110 00:05:49,952 --> 00:05:50,252 Sure. 111 00:05:50,252 --> 00:05:50,732 Yeah. 112 00:05:50,972 --> 00:05:55,322 It's sort of helpful to think of these nontuberculous mycobacteria as 113 00:05:55,322 --> 00:05:57,512 being divided into two major groups. 114 00:05:57,512 --> 00:06:02,162 Those that grow on solid media from subculture within seven days. 115 00:06:02,162 --> 00:06:03,332 Those are the rapid growers. 116 00:06:03,782 --> 00:06:07,682 And then those that grow after seven days, those are the slow growers, and that's 117 00:06:07,682 --> 00:06:11,582 important because they have different diagnosis, different treatment, and 118 00:06:11,582 --> 00:06:13,262 they look different in the laboratory. 119 00:06:13,361 --> 00:06:15,526 And Reeti, do you know anything special? 120 00:06:15,526 --> 00:06:19,896 What makes Mycobacteria special in terms of their cell wall or, or capsule 121 00:06:20,066 --> 00:06:24,101 compared to, let's say your typical gram-positive or gram-negative bacteria? 122 00:06:25,366 --> 00:06:29,956 Yeah, mycobacteria are special because they have this unique cell wall. 123 00:06:30,006 --> 00:06:35,616 Their outer cell wall is kind of, um, embedded with these mycolic acids that 124 00:06:35,616 --> 00:06:39,571 make them very resistant t o things going into the cell and things coming 125 00:06:39,571 --> 00:06:43,531 out, which means that all of a sudden they become impermeable to things like 126 00:06:43,561 --> 00:06:45,721 plasmin, so they can't mutate that way. 127 00:06:45,991 --> 00:06:49,501 They become impermeable to antibiotics, and so that has a lot of 128 00:06:49,501 --> 00:06:52,681 implications on how we manage them. 129 00:06:52,922 --> 00:06:53,702 Oh, awesome. 130 00:06:53,882 --> 00:06:55,472 Chuck, do you have anything to add to that? 131 00:06:56,732 --> 00:07:00,632 Well, the only thing I would say is that even though we have, uh, so many species, 132 00:07:00,692 --> 00:07:04,697 uh, fortunately most of them don't harm us, I. Um, this'll come back when we 133 00:07:04,697 --> 00:07:09,267 talk about the laboratory and why it's so important to know which species has 134 00:07:09,267 --> 00:07:11,097 been isolated from, uh, your patient. 135 00:07:11,555 --> 00:07:13,215 Sara, do you have any other questions? 136 00:07:13,215 --> 00:07:14,655 Is that a good intro? 137 00:07:15,270 --> 00:07:15,630 Yeah. 138 00:07:15,630 --> 00:07:18,720 I'm gonna bring you into clinic with me today and tell you 139 00:07:18,720 --> 00:07:20,160 about someone who's shown up. 140 00:07:20,550 --> 00:07:22,230 Um, so we're in clinic. 141 00:07:22,350 --> 00:07:27,520 We have a 70-year-old woman who's been referred for possible NTM infection. 142 00:07:27,880 --> 00:07:32,020 So to give you a little background, she had been seen in the emergency room 143 00:07:32,020 --> 00:07:37,750 actually for some urinary symptoms, got a CT of her abdomen pelvis to rule 144 00:07:37,750 --> 00:07:42,830 out kidney stones, hydro nephrosis and they notice that, in some of those cuts 145 00:07:42,830 --> 00:07:47,150 towards the base of the lungs that there's some scattered tree and bud nodularity. 146 00:07:47,540 --> 00:07:52,160 And so she has a follow-up CT chest that shows some subacute versus 147 00:07:52,160 --> 00:07:56,063 chronic changes that are consistent with bronchiectasis, more of those 148 00:07:56,063 --> 00:07:59,993 tree and bud nodularities, and then a couple scattered pulmonary nodules, 149 00:07:59,993 --> 00:08:02,333 all pretty small, under a centimeter. 150 00:08:03,308 --> 00:08:06,938 And so when you talking to her, she kind of reflects back and says, you know, 151 00:08:07,358 --> 00:08:09,758 I guess I always did have bronchitis. 152 00:08:09,998 --> 00:08:13,238 Every time I had a cold, it progressed to this chest cold. 153 00:08:13,578 --> 00:08:16,458 It happens probably three to four times a year. 154 00:08:16,548 --> 00:08:20,628 And in between she has some rare intermittent cough, um, usually 155 00:08:20,628 --> 00:08:25,038 non-productive and has a little bit of chest pressure, thinks her 156 00:08:25,038 --> 00:08:26,628 weight has been mostly stable. 157 00:08:26,628 --> 00:08:29,513 She kind of feels like she hasn't been paying attention to it. 158 00:08:30,023 --> 00:08:33,473 Um, she, herself is a lifetime non-smoker, but notes that both of 159 00:08:33,473 --> 00:08:38,093 her parents smoked heavily in the home until she became 18 and moved out. 160 00:08:38,693 --> 00:08:41,273 And she spends most of her time in Florida, travels 161 00:08:41,273 --> 00:08:44,193 frequently around various places. 162 00:08:44,193 --> 00:08:47,163 But she's just in general a pretty active person. 163 00:08:47,163 --> 00:08:51,336 She kayaks, she hikes, she runs and she's just noticed that her activity 164 00:08:51,336 --> 00:08:56,511 recently has gone down and she blamed it mostly on just getting older. 165 00:08:56,941 --> 00:09:01,321 She does have a hot tub as well as an outdoor salt water pool at her home 166 00:09:01,321 --> 00:09:05,401 in Florida, and so we're not even gonna get to micro results right away. 167 00:09:05,401 --> 00:09:08,251 I'm gonna pause here and just ask what you're thinking 168 00:09:08,251 --> 00:09:10,381 about for this patient so far. 169 00:09:10,381 --> 00:09:13,471 You know, does this story fit with NTM pulmonary disease? 170 00:09:14,228 --> 00:09:17,108 What other information are you gonna be trying to gather to 171 00:09:17,108 --> 00:09:18,578 help put this all together? 172 00:09:18,771 --> 00:09:21,411 Yeah, I'll, I'll, I'll speak to this first. 173 00:09:21,441 --> 00:09:26,571 Um, you know, I think I saw this same patient, uh, multiple times last 174 00:09:26,571 --> 00:09:27,981 week since she must be moving around. 175 00:09:28,731 --> 00:09:32,961 Um, so, you know, this is pretty classic for us, right? 176 00:09:32,961 --> 00:09:38,021 This, this postmenopausal woman who comes in with a cough, maybe some 177 00:09:38,051 --> 00:09:40,481 declining, uh, exercise tolerance. 178 00:09:41,161 --> 00:09:44,731 And it's not unusual these days to have these incidental diagnoses 179 00:09:44,731 --> 00:09:47,851 made where they often get a CT of the abdomen and they see the base 180 00:09:47,851 --> 00:09:51,871 of the lungs and they, they see the bronchiectasis and or the tree and bud. 181 00:09:51,871 --> 00:09:52,921 And that's really good, right? 182 00:09:52,921 --> 00:09:57,151 Because this is usually an early diagnosis earlier than if we'd 183 00:09:57,151 --> 00:09:59,941 waited for them to come in because of their cough, which could have 184 00:10:00,121 --> 00:10:02,071 possibly been years from that time. 185 00:10:02,731 --> 00:10:04,081 Uh, so, you know, cough. 186 00:10:04,711 --> 00:10:06,131 And fatigue the most common. 187 00:10:06,311 --> 00:10:09,036 She didn't mention fatigue, but cough and fatigue. 188 00:10:09,036 --> 00:10:12,546 About 80% of patients with pulmonary NTM present with that, 189 00:10:13,146 --> 00:10:14,946 um, some shortness of breath. 190 00:10:14,976 --> 00:10:16,356 It's usually a productive cough. 191 00:10:16,356 --> 00:10:19,326 It's like this case, if you catch 'em early, it's often a dry cough. 192 00:10:20,076 --> 00:10:23,946 Um, and, and that doesn't trigger people that you know, that, uh, 193 00:10:23,976 --> 00:10:27,036 it's, when it becomes productive and they're failing antibiotics, 194 00:10:27,036 --> 00:10:28,776 then sometimes they'll order the CT. 195 00:10:29,376 --> 00:10:31,806 Uh, so she was lucky that this was found earlier. 196 00:10:32,401 --> 00:10:36,431 Radiologic findings, we always talk about kind of two different types, which 197 00:10:36,431 --> 00:10:38,981 is the, uh, what is called the classic. 198 00:10:39,011 --> 00:10:42,131 And by classic it means, it was what was described many years ago, which 199 00:10:42,131 --> 00:10:46,871 is fibro cavitary, upper lobe cavitary with volume loss looks like TB. 200 00:10:47,291 --> 00:10:50,951 They often enter the healthcare system and a TB clinic, and then they 201 00:10:50,951 --> 00:10:55,496 don't grow TB. They grow MAC and then they, they come back out to, to us. 202 00:10:55,586 --> 00:10:58,586 And the other, which now I would say is kind of the classic, the more 203 00:10:58,586 --> 00:11:02,366 common is the nodular bronchiectatic disease, which it sounds like 204 00:11:02,426 --> 00:11:06,176 the she has with bronchiectasis and some tree and bud nodularity. 205 00:11:07,266 --> 00:11:11,706 All of these things should make the clinicians suspect pulmonary NTM. 206 00:11:12,366 --> 00:11:16,516 Um, and that should lead to getting a culture, a respiratory 207 00:11:16,516 --> 00:11:18,046 culture to try to confirm that. 208 00:11:19,591 --> 00:11:24,171 And unlike TB, I mean, as you know, um, we don't make a diagnosis 209 00:11:24,171 --> 00:11:27,711 just because someone grew an NTM because Vu said earlier, these 210 00:11:27,711 --> 00:11:28,791 things are found everywhere. 211 00:11:28,791 --> 00:11:32,631 We all were showering in them, drinking them, swimming in them. 212 00:11:32,631 --> 00:11:34,491 We're we're surrounded by them. 213 00:11:34,491 --> 00:11:39,322 So we, we came up with these diagnostic criteria back in 2007. 214 00:11:39,906 --> 00:11:45,606 But let me just tell you now, in 2025, no one has validated these criteria, 215 00:11:45,846 --> 00:11:50,346 so they should be used as a guideline, you know, there, and, and that is 216 00:11:50,346 --> 00:11:54,696 that we look for symptoms consistent with NTM radiographic findings. 217 00:11:54,696 --> 00:11:58,621 And then we confirm that with, uh, the laboratory, uh, which 218 00:11:58,866 --> 00:12:02,496 is a critical component of this, uh, diagnostic algorithm. 219 00:12:02,730 --> 00:12:05,060 So we take a peek at her records. 220 00:12:05,060 --> 00:12:10,010 We find that she has one expectorated sputum culture from about six months ago 221 00:12:10,430 --> 00:12:15,680 that had Mycobacterium chimera and she had a second sputum culture that was drawn a 222 00:12:15,680 --> 00:12:19,430 couple months later that has M abscessus. 223 00:12:19,490 --> 00:12:24,773 And so we make a plan now to gather more information, get multiple sputa, and so, 224 00:12:24,983 --> 00:12:27,443 you know, why does testing take so long? 225 00:12:27,443 --> 00:12:32,303 You know, why can't we develop a rapid test to detect NTM like we have for TB? 226 00:12:32,963 --> 00:12:35,603 Yeah, testing does take a long time, right? 227 00:12:35,633 --> 00:12:41,288 Culture is six to eight weeks, and that's just really because we are waiting for 228 00:12:41,288 --> 00:12:47,048 mycobacteria to grow to detectable levels and they only double once every 24 hours. 229 00:12:47,258 --> 00:12:49,928 And then of course, once we get a positive, there's more 230 00:12:49,928 --> 00:12:52,358 time needed to identify it. 231 00:12:52,928 --> 00:12:56,588 And then once we identify it, it takes at least two to four weeks 232 00:12:56,588 --> 00:13:00,728 to grow up enough biomass and actually do susceptibility testings. 233 00:13:01,928 --> 00:13:05,438 So molecular testing is definitely a question I get quite often 234 00:13:05,678 --> 00:13:09,308 about doing that directly from a specimen so we can try to speed 235 00:13:09,338 --> 00:13:13,488 up results for an NTM diagnosis. 236 00:13:13,638 --> 00:13:16,968 I mean, we do this for TB and it works, but it's a little bit more 237 00:13:16,968 --> 00:13:23,538 nuanced for NTM because unlike TB, NTM are not always considered pathogens. 238 00:13:23,538 --> 00:13:28,398 Just detecting an NTM from a sputum could be a contaminant, it could be a dead bug, 239 00:13:28,848 --> 00:13:31,308 it could be DNA from a previous exposure. 240 00:13:32,013 --> 00:13:34,413 And so a positive result doesn't necessarily mean anything. 241 00:13:34,713 --> 00:13:36,993 And then the flip side is true as well. 242 00:13:36,993 --> 00:13:40,473 A negative result doesn't necessarily mean anything either. 243 00:13:40,533 --> 00:13:45,423 A PCR could be falsely negative because our assay is too broad, it's not 244 00:13:45,423 --> 00:13:47,793 sensitive enough or it's too narrow. 245 00:13:47,793 --> 00:13:50,863 We've just focused on a few NTM and miss the other NTM 246 00:13:50,883 --> 00:13:52,233 that's actually in our sample. 247 00:13:53,163 --> 00:13:57,573 So molecular testing has the ability to speed up testing. 248 00:13:58,053 --> 00:14:03,093 It can do more than ID, it can look for drug resistance markers, so it 249 00:14:03,093 --> 00:14:05,193 has a lot of, a lot of opportunity. 250 00:14:05,433 --> 00:14:09,303 We just need the right test designed optimally that will 251 00:14:09,303 --> 00:14:12,963 actually give us enough information to change our management. 252 00:14:12,963 --> 00:14:14,193 We're not quite there yet. 253 00:14:14,698 --> 00:14:17,728 Maybe I can ask a question, Reeti, how, how often do you 254 00:14:17,728 --> 00:14:19,438 see a mixed infection like this? 255 00:14:20,698 --> 00:14:24,208 Mixed infections are actually fairly frequent in our samples. 256 00:14:24,208 --> 00:14:28,888 About two to 12% will have at least two mycobacteria, but I don't know 257 00:14:28,888 --> 00:14:30,418 what that looks like from a patient. 258 00:14:30,958 --> 00:14:32,788 Um, number of patients. 259 00:14:32,788 --> 00:14:34,528 How often do you see co-infections? 260 00:14:35,533 --> 00:14:37,603 Yeah, it's more, it's, I would say more common. 261 00:14:37,633 --> 00:14:39,883 You know, we published a number of years ago our experience with 262 00:14:39,883 --> 00:14:44,413 abscessus and, uh, 55% of our patients with pulmonary abscessus 263 00:14:44,413 --> 00:14:47,263 had concurrent or previously had MAC. 264 00:14:47,263 --> 00:14:51,163 So it that, you know, it's pretty common to see mixed infections. 265 00:14:51,475 --> 00:14:55,855 And one reason why people hearing this might see the discrepancies is that 266 00:14:55,855 --> 00:14:59,965 from a lab point of view, Reeti is comparing in a single sample, two to 267 00:14:59,965 --> 00:15:07,345 12 or two to x, y, z percent is growing two different NTM in the same sample. 268 00:15:07,345 --> 00:15:10,045 Whereas Chuck is talking about from a whole patient who has 269 00:15:10,045 --> 00:15:11,695 cough with multiple samples. 270 00:15:12,055 --> 00:15:16,390 So multiple samples, you're more likely to have a mix of different NTM over 271 00:15:16,390 --> 00:15:20,650 several samples, so that's why you might see the discrepancy in the percentage. 272 00:15:21,925 --> 00:15:22,195 Yeah. 273 00:15:23,335 --> 00:15:27,835 And you know, your paper has this really nice focus on, you know, 274 00:15:27,895 --> 00:15:32,035 patient-centered care and how we can walk through these discussions with 275 00:15:32,035 --> 00:15:33,655 our patients, which is really hard. 276 00:15:33,965 --> 00:15:39,215 Before we talk anything about antibiotics, I thought we could pit stop there and, 277 00:15:39,635 --> 00:15:43,025 um, have you share some of that about how you approach these cases, how 278 00:15:43,025 --> 00:15:47,285 you talk about the goals of treatment and, and set expectations with them. 279 00:15:47,765 --> 00:15:50,975 And I, I think part of that of course is counseling on sort of risks. 280 00:15:51,135 --> 00:15:53,025 And, and management of comorbidities. 281 00:15:53,025 --> 00:15:57,885 But for such a huge nebulous topic, especially in the early stages when 282 00:15:57,885 --> 00:16:02,745 you don't have micro, I think, um, many of us very much welcome resources 283 00:16:02,745 --> 00:16:07,005 like this that help set the stage, but I'd love to hear your insight. 284 00:16:08,240 --> 00:16:08,910 Yeah, of course. 285 00:16:08,910 --> 00:16:10,440 Well, I can start us out. 286 00:16:10,440 --> 00:16:12,630 I know that like you said, it is nebulous. 287 00:16:12,720 --> 00:16:15,600 Um, but you know, you alluded to something. 288 00:16:16,610 --> 00:16:18,140 Uh, really important that you said. 289 00:16:18,200 --> 00:16:20,600 A lot of times we're still waiting on micro, right? 290 00:16:20,600 --> 00:16:25,430 And I think the non nebulous part is in the beginning is that let's get 291 00:16:25,430 --> 00:16:30,290 the diagnosis correct first, let's make sure they truly, truly have NTM 292 00:16:30,290 --> 00:16:34,610 pulmonary disease rather than just colonization or something else going on. 293 00:16:34,910 --> 00:16:39,080 But maybe they accidentally grew an NTM from one sputum, uh, culture. 294 00:16:39,650 --> 00:16:40,250 So, you know. 295 00:16:41,075 --> 00:16:45,395 Kind of reiterating what Chuck said in, in the 2020 guidelines, and that started 296 00:16:45,395 --> 00:16:50,675 from the 2007, the general guidelines, you need to meet three criteria in order to 297 00:16:51,425 --> 00:16:53,555 be diagnosed with NTM pulmonary disease. 298 00:16:53,555 --> 00:16:58,965 That is one, the microbiologic criteria on where you have to have repeated 299 00:16:58,965 --> 00:17:02,565 growth of the same species or subspecies. 300 00:17:03,105 --> 00:17:04,455 Radiologic criteria. 301 00:17:04,455 --> 00:17:09,345 So imaging, particularly chest CT, consistent with NTM pulmonary disease. 302 00:17:09,435 --> 00:17:12,165 Could be cavitary, could be nodular bronchiectatic. 303 00:17:12,885 --> 00:17:18,265 And then finally, symptoms compatible with NTM pulmonary disease 304 00:17:18,805 --> 00:17:20,515 while excluding other diagnosis. 305 00:17:20,515 --> 00:17:24,925 Now, this is a big caveat because you probably know yourself, some patients will 306 00:17:24,925 --> 00:17:28,255 deny symptoms or they do have symptoms, but they just don't recognize it. 307 00:17:28,255 --> 00:17:30,715 So that itself is a little nebulous. 308 00:17:30,715 --> 00:17:35,425 But during the first meeting, especially if they only have one or maybe just 309 00:17:35,425 --> 00:17:40,205 two sputums, and you don't have a convincing picture, getting to the 310 00:17:40,205 --> 00:17:44,285 right diagnosis first is the first important step of patient-centered care. 311 00:17:45,940 --> 00:17:49,445 Yeah, I mean, you know, one of the first, uh, PICO questions that we 312 00:17:49,445 --> 00:17:53,045 addressed in the 2020 guidelines was, uh, should you start treatment? 313 00:17:53,405 --> 00:17:57,785 So, you know, you weigh what Vu said, the whole picture, uh, symptoms, 314 00:17:57,995 --> 00:18:03,155 microbiology and radiology to try to make a decision if you're going to treat. 315 00:18:03,795 --> 00:18:08,805 If you decide to treat, it is a very important at the very beginning, uh, 316 00:18:08,805 --> 00:18:11,085 to go through the goals of treatment. 317 00:18:11,085 --> 00:18:15,345 And, and this is where the discussion between the patient and the physician 318 00:18:15,345 --> 00:18:20,640 or provider is critical because, um, we're not gonna make that decision. 319 00:18:20,820 --> 00:18:23,850 Uh, the patient ultimately will make that decision and we need 320 00:18:23,850 --> 00:18:28,170 to make sure that we're providing them with realistic expectations. 321 00:18:28,680 --> 00:18:33,750 And unlike TB, it's, the discussion is always the same, uh, because we expect to 322 00:18:33,750 --> 00:18:38,610 cure our patients with drug susceptible TB and most even our drug resistant here. 323 00:18:38,610 --> 00:18:39,990 That is not always the case. 324 00:18:40,020 --> 00:18:43,410 So that discussion takes some kind of a different flavor, depending if they 325 00:18:43,410 --> 00:18:48,630 have mycobacterium kansasii where we can treat and cure 95% of the time. 326 00:18:49,050 --> 00:18:51,630 Uh, MAC, where it's more like 70 to 80%. 327 00:18:52,140 --> 00:18:57,360 And then the discussion with Mycobacterium abscessus is that, you know, cure 328 00:18:57,660 --> 00:18:59,220 really is difficult to achieve. 329 00:18:59,220 --> 00:19:02,560 And Vu knows that when people come here, I tell them we don't 330 00:19:02,560 --> 00:19:04,630 use the cure word with abscessus. 331 00:19:05,020 --> 00:19:09,430 Uh, we use the control word first, and if we get to cure, that's fantastic, 332 00:19:09,960 --> 00:19:14,370 but that's not realistic discussion, and, uh, a lot of patients who 333 00:19:14,370 --> 00:19:16,110 come to us are failing treatment. 334 00:19:16,110 --> 00:19:20,850 They're not culture converting, and, and they're frustrated because they 335 00:19:20,850 --> 00:19:26,190 were told they would be cured and, and it was not a realistic expectation. 336 00:19:26,766 --> 00:19:31,666 So when we do get NTM that grows in culture, you mentioned we need to identify 337 00:19:31,666 --> 00:19:37,066 it, of course, and your paper talks a bit about how those kind of imprecise or 338 00:19:37,066 --> 00:19:39,616 challenging components of identification. 339 00:19:39,616 --> 00:19:44,776 So why as like for ID learners on here that are listening, why 340 00:19:44,776 --> 00:19:48,346 does it matter for them to know the identification beyond just the 341 00:19:48,346 --> 00:19:49,891 complex level for these mycobacteria? 342 00:19:51,726 --> 00:19:56,196 One of the biggest reasons for a full and accurate identification is because 343 00:19:56,196 --> 00:19:57,966 of differences in treatment patterns. 344 00:19:58,026 --> 00:20:01,476 We know that slow growers and rapid growers have different treatment patterns, 345 00:20:01,806 --> 00:20:06,351 but even within these groups, even within closely related organisms like 346 00:20:06,351 --> 00:20:12,246 the abscessus subspecies, they can carry resistance genes at different rates. 347 00:20:12,616 --> 00:20:14,916 So for example, the erm gene. 348 00:20:15,346 --> 00:20:19,516 Erm genes cause inducible resistance to macrolides and some abscessus 349 00:20:19,516 --> 00:20:21,886 subspecies have them, some don't. 350 00:20:22,246 --> 00:20:24,406 Same thing with the fortuitum complex. 351 00:20:24,496 --> 00:20:28,006 Some of those species carry an erm gene and some don't. 352 00:20:28,576 --> 00:20:32,746 Knowing which mycobacteria you are actually dealing with will help you 353 00:20:32,746 --> 00:20:36,866 pick the right drug, especially the important drugs like the macrolides. 354 00:20:38,346 --> 00:20:40,126 There's a few other reasons too, I think. 355 00:20:40,126 --> 00:20:41,536 Vu, do you wanna speak to those? 356 00:20:42,171 --> 00:20:44,661 Of course, so, you know, Reeti said it best. 357 00:20:44,871 --> 00:20:49,761 Uh, treatment patterns will, will change based on the species and subspecies. 358 00:20:49,761 --> 00:20:52,461 But another thing too is kind of going back to diagnosis. 359 00:20:52,901 --> 00:20:55,931 It helps us determine whether a species or subspecies is likely 360 00:20:55,931 --> 00:20:57,431 causing disease versus not. 361 00:20:57,971 --> 00:21:02,201 So again, part of the diagnostic criterion for microbiology is repeated 362 00:21:02,201 --> 00:21:06,941 growth of the same species and subspecies, and it convinces that that 363 00:21:06,941 --> 00:21:09,401 is more likely to be disease causing. 364 00:21:09,821 --> 00:21:13,481 When different species subspecies grow kind of sporadically, 365 00:21:13,481 --> 00:21:17,956 which we often see too, and none of them has grown repeatedly. 366 00:21:17,956 --> 00:21:21,436 It suggests that these cultures are more likely, I'm not saying absolutely, but 367 00:21:21,436 --> 00:21:23,956 just more likely to be colonization. 368 00:21:24,766 --> 00:21:29,056 And in the case of identification of MAC, the most lab would call it simply 369 00:21:29,056 --> 00:21:34,536 M.avium complex, or I've seen M.avium- intracellulare group, various renditions 370 00:21:34,536 --> 00:21:39,276 of that, but basically, remember a complex, and Chuck will always tell 371 00:21:39,276 --> 00:21:43,086 you this, A complex is a collection of different species and subspecies. 372 00:21:43,516 --> 00:21:46,936 And knowing that just a complex doesn't help us decipher whether this 373 00:21:46,936 --> 00:21:50,986 is the same species or subspecies growing and therefore likely causing 374 00:21:50,986 --> 00:21:53,626 disease or versus just colonization. 375 00:21:54,901 --> 00:21:58,921 It also helps providers try to sort out if somebody is responding to 376 00:21:58,921 --> 00:22:04,711 treatment or if they are just getting re-exposed to another very similar bug 377 00:22:04,831 --> 00:22:06,541 that we haven't differentiated out. 378 00:22:07,261 --> 00:22:12,451 Um, and we can also, by knowing exactly what we have, we can start 379 00:22:12,451 --> 00:22:16,047 identifying organisms that could potentially be causing outbreaks. 380 00:22:16,317 --> 00:22:18,117 And that's actually happened a few times. 381 00:22:18,117 --> 00:22:25,197 We know that M. intracellular subspecies chimaera can be associated 382 00:22:25,197 --> 00:22:29,397 with outbreaks in heart surgeries with these heater cooler units. 383 00:22:29,757 --> 00:22:35,472 We have recently found an outbreak, um, of M.abscessus subspecies 384 00:22:35,472 --> 00:22:38,852 masiliense in stem cells. 385 00:22:38,912 --> 00:22:42,662 Um, so that's another reason why we wanna do that. 386 00:22:43,127 --> 00:22:49,532 And so reaching out to your laboratory and requesting that full identification 387 00:22:49,712 --> 00:22:53,602 as well as any potential drug markers that may be associated with the bugs 388 00:22:54,142 --> 00:22:56,542 may be really important for you to know. 389 00:22:56,842 --> 00:23:01,192 But something I'd like to point out is that it's not always possible 390 00:23:01,282 --> 00:23:03,262 for your lab to be able to do it. 391 00:23:03,862 --> 00:23:08,307 Um, there are actually dozens of tests available for NTM testing, 392 00:23:08,577 --> 00:23:12,147 but only like one or two of them are available in the US. 393 00:23:12,627 --> 00:23:15,177 Um, so access is a real problem. 394 00:23:15,177 --> 00:23:19,857 Even our laboratory, we get our tests from Europe and they get 395 00:23:19,857 --> 00:23:22,437 stuck in customs every single time. 396 00:23:22,947 --> 00:23:27,327 Um, validating these tests is difficult, especially when you 397 00:23:27,327 --> 00:23:29,337 don't see a lot of these organisms. 398 00:23:29,757 --> 00:23:34,582 So a lot of providers may have to rely on reference labs to 399 00:23:34,582 --> 00:23:35,752 get the results that they need. 400 00:23:37,387 --> 00:23:39,457 Yeah, I might, uh, add to this. 401 00:23:39,457 --> 00:23:43,177 Mycobacterium avium complex, I like to say is probably more 402 00:23:43,177 --> 00:23:45,127 complex than you recognize. 403 00:23:45,457 --> 00:23:48,007 So we used to have the MAI, right? 404 00:23:48,037 --> 00:23:51,757 That's when we knew there were two species, avium and intracellular. 405 00:23:51,757 --> 00:23:55,327 But now there are 10 species and, uh, two of them avium. 406 00:23:55,627 --> 00:23:59,577 It has four subspecies, and intracellulare has three subspecies. 407 00:23:59,647 --> 00:24:00,257 Chimaera, 408 00:24:00,712 --> 00:24:05,002 which used to be a species, and yongonense, which used to be a species, 409 00:24:05,002 --> 00:24:09,232 they're now subspecies and therefore many labs will just stop at the 410 00:24:09,232 --> 00:24:11,482 intracellulare and you won't know. 411 00:24:11,512 --> 00:24:14,722 So for example, I mean this was a real life example during the heater 412 00:24:14,722 --> 00:24:18,922 cooler unit, uh, outbreak years ago, unfortunately, believe it or not, 413 00:24:18,922 --> 00:24:21,442 still happening, but uh, at its height. 414 00:24:22,042 --> 00:24:25,522 Um, I know of a hospital that they ran their clinical micro 415 00:24:25,522 --> 00:24:28,532 logs and they grew no chimaera. 416 00:24:29,032 --> 00:24:30,502 They were so excited. 417 00:24:30,502 --> 00:24:33,802 They had no chimaera cases until they figured out their 418 00:24:33,802 --> 00:24:35,412 lab didn't identify chimaera. 419 00:24:35,782 --> 00:24:37,472 They just stopped at intracellulare. 420 00:24:37,882 --> 00:24:42,742 So, uh, ultimately they did have cases, so first outbreak investigation. 421 00:24:42,742 --> 00:24:48,082 But the, the other is of those 10 species, I bet you most, uh, uh, providers 422 00:24:48,082 --> 00:24:52,222 don't know all of those names because they don't get it reported to them. 423 00:24:52,222 --> 00:24:53,692 So they don't even know they exist. 424 00:24:53,692 --> 00:24:55,132 But let me give you an example. 425 00:24:55,432 --> 00:24:57,982 You have a patient, some tree and bud Nodularity. 426 00:24:58,597 --> 00:25:03,787 Um, if they grew M.avium three times, you, particularly if they were symptomatic, 427 00:25:03,817 --> 00:25:05,707 you'd, you'd consider treating them. 428 00:25:06,007 --> 00:25:07,637 But what if they grew vulneris? 429 00:25:08,407 --> 00:25:11,377 Well, that's MAC, that's one of those MAC species. 430 00:25:11,377 --> 00:25:12,877 I probably wouldn't treat that. 431 00:25:12,877 --> 00:25:15,697 I'd probably just go right to airway clearance and see if I 432 00:25:15,697 --> 00:25:19,087 could clear that without, because this clearly not as pathogenic. 433 00:25:19,537 --> 00:25:24,607 The other, um, ones, um, that are within Mac, you, they're just not as 434 00:25:24,607 --> 00:25:26,707 pathogenic as avium and intracellular. 435 00:25:26,707 --> 00:25:32,587 So, most providers in the US don't know what actually is growing in their 436 00:25:32,587 --> 00:25:34,447 patients, uh, respiratory specimen. 437 00:25:34,849 --> 00:25:38,127 Many people who listen probably know that there are these available 438 00:25:38,127 --> 00:25:40,866 guidelines and consensus articles for when we do wanna treat our 439 00:25:40,866 --> 00:25:43,026 patients with NTM pulmonary disease. 440 00:25:43,049 --> 00:25:47,922 And certainly your paper is focused on kind of giving a more, I'd say 441 00:25:48,267 --> 00:25:51,837 broad approach and framework for people to start thinking about this 442 00:25:51,849 --> 00:25:53,647 when they're selecting antibiotics. 443 00:25:53,647 --> 00:25:57,157 And I'm gonna highlight Figure five from, from your paper that hopefully 444 00:25:57,157 --> 00:25:58,897 folks have pulled up and can look at. 445 00:25:58,901 --> 00:26:00,131 What, what things should we know? 446 00:26:00,475 --> 00:26:04,135 After you implement step one and you decide to start antibiotics, then 447 00:26:04,135 --> 00:26:07,345 in step two you must start with the macrolide if the target NTM in a 448 00:26:07,345 --> 00:26:12,055 specific isolate from the patient is macrolide susceptible, your whole 449 00:26:12,055 --> 00:26:13,855 regimen will build around this macrolide. 450 00:26:14,425 --> 00:26:17,185 This is because the macrolide and aminoglycoside are the two most 451 00:26:17,185 --> 00:26:20,155 important classes of antibiotics against NTM that are susceptible to them. 452 00:26:20,695 --> 00:26:23,365 With the amino glycoside reserved for severe or treatment limited 453 00:26:23,365 --> 00:26:25,105 disease because of toxicity. 454 00:26:25,465 --> 00:26:26,845 Something that we'll touch on later. 455 00:26:27,625 --> 00:26:31,885 In MAC pulmonary disease, sputum conversion rate goes from 70 to 95% 456 00:26:32,065 --> 00:26:36,355 when the MAC is macrolide susceptible down to five to 36% when is not. 457 00:26:36,399 --> 00:26:41,488 We see the same pattern in M abscessus from 72 to 88% in macrolide susceptible 458 00:26:41,518 --> 00:26:44,578 down to 25 to 35% in macrolide resistance. 459 00:26:44,611 --> 00:26:45,931 This leads us to step three. 460 00:26:46,786 --> 00:26:51,766 If you have an SGM or a slowly growing mycobacteria like Mac, you need to add 461 00:26:51,766 --> 00:26:56,446 ethambutol to protect the macrolide, to prevent the isolate from developing, 462 00:26:56,446 --> 00:27:00,893 acquired macrolide resistance, irrespective of the ethambutol MIC. 463 00:27:01,463 --> 00:27:05,693 This is why NJH does not report ethambutol MICs anymore in their MIC 464 00:27:05,693 --> 00:27:10,238 panels for SGM because many providers were incorrectly dropping ethambutol 465 00:27:10,268 --> 00:27:12,668 when they saw an elevated ethambutol MIC. 466 00:27:13,358 --> 00:27:18,908 And I think this is a nice lead in, uh, into step four, which will heavily involve 467 00:27:18,908 --> 00:27:23,708 the whole discussion about interpreting MICs in NTM disease in general. 468 00:27:23,938 --> 00:27:26,893 How do we use our susceptibility results? 469 00:27:26,893 --> 00:27:29,518 You know, we send our sample to National Jewish, we get it back. 470 00:27:29,768 --> 00:27:31,898 How do we understand those? 471 00:27:31,898 --> 00:27:33,098 Are they reliable? 472 00:27:33,369 --> 00:27:36,274 I, I'll start with the testing and then you guys can take it 473 00:27:36,384 --> 00:27:36,674 Okay. 474 00:27:36,744 --> 00:27:37,044 Alright. 475 00:27:37,156 --> 00:27:43,156 As much as I love lab testing, the thing to know about NTM susceptibility testing 476 00:27:43,156 --> 00:27:47,656 is that it just doesn't correlate with clinical response as well as we'd like. 477 00:27:48,316 --> 00:27:53,746 Um, we know that AST results are fairly reliable for some drugs like amikacin and 478 00:27:53,746 --> 00:27:58,966 macrolides and rifampin for M.kansasii, but the others maybe not so much. 479 00:27:59,626 --> 00:28:02,176 Um, but why, why is it like that? 480 00:28:02,356 --> 00:28:04,936 And I think there's a few technical reasons. 481 00:28:05,656 --> 00:28:07,786 A big one is the way we do testing. 482 00:28:08,116 --> 00:28:14,086 We use broth micro dilution, which is very routinely used in bacterial testing. 483 00:28:14,086 --> 00:28:19,006 We borrowed the method from routine bacteria, and it works very well for 484 00:28:19,006 --> 00:28:23,656 routine bacteria, but the premise of the technique is to test one bug 485 00:28:24,016 --> 00:28:27,226 against another drug independently. 486 00:28:27,226 --> 00:28:29,026 So one bug, one drug independently. 487 00:28:29,866 --> 00:28:32,026 But that's not how NTM treatment works. 488 00:28:32,026 --> 00:28:37,066 We need to treat NTM with three, four more drugs, and sometimes those 489 00:28:37,156 --> 00:28:40,666 drugs work synergistically, sometimes antagonistically, but we're not 490 00:28:40,666 --> 00:28:44,596 testing them that way because we just don't have the methods yet to do it. 491 00:28:45,631 --> 00:28:47,761 Another possibility is that we're not accounting for 492 00:28:47,761 --> 00:28:49,951 heterogeneity of NTM infection. 493 00:28:50,191 --> 00:28:53,941 We know that mycobacterium tuberculosis is heterogeneous. 494 00:28:54,001 --> 00:28:56,911 That's why we test it with a completely different method. 495 00:28:57,181 --> 00:29:02,471 We use the proportion method, but for NTM, again, we use broth micro dilution. 496 00:29:03,121 --> 00:29:08,461 We pick one colony and we test it against all these drugs, and this ignores the 497 00:29:08,461 --> 00:29:13,211 probability that all the bugs from the patient are not going to be the same. 498 00:29:13,901 --> 00:29:16,121 And then there's the sheer length of time it takes. 499 00:29:16,451 --> 00:29:20,861 We have to incubate these mycobacteria with the various drugs for days, 500 00:29:20,861 --> 00:29:24,701 sometimes up to two weeks just to get enough growth to read. 501 00:29:25,091 --> 00:29:28,161 And by then the drugs themselves might be breaking down. 502 00:29:28,491 --> 00:29:28,781 Yeah. 503 00:29:28,914 --> 00:29:29,274 Yep. 504 00:29:29,334 --> 00:29:29,964 Pretty much. 505 00:29:31,494 --> 00:29:35,784 And, um, I mean, to add on to the complexity or, so that's just the testing 506 00:29:35,784 --> 00:29:38,959 part, but let's say hypothetically for whatever antibiotics and bug that 507 00:29:38,959 --> 00:29:40,999 you have, the test is fairly accurate. 508 00:29:41,449 --> 00:29:45,829 Why do some combinations don't have quote unquote, uh, in 509 00:29:45,829 --> 00:29:48,049 vitro and in vivo correlation? 510 00:29:48,409 --> 00:29:51,469 And most of the time it's actually because of a lack of data. 511 00:29:51,499 --> 00:29:54,469 There's so many bugs, there's so many antibiotics, there's just no. 512 00:29:54,904 --> 00:30:00,484 No one did enough to do studies to say confirming that the this MIC at this break 513 00:30:00,484 --> 00:30:02,914 point will lead to this good outcome. 514 00:30:03,604 --> 00:30:08,344 Um, there are a few bugs and antibiotics combination that has 515 00:30:08,344 --> 00:30:12,034 been looked at with some decent data that show there is no correlation. 516 00:30:12,064 --> 00:30:18,754 That's like rifampin and ethambutol in MAC or INH in M.kansasii, but that's 517 00:30:18,754 --> 00:30:23,774 only a few where there's actually some decent, maybe trials slash observational 518 00:30:23,774 --> 00:30:27,584 clinical data saying that, okay, we looked at it and there actually is 519 00:30:27,584 --> 00:30:33,614 no, uh, correlation, at least at this breakpoint, but to further add complexity. 520 00:30:33,644 --> 00:30:39,644 Maybe one other reason is because clinical outcomes also depends on the 521 00:30:39,644 --> 00:30:42,554 host, not just purely killing the bug. 522 00:30:42,914 --> 00:30:47,204 You can kill the bugs all you want, but if you have a airway that is 523 00:30:47,204 --> 00:30:48,974 malformed from bronchiectasis. 524 00:30:49,609 --> 00:30:53,059 They're just gonna be stuck there, and you're not gonna get somewhat equivalent 525 00:30:53,059 --> 00:30:56,089 to maybe source control inside the lungs. 526 00:30:57,319 --> 00:30:59,029 Let's look at it and a different analogy. 527 00:30:59,029 --> 00:31:01,979 Let's look at, let's say, MSSA, you know, Staph aureus. 528 00:31:01,999 --> 00:31:04,529 So we know MIC matters in Staph aureus. 529 00:31:04,549 --> 00:31:09,319 That's why there's MSSA, MRSA, but the MSSA, no matter how much 530 00:31:09,319 --> 00:31:14,539 nafcillin or cefazolin you give them, if they have an undrained abscess. 531 00:31:15,244 --> 00:31:16,414 Patient's not gonna get better. 532 00:31:16,444 --> 00:31:19,684 And as ID doctors for us, that's a no brainer. 533 00:31:19,774 --> 00:31:25,244 So are you gonna say nafcillin and cefazolin MICs don't matter in MSSA? 534 00:31:25,264 --> 00:31:25,684 No. 535 00:31:25,714 --> 00:31:27,634 'cause we know it's a source control issue. 536 00:31:28,744 --> 00:31:29,584 Almost the same. 537 00:31:29,584 --> 00:31:31,054 Not perfectly analogous. 538 00:31:31,354 --> 00:31:34,714 Maybe it's the same thing in N TM pulmonary disease with 539 00:31:34,714 --> 00:31:39,004 these bronchiectatic airways that the NTM just gets stuck. 540 00:31:39,004 --> 00:31:41,944 Or even if you get 'em out with airway clearance. 541 00:31:42,424 --> 00:31:46,684 The patients might inhale them back, so therefore they don't get, quote, the 542 00:31:46,684 --> 00:31:51,274 clinical outcomes you would expect purely from a bug killing MIC point of view. 543 00:31:52,246 --> 00:31:55,786 The only thing I would add is there are two drugs for which we do 544 00:31:55,786 --> 00:31:59,656 believe the MIC determinations, and that's the macrolides and amikacin. 545 00:31:59,956 --> 00:32:05,136 So I do want, I do want the listeners to, to believe those MICs and that those 546 00:32:05,136 --> 00:32:09,956 cut points that determine susceptibility from resistance, and those are based 547 00:32:09,956 --> 00:32:15,376 on trials, uh, data that show that there is worse outcomes when, uh, 548 00:32:15,406 --> 00:32:17,686 we're above those MIC breakpoints. 549 00:32:18,616 --> 00:32:19,576 But then that's it. 550 00:32:19,726 --> 00:32:22,906 You know, the rest, uh, are laboratory derived cut points. 551 00:32:23,296 --> 00:32:26,506 That doesn't mean they're not useful, it just means they're 552 00:32:26,506 --> 00:32:28,756 not as definitive of a cut point. 553 00:32:28,816 --> 00:32:32,986 And so, you know, when I have to build a regimen for Mycobacterium 554 00:32:32,986 --> 00:32:36,916 abscessus, um, I. You know, I'm gonna look down that list. 555 00:32:36,916 --> 00:32:41,366 And there are some, I believe, more like imipenem was mentioned by Reeti. 556 00:32:41,386 --> 00:32:44,676 It's an unstable compound by the time we read the rapid 557 00:32:44,776 --> 00:32:46,006 grower at three to five days. 558 00:32:46,006 --> 00:32:49,636 I don't know what the concentration is, so I, I don't pay attention to that one. 559 00:32:50,176 --> 00:32:53,296 Uh, but other drugs that are more stable that I do tend to 560 00:32:53,296 --> 00:32:54,556 pay a little bit more attention. 561 00:32:55,066 --> 00:32:58,846 But even if they cross that magic resistant cut point, that 562 00:32:58,846 --> 00:33:01,606 doesn't mean I'm not going to use them as I build that regimen. 563 00:33:02,251 --> 00:33:06,871 Uh, because we know, we see people respond to treatment even when drugs 564 00:33:06,871 --> 00:33:10,201 are in the regimen that don't look that active, but it's all we have. 565 00:33:10,466 --> 00:33:11,036 Exactly. 566 00:33:11,036 --> 00:33:11,486 Exactly. 567 00:33:11,536 --> 00:33:14,056 I think a lot as Id doctors, we love that, right? 568 00:33:14,056 --> 00:33:15,496 We love antibiotics, we love MICs. 569 00:33:16,511 --> 00:33:18,521 What's the lowest MIC and what's the best antibiotic? 570 00:33:19,031 --> 00:33:24,521 But, uh, at National Jewish, uh, I learned the importance of treating the underlying 571 00:33:24,521 --> 00:33:29,486 disease, whether it's bronchiectasis, COPD, acid reflux, et cetera. 572 00:33:29,936 --> 00:33:31,286 Optimizing nutrition. 573 00:33:31,796 --> 00:33:37,016 And finally, if they have bronchiectasis airway clearance therapy, airway clearance 574 00:33:37,016 --> 00:33:38,756 therapy, airway clearance therapy. 575 00:33:38,756 --> 00:33:43,856 So that's why in figure five at the very top, the number one is do those three 576 00:33:43,856 --> 00:33:46,736 things, then think antibiotics after. 577 00:33:47,006 --> 00:33:51,626 And that's gonna be a big lesson for a lot of, uh, purely ID folks out there 578 00:33:51,626 --> 00:33:53,846 who are not familiar with air clearance. 579 00:33:54,176 --> 00:33:57,191 They just deal with the antibiotics part, but I want them to understand 580 00:33:57,191 --> 00:33:58,951 the importance of air airway clearance. 581 00:33:59,369 --> 00:34:01,859 Yeah, and I feel like that's a big part of it, is finding a good 582 00:34:02,774 --> 00:34:06,434 pulmonologist to partner with if, if you're not, if you need help 583 00:34:06,434 --> 00:34:09,854 thinking about those and managing the, especially the airway clearance. 584 00:34:10,604 --> 00:34:15,614 Yeah, I, I have run into a number of ID docs in the past few years that 585 00:34:16,634 --> 00:34:20,114 they start the airway clearance because the pulmonary docs are not doing it. 586 00:34:20,679 --> 00:34:21,099 Mm-hmm. 587 00:34:21,164 --> 00:34:24,674 And, uh, and I applaud them because, uh, they're watching 588 00:34:24,674 --> 00:34:28,814 videos and trying to learn, you know, more about airway clearance. 589 00:34:28,814 --> 00:34:31,764 'cause at the end of the day the patient in front of us is who we're trying to 590 00:34:31,764 --> 00:34:36,174 help, and we sometimes have to do things that we, we may not have been trained in. 591 00:34:36,534 --> 00:34:39,559 But if we don't have that available around us, then let's do it. 592 00:34:40,159 --> 00:34:40,759 Perfect. 593 00:34:40,789 --> 00:34:42,709 So, I made this patient up and. 594 00:34:43,294 --> 00:34:45,814 I kind of gave a background saying that they've had a 595 00:34:45,814 --> 00:34:47,344 culture that's had MAC in it. 596 00:34:47,344 --> 00:34:52,684 There's been one with M.abscessus, and you know, I'm gonna leave this broad and just 597 00:34:52,684 --> 00:34:57,154 say we repeated cultures and there there could be a variety of things that happen. 598 00:34:57,154 --> 00:35:01,714 You know, maybe we have a couple cultures that subsequently have MAC, 599 00:35:01,744 --> 00:35:04,094 that maybe we confirm M.abscessus. 600 00:35:04,114 --> 00:35:05,344 Maybe it's a mixture. 601 00:35:05,494 --> 00:35:10,134 And rather than just picking one and focusing on that, I thought maybe you 602 00:35:10,134 --> 00:35:14,514 could kind of compare and contrast the types of possibilities and the context of 603 00:35:14,514 --> 00:35:19,554 that treatment framework that you gave, like how you make decisions more than us 604 00:35:19,554 --> 00:35:21,954 focusing on kind of one specific example. 605 00:35:22,088 --> 00:35:23,948 So, I mean, this is a tough question, right? 606 00:35:23,948 --> 00:35:28,128 So let's say they're growing multiple organism over a series of, uh, sputa. 607 00:35:28,148 --> 00:35:33,458 So they're growing, let's say M.abscessus same subspecies or MAC, MAC.. And 608 00:35:33,458 --> 00:35:34,718 then they, they're intermingled. 609 00:35:34,718 --> 00:35:34,988 So. 610 00:35:36,173 --> 00:35:39,983 You have to find the one that grows the most and that's likely the one 611 00:35:40,073 --> 00:35:41,453 that's driving, that's the primary one. 612 00:35:41,573 --> 00:35:48,593 So let's say, you know, it is M.abscessus masiliense, um, growing four different 613 00:35:48,593 --> 00:35:53,693 times and you get two other cultures that's also MAC, that and maybe M 614 00:35:53,693 --> 00:35:55,283 subspecies something, something. 615 00:35:55,528 --> 00:35:59,323 So you know, you're going want to treat M.abscessus (assuming they 616 00:35:59,323 --> 00:36:01,163 meet the diagnostic criteria). 617 00:36:01,874 --> 00:36:03,489 Should you ignore the MAC? 618 00:36:03,639 --> 00:36:04,539 That's the question. 619 00:36:04,539 --> 00:36:04,989 Right? 620 00:36:05,109 --> 00:36:06,609 Um, and that's a tough one. 621 00:36:06,609 --> 00:36:09,879 And we see this is where a lot of nuance come into play. 622 00:36:10,389 --> 00:36:16,359 And it comes down to the macrolide, the macrolide, and protecting the macrolide. 623 00:36:16,809 --> 00:36:22,239 So if we are treating the M abscessus with a macrolide therapy, which we likely are, 624 00:36:22,269 --> 00:36:26,559 'cause it's massiliense and we wanna use a macrolide when we can, and I'm assuming 625 00:36:26,559 --> 00:36:29,409 that the Mac is also macrolide resistant. 626 00:36:30,069 --> 00:36:34,194 If you're just treating the M abscessus without any other MAC drug, 627 00:36:34,584 --> 00:36:39,804 you're basically subjecting that MAC to evolutionary pressure with just 628 00:36:39,804 --> 00:36:42,144 purely monotherapy with azithromycin. 629 00:36:43,134 --> 00:36:48,654 So even in this case, even if we don't think the MAC is driving the disease and 630 00:36:48,654 --> 00:36:51,144 it's only secondary slash colonization. 631 00:36:51,699 --> 00:36:54,219 We don't want it to become macrolide resistant. 632 00:36:54,699 --> 00:36:59,379 So in this case, we might throw on ethambutol in addition to the M abscessus 633 00:36:59,379 --> 00:37:05,649 regimen, broadening it to cover both organism, understanding that we're 634 00:37:05,649 --> 00:37:10,269 trying to treat only the M abscessus, but we're also preventing macrolide 635 00:37:10,269 --> 00:37:12,519 resistant development in the MAC. 636 00:37:14,519 --> 00:37:15,349 How did I do, Chuck? 637 00:37:15,414 --> 00:37:19,584 Well, you learned, you learned well, Vu, um, protect the macrolide. 638 00:37:19,584 --> 00:37:20,514 That's the mantra. 639 00:37:20,904 --> 00:37:26,154 Um, and these, these are often very complex decisions and, and sometimes 640 00:37:26,154 --> 00:37:30,354 we can't define a dominant one to go after and we have to treat both. 641 00:37:30,354 --> 00:37:31,284 But you can do that. 642 00:37:31,284 --> 00:37:32,034 We have to do it. 643 00:37:32,544 --> 00:37:35,214 Uh, that's usually gonna take about five drugs to do that. 644 00:37:35,244 --> 00:37:36,474 So it's not easy. 645 00:37:36,984 --> 00:37:40,554 Um, and I would just say this is when I would consider calling a friend. 646 00:37:40,974 --> 00:37:46,584 Uh, trying to get some encouragement with the, uh, the best way to approach this. 647 00:37:46,944 --> 00:37:51,274 Uh, because unfortunately we do see people referred here who 648 00:37:51,694 --> 00:37:55,114 developed macrolide resistance because one of the two was treated. 649 00:37:55,489 --> 00:37:59,429 And, uh, one drug was exposed to basically monotherapy and 650 00:37:59,449 --> 00:38:01,219 they're now macrolide resistant. 651 00:38:01,219 --> 00:38:08,059 And whether that's abscessus or macrolide resistant, uh, Mac, you know, you've taken 652 00:38:08,059 --> 00:38:11,719 someone who's likely to be cured now to someone who's likely not to be cured. 653 00:38:12,092 --> 00:38:17,972 I think one other sort of branch that I thought we could just touch on is how 654 00:38:17,972 --> 00:38:22,682 you adjust your approach if patients have severe or treatment limited disease. 655 00:38:22,682 --> 00:38:27,872 And maybe actually just starting by saying how you explain what is considered 656 00:38:27,872 --> 00:38:29,792 severe or treatment limited disease. 657 00:38:30,512 --> 00:38:31,982 Okay, I'll, I'll talk about this. 658 00:38:31,982 --> 00:38:34,742 So severe is a little more easy. 659 00:38:34,742 --> 00:38:38,042 Like usually when I, for the sake of this paper, only severe was 660 00:38:38,042 --> 00:38:40,232 referring to cavitary disease. 661 00:38:40,232 --> 00:38:44,882 So any form of cavitary disease, or even if they have nodular bronchiectatic, 662 00:38:44,882 --> 00:38:49,942 but very profound, like multiple lobes, a lot of involvement of nodule 663 00:38:49,942 --> 00:38:54,592 bronchiectatic and the patient's really sick, and a BMI of 15 or something. 664 00:38:54,652 --> 00:38:56,872 I would consider that severe even without cavity. 665 00:38:58,192 --> 00:39:03,472 Treatment Limited is a term we designed just for this paper, and 666 00:39:03,472 --> 00:39:08,482 it's not well established as standard terminology in the NTM world. 667 00:39:08,702 --> 00:39:12,782 Because we're basically combining for the sake of word count limitation 668 00:39:12,782 --> 00:39:17,132 and meeting it, we just basically squeeze in treatment refractory meaning 669 00:39:17,672 --> 00:39:22,502 NTM disease that got treated with guideline based therapy and by six 670 00:39:22,502 --> 00:39:24,182 months still haven't culture converted. 671 00:39:24,722 --> 00:39:28,392 Um, that's based on MAC, but we are extrapolating it to other NTM. 672 00:39:28,412 --> 00:39:31,622 But basically that's the MAC term for treatment refractory MAC. 673 00:39:32,102 --> 00:39:40,412 But we're also adding in NTM where their primary best drug is resistant to. 674 00:39:40,412 --> 00:39:44,522 So for example, macrolide resistant, uh, MAC will be. 675 00:39:45,152 --> 00:39:48,422 I will squeeze it into treatment limited disease 676 00:39:48,422 --> 00:39:49,892 'cause you can't use a macrolide. 677 00:39:50,342 --> 00:39:54,452 So for the sake of the paper, I squeeze those two two in simply 678 00:39:54,452 --> 00:39:59,252 because I think the next step would be something that a lot of ID doctors 679 00:39:59,252 --> 00:40:03,152 or most doctors are afraid of, and that is adding on IV amikacin. 680 00:40:05,492 --> 00:40:06,902 Chuck, do you have anything else to add? 681 00:40:08,327 --> 00:40:15,447 Yeah, I mean, I think now the, the other option is ALIS, um, amikacin liposome, 682 00:40:15,847 --> 00:40:20,137 um, installation suspension, which, you know, in the 2020 guidelines was frankly 683 00:40:20,137 --> 00:40:22,537 one of the few novel recommendations. 684 00:40:22,927 --> 00:40:27,367 Um, and it was one of only four strong recommendations in the whole guideline. 685 00:40:27,697 --> 00:40:31,477 And it's because we had phase two and phase three randomized data showing, um, 686 00:40:31,837 --> 00:40:36,472 that in people with treatment refractory MAC, that if you added ALIS to guideline 687 00:40:36,472 --> 00:40:42,412 based therapy, culture conversion was 30% by four months versus only about 9%. 688 00:40:42,472 --> 00:40:44,332 And people who didn't get it. 689 00:40:44,452 --> 00:40:47,212 And so that, so that, you know, did make it into the guidelines. 690 00:40:47,212 --> 00:40:48,532 Of course it was FDA approved. 691 00:40:49,132 --> 00:40:55,162 Um, also, so I still think though, that if it's cavitary disease that 692 00:40:55,162 --> 00:40:59,002 you're looking at and you haven't already given them IV amikacin. 693 00:40:59,557 --> 00:41:03,307 I would probably give IV Amikacin in that setting and then transition 694 00:41:03,307 --> 00:41:04,807 them after a couple of months. 695 00:41:05,167 --> 00:41:08,467 Now, this is not in the guidelines, this is that art of medicine. 696 00:41:08,797 --> 00:41:12,487 Um, but it's some, it's something to, uh, I think consider, but I, 697 00:41:12,697 --> 00:41:16,537 but I do think it gives us, ALIS gives us another tool, uh, to use. 698 00:41:16,868 --> 00:41:19,033 Do you guys wanna talk about surgery at all? 699 00:41:20,263 --> 00:41:24,903 Yeah, I mean, I, I figured, since these episode, we obviously can't 700 00:41:24,903 --> 00:41:27,903 cover such a huge topic in, in one. 701 00:41:27,903 --> 00:41:32,523 So I, that's why I thought we'd focus on the framework and maybe spend the rest 702 00:41:32,523 --> 00:41:36,753 of the time thinking about how we monitor these patients, what are other therapies? 703 00:41:36,753 --> 00:41:41,313 And that actually was gonna be one of my questions of what, when 704 00:41:41,313 --> 00:41:45,513 and how you identify patients to refer for surgical resection. 705 00:41:45,933 --> 00:41:47,703 Um, and, and how you think about that. 706 00:41:47,945 --> 00:41:53,285 So for surgery, you know, we do it a lot at NJH 'cause we have a surgeon 707 00:41:53,285 --> 00:41:57,875 who is a well-known expert in it, but usually they should be referred for 708 00:41:57,975 --> 00:42:03,105 evaluation for lung surgery if they have very uncontrolled, severe symptoms, 709 00:42:03,105 --> 00:42:07,635 most commonly is, uh, hemoptysis, that doesn't improve on any treatment, 710 00:42:08,445 --> 00:42:10,425 particularly if they have focal disease. 711 00:42:10,455 --> 00:42:13,185 Uh, doesn't mean you have to be perfectly focal and unifocal. 712 00:42:13,485 --> 00:42:16,965 It could be I. You know, it could be widespread, but mainly the disease, 713 00:42:16,995 --> 00:42:20,685 the biggest disease side is in a single segment or lobe of a lung. 714 00:42:21,255 --> 00:42:24,705 And if we think they're unlikely to achieve response 715 00:42:24,705 --> 00:42:26,505 by antibiotic therapy alone. 716 00:42:26,505 --> 00:42:32,505 So in this case, a lot of times we refer to patients with macrolide resistant MAC 717 00:42:32,925 --> 00:42:39,380 that maybe have a severely bronchiectatic right middle lobe to get that right middle 718 00:42:39,380 --> 00:42:44,835 lobe removed, and that's our most common, um, surgical referral at National Jewish. 719 00:42:45,261 --> 00:42:48,531 Yeah, we, we, you know, we, we do a lot of surgery. 720 00:42:48,531 --> 00:42:53,301 It's done at the University of Colorado by Dr. John, uh, Mitchell, who's basically 721 00:42:53,301 --> 00:42:56,121 done all our surgeries for over 20 years. 722 00:42:56,121 --> 00:42:59,511 He's probably done about a thousand patients by this time, and he has 723 00:42:59,511 --> 00:43:02,361 almost all of it, uh, uh, robotically. 724 00:43:03,021 --> 00:43:04,521 Um, so he's pretty amazing. 725 00:43:04,591 --> 00:43:08,401 It's still a very small minority of the number of patients we 726 00:43:08,401 --> 00:43:10,141 see that actually go to surgery. 727 00:43:10,861 --> 00:43:14,551 And, uh, to Vu's point, they're, you know, they often have resistant 728 00:43:14,551 --> 00:43:19,801 organisms, may have already been failing therapy, uh, have focal disease, 729 00:43:19,801 --> 00:43:24,001 probably cavitary disease is the most common reason people go, uh, to 730 00:43:24,001 --> 00:43:26,071 surgery, but they do well afterwards. 731 00:43:26,131 --> 00:43:26,461 Um. 732 00:43:27,526 --> 00:43:32,296 Um, he's, he's published with a robotic approach, you know, a 7% complication 733 00:43:32,296 --> 00:43:37,156 rate, which is very low, zero mortality in 20 years, at the time of surgery. 734 00:43:37,906 --> 00:43:41,986 Um, and culture conversion rates of 80 plus percent. 735 00:43:41,986 --> 00:43:44,866 In fact, if you look at 15 studies, we did a systematic 736 00:43:44,866 --> 00:43:46,246 review part of the guidelines. 737 00:43:46,696 --> 00:43:47,236 Um. 738 00:43:47,881 --> 00:43:50,611 The culture conversion rate was 80 to a hundred percent. 739 00:43:50,611 --> 00:43:55,171 So at least on the micro biologics how you are, you are now getting control. 740 00:43:55,801 --> 00:44:00,631 We always say it may not lead to cure, but it will help us get control. 741 00:44:00,955 --> 00:44:01,245 Yeah. 742 00:44:01,556 --> 00:44:06,056 And you know, from, you're experience seeing a lot of these patients, I 743 00:44:06,356 --> 00:44:10,856 thought maybe I would just ask if you have any big take homes or pearls 744 00:44:10,856 --> 00:44:16,321 for us to consider for those who are on therapy, either monitoring their 745 00:44:16,321 --> 00:44:20,911 response or monitoring for adverse effects of the uh, antimicrobials. 746 00:44:22,996 --> 00:44:27,886 Yeah, I would say, you know, you kind of need to have pretty frequent follow up. 747 00:44:28,456 --> 00:44:32,866 Uh, but more importantly, the thing that we see lacking the most among 748 00:44:33,206 --> 00:44:37,226 a lot of referring providers is that they, they don't get surveillance 749 00:44:37,226 --> 00:44:38,576 cultures frequently enough. 750 00:44:38,966 --> 00:44:42,161 And ideally, we want, once they start therapy. 751 00:44:42,161 --> 00:44:47,831 We do want, uh, repeat sputum every one to two month as possible. 752 00:44:47,981 --> 00:44:52,871 And this is helpful because it determines, um, length, total length 753 00:44:52,901 --> 00:44:58,721 of treatment and help monitor, um, disease treatment progress. 754 00:44:59,135 --> 00:45:01,650 You know, we have to balance the treatment response that we're 755 00:45:01,650 --> 00:45:03,600 evaluating with the adverse, uh, events. 756 00:45:03,600 --> 00:45:05,340 And, and unfortunately we know those are common. 757 00:45:06,000 --> 00:45:10,300 Um, and, and it's just part of, of the, in the management of these patients. 758 00:45:10,900 --> 00:45:15,340 Um, so the things that we're looking at are, you know, usually a complete blood 759 00:45:15,340 --> 00:45:17,350 count, comprehensive metabolic panel. 760 00:45:18,055 --> 00:45:20,995 Uh, that's kind of goes without saying, but I think the thing to 761 00:45:20,995 --> 00:45:24,355 remember is that ethambutol can produce optic neuritis and although it's 762 00:45:24,355 --> 00:45:26,365 not common, it can be catastrophic. 763 00:45:26,365 --> 00:45:31,045 So we really want those, uh, uh, those patients receiving ethambutol 764 00:45:31,045 --> 00:45:35,395 to have, uh, visual acuity monitoring, red, green color discrimination. 765 00:45:35,725 --> 00:45:39,325 No one has ever studied the optimal frequency in which that should be done. 766 00:45:39,325 --> 00:45:43,645 And we really kind of get, get into details and the guidelines on this. 767 00:45:43,735 --> 00:45:44,005 Um. 768 00:45:44,710 --> 00:45:48,700 But, but I, I think that, uh, it's a very important, uh, thing to do. 769 00:45:49,030 --> 00:45:54,490 What we tell patients is, um, read the same font every day, you know, 770 00:45:54,490 --> 00:45:58,060 because don't wait till your next, uh, ophthalmology appointment. 771 00:45:58,120 --> 00:46:00,550 Uh, but just every day, same font. 772 00:46:00,880 --> 00:46:05,450 If you feel like you're seeing some visual decrement, then you stop the drug. 773 00:46:05,450 --> 00:46:09,470 We empower the patient to feel you stop the drug and you inform us. 774 00:46:09,830 --> 00:46:11,090 And then we'll go from there. 775 00:46:11,090 --> 00:46:11,180 Mm-hmm. 776 00:46:12,080 --> 00:46:13,490 Um, and so I think that's important. 777 00:46:13,490 --> 00:46:20,070 And the other is amikacin ototoxicity is unfortunately a common adverse event. 778 00:46:20,070 --> 00:46:22,920 So we wanna monitor audiograms for that. 779 00:46:22,920 --> 00:46:26,380 We usually do baseline if they're getting iv, we, we 780 00:46:26,380 --> 00:46:28,090 typically do monthly audiograms. 781 00:46:28,660 --> 00:46:32,620 But one thing we're seeing is people with, um, ALIS are not getting audiograms, but 782 00:46:32,620 --> 00:46:37,450 it's still possible, much less common with than with iv, but it is possible. 783 00:46:37,810 --> 00:46:42,850 So same thing we do baseline audiogram on someone beginning ALIS, and, and 784 00:46:42,850 --> 00:46:46,900 then we, we check much less frequency anywhere between three and six months, 785 00:46:47,050 --> 00:46:50,800 probably three months if someone who we see already has a little hearing 786 00:46:50,800 --> 00:46:53,320 loss, maybe six and someone who doesn't. 787 00:46:53,710 --> 00:46:56,650 Um, but I think both should be monitored. 788 00:46:56,890 --> 00:46:57,130 Excellent. 789 00:46:58,290 --> 00:47:02,340 To start closing us out, I'm gonna change gears and just ask 790 00:47:02,370 --> 00:47:05,610 you guys what is on the horizon? 791 00:47:05,610 --> 00:47:10,380 Like, what are you excited to learn more about, understand better, 792 00:47:10,410 --> 00:47:13,020 maybe studies that are in process. 793 00:47:13,270 --> 00:47:16,960 What should we all get excited to, to learn about in the coming years about NTM? 794 00:47:19,025 --> 00:47:20,980 Well, I'll, I'll probably take this one. 795 00:47:21,130 --> 00:47:21,850 Um. 796 00:47:22,510 --> 00:47:26,770 There are a number of clinical trials that are occurring and number of drugs 797 00:47:26,770 --> 00:47:31,560 in the pipeline that, uh, have not quite made it, uh, to the clinical trial arena. 798 00:47:31,620 --> 00:47:33,000 But I hopefully will. 799 00:47:33,000 --> 00:47:37,530 Some of the things that I think we're very excited, exciting is, um, and things 800 00:47:37,530 --> 00:47:41,840 that we're interested in here at National Jewish, some of the new drugs, for 801 00:47:41,840 --> 00:47:47,240 example, ALIS is in, uh, has, uh, enrolled into a trial for treatment naive Mac. 802 00:47:47,735 --> 00:47:50,375 Uh, not waiting till they get refractory. 803 00:47:50,405 --> 00:47:54,845 And there were two trials, and the first has been resulted and, uh, it was a 804 00:47:54,845 --> 00:47:59,405 very positive trial in, uh, pretty much every way, both primary and secondary. 805 00:47:59,405 --> 00:48:01,505 And so it's in now a larger trial. 806 00:48:01,505 --> 00:48:02,615 That was a six month trial. 807 00:48:02,615 --> 00:48:06,195 This is, we're waiting for the results of a 52, uh, wk 808 00:48:06,215 --> 00:48:07,835 trial and that ends in October. 809 00:48:07,955 --> 00:48:11,435 So we we're gonna know, hopefully later this year, the results of that. 810 00:48:11,915 --> 00:48:15,140 Uh, omadacycline, uh, completed a phase two trial. 811 00:48:15,140 --> 00:48:16,850 Also very positive trial. 812 00:48:17,090 --> 00:48:21,170 This was in, this was a monotherapy trial in people with mycobacterium abscessus, 813 00:48:21,380 --> 00:48:23,330 and again, primary and secondary. 814 00:48:23,630 --> 00:48:24,770 Uh, very positive. 815 00:48:24,770 --> 00:48:28,370 And we look forward to see that drug and we're using it now, but we would 816 00:48:28,370 --> 00:48:31,130 like to see evidence to, uh, help us. 817 00:48:31,280 --> 00:48:35,840 Uh, inhaled clofazamine is a trial that is beginning now and is already enrolling, 818 00:48:35,990 --> 00:48:40,280 and so that's a very interesting approach of giving very intermittent inhalational 819 00:48:40,430 --> 00:48:42,890 treatments because of the long half-life. 820 00:48:43,070 --> 00:48:47,150 Um, uh, mycobacteriophage, uh, this is, you know, also not, 821 00:48:47,180 --> 00:48:49,880 not just with mycobacteria, but with bacteria in general. 822 00:48:49,880 --> 00:48:53,210 It's a very interesting area, uh, of investigation. 823 00:48:53,750 --> 00:48:57,740 Uh, there are trials for pseudomonas, but there are no NTM trials now, but there are 824 00:48:57,740 --> 00:49:00,740 cohorts, uh, that are being, uh, studied. 825 00:49:00,800 --> 00:49:01,910 So that's pretty cool. 826 00:49:02,660 --> 00:49:07,010 I, I will end, uh, I think with, um, uh, something called orc. 827 00:49:07,070 --> 00:49:08,420 ORC is a compound. 828 00:49:08,720 --> 00:49:13,070 That an aurine model was basically a hundred percent protective against 829 00:49:13,070 --> 00:49:15,320 ototoxicity from an amino glycoside. 830 00:49:16,030 --> 00:49:19,270 That trial is beginning now several sites under the leadership of 831 00:49:19,270 --> 00:49:21,100 Kevin Winthrop at, uh, Oregon. 832 00:49:21,640 --> 00:49:25,990 Uh, but we're very excited to see, you know, can we take an active drug 833 00:49:25,990 --> 00:49:29,950 like the aminoglycosides and make them safe or safer than they are now? 834 00:49:30,565 --> 00:49:33,745 But anyway, I, I think a lot of things that are very exciting are happening. 835 00:49:33,745 --> 00:49:37,135 We could, we'd have to do a whole nother podcast to talk about them. 836 00:49:39,455 --> 00:49:40,115 That's great. 837 00:49:40,265 --> 00:49:43,925 Um, very exciting to hear all those. 838 00:49:43,925 --> 00:49:47,225 And I guess I'll just open it up, you know, for any closing 839 00:49:47,225 --> 00:49:48,275 thoughts you guys have. 840 00:49:48,275 --> 00:49:50,315 Anything else that we didn't cover so far? 841 00:49:50,840 --> 00:49:57,415 I guess I'll just reinforce the unofficial title of this talk, which is protect the 842 00:49:57,415 --> 00:50:03,355 macrolide, protect the macrolide, protect the macrolide, but uh, in addition, um, 843 00:50:03,835 --> 00:50:07,885 do airway clearance therapy if they have bronchiectasis and for slowly growing 844 00:50:07,885 --> 00:50:13,045 mycobacteria, particularly MAC, do not drop ethambutol because ethambutol, 845 00:50:13,045 --> 00:50:15,205 guess what protects the macrolide. 846 00:50:15,235 --> 00:50:20,245 So please do not drop ethambutol from your MAC regimen unless 847 00:50:20,305 --> 00:50:22,345 the patient is, uh, going blind. 848 00:50:23,620 --> 00:50:23,860 Yeah. 849 00:50:23,860 --> 00:50:28,630 And, and also don't treat him only with a macrolide and a rifamycin because the 850 00:50:28,630 --> 00:50:30,880 rifamycin does not protect the macrolide. 851 00:50:31,935 --> 00:50:32,545 Correct. 852 00:50:33,040 --> 00:50:36,730 And I guess the other thing we should do, we should thank the authors. 853 00:50:37,030 --> 00:50:38,290 We're not the only authors. 854 00:50:38,290 --> 00:50:44,440 And uh, and there was a cat theme here, so Vu, he adopted two cats, but to get this 855 00:50:44,440 --> 00:50:46,450 thing written, he had to herd the cats. 856 00:50:46,690 --> 00:50:48,310 And he did an incredible job of that. 857 00:50:49,255 --> 00:50:49,585 Yeah. 858 00:50:49,705 --> 00:50:50,305 Oh, thank you. 859 00:50:50,305 --> 00:50:52,540 Yeah, the authors were amazing. 860 00:50:52,540 --> 00:50:55,180 Like all, I think 12 of them. 861 00:50:55,300 --> 00:51:00,640 Um, I remember getting the, the bits and pieces of everyone, and I know, 862 00:51:00,700 --> 00:51:05,290 um, CID said 5,000 words and then I put it all together and it was 9,000 863 00:51:05,290 --> 00:51:11,080 words and I was like, wow, that's, this is gonna be, this is gonna be fun. 864 00:51:11,080 --> 00:51:14,835 It is like telling your cats to like stop eating, but they keep eating 865 00:51:14,895 --> 00:51:18,825 kind of equivalent, you know, it's like, okay, how do you stop 'em? 866 00:51:18,825 --> 00:51:21,375 But yeah, they were, I mean the authors were amazing. 867 00:51:21,465 --> 00:51:25,095 Obviously Reeti and Chuck, but the others particularly, I'm gonna give a shout 868 00:51:25,095 --> 00:51:28,455 out to the very, one of the very middle author who doesn't get enough credit. 869 00:51:28,455 --> 00:51:30,575 His name is Vinicius, he wears multiple hats. 870 00:51:30,575 --> 00:51:33,665 He's like a microbiologist and data analyst and research all at the same time. 871 00:51:33,665 --> 00:51:37,175 But he's the one who actually kind of designed these figures, like 872 00:51:37,175 --> 00:51:40,905 particularly that, that fancy figure one with that giant mycobacterium. 873 00:51:41,285 --> 00:51:41,465 Yeah. 874 00:51:41,465 --> 00:51:42,125 He drew that. 875 00:51:42,125 --> 00:51:45,635 I drafted a really ugly version of that, um, pen and paper, and he made 876 00:51:45,635 --> 00:51:47,855 it like not ugly, which is great. 877 00:51:48,185 --> 00:51:49,625 Oh, and Chuck has it right there. 878 00:51:49,710 --> 00:51:49,930 Wow. 879 00:51:52,265 --> 00:51:53,945 I love a good graphic. 880 00:51:53,945 --> 00:51:56,255 This is place to give a shoutout for that. 881 00:51:56,255 --> 00:51:56,555 Yeah. 882 00:51:57,628 --> 00:51:58,198 Awesome. 883 00:51:58,618 --> 00:52:03,208 Um, well I am just, again, very, very grateful that you 884 00:52:03,208 --> 00:52:04,888 guys took the time to do this. 885 00:52:06,448 --> 00:52:07,558 Yeah, it was a pleasure. 886 00:52:07,558 --> 00:52:08,098 Thanks for 887 00:52:08,323 --> 00:52:08,623 Thanks. 888 00:52:08,628 --> 00:52:08,898 Thanks. 889 00:52:10,463 --> 00:52:10,753 Yeah. 890 00:52:11,338 --> 00:52:11,728 Appreciate 891 00:52:11,823 --> 00:52:14,403 thanks again to our guests for joining Febrile Today. 892 00:52:14,823 --> 00:52:19,323 Make sure to check out their State of the Art Review in CID entitled 893 00:52:19,353 --> 00:52:24,603 Nontuberculous Mycobacterial Pulmonary Disease Patients Principles and Prospects. 894 00:52:24,757 --> 00:52:28,597 Check out the website Febrile podcast.com where you'll find the Consult Notes, 895 00:52:28,897 --> 00:52:31,987 which are written supplements of the episodes of links to references, 896 00:52:32,257 --> 00:52:35,197 our library of ID infographics, and a link to the merch store. 897 00:52:36,097 --> 00:52:39,997 Febrile is produced with support from the Infectious Diseases Society of America. 898 00:52:41,107 --> 00:52:44,287 Please reach out if you have any suggestions for future shows or 899 00:52:44,287 --> 00:52:45,877 wanna be more involved with Febrile. 900 00:52:46,177 --> 00:52:46,987 Thanks for listening. 901 00:52:47,257 --> 00:52:48,997 Stay safe and we'll see you next time.