1 00:00:06,617 --> 00:00:07,397 Hi everyone. 2 00:00:07,427 --> 00:00:11,627 Welcome to Febrile, a cultured podcast about all things infectious disease. 3 00:00:12,077 --> 00:00:15,827 We use consult questions to dive into ID clinical reasoning, diagnostics 4 00:00:15,827 --> 00:00:17,057 and antimicrobial management. 5 00:00:17,987 --> 00:00:20,777 I'm Sara Dong, your host and a Med-Peds ID doc. 6 00:00:21,877 --> 00:00:23,557 I am looking forward to our episode today. 7 00:00:23,557 --> 00:00:25,957 We have three guests that are joining us. 8 00:00:26,257 --> 00:00:28,297 I will start with Dr. Tom Schmidt. 9 00:00:29,017 --> 00:00:32,497 Tom is a second year ID fellow at the University of Minnesota. 10 00:00:32,857 --> 00:00:36,427 He is interested in general ID, critical care, and the impact of a 11 00:00:36,427 --> 00:00:38,617 changing climate on infectious diseases. 12 00:00:39,302 --> 00:00:40,172 Hey, this is Tom. 13 00:00:40,202 --> 00:00:41,097 Uh, happy to be here 14 00:00:41,897 --> 00:00:43,837 Next I'll introduce Dr. Nate Bahr. 15 00:00:44,237 --> 00:00:47,567 Nate is an Associate Professor in the Division of Infectious Diseases 16 00:00:47,567 --> 00:00:49,007 at the University of Minnesota. 17 00:00:49,817 --> 00:00:54,497 His areas of interest include histoplasmosis, the changing epidemiology 18 00:00:54,497 --> 00:00:59,897 of fungal infections, drug pricing, and cryptococcal and TB meningitis. 19 00:01:00,987 --> 00:01:04,827 Nate is a co-chair of the Education Committee of the Mycoses Study Group 20 00:01:04,827 --> 00:01:08,697 Education and Research Consortium (MSGERC), along with Dr. Jessica Little. 21 00:01:09,002 --> 00:01:09,902 Hey, this is Nate. 22 00:01:10,232 --> 00:01:11,087 Excited to join. 23 00:01:12,222 --> 00:01:15,642 And rounding out our crew today is Dr. George R. Thompson. 24 00:01:16,372 --> 00:01:20,197 GR is a Professor of Medicine at the University of California Davis School of 25 00:01:20,197 --> 00:01:24,337 Medicine, and he has a joint appointment in the Departments of Medical Microbiology 26 00:01:24,337 --> 00:01:28,757 and Immunology and Internal Medicine in the Division of Infectious Diseases. 27 00:01:29,507 --> 00:01:33,827 He specializes in the care of patients with invasive fungal infections and has 28 00:01:33,827 --> 00:01:38,867 research interest in fungal diagnostics, clinical trials, novel antifungal 29 00:01:38,867 --> 00:01:40,877 agents, and host immunogenetics. 30 00:01:41,190 --> 00:01:42,960 Hey, I, I'm GR Thompson from UC Davis. 31 00:01:42,960 --> 00:01:43,710 Thanks for having me. 32 00:01:44,200 --> 00:01:44,980 Welcome. 33 00:01:45,340 --> 00:01:49,720 So as everyone's favorite cultured podcast, we love to hear about a 34 00:01:49,720 --> 00:01:52,970 little piece of culture, something that brings you happiness. 35 00:01:52,970 --> 00:01:56,630 So I, I generally think, uh, and most folks I think know this about me, 36 00:01:56,630 --> 00:02:00,200 one of the things that brings me the most joy besides my children is I 37 00:02:00,200 --> 00:02:02,240 absolutely love birds and birdwatching. 38 00:02:02,290 --> 00:02:06,640 My favorite birds are white breast and nut hatch, and the golden eagle. 39 00:02:07,435 --> 00:02:11,245 I literally recorded something earlier this week that they also said birding. 40 00:02:11,425 --> 00:02:11,875 Amazing. 41 00:02:14,365 --> 00:02:15,145 What about you, GR? 42 00:02:16,435 --> 00:02:20,515 Um, I, I spend most of my time chasing around my, my teenagers, trying to 43 00:02:20,515 --> 00:02:22,045 figure out where they are in the world. 44 00:02:22,425 --> 00:02:25,785 They've all picked up different sports that started during Covid, so I've 45 00:02:25,785 --> 00:02:29,535 had to learn a lot about lacrosse and, and my son's sort of an avid golfer. 46 00:02:29,535 --> 00:02:32,205 So by proxy, those are my three biggest interests right now. 47 00:02:32,560 --> 00:02:36,760 My wife though, is an avid bird watcher, so the red wing black bird in 48 00:02:36,760 --> 00:02:38,620 our backyard is frequently discussed. 49 00:02:39,475 --> 00:02:44,635 Yeah, I didn't realize the Venn diagram of ID and birding was, uh, so overlapped. 50 00:02:45,622 --> 00:02:46,882 Um, and then how about you, Nate? 51 00:02:47,852 --> 00:02:50,602 Well, uh, those birds could have been made up for all I know. 52 00:02:50,632 --> 00:02:54,572 So, I mess up your Venn diagram. 53 00:02:54,972 --> 00:02:58,592 For me it tends to be about my kids, outside as well. 54 00:02:58,592 --> 00:03:02,792 So, uh, I've had a lot of fun with them playing in the snow this winter 55 00:03:02,792 --> 00:03:06,992 and now it's getting warm, so we're enjoying that transition and, so I'm 56 00:03:06,992 --> 00:03:08,252 chasing them around and it's great. 57 00:03:08,702 --> 00:03:09,122 Love it. 58 00:03:09,392 --> 00:03:11,432 Yeah, spring is basically around the corner. 59 00:03:11,432 --> 00:03:12,332 It's almost here. 60 00:03:12,332 --> 00:03:16,692 Well, I wanted to start by just asking Nate to give folks a little introduction, 61 00:03:16,722 --> 00:03:20,912 because you had reached out to me with Jessica Little from the Mycoses 62 00:03:20,932 --> 00:03:25,492 Study Group, and I think that probably some of our listeners are involved or 63 00:03:25,492 --> 00:03:29,852 have heard of some of the initiatives and and work that the group's done. 64 00:03:29,852 --> 00:03:34,522 But I'd love it if you could orient people to that group and maybe let 65 00:03:34,522 --> 00:03:37,012 them know if they're interested, how they could get involved. 66 00:03:39,067 --> 00:03:46,387 So, Mycoses Study Group, um, it's actually the Mycoses Study Group Education and 67 00:03:46,387 --> 00:03:51,032 Research Consortium, which just as you can tell, it's, it's very short and easy. 68 00:03:51,472 --> 00:03:55,072 Um, but it does emphasize the correct things and, and those are 69 00:03:55,522 --> 00:03:57,472 big things that we're interested in. 70 00:03:57,552 --> 00:04:01,242 We wanna help further education around fungal disease. 71 00:04:01,572 --> 00:04:03,932 And so, this is part of that effort. 72 00:04:03,932 --> 00:04:08,102 We want to get information out that's important to, to clinicians 73 00:04:08,342 --> 00:04:09,752 related to fungal disease. 74 00:04:09,972 --> 00:04:15,247 We do that in a number of ways, but this is sort of an initiative to 75 00:04:15,247 --> 00:04:19,707 try to make sure we're doing that in any way that can reach people, and, 76 00:04:19,707 --> 00:04:21,297 and this reaches a lot of people. 77 00:04:21,397 --> 00:04:25,087 In research, this group has been involved in a lot of very important research 78 00:04:25,087 --> 00:04:30,147 studies over the years, and so, uh, a lot of the major figures that you're 79 00:04:30,147 --> 00:04:34,817 reading their papers in, in fungal diseases, many of them are involved, 80 00:04:35,047 --> 00:04:38,397 and often the Mycoses Study group has helped coordinate some of those studies. 81 00:04:38,877 --> 00:04:41,977 So if people are interested, they can go to the website. 82 00:04:42,067 --> 00:04:43,327 That's pretty easy to find. 83 00:04:43,637 --> 00:04:44,717 That's a good place to start. 84 00:04:44,717 --> 00:04:47,987 They can always email any of us as well, and we'll help send 85 00:04:47,987 --> 00:04:48,917 them in the right direction. 86 00:04:48,917 --> 00:04:53,987 But it's a group that, that, uh, is easy to become a part of and, and we're happy 87 00:04:53,987 --> 00:04:55,847 to have new members and get them involved. 88 00:04:56,392 --> 00:05:00,292 I realize what I should do is ask you if you ever abbreviate 89 00:05:00,432 --> 00:05:05,722 M-S-G-E-R-C and say it any other way other than Mycoses Study Group. 90 00:05:06,272 --> 00:05:07,767 I get confused, so no, I don't. 91 00:05:09,707 --> 00:05:10,157 Love it. 92 00:05:10,897 --> 00:05:11,517 Um, awesome. 93 00:05:11,747 --> 00:05:16,812 Well, Tom is going to take us through a case today, so I'm gonna hand over to him. 94 00:05:17,480 --> 00:05:17,870 Perfect. 95 00:05:17,870 --> 00:05:24,200 So we have a 50-year-old man who presented to the ED in the midwest US 96 00:05:24,540 --> 00:05:31,030 with a two week history of fatigue, low grade fevers, chills, and a new cough. 97 00:05:31,240 --> 00:05:33,010 Cough has been non-productive. 98 00:05:33,040 --> 00:05:34,270 No hemoptysis. 99 00:05:34,990 --> 00:05:38,380 He was previously prescribed a short course of antibiotics from an urgent 100 00:05:38,380 --> 00:05:43,240 care for pneumonia and given IDSA guidelines had done amoxicillin 101 00:05:43,270 --> 00:05:47,620 monotherapy at that point, didn't really make much of a difference in symptoms. 102 00:05:48,520 --> 00:05:50,800 And his history, mostly healthy. 103 00:05:50,890 --> 00:05:54,100 Has a history of hypertension, well controlled, type two 104 00:05:54,100 --> 00:05:56,080 diabetes, also well controlled. 105 00:05:56,855 --> 00:05:59,680 On exam, he is afebrile with normal vitals. 106 00:06:00,495 --> 00:06:03,625 O2 (oxygen) saturation on room air is 91%. 107 00:06:04,375 --> 00:06:07,555 On exam, some bronchi on auscultation. 108 00:06:08,175 --> 00:06:09,595 is otherwise unremarkable. 109 00:06:10,615 --> 00:06:14,275 We do get a chest x-ray that does show an infiltrate in the right upper lobe. 110 00:06:15,275 --> 00:06:16,680 So what do you guys think is going on? 111 00:06:16,960 --> 00:06:18,880 What would be going through your mind at this point? 112 00:06:20,675 --> 00:06:24,060 I think from my perspective, I guess as a fellow, certainly the things 113 00:06:24,060 --> 00:06:27,350 I would be thinking about are, do we have the right, diagnosis? 114 00:06:27,510 --> 00:06:31,920 In terms of if we're saying that this is a pneumonia, a bacterial pneumonia, 115 00:06:32,400 --> 00:06:36,030 generally if they got outpatient treatment, it may just be things 116 00:06:36,030 --> 00:06:38,040 like a monotherapy of amoxicillin. 117 00:06:38,400 --> 00:06:41,370 Um, are we missing the organism there? 118 00:06:41,775 --> 00:06:43,965 Is it something that's non bacterial? 119 00:06:44,115 --> 00:06:45,645 Is it a fungal infection? 120 00:06:46,125 --> 00:06:49,905 Uh, certainly I'd be less likely thinking of a viral infection, giving 121 00:06:49,905 --> 00:06:55,045 the two week duration of symptoms, or thinking of other, uh, like 122 00:06:55,045 --> 00:06:56,455 a parasite, something like that. 123 00:06:56,455 --> 00:07:00,540 So overall I would be thinking of a bacterial infection that's not being 124 00:07:00,540 --> 00:07:04,680 treated by what we prescribed or thinking of, uh, fungal infections 125 00:07:04,680 --> 00:07:08,400 as well, given the chronic or the two week course of symptoms. 126 00:07:08,698 --> 00:07:09,718 Yeah, I agree. 127 00:07:09,718 --> 00:07:11,878 I mean, I, I think when you get to two weeks, you start 128 00:07:11,878 --> 00:07:13,138 to question the diagnosis. 129 00:07:13,138 --> 00:07:15,538 Did we give an antibiotic that that missed the pathogen? 130 00:07:15,538 --> 00:07:17,038 Is this an atypical pneumonia? 131 00:07:17,368 --> 00:07:20,548 You know, two weeks is a bit long, but we've had, you know, big Mycoplasma 132 00:07:20,548 --> 00:07:21,958 outbreak over the last year. 133 00:07:22,348 --> 00:07:24,538 You know, pertussis still increases in frequency. 134 00:07:24,538 --> 00:07:27,058 Those patients, even with the right antibiotic, are gonna cough and 135 00:07:27,058 --> 00:07:28,948 feel bad for weeks or even months. 136 00:07:29,908 --> 00:07:32,338 I don't know much about the social history, but, you know, we talked 137 00:07:32,338 --> 00:07:36,868 about our love of birds, but, uh, you know, chlamydial infections, right? 138 00:07:36,868 --> 00:07:39,418 Maybe, you know, that have been missed with amoxicillin. 139 00:07:39,418 --> 00:07:41,218 I think there's a lot of possibilities. 140 00:07:41,486 --> 00:07:44,856 And we've brought up fungal disease and, um, you know, that's what I 141 00:07:44,856 --> 00:07:46,416 love to talk about, so I just will. 142 00:07:46,836 --> 00:07:50,556 But, you know, we've talked with the IDSA quite a bit about the pneumonia guidelines 143 00:07:50,556 --> 00:07:55,093 because they're pretty silent on the endemic mycoses right now, and if you look 144 00:07:55,243 --> 00:07:58,363 at the incidence, depending on where you practice in the United States, you know, 145 00:07:58,363 --> 00:08:02,833 there's, there's one paper that shows in Houston, Histoplasma is maybe 8% of the 146 00:08:02,833 --> 00:08:06,338 patients that come in with respiratory complaints in that particular study. 147 00:08:06,788 --> 00:08:09,248 Central Valley of California, it's up to, you know, a quarter of all 148 00:08:09,248 --> 00:08:12,498 CAP (community acquired pneumonia) is actually from coccidioidomycosis. 149 00:08:12,518 --> 00:08:15,278 And then Nate, if you want to comment, I don't know how frequent 150 00:08:15,278 --> 00:08:20,258 blasto is a cause of, of CAP, uh, up north, but probably not zero. 151 00:08:20,258 --> 00:08:24,068 So, um, yeah, so, so, so the, the big endemics, you know, we, we 152 00:08:24,068 --> 00:08:25,748 definitely consider and talk about. 153 00:08:26,210 --> 00:08:30,530 Yeah, and I think you're getting to a good point there, GR, because 154 00:08:30,530 --> 00:08:32,030 it, it, it matters where you are. 155 00:08:32,030 --> 00:08:34,490 Of course, risk is different depending on where you are. 156 00:08:34,790 --> 00:08:38,540 But we are starting to understand that our, notion of where you are with these 157 00:08:38,540 --> 00:08:43,070 endemic mycoses maybe is a little off and they're not, in some cases as, 158 00:08:43,070 --> 00:08:45,050 as restricted as we we once thought. 159 00:08:45,050 --> 00:08:48,090 So, you know, knowing where you are, but also understanding the patient's 160 00:08:48,090 --> 00:08:50,990 history a little better and, and if you haven't thought about them in a 161 00:08:50,990 --> 00:08:55,150 while, maybe that's a good time to go find some updated maps and data. 162 00:08:55,270 --> 00:08:55,710 They're out there. 163 00:08:56,261 --> 00:09:01,151 You know, while we're on that topic, would, would you maybe comment a little 164 00:09:01,151 --> 00:09:05,831 bit on some of the recent literature and, you know, knowledge about these 165 00:09:05,831 --> 00:09:08,751 expanding maps for endemic mycoses. 166 00:09:08,771 --> 00:09:12,431 So, for example, Nate, I've definitely shared the paper that you've worked on 167 00:09:12,431 --> 00:09:16,404 called Redrawing the Maps for Endemic Mycoses, and I try to reinforce the 168 00:09:16,404 --> 00:09:21,924 concept that we need to rethink these, you know, quote classic geographic 169 00:09:21,924 --> 00:09:27,594 boundaries and not take something off the differential entirely based on location. 170 00:09:28,594 --> 00:09:33,544 But I know there is also some thinking as well that for some of these papers, just 171 00:09:33,544 --> 00:09:37,324 because someone is diagnosed in a certain place, that that doesn't mean that the 172 00:09:37,324 --> 00:09:39,544 fungus is present in that environment. 173 00:09:40,054 --> 00:09:43,534 Um, but I think that's balanced with the fact that we clearly have signals that 174 00:09:43,534 --> 00:09:45,554 these fungi are an expanding locations. 175 00:09:45,574 --> 00:09:51,619 So how do you, uh, sort through that and, and think about this sort 176 00:09:51,619 --> 00:09:53,569 of spread of endemics as a whole. 177 00:09:53,967 --> 00:09:57,477 Yeah, so I, it depends on the approach. 178 00:09:57,507 --> 00:10:00,627 I think that's one thing to think about when you're looking at any 179 00:10:00,627 --> 00:10:01,857 of these sort of papers, right? 180 00:10:01,857 --> 00:10:06,942 So, our redrawing the maps for endemic fungi paper, that was all 181 00:10:06,942 --> 00:10:08,262 based on published literature. 182 00:10:08,292 --> 00:10:11,712 So that has an inherent limitation to it, right? 183 00:10:11,712 --> 00:10:16,182 So there's definitely cases happening that, that are not included there. 184 00:10:16,562 --> 00:10:21,812 There's also the, the very relevant point that simply having a case 185 00:10:21,812 --> 00:10:25,022 somewhere doesn't mean it's in the soil nearby or things like that. 186 00:10:25,022 --> 00:10:27,302 You need to know a lot more details, right. 187 00:10:27,392 --> 00:10:33,092 Um, you need to know while it's, it's interesting if you, if you found some 188 00:10:33,092 --> 00:10:39,162 cases of histo in Alaska, but did they, you know, just come from Kansas City? 189 00:10:39,432 --> 00:10:40,752 Um, that's pretty relevant. 190 00:10:41,092 --> 00:10:42,472 That's, that's all kind of important. 191 00:10:42,682 --> 00:10:45,562 You know, there have been some interesting things like, you know, histo has been 192 00:10:45,562 --> 00:10:48,262 found in soil in Antarctica, for instance. 193 00:10:48,562 --> 00:10:53,602 Um, so there, there is some of this where our, our sort of traditional understanding 194 00:10:53,602 --> 00:10:55,042 of this definitely has holes. 195 00:10:55,042 --> 00:10:59,382 I think it's probably right to both at the same time think, there are 196 00:10:59,382 --> 00:11:04,302 areas where the risk is much higher and there's also probably more areas at 197 00:11:04,302 --> 00:11:05,832 risk than we traditionally thought of. 198 00:11:05,832 --> 00:11:09,972 So I think one important take home would be if you're in an area where 199 00:11:09,972 --> 00:11:14,757 you think to yourself, well, it can't be cocci, because of where I live, it 200 00:11:14,757 --> 00:11:17,217 can't be histo because of where I live. 201 00:11:17,337 --> 00:11:19,347 That alone shouldn't totally rule it out. 202 00:11:19,617 --> 00:11:22,497 Um, it's part of the calculus, but you need to think of it a 203 00:11:22,497 --> 00:11:25,707 little more than just ruling it out because of where you live. 204 00:11:26,557 --> 00:11:27,307 That's my thought. 205 00:11:27,696 --> 00:11:28,836 Yeah, thanks so much. 206 00:11:28,866 --> 00:11:31,686 Well, Tom, can you update us on our patient. 207 00:11:32,267 --> 00:11:36,797 So the patient is able to produce some sputum, uh, which 208 00:11:36,797 --> 00:11:38,177 is ultimately sent for culture. 209 00:11:38,597 --> 00:11:43,067 Due to progressive symptoms, he is ultimately admitted and placed on 210 00:11:43,067 --> 00:11:48,047 broad IV antibiotic therapy with vancomycin and piperacillin-tazobactam 211 00:11:48,437 --> 00:11:50,167 and then azithromycin as well. 212 00:11:50,917 --> 00:11:53,897 He's noted to have a few intermittent fevers and ongoing cough. 213 00:11:54,227 --> 00:11:57,377 Sputum culture grows typical respiratory flora. 214 00:11:58,197 --> 00:12:02,247 A CT scan is obtained of the chest that shows a wedge-shaped 215 00:12:02,247 --> 00:12:07,197 peripheral nodular focus in posterior area of the right upper lobe. 216 00:12:07,887 --> 00:12:09,207 You get some additional history. 217 00:12:10,047 --> 00:12:13,217 He lives in the upper Midwest with his wife and partner. 218 00:12:13,217 --> 00:12:16,047 They have a dog and a guinea pig at home. 219 00:12:16,797 --> 00:12:18,267 He works as an architect. 220 00:12:19,047 --> 00:12:22,677 In the last year, he's traveled to Denmark for a vacation about six months ago. 221 00:12:23,417 --> 00:12:25,757 He also traveled to Florida for a work meeting. 222 00:12:26,777 --> 00:12:30,677 He has family in Arizona and most recently had a three week trip to 223 00:12:30,677 --> 00:12:32,957 visit family and meet his new niece. 224 00:12:33,707 --> 00:12:35,507 So you have some more social history. 225 00:12:35,507 --> 00:12:37,157 What do you guys think now? 226 00:12:37,546 --> 00:12:40,826 Yeah, so we talked a little bit about the differential diagnoses of these 227 00:12:40,826 --> 00:12:44,396 patients with non-responding pneumonia, and this really shows that that approach 228 00:12:44,396 --> 00:12:47,756 is essential because this patient, I mean, it's always hard to tell how ill 229 00:12:47,756 --> 00:12:51,776 they are in a, in a text-based format or discussion, but they've gotten sick 230 00:12:51,776 --> 00:12:54,806 enough to warrant admission with broad spectrum antibiotics, so presumably 231 00:12:54,806 --> 00:12:58,616 they've gotten quite a bit worse and that really shows that just taking 232 00:12:58,616 --> 00:13:02,186 a very detailed social history at times can avoid escalation symptoms. 233 00:13:02,186 --> 00:13:04,256 And then, you know, this can be a very costly admission. 234 00:13:04,331 --> 00:13:06,611 This is not stewardship savvy approach, right? 235 00:13:06,611 --> 00:13:10,781 They're getting vanc, pip-tazo, and azithromycin, for what could very well 236 00:13:10,781 --> 00:13:12,611 be an atypical or endemic pathogen. 237 00:13:13,481 --> 00:13:15,521 Azithro is gonna cover most of the atypicals. 238 00:13:16,007 --> 00:13:18,987 We don't hear uh, risk factors for pneumocystis or something like 239 00:13:19,007 --> 00:13:20,927 HIV or transplant or et cetera. 240 00:13:21,467 --> 00:13:24,887 So I think they're pretty well covered for, for most of the, the typical causes. 241 00:13:24,977 --> 00:13:30,022 But, but the endemic mycoses really aren't, aren't covered as far as 242 00:13:30,282 --> 00:13:31,852 their diagnostic approach or treatment. 243 00:13:31,852 --> 00:13:34,102 And then, you know, what do you get from a dog? 244 00:13:34,102 --> 00:13:36,952 Like, I don't know what kind of dog they have, you know, uh, kennel 245 00:13:36,952 --> 00:13:39,932 cough or, you know, parapertussis, I guess is in the differential. 246 00:13:39,932 --> 00:13:42,292 That doesn't seem like it usually warrants admission. 247 00:13:42,292 --> 00:13:42,802 Guinea pig. 248 00:13:42,802 --> 00:13:46,572 Nothing really comes to mind from respiratory causes of that. 249 00:13:46,572 --> 00:13:51,052 Guinea pigs are very allergenic, um, but, but doesn't really warrant hospital 250 00:13:51,052 --> 00:13:53,392 admission, then travel to Denmark. 251 00:13:53,392 --> 00:13:55,042 That doesn't really raise any red flags. 252 00:13:55,042 --> 00:13:59,212 Florida has a little bit of histoplasma, uh, down, you know, in the, I mean, 253 00:13:59,212 --> 00:14:00,982 histo is ubiquitous across the globe. 254 00:14:01,462 --> 00:14:04,132 Uh, you know, we, we commonly teach it in med school that it's just 255 00:14:04,132 --> 00:14:07,192 in this sort of Mississippi River Valley, but that's really not correct. 256 00:14:07,822 --> 00:14:09,922 But this history of travel to Arizona. 257 00:14:10,807 --> 00:14:14,287 Again, where in Arizona, you know, if it's, if it's up in northern Arizona, 258 00:14:14,287 --> 00:14:18,277 it's probably not any valley fever up there, but certainly Phoenix, you 259 00:14:18,277 --> 00:14:22,027 know, Tucson, Scottsdale, the, the real hotspots for travel and vacation. 260 00:14:22,387 --> 00:14:25,967 This three week timeframe certainly may have been exposed there. 261 00:14:26,057 --> 00:14:28,697 I don't know what time has gone by since he's returned to the Midwest, 262 00:14:28,697 --> 00:14:33,107 but that, you know, I'm gonna really wanna key in on that for, you know, some 263 00:14:33,107 --> 00:14:34,847 more details of his travel certainly. 264 00:14:36,512 --> 00:14:39,507 Uh, I got one thing to add related to the dog. 265 00:14:39,747 --> 00:14:43,637 So, dogs actually can sometimes, unfortunately, give very 266 00:14:43,637 --> 00:14:45,487 good clues for blastomycosis. 267 00:14:45,487 --> 00:14:48,427 I've it's at least more than one hand. 268 00:14:48,697 --> 00:14:52,447 Um, the amount of times that I've had patients tell me that their 269 00:14:52,447 --> 00:14:56,227 dog was sick with blastomycosis coming in with respiratory failure. 270 00:14:56,737 --> 00:14:59,837 So, they may not know they have it yet, but they know their dog 271 00:14:59,837 --> 00:15:04,007 had it, and that can be actually a really helpful history clue. 272 00:15:04,652 --> 00:15:06,182 Wow, that's so interesting. 273 00:15:07,126 --> 00:15:11,116 Well, how would you approach sending diagnostics up, right? 274 00:15:11,116 --> 00:15:14,406 Because we're talking about some of these fungal infections and have 275 00:15:14,406 --> 00:15:17,646 kind of this undifferentiated case, which, which tests should we send off? 276 00:15:18,486 --> 00:15:21,246 That's a great question and I think creates a lot of confusion, 277 00:15:21,246 --> 00:15:23,976 particularly if you don't do this all the time because there's a number 278 00:15:23,976 --> 00:15:28,511 of different tests available for coccidioidomycosis um, and you probably 279 00:15:28,511 --> 00:15:29,771 can't determine which one you send. 280 00:15:29,771 --> 00:15:32,561 It's probably just on the workflow of your particular institution. 281 00:15:32,561 --> 00:15:37,501 So most hospitals will send an EIA test first for IgM and IgG 282 00:15:37,501 --> 00:15:40,571 detection, and that's considered kind of a screening test. 283 00:15:40,797 --> 00:15:44,217 The CDC published their endemic algorithm for diagnostics just 284 00:15:44,217 --> 00:15:45,747 about six months ago or so. 285 00:15:46,642 --> 00:15:52,152 And if either of those test IgM, IgG, or both are positive by EIA, then 286 00:15:52,152 --> 00:15:56,162 you do additional testing with immuno diffusion and complement fixation. 287 00:15:56,422 --> 00:16:00,472 And the reason you do that is the complement fixation titer, um, is 288 00:16:00,472 --> 00:16:03,622 correlated with their symptoms, and also you can follow those 289 00:16:03,622 --> 00:16:06,052 serially over time prognostically. 290 00:16:06,232 --> 00:16:10,102 They, they do tend to correlate with the disease burden, so it can be really 291 00:16:10,102 --> 00:16:12,802 helpful for some of the vague symptoms that you're not clear if they're 292 00:16:12,802 --> 00:16:14,542 unrelated to their infection or not. 293 00:16:14,821 --> 00:16:17,741 The last test I'd mentioned is the cocci antigen test. 294 00:16:18,331 --> 00:16:21,871 For people who are immunocompetent, that's not a great test. 295 00:16:21,961 --> 00:16:25,291 Um, we typically reserve that one for people who are 296 00:16:25,291 --> 00:16:26,881 so highly immunocompromised. 297 00:16:26,881 --> 00:16:31,001 They may not make antibodies, so, you know, very, uh, immunocompromised 298 00:16:31,001 --> 00:16:34,421 states like solid organ transplant, bone marrow transplant, or, 299 00:16:34,481 --> 00:16:36,851 um, HIV with very few T cells. 300 00:16:36,881 --> 00:16:37,901 So that's really the group. 301 00:16:37,901 --> 00:16:40,454 We reserve antigen testing from the blood or urine 302 00:16:40,754 --> 00:16:46,469 In, in non-cocci diagnostics, I, I can add, with both Blasto and Histo, 303 00:16:46,584 --> 00:16:48,274 we can send antigen testing out. 304 00:16:48,554 --> 00:16:53,624 Blasto can often be caught with just a KOH prep on a respiratory sample. 305 00:16:53,904 --> 00:16:58,704 So it, it isn't perfect by any means, but it's pretty quick so that's a good thing. 306 00:16:59,034 --> 00:17:02,604 Um, particularly since many of these antigen tests we're sending out to get 307 00:17:02,964 --> 00:17:04,374 done and, and they can take a while. 308 00:17:05,334 --> 00:17:10,224 So those, those can be pretty useful, um, in, in this sort of patient too. 309 00:17:10,224 --> 00:17:14,234 And, you know, the patient lives in the upper Midwest and so in addition to the 310 00:17:14,234 --> 00:17:16,274 Arizona travel, I think that's important. 311 00:17:16,304 --> 00:17:19,604 Like the sort of geo geographic stuff is pointing us in a 312 00:17:19,604 --> 00:17:20,924 couple directions at this point. 313 00:17:21,109 --> 00:17:25,669 So for this case, when you examine this patient, like let's say we were 314 00:17:25,669 --> 00:17:28,809 talking through all these fungal infections, are there things that 315 00:17:28,809 --> 00:17:33,504 you're looking for on the exam to help you with the differential? 316 00:17:34,182 --> 00:17:38,437 I, I think definitely, you know, we've talked about the three major endemic 317 00:17:38,437 --> 00:17:42,487 pathogens in the United States, you know, histoplasma in an immunocompetent 318 00:17:42,487 --> 00:17:46,687 patient, they're really not gonna have oral lesions, some of those things. 319 00:17:46,927 --> 00:17:49,117 Blasto probably could have some skin lesions. 320 00:17:49,117 --> 00:17:50,497 Nate, feel free to jump in. 321 00:17:50,547 --> 00:17:53,187 You know, much more common to have skin lesions in those, in 322 00:17:53,187 --> 00:17:54,177 the immunocompetent patients. 323 00:17:54,177 --> 00:17:58,137 And then for Cocci with primary pulmonary pneumonia, which is 324 00:17:58,137 --> 00:18:00,597 what this seems likely to be. 325 00:18:00,717 --> 00:18:04,227 You know, if there's a rash that's, that really pushes you in the direction 326 00:18:04,227 --> 00:18:10,067 of coccidioides as the cause, or if you see an eosinophilia on their, uh, 327 00:18:10,097 --> 00:18:13,457 differential with their CBC, that's also gonna sort of push you in that direction. 328 00:18:14,117 --> 00:18:16,337 Um, so that's kind of the general approach to exam. 329 00:18:16,517 --> 00:18:20,657 you know, we haven't confirmed this as coccidioides yet, but if we do, you know, 330 00:18:20,657 --> 00:18:24,347 the next two things are to, to really check for risk factors for complicated 331 00:18:24,347 --> 00:18:28,277 infection or check if they already have complications of the disease. 332 00:18:28,277 --> 00:18:31,217 And so we do focus our, our exam on those findings as well. 333 00:18:33,127 --> 00:18:38,472 And what's like a typical skin finding for blasto that folks might see? 334 00:18:39,777 --> 00:18:42,597 Yeah, I, well, they can vary a bit, so I, I hate, 335 00:18:42,612 --> 00:18:44,142 I put typical in quotations. 336 00:18:45,057 --> 00:18:45,987 yeah, I don't know. 337 00:18:45,987 --> 00:18:48,177 I'm not in, that's a little hard. 338 00:18:48,417 --> 00:18:48,807 Um. 339 00:18:50,097 --> 00:18:50,637 They vary a bit. 340 00:18:50,637 --> 00:18:53,997 So the thing that should stick in your head is this sort of presentation plus 341 00:18:53,997 --> 00:18:58,577 skin findings, in a area with risk factors, blasto should be on the radar. 342 00:18:58,870 --> 00:19:02,217 Fair enough, so we do get labs and our diagnostics back. 343 00:19:02,607 --> 00:19:07,067 We have a coccidioides EIA positive IgM 1.8. 344 00:19:07,247 --> 00:19:12,737 Uh, IgG 4.0 and positive is greater than or equal to 1.5. 345 00:19:13,697 --> 00:19:19,077 Coccidioides antibody by complement fixation is positive at 1:8. 346 00:19:19,727 --> 00:19:21,257 Other testing is obtained. 347 00:19:21,257 --> 00:19:27,032 Interferon gamma release assay, cryptococcal antigen, histo and 348 00:19:27,032 --> 00:19:30,272 blasto antigen and serologies, all of which are negative. 349 00:19:31,572 --> 00:19:33,552 So, yeah, thanks for those labs that, that's helpful. 350 00:19:33,552 --> 00:19:36,642 I think that really does help firm up the diagnosis of primary 351 00:19:36,642 --> 00:19:38,862 pulmonary coccidioidomycosis. 352 00:19:38,922 --> 00:19:41,082 You've got a positive IgM and then you've already got a 353 00:19:41,082 --> 00:19:43,222 complement fixation titer of 1:8. 354 00:19:43,242 --> 00:19:48,062 So that really suggests exposure has been more than three or four weeks ago. 355 00:19:48,722 --> 00:19:53,822 Um, so I guess that sort of fits with his, his trip to Arizona, and then so the 356 00:19:53,822 --> 00:19:57,752 titer of one to eight, that's also sort of consistent broadly with someone that 357 00:19:57,752 --> 00:19:59,732 might warrant admission to the hospital. 358 00:19:59,852 --> 00:20:04,272 It can have a ref reflects a, a fairly significant burden of disease, but 359 00:20:04,272 --> 00:20:07,652 titers are really most helpful to follow in a single patient longitudinally. 360 00:20:07,652 --> 00:20:10,542 So a titer of 1:8 different patients may manifest quite differently. 361 00:20:12,002 --> 00:20:13,462 So it's not quite as predictive. 362 00:20:14,427 --> 00:20:17,397 We do know that titers above 1:16. 363 00:20:17,417 --> 00:20:22,097 So 1:32 or higher, 50% of those patients are gonna have disseminated infection. 364 00:20:22,097 --> 00:20:24,947 So that's a group really to focus on if they have high titers. 365 00:20:25,727 --> 00:20:28,727 There's a tremendous difference in what lab runs your titers. 366 00:20:28,847 --> 00:20:31,697 So labs that do a micro titers, so those would be the big reference 367 00:20:31,697 --> 00:20:33,437 labs, ARUP, Quest, et cetera. 368 00:20:33,857 --> 00:20:38,657 Those titers on in general run higher than the more specialized cocci tests. 369 00:20:38,657 --> 00:20:42,537 So, um, you can't compare one lab's complement fixation 370 00:20:42,537 --> 00:20:44,072 test to a different labs. 371 00:20:44,132 --> 00:20:46,412 It needs to be done at the same, same location. 372 00:20:47,202 --> 00:20:51,212 And then the general approach, this patient was uh, 50, so, you know, 373 00:20:51,302 --> 00:20:55,112 um, uh, I'm almost 50, so that's just barely middle aged now, I guess. 374 00:20:55,362 --> 00:20:59,412 That that's not really associated with, with risks for bad infection by age. 375 00:20:59,472 --> 00:21:03,312 Uh, we know patients older than 65 have a rougher time, just like with almost every 376 00:21:03,312 --> 00:21:07,502 infection, but this is a, a male patient, and we do know that males versus females 377 00:21:07,502 --> 00:21:12,422 have a, about a six to one ratio of, of  coccidioidomycosis, uh, acquisition. 378 00:21:13,262 --> 00:21:14,882 And the reasons for that are unclear. 379 00:21:14,882 --> 00:21:17,762 We've, we've wondered if that's, you know, sociologic, just differences 380 00:21:17,762 --> 00:21:19,442 in hobbies, occupations, et cetera. 381 00:21:19,977 --> 00:21:23,457 But we've actually looked at our veterinary animals and a primate cohort 382 00:21:23,487 --> 00:21:25,437 and saw the same thing across the board. 383 00:21:25,877 --> 00:21:30,047 The male primates, male dogs all acquired, you know, cocci at a greater rate 384 00:21:30,047 --> 00:21:32,117 than the female, uh, dogs or primates. 385 00:21:32,117 --> 00:21:34,607 And then if, if the dogs were actually castrated, they're, they're 386 00:21:34,607 --> 00:21:36,227 risk return to the same as females. 387 00:21:36,707 --> 00:21:38,507 So we do think it's probably biologic. 388 00:21:38,507 --> 00:21:41,627 And we know that cocci uses a number of different hormone receptors. 389 00:21:41,627 --> 00:21:44,657 It can probably use those as either growth factors or carbon sources. 390 00:21:45,227 --> 00:21:45,707 Um. 391 00:21:46,047 --> 00:21:48,627 And so we think that's the major issue is just the testosterone. 392 00:21:48,717 --> 00:21:51,297 Men, we hate to admit this, our immune systems are weaker. 393 00:21:51,657 --> 00:21:53,277 That's why we get things like man flu. 394 00:21:53,637 --> 00:21:57,877 Um, also that the sex hormones, you know, the second and third trimester of 395 00:21:57,877 --> 00:22:02,077 pregnancy, when, when women have higher estrogen levels, that's also a risk 396 00:22:02,077 --> 00:22:03,917 factor for bad infection with cocci. 397 00:22:03,937 --> 00:22:07,327 We see people disseminate, uh, in their second and third trimester of pregnancy. 398 00:22:07,327 --> 00:22:09,907 So all those are things we kind of consider. 399 00:22:09,917 --> 00:22:12,407 This patient wasn't described as immunocompromised. 400 00:22:12,887 --> 00:22:16,887 We do know that, that sadly not only has this sex predisposition for 401 00:22:16,887 --> 00:22:20,817 bad disease, but there's certain, genomic ancestries, you know, those 402 00:22:20,817 --> 00:22:23,967 from Oceana, like our Filipino patients, Marshall Islands, et cetera. 403 00:22:24,117 --> 00:22:27,357 They, they have risks for, for worse outcomes with cocci as do our 404 00:22:27,357 --> 00:22:29,367 patients of African genomic ancestry. 405 00:22:30,207 --> 00:22:32,577 The genetics of that have been, uh, worked out a bit. 406 00:22:32,637 --> 00:22:35,667 Uh, probably about 50% of the patients have been explained some really great 407 00:22:35,667 --> 00:22:39,897 work done by the NIH, uh, Steve Holland and Amy Sue did a lot of that work with, 408 00:22:39,897 --> 00:22:44,547 with sort of our patients in a group from Arizona, but there's still a lot to 409 00:22:44,547 --> 00:22:46,167 learn, you know, how do we predict these? 410 00:22:46,267 --> 00:22:48,757 And even all those risk factors we understand, we still examine 411 00:22:48,757 --> 00:22:50,157 these patients really carefully. 412 00:22:50,337 --> 00:22:53,927 Image anything that hurts, kind of approach 'em like Staph aureus, if it 413 00:22:53,927 --> 00:22:58,147 hurts, look at it more closely, and, and just check for complications. 414 00:22:58,147 --> 00:23:00,352 So that's kind of our big picture approach to these patients. 415 00:23:00,837 --> 00:23:04,947 Well, maybe what we can do is also talk about treatment options and 416 00:23:05,017 --> 00:23:07,477 general thoughts on, on therapy. 417 00:23:09,307 --> 00:23:13,477 Yeah, I think, I think therapy in our, our view of treatment is, it depends who 418 00:23:13,477 --> 00:23:15,557 you ask in the field of, of coccidioides. 419 00:23:15,577 --> 00:23:18,067 So there's sort of two camps, you know, there, there's sort of 420 00:23:18,067 --> 00:23:20,737 a group of physicians that say, well, most patients historically 421 00:23:20,737 --> 00:23:21,997 did well even without treatment. 422 00:23:21,997 --> 00:23:25,177 So if they have pretty mild symptoms, maybe don't treat 'em at all. 423 00:23:25,887 --> 00:23:27,057 I think this patient's different. 424 00:23:27,057 --> 00:23:29,457 They're clearly sick enough to be in the hospital, so they're 425 00:23:29,457 --> 00:23:30,987 gonna need antifungal therapy. 426 00:23:32,397 --> 00:23:34,887 Generally most patients start on fluconazole. 427 00:23:34,977 --> 00:23:39,627 Um, in vitro that's probably the least effective drug, probably a mold active 428 00:23:39,627 --> 00:23:42,047 azole, itra, posa, vori, isavuconazole. 429 00:23:42,064 --> 00:23:46,787 All those are more effective in vitro. You know, we have only one comparative 430 00:23:46,787 --> 00:23:49,097 study looking at fluconazole versus itra. 431 00:23:49,402 --> 00:23:53,537 The itra patients generally did better, but our approach would be to 432 00:23:53,537 --> 00:23:55,067 start this patient on fluconazole. 433 00:23:56,007 --> 00:23:59,847 Generally a higher dose, more like 600 or 800 milligrams per 434 00:23:59,847 --> 00:24:01,647 day if they're a 70 kilo person. 435 00:24:02,367 --> 00:24:06,277 If they don't respond over just, you know, several weeks or a month, or if 436 00:24:06,277 --> 00:24:10,327 they have side effects, which a lot of the patients do from fluconazole, alopecia, 437 00:24:10,327 --> 00:24:14,527 cheilitis, xerosis, all that sounds benign until you've gotta deal with it 438 00:24:14,527 --> 00:24:18,727 for a while, you know, we're pretty quick to put them on a drug that we think has 439 00:24:18,727 --> 00:24:21,602 fewer side effects and more efficacy. 440 00:24:21,782 --> 00:24:25,622 So, you know, itraconazole, this is a 50-year-old, you're not too worried 441 00:24:25,622 --> 00:24:28,622 about heart failure yet, but, but that's definitely something to think about with 442 00:24:28,622 --> 00:24:31,122 itraconazole, uh, as a negative inotrope. 443 00:24:32,142 --> 00:24:36,862 Posaconazole, uh, looks at least in vitro, like it might be the most effective azole. 444 00:24:37,492 --> 00:24:40,302 Does cause hypertension, and about a third of patients causes a 445 00:24:40,302 --> 00:24:42,222 pseudo hyperaldosteronism syndrome. 446 00:24:42,792 --> 00:24:46,692 Voriconazole, if you think about the regions that have cocci with, with Arizona 447 00:24:46,692 --> 00:24:48,552 and California, there's a lot of sunshine. 448 00:24:48,552 --> 00:24:52,482 So putting patients in those regions on vori as a photosensitizer can be 449 00:24:52,867 --> 00:24:56,097 really difficult and in long-term use skin cancer, of course. 450 00:24:56,757 --> 00:24:59,587 And then isavuconazole, we don't have as much data, but we've used a lot 451 00:24:59,587 --> 00:25:03,667 of that, very effective and, and very benign, uh, doesn't tend to have a 452 00:25:03,667 --> 00:25:04,957 lot of side effects with that drug. 453 00:25:04,957 --> 00:25:06,577 So that's, that's our general approach. 454 00:25:07,057 --> 00:25:10,027 I probably wouldn't give this person amphotericin B, I mean, again, it's 455 00:25:10,027 --> 00:25:13,747 kind of hard to tell how sick they are you know, this, this format, but unless 456 00:25:13,747 --> 00:25:18,629 they really are, are compromised from a respiratory standpoint, um, I'd probably 457 00:25:18,629 --> 00:25:21,809 try to give them an azole and tell them, you know, over the next few weeks you 458 00:25:21,809 --> 00:25:23,579 should start feeling better and improving. 459 00:25:23,969 --> 00:25:26,819 And then I'd really look out for the development of erythema nodosum. 460 00:25:27,239 --> 00:25:29,849 When they have that, that's a favorable prognostic sign. 461 00:25:30,779 --> 00:25:33,789 It's a panniculitis, inflammation of the fat, typically on the shins. 462 00:25:33,789 --> 00:25:35,429 We do see it on the forearms as well. 463 00:25:36,039 --> 00:25:37,689 And that's not disseminated infection. 464 00:25:37,689 --> 00:25:41,529 That's a sign that you've, you're starting to develop Th1 immunity to 465 00:25:41,529 --> 00:25:43,549 the underlying, coccidioides species. 466 00:25:43,569 --> 00:25:45,969 So, so those are all the things we approach in kind of that 467 00:25:45,969 --> 00:25:47,589 first, you know, four week window. 468 00:25:48,444 --> 00:25:53,064 So how do you decide on, uh, approaching CNS disease? 469 00:25:54,185 --> 00:25:55,205 That's a great question. 470 00:25:55,235 --> 00:25:59,165 'cause even uncomplicated pulmonary infection, they often have headache. 471 00:25:59,745 --> 00:26:03,215 In the past if they had a high titer, everyone received a lumbar puncture 472 00:26:03,215 --> 00:26:04,715 looking for disseminated disease. 473 00:26:05,145 --> 00:26:08,715 One of our fellows wrote a paper about that a number of years ago and showed 474 00:26:08,805 --> 00:26:12,600 if your headache is not changing in character, you know, more frequent 475 00:26:12,630 --> 00:26:18,630 escalating in severity, timing, et cetera, and you have no other CNS symptoms, it's 476 00:26:18,630 --> 00:26:20,340 not worthwhile to do a lumbar puncture. 477 00:26:20,340 --> 00:26:21,840 You're just gonna get negative results. 478 00:26:21,930 --> 00:26:24,870 And that was a multicenter study that, that sort of changed the 479 00:26:24,870 --> 00:26:26,670 dogma associated with that practice. 480 00:26:27,480 --> 00:26:30,380 We really need to find a good reason in adult immunocompetent 481 00:26:30,380 --> 00:26:32,290 patient to do a lumbar puncture. 482 00:26:32,290 --> 00:26:35,290 I mean, we think of those as fairly benign, but CSF 483 00:26:35,350 --> 00:26:36,740 leaks are, are fairly common. 484 00:26:36,740 --> 00:26:38,750 That's, that's sort of morbid for the patients. 485 00:26:38,750 --> 00:26:40,940 That causes more headache, that definitely won't help them. 486 00:26:41,540 --> 00:26:44,030 Um, so we, we try to only do that for people we really 487 00:26:44,030 --> 00:26:44,895 feel like we're gonna help. 488 00:26:45,770 --> 00:26:49,900 How about somebody that is more immune compromised? 489 00:26:50,430 --> 00:26:51,970 Does that change your thoughts? 490 00:26:52,705 --> 00:26:53,455 Definitely does. 491 00:26:53,485 --> 00:26:57,385 If, if they're immunocompromised, we definitely have a much lower 492 00:26:57,385 --> 00:26:58,945 threshold to do a lumbar puncture. 493 00:26:58,975 --> 00:27:00,745 We still approach it generally the same. 494 00:27:00,745 --> 00:27:04,305 They need to have a compelling reason, you know, some kind of a symptom 495 00:27:04,305 --> 00:27:06,965 that's correlated with CNS infection. 496 00:27:06,985 --> 00:27:10,375 We, we don't just do those on a routine basis like we do with cryptococcus, right? 497 00:27:10,375 --> 00:27:13,165 Any crypto infection, they get a lumbar puncture for the most part, but 498 00:27:13,165 --> 00:27:17,455 we don't tend to do that cocci, but I'd say we have a very low threshold. 499 00:27:18,002 --> 00:27:21,782 GR knows my crypto background, so he knows that I'm lumbar puncture happy. 500 00:27:23,537 --> 00:27:23,987 It's all right. 501 00:27:23,987 --> 00:27:26,632 We love a good lumbar puncture, but we also try to avoid them 502 00:27:26,632 --> 00:27:28,402 after we've caused some CSF leaks. 503 00:27:29,002 --> 00:27:33,712 And I guess one other tangent that I'll ask is, let's say this patient 504 00:27:33,712 --> 00:27:37,942 wasn't responding or you know, is running into issues down the road. 505 00:27:37,942 --> 00:27:39,802 Is resistance common? 506 00:27:39,802 --> 00:27:42,022 Is that something that we should be worried about? 507 00:27:43,477 --> 00:27:46,597 So patients who don't respond to therapy are pretty interesting. 508 00:27:46,597 --> 00:27:49,417 It's, it's fortunately, a fairly small group that doesn't 509 00:27:49,417 --> 00:27:51,067 respond to a second triazole. 510 00:27:51,067 --> 00:27:53,917 We mentioned we'd start with fluconazole probably, and then maybe a second 511 00:27:53,917 --> 00:27:55,327 triazole later without a response. 512 00:27:55,327 --> 00:27:57,907 But patients that don't respond to a second triazole are maybe 513 00:27:57,907 --> 00:27:59,497 10 to 15% of those patients. 514 00:27:59,550 --> 00:28:03,010 I think the field has always said resistance doesn't really occur in cocci. 515 00:28:03,030 --> 00:28:04,650 To me, that seems sort of odd. 516 00:28:04,650 --> 00:28:07,650 Why would cocci be such an outlier that there's no resistance? 517 00:28:08,420 --> 00:28:11,570 Certainly clinical resistance occurs, you know, even if it's in vitro, 518 00:28:11,570 --> 00:28:12,680 it's supposed to be susceptible. 519 00:28:12,680 --> 00:28:15,757 The patient may not respond, but I think the good news is we have a number 520 00:28:15,757 --> 00:28:19,207 of new drugs sort of on the way that are in phase two and three trials, and 521 00:28:19,207 --> 00:28:21,477 so it'd be olorofim and fosmanogepix. 522 00:28:22,537 --> 00:28:27,067 The bad part of that though, is some of the environmental antifungals that 523 00:28:27,067 --> 00:28:32,372 are put down to deal with things like alternaria with almonds, uh, you know, 524 00:28:32,522 --> 00:28:34,142 aspergillus on peanuts, et cetera. 525 00:28:34,532 --> 00:28:38,802 So this other drug ipflufenoquin actually works just like olorofim 526 00:28:39,242 --> 00:28:43,922 and uh, aminopyrifen works just like fosmanogepix, so if we put those down in 527 00:28:43,922 --> 00:28:47,612 high concentrations in the environment, we may actually lose susceptibility 528 00:28:47,612 --> 00:28:51,347 to these fungal pathogens before the patients have even seen the drugs. 529 00:28:52,577 --> 00:28:55,727 And with that, we're really hopeful that some of these silos 530 00:28:55,727 --> 00:28:59,117 of regulatory authorities can get on the same, same page. 531 00:28:59,117 --> 00:29:00,137 And, and they really have. 532 00:29:00,137 --> 00:29:03,857 The CDC has has led that with the EPA to try to break down some of 533 00:29:03,857 --> 00:29:06,587 these barriers where, what's approved for the environment, you know, 534 00:29:06,587 --> 00:29:10,817 the, the, the true One Health one world effects can be evaluated to 535 00:29:10,817 --> 00:29:12,467 prevent, uh, spread of resistance. 536 00:29:12,467 --> 00:29:14,807 And, and, you know, we've been very ahead of that game over the last, 537 00:29:15,062 --> 00:29:17,852 you know, 20 years with antibiotics and chickens and those kind of 538 00:29:17,852 --> 00:29:21,930 things, but we sort of neglected antifungals on our agricultural crops. 539 00:29:22,105 --> 00:29:26,942 So this recent consortium is gonna hopefully solve that problem, but 540 00:29:26,982 --> 00:29:30,532 it it still gets at the question, we're always gonna have resistance. 541 00:29:30,532 --> 00:29:33,592 You know, we're in a constant battle with all these microbial pathogens. 542 00:29:33,592 --> 00:29:35,962 We create a new drug, they figure it out over time. 543 00:29:36,412 --> 00:29:40,252 You know, I'm always reminded of penicillin resistance was described in 544 00:29:40,252 --> 00:29:44,002 the lab before a patient had ever seen penicillin during the advent of that. 545 00:29:44,002 --> 00:29:47,932 So we, we, we need to really continue to search for new drugs because this 546 00:29:47,932 --> 00:29:49,502 is gonna be an ongoing war forever. 547 00:29:49,770 --> 00:29:50,020 Yeah. 548 00:29:50,020 --> 00:29:53,579 So, you know, and that's, that's a great point because, of course many 549 00:29:53,579 --> 00:29:58,242 of our new drugs come from, from very basic research at the beginning, right? 550 00:29:58,242 --> 00:30:03,342 So new mechanisms are discovered, and they eventually lead to a drug discovery. 551 00:30:03,342 --> 00:30:07,762 So, you know, this is a, a, great sort of segue to, to simply state 552 00:30:07,762 --> 00:30:12,442 that we need definitely continued investment in, in mycotic diseases. 553 00:30:12,742 --> 00:30:17,142 It's interesting when I started doing research as a fellow, I started working 554 00:30:17,142 --> 00:30:22,567 in in crypto meningitis and I, I was sort of shocked at how relatively 555 00:30:22,597 --> 00:30:26,077 little research was done compared to some other things that I knew about. 556 00:30:26,694 --> 00:30:29,214 and then I started getting interest in TB meningitis and I thought, 557 00:30:29,214 --> 00:30:30,414 wow, crypto has it really good. 558 00:30:30,414 --> 00:30:35,784 I. And then I got into doing blasto and, and I've realized that there is somewhere 559 00:30:35,784 --> 00:30:37,674 to go with less and less investment. 560 00:30:37,764 --> 00:30:43,134 So, um, we need to learn a lot about this stuff and we need 561 00:30:43,134 --> 00:30:44,874 continued investment in science. 562 00:30:44,964 --> 00:30:49,104 Um, this is, this is the only way we're gonna continue to find out better 563 00:30:49,104 --> 00:30:52,134 ways to treat things, better ways to diagnose things, who's at risk. 564 00:30:52,637 --> 00:30:55,367 It's not time to, to stop. 565 00:30:55,607 --> 00:30:57,137 We need to continue to invest. 566 00:30:57,347 --> 00:30:59,417 Yeah, that is such an important point. 567 00:30:59,787 --> 00:31:01,377 Tom, any other questions that you have? 568 00:31:01,917 --> 00:31:05,847 . Thinking more generally, it's important for us to think about the intersection 569 00:31:05,847 --> 00:31:08,187 of infection and climate change. 570 00:31:08,547 --> 00:31:12,687 We'd love to hear from the both of you, uh, any insight you have into 571 00:31:12,687 --> 00:31:17,447 how many of the recent wildfires might impact coccidiomycosis. 572 00:31:18,140 --> 00:31:19,460 Yeah, that's a great question. 573 00:31:19,600 --> 00:31:23,170 We really had, had thought a lot about wildfires, particularly during covid. 574 00:31:23,320 --> 00:31:25,300 You know, we're cooped up in the house and then it starts 575 00:31:25,300 --> 00:31:26,740 being smoky every everywhere. 576 00:31:26,740 --> 00:31:30,250 And we affectionately called that "smovid" in, uh, California. 577 00:31:30,930 --> 00:31:35,010 But during that time we started to really think about the amount of debris that 578 00:31:35,010 --> 00:31:37,770 was being deposited by the wildfires. 579 00:31:37,770 --> 00:31:39,840 You know, you could just walk out on the sidewalk and see 580 00:31:39,840 --> 00:31:41,220 debris from, from the smoke. 581 00:31:41,220 --> 00:31:44,305 And the particulate matter we had started to question, does this 582 00:31:44,305 --> 00:31:46,195 actually carry living organisms? 583 00:31:46,855 --> 00:31:49,975 And in conjunction with Leda Kobziar and her group who studies this, 584 00:31:49,975 --> 00:31:53,755 she actually flies drones over wildfires to collect smoke samples. 585 00:31:54,355 --> 00:31:57,955 Found that there is this living component of smoke and founded this new field 586 00:31:57,955 --> 00:32:02,605 pyroaerobiology and you know, is published on that in Science a number of years ago. 587 00:32:03,272 --> 00:32:07,922 You know, has found really a a who's who of opportunistic fungi with that, you 588 00:32:07,922 --> 00:32:12,772 know, um, cryptococcus, cladosporium, mucorales, aspergillus, et cetera. 589 00:32:13,462 --> 00:32:18,022 Has not found cocci in that, so that does create the question, you know, 590 00:32:18,292 --> 00:32:19,792 uh, fire does create its own weather. 591 00:32:19,792 --> 00:32:22,942 It sort of pulls smoke through the surrounding soil and vegetation 592 00:32:22,942 --> 00:32:26,512 and can pull that up, you know, even into the upper atmosphere. 593 00:32:26,512 --> 00:32:29,337 And, and maybe one of the ways pathogens travel very long distances. 594 00:32:30,872 --> 00:32:34,052 But cocci requires drought as part of its lifecycle. 595 00:32:34,352 --> 00:32:37,442 Fire obviously needs drought just to start large fires. 596 00:32:37,442 --> 00:32:40,402 It does cause the question of these just true, true but unrelated. 597 00:32:41,332 --> 00:32:44,422 And then the, the group at UCSF has published a nice paper just 598 00:32:44,422 --> 00:32:47,482 a few years ago that did really show this correlation that. 599 00:32:47,542 --> 00:32:51,052 They published that I think in Lancet Planetary Health using administrative 600 00:32:51,052 --> 00:32:54,142 data from a number of hospitals and did show this very close correlation 601 00:32:54,142 --> 00:32:57,687 between wildfire smoke and the number of coccidioides cases. 602 00:32:57,687 --> 00:32:59,487 So we do think there's a close association. 603 00:32:59,487 --> 00:33:01,956 We know firefighters get a lot of cocci. 604 00:33:02,250 --> 00:33:04,980 Unfortunately a lot of the firefighter service is, is, you 605 00:33:04,980 --> 00:33:06,660 know, California prisoners out here. 606 00:33:07,260 --> 00:33:08,310 Um, and it's just hot. 607 00:33:08,340 --> 00:33:09,870 They don't wanna wear protective gear. 608 00:33:09,930 --> 00:33:11,340 It's too hot to, to keep that on. 609 00:33:11,340 --> 00:33:13,560 They're, they're not actually out there putting out the fire, but they're 610 00:33:13,560 --> 00:33:17,220 doing high risk activities like cutting fire breaks, you know, they're deep 611 00:33:17,220 --> 00:33:20,790 down in the soil or, or digging up a lot of soil, potentially exposing 612 00:33:20,790 --> 00:33:23,340 them to, spores in that environment. 613 00:33:23,865 --> 00:33:27,870 so, so it's, it's a confluence of a number of factors, you know, we think, but an 614 00:33:27,870 --> 00:33:29,670 area that's ripe for additional work. 615 00:33:30,883 --> 00:33:33,373 Those papers are so cool. 616 00:33:33,403 --> 00:33:38,023 I've, I've pulled some of them for, for puscast and, um, just 617 00:33:38,023 --> 00:33:39,473 like found them so fascinating. 618 00:33:40,263 --> 00:33:42,128 Oh Leda flying those drones over stuff. 619 00:33:42,128 --> 00:33:42,498 It's cool. 620 00:33:42,538 --> 00:33:42,908 Yeah. 621 00:33:42,998 --> 00:33:43,598 That's very cool. 622 00:33:43,838 --> 00:33:44,168 Yeah. 623 00:33:44,685 --> 00:33:46,965 Nate, is there anything else that you wanna add? 624 00:33:47,645 --> 00:33:49,235 Um, do I want to add something? 625 00:33:49,235 --> 00:33:52,385 I mean, for cocci, I, I don't, I mean, I, you know, 626 00:33:52,720 --> 00:33:54,290 I,, can only say cocci. 627 00:33:54,310 --> 00:33:57,130 I can't say the whole thing, uh, without stumbling so 628 00:33:57,295 --> 00:33:58,195 No one can. 629 00:33:58,195 --> 00:33:58,915 It's impossible. 630 00:34:00,445 --> 00:34:03,355 do you, do you wanna talk about hurricanes and mold or, uh, 631 00:34:03,385 --> 00:34:04,585 tornadoes or any of that stuff? 632 00:34:04,635 --> 00:34:04,875 Yeah. 633 00:34:04,875 --> 00:34:09,345 Before I, I came back to Minnesota, I was in Kansas City and not long before 634 00:34:09,345 --> 00:34:13,815 that, um, there had been a really big tornado in, in Joplin, Missouri. 635 00:34:14,205 --> 00:34:19,575 And after that there was an amazing amount of, of sort of rare mold 636 00:34:19,575 --> 00:34:23,160 infections, things that people weren't used to seeing very often, but were 637 00:34:23,160 --> 00:34:25,320 seeing quite frequently after that. 638 00:34:25,600 --> 00:34:28,970 So these, you know, these weather events, when they do things to soil, 639 00:34:28,970 --> 00:34:31,100 they, they tend to carry mold with them. 640 00:34:31,100 --> 00:34:35,330 And so it's, it's sort of an important point to think of if 641 00:34:35,330 --> 00:34:39,110 something like that, you know, if, if some big weather happening in your 642 00:34:39,135 --> 00:34:42,970 area, you're pretty likely to see more of that sort of thing happen. 643 00:34:43,962 --> 00:34:47,682 Thanks so much to Tom, GR, and Nate for joining Febrile today. 644 00:34:47,682 --> 00:34:51,492 Hopefully this got you excited to hear about fungal infections, so you can check 645 00:34:51,492 --> 00:34:57,192 out the Mycoses Study Group Education and Research Consortium for more learning. 646 00:34:57,252 --> 00:35:02,262 Their webpage is posted on the website as well as in the episode info. 647 00:35:02,757 --> 00:35:08,967 I also encourage you to check out a recent webinar that had Dr. GR Thompson, 648 00:35:09,327 --> 00:35:13,667 who is here with us on the episode, as well as Dr. Fariba Donovan, talking about 649 00:35:13,667 --> 00:35:16,727 cocci in the aftermath of the wildfires. 650 00:35:16,727 --> 00:35:21,135 So we will put a link to that webinar, which was, um, hosted just this past week. 651 00:35:21,254 --> 00:35:25,784 You can check out the website febrile podcast.com to find the Consult Notes, 652 00:35:25,784 --> 00:35:29,174 which are written supplements to the episodes with links to references, 653 00:35:29,564 --> 00:35:32,654 our library of ID infographics, and a link term merch store. 654 00:35:33,524 --> 00:35:37,214 Febrile is produced with support from the Infectious Diseases Society of America. 655 00:35:37,277 --> 00:35:40,217 Please reach out if you have any suggestions for future shows or want 656 00:35:40,217 --> 00:35:41,537 to be more involved with Febrile. 657 00:35:41,837 --> 00:35:42,647 Thanks for listening. 658 00:35:42,797 --> 00:35:44,477 Stay safe and I'll see you next time.