1 00:00:14,040 --> 00:00:14,910 Sara Dong: Hi everyone. 2 00:00:14,940 --> 00:00:19,320 Welcome to Febrile, a cultured podcast about all things infectious disease. 3 00:00:19,590 --> 00:00:25,230 We use consult questions to dive into ID clinical reasoning, diagnostics, and anti-microbial management. 4 00:00:25,680 --> 00:00:28,610 I'm Sara Dong, your host and a Med-Peds ID fellow. 5 00:00:29,080 --> 00:00:35,170 Here on Febrile, we use patient cases and chat with ID discussants to learn more about high yield ID topics. 6 00:00:35,400 --> 00:00:38,769 Cesar co-host today is Dr. 7 00:00:38,769 --> 00:00:40,090 Cesar Berto. 8 00:00:40,420 --> 00:00:53,279 He is a chief resident at Jacobi Medical Center and Albert Einstein College of Medicine, but as now an incoming ID fellow at the combined Massachusetts General and Brigham and Women's Hospital ID fellowship program. 9 00:00:54,220 --> 00:00:56,300 Joining us as our discussant is Dr. 10 00:00:56,300 --> 00:00:57,450 Shweta Anjan. 11 00:00:57,980 --> 00:00:58,260 Dr. 12 00:00:58,260 --> 00:01:02,440 Anjan is a transplant ID physician at the Miami Transplant Institute. 13 00:01:02,590 --> 00:01:12,070 She is an Assistant Professor in Clinical Medicine and the associate Program Director of the Transplant ID Fellowship program at the University of Miami Miller School of Medicine. 14 00:01:12,640 --> 00:01:14,050 I'm so glad you guys are here. 15 00:01:14,320 --> 00:01:19,350 We always start with our one question as a cultured podcast. 16 00:01:19,350 --> 00:01:24,850 We'd love to hear about a little piece of culture that you enjoyed recently or brought you some happiness. 17 00:01:25,990 --> 00:01:26,360 Cesar Berto: Sure. 18 00:01:26,360 --> 00:01:32,654 Um, one of the things that I recently enjoyed was a musical Broadway "Come from Away.". 19 00:01:32,865 --> 00:01:45,104 It's actually a Canadian musical about a real history of the 38 planes that, uh, suddenly during 9/11 had to, um, land in a very small town in Canada. 20 00:01:45,104 --> 00:01:50,655 And it tells the events of how those passengers face this, um, it's actually on apple TV. 21 00:01:51,495 --> 00:01:56,745 So it was really very nice, very well executed and, uh, uh, very sentimental. 22 00:01:56,745 --> 00:01:57,275 Shweta Anjan: Hey. 23 00:01:59,355 --> 00:02:00,535 Hi, Sara and Cesar. 24 00:02:01,065 --> 00:02:10,665 um, I think I'd have to say little piece of culture have enjoyed recently, but have to be like a combination of K-pop. 25 00:02:12,525 --> 00:02:14,265 Sara Dong: Oh, you're talking my language. 26 00:02:14,435 --> 00:02:22,274 Shweta Anjan: The Peloton instructors, a lot of them play all the pop music during like all those Peloton sessions. 27 00:02:24,284 --> 00:02:25,665 It's actually made me Google all of them. 28 00:02:25,665 --> 00:02:27,735 So we're making progress here. 29 00:02:28,515 --> 00:02:28,904 Sara Dong: Yeah. 30 00:02:29,175 --> 00:02:30,015 Well, you can share it. 31 00:02:30,015 --> 00:02:31,964 You can share any of those playlists with me. 32 00:02:31,964 --> 00:02:33,555 That sounds like something I would love. 33 00:02:35,175 --> 00:02:41,834 Um, well today's consult question is about recommendations for working up a cavitary lung lesion. 34 00:02:42,344 --> 00:02:44,685 Uh, so I will hand it over. 35 00:02:45,464 --> 00:02:45,854 Cesar Berto: Okay. 36 00:02:46,394 --> 00:02:58,115 So today we have the case of a 60 year old woman who is status-post lung transplantation, who has been admitted for two weeks of fever, asthenia, productive cough, and exertional dyspnea. 37 00:02:58,635 --> 00:03:05,714 Uh, his past medical history is remarkable for, uh, bilateral lung transplantation 6 months ago due to severe emphysema. 38 00:03:06,524 --> 00:03:12,395 She is CMV uh, donor positive recipient negative, and is currently on prophylaxis. 39 00:03:12,920 --> 00:03:19,600 Her current medications includes triple immunosuppressive therapy -- tacrolimus, mycophenolate, and prednisone. 40 00:03:20,200 --> 00:03:23,740 And in terms of prophylaxis, she is on valganciclovir and atovaquone. 41 00:03:24,640 --> 00:03:29,650 Her social history, um, remarkable is that she lives in Las Vegas, Nevada. 42 00:03:30,190 --> 00:03:31,660 She is currently retired. 43 00:03:31,690 --> 00:03:34,090 She spends her weekends hiking. 44 00:03:34,300 --> 00:03:36,810 She does not have any pets or no recent travels. 45 00:03:37,180 --> 00:03:43,570 The physical exam of this patient um, shows, uh, tachycardic patient with decreased breath sounds in the right lower lobe. 46 00:03:44,650 --> 00:03:53,980 Uh, and additionally, on the physical exam, we're able to find, uh, tender one by one centimeter ulcerated lesion of the left ankle without any purulent secretions. 47 00:03:54,850 --> 00:04:02,440 Um, the CT scan of this patient shows a right lower lobe consolidation with a two centimeter lesion, um, with peripheral cavitation. 48 00:04:03,650 --> 00:04:08,120 So, how would you approach to this patient who's presented with lung and skin findings? 49 00:04:08,960 --> 00:04:09,120 Shweta Anjan: Okay. 50 00:04:09,120 --> 00:04:11,940 That's a very interesting case, Cesar, thank you for that. 51 00:04:12,750 --> 00:04:27,380 Um, so to begin with, I know, like for the purposes of the session, um, this is the social history and everything you've provided, but I would definitely request for more history in terms of. 52 00:04:27,380 --> 00:04:29,830 Where was she born and raised. 53 00:04:30,010 --> 00:04:38,470 Has she lived in Nevada all her life, or did she find herself moving either like within the USA or internationally. 54 00:04:39,080 --> 00:04:56,915 that would put her at risk for different endemic fungi, which is just the first little bell that went off in my head when you said skin lesion and cavitary lung lesion, you know, Um, and then some more information about her underlying condition that led up to the transplant. 55 00:04:57,345 --> 00:05:03,035 Like she has emphysema, but why would, um, a female have emphysema? 56 00:05:03,065 --> 00:05:07,295 Is there a history of smoking, you know, any other medical history we need to think about? 57 00:05:07,295 --> 00:05:09,425 Auto-immune conditions, for example. 58 00:05:10,120 --> 00:05:15,100 Also, um, you didn't cover drug use or marijuana use, you know. 59 00:05:15,180 --> 00:05:24,060 Sure, like most transplant patients are very careful with regards to marijuana smoking, but it's still, um, something I would like to know. 60 00:05:24,450 --> 00:05:32,850 So coming up with a more broad differential diagnosis, and then we can narrow it down to specific features of our patients. 61 00:05:34,480 --> 00:05:40,385 The way I think through things is consider infections and noninfectious causes also. 62 00:05:40,385 --> 00:05:43,895 So you have like a table with one side that says infections. 63 00:05:43,895 --> 00:05:46,535 And the other side that has non-infectious causes. 64 00:05:47,195 --> 00:05:57,515 When you go through infectious causes, you look at the big four -- bacterial, viral, fungal, parasitic, and try to see which one would fit this picture. 65 00:05:57,965 --> 00:06:08,645 So we're looking at an immunocompromised host so, if you had to think of bacterial causes here, can, you can say like Staph aureus and MRSA can cause cavitary lesions. 66 00:06:08,705 --> 00:06:16,825 And if there's bacteremia and an hematogenous spread, you know, they could also be some skin lesions or cutaneous abscesses resulting from that. 67 00:06:17,525 --> 00:06:23,075 And then other, um, other bacteria like Rhodococcus, which is not very common. 68 00:06:23,575 --> 00:06:30,445 And she doesn't have a history of contact with animals, but it's still possible in transplant patients. 69 00:06:31,045 --> 00:06:39,385 And consider gram negative bacteria like Pseudomonas and Klebsiella, that can also cause more of a, um, echythma when it comes to a skin lesion. 70 00:06:39,805 --> 00:06:42,565 Um, and rarely cavitary lesion. 71 00:06:43,435 --> 00:06:54,745 The big thing to also consider is mycobacteria, non TB mycobacteria (NTM) especially, um, I'm assuming this patient would have had screening for TB pre-transplant. 72 00:06:55,375 --> 00:07:06,205 Hopefully there was a Quantiferon that was checked and negative, but it is still possible for her to either have donor derived TB or have, um, new TB infection. 73 00:07:06,565 --> 00:07:10,645 So keep, you know, tuberculosis, non TB mycobacteria also on top of the list. 74 00:07:11,695 --> 00:07:16,165 And in a different part of the country, I would say consider zoonoses like tularemia. 75 00:07:16,585 --> 00:07:19,795 You know, she obviously has had no contact with rabbits. 76 00:07:20,245 --> 00:07:30,925 So I wouldn't put that high on my list, but it's usually the board question where you have pulmonary symptoms and this ulcerative glandular lesion somewhere on the hand or leg. 77 00:07:31,435 --> 00:07:34,615 Um, and you have to consider rabbits and tularemia. 78 00:07:35,125 --> 00:07:35,455 All right. 79 00:07:35,455 --> 00:07:36,355 So that's bacterial. 80 00:07:36,775 --> 00:07:39,955 I think my favorite out of this will be working through the fungal etiology. 81 00:07:40,945 --> 00:07:44,005 So she is a lung transplant patient. 82 00:07:44,485 --> 00:07:48,465 Um, a question I would have is, was she on any antifungal prophylaxis? 83 00:07:48,935 --> 00:07:54,490 Because some centers choose to put their lung transplant patients on prophylaxis for six to 12 months. 84 00:07:54,880 --> 00:07:56,500 I know we do that here in Miami. 85 00:07:56,560 --> 00:07:59,170 They're on voriconazole prophylaxis for 12 months. 86 00:08:00,010 --> 00:08:10,990 That being said, just because they're on prophylaxis does not mean that they cannot have breakthrough infections or fungal infections in general because of sub-therapeutic antifungal levels. 87 00:08:11,380 --> 00:08:17,750 So when you think about fungal infections in these patients, I would consider aspergillosis as my number 1. 88 00:08:18,440 --> 00:08:19,855 And then other molds. 89 00:08:20,925 --> 00:08:26,065 Mucor would be rare and she should be a lot more sicker if she had that and it was disseminated. 90 00:08:26,695 --> 00:08:30,505 Um, Fusarium also causes a skin rash, another board question. 91 00:08:30,535 --> 00:08:43,165 One of the few that actually grows in blood culture, um, and the other endemic fungi, for example, Cryptococcus can definitely cause pulmonary cryptococcosis with the cavitary lesion and skin rashes. 92 00:08:44,005 --> 00:08:51,155 And, um, specific to where she is in the Southwest, I would say even Coccidioidomycosis. 93 00:08:51,224 --> 00:08:54,645 She's, she is in Nevada, which puts her at risk. 94 00:08:54,645 --> 00:08:55,874 She's out hiking. 95 00:08:56,385 --> 00:09:01,305 Um, she's definitely had exposure to, um, air and soil, I would say. 96 00:09:01,305 --> 00:09:01,484 So. 97 00:09:02,295 --> 00:09:04,575 And, uh, coming to endemic fungi. 98 00:09:04,755 --> 00:09:12,074 So you think about Histoplasma and blastomycosis also that has similar presentations with pulmonary and skin involvement. 99 00:09:12,765 --> 00:09:16,785 The map for the geographic burden of Histoplasma has been changing. 100 00:09:17,295 --> 00:09:27,185 So initially, while we classically learned that it's mostly like the Midwest and Ohio and Mississippi valley, now it is also seen in the South. 101 00:09:27,410 --> 00:09:30,200 So it's also there in the Southeast and Florida and Texas. 102 00:09:30,740 --> 00:09:36,620 And it seems to be moving more to the West, that new geographic distribution map for Histoplasma. 103 00:09:36,920 --> 00:09:37,700 So that's it. 104 00:09:37,700 --> 00:09:38,750 But the fungal. 105 00:09:39,350 --> 00:09:50,949 Um, viral etiologies, it's uncommon for any of the viruses to cause a cavitary lesion and skin lesions, and sometimes they rarely, maybe a herpes virus can do that, but that's unlikely. 106 00:09:51,859 --> 00:09:52,930 Parasites. 107 00:09:53,584 --> 00:10:00,364 So one of the parasites I respect is Strongyloides, just because of what it's capable of doing. 108 00:10:01,144 --> 00:10:06,935 So it can cause pulmonary lesions like a consolidation and can cause a skin rash. 109 00:10:07,804 --> 00:10:10,534 But the skin rash, it's not generally, usually not a nodule. 110 00:10:10,534 --> 00:10:13,354 It's more of a diffuse rash, or it looks like purpura really. 111 00:10:14,014 --> 00:10:18,504 And other pulmonary parasites like schistosomiasis, you know, the lung flukes. 112 00:10:19,414 --> 00:10:23,494 You can see um, pulmonary hydatid cysts, unlikely in this lady. 113 00:10:23,674 --> 00:10:25,384 I think that's it with the parasites. 114 00:10:25,804 --> 00:10:41,820 Um, and then coming to the noninfectious causes with her being a recent lung transplant and being out in the sun, I would say there's a high chance of skin cancer or melanoma, which could present with a lung lesion and a skin lesion. 115 00:10:42,150 --> 00:10:50,010 Also think about primary, um, pulmonary adenocarcinoma with lung mets [metastases] and the malignancy section. 116 00:10:50,880 --> 00:10:56,970 Possibility of auto immune diseases like sarcoid or granulomatosis with polyangiitis. 117 00:10:57,450 --> 00:11:02,824 Though auto-immune conditions would be subdued because she's already on immunosuppressants. 118 00:11:03,275 --> 00:11:11,495 So I'd be surprised if it was auto immune because she's already on tacrolimus and prednisone, but should, um, you know, dial down the symptoms from that. 119 00:11:12,245 --> 00:11:14,435 So to narrow it down to our patient. 120 00:11:14,435 --> 00:11:19,405 So you're presented lung transplant patient who is six months from transplant. 121 00:11:19,730 --> 00:11:24,840 She lives in Nevada, which is this dry climate with occasional winds. 122 00:11:25,190 --> 00:11:27,860 She likes hiking and spending time outdoors. 123 00:11:28,250 --> 00:11:34,970 So I would say our patient is at risk for bacterial or a fungal infection she could have inhaled. 124 00:11:36,290 --> 00:11:44,570 So my top three in her would be a non TB mycobacteria, so it could be M abscessus or M.avium or M.kansasii. 125 00:11:45,440 --> 00:11:54,270 Um, a fungal infection like Aspergillus, Cocci, or Cryptococcus and, um, Nocardia. 126 00:11:55,550 --> 00:12:00,020 Malignancy is still a possibility, and of course we will know more as we start to work this patient up. 127 00:12:00,410 --> 00:12:07,310 Now approach to like the early steps of approach to getting to a diagnosis, start with blood cultures. 128 00:12:07,340 --> 00:12:08,630 That will definitely help us. 129 00:12:09,230 --> 00:12:11,690 Um, and noninvasive fungal markers. 130 00:12:11,720 --> 00:12:18,890 You can learn a lot from the serum Aspergillus galactomannan and Cryptococcal antigen, Coccidioides antibody. 131 00:12:20,060 --> 00:12:25,660 And, um, the best part about having skin lesions in transplant patients is that you can get them biopsied. 132 00:12:25,660 --> 00:12:29,900 So it's like the one thing I tell every fellow and every medical student, I can catch hold of. 133 00:12:29,990 --> 00:12:31,760 If there's a rash, you biopsy that. 134 00:12:32,120 --> 00:12:38,510 It'll give us so many answers and fast answers that, um, even cultures cannot get back to you that quickly. 135 00:12:39,619 --> 00:12:47,160 So I would say push for invasive testing, call dermatology, biopsy the rash, send it for culture and for pathology. 136 00:12:47,620 --> 00:12:52,170 Let both the micro lab and pathology know what you're looking for, what you're considering in your patients. 137 00:12:52,710 --> 00:12:59,420 Um, especially so Pathology can work on special stains for AFB and uh fungal staining. 138 00:13:00,709 --> 00:13:04,850 And then after the skin, I would say, um, go after the pulmonary nodule. 139 00:13:05,010 --> 00:13:08,850 Consider invasive testing for the pulmonary nodule and the cavitary lesion. 140 00:13:09,610 --> 00:13:11,770 Request for bronchoscopy and BAL. 141 00:13:12,285 --> 00:13:12,755 Cesar Berto: Thank you Dr. 142 00:13:12,755 --> 00:13:16,035 Anjan, that was a very, very complete differential. 143 00:13:16,305 --> 00:13:19,785 And so to complete some of the history information. 144 00:13:19,845 --> 00:13:23,805 The patient is a former smoker, and the reason for transplantation was that. 145 00:13:24,255 --> 00:13:33,235 In terms of her pre-transplant screening, basically everything was negative including a Quantiferon except for the CMV that is a high risk. 146 00:13:33,625 --> 00:13:35,305 And, uh, she is on prophylaxis. 147 00:13:36,069 --> 00:13:38,500 In terms of the workup that was done in the hospital. 148 00:13:38,740 --> 00:13:41,020 So of course blood cultures were collected. 149 00:13:41,020 --> 00:13:42,660 Fungal markers were sent. 150 00:13:42,890 --> 00:13:46,129 She was started empirically on vancomycin and cefepime. 151 00:13:46,420 --> 00:13:48,520 And then as you said, a skin biopsy was pursued. 152 00:13:49,270 --> 00:13:57,550 We got the result of the skin biopsy and it shows a Gram positive branching and beaded rods surrounded by extensive inflammation. 153 00:13:58,180 --> 00:14:01,470 Cultures of the biopsy were also sent and they were in progress. 154 00:14:02,570 --> 00:14:10,670 While waiting on these cultures, what do you think should be the best antibiotic regimen and how do these change your differential? 155 00:14:11,450 --> 00:14:11,750 Shweta Anjan: Okay. 156 00:14:11,750 --> 00:14:16,190 So the gram-positive branching and beaded rods definitely helped. 157 00:14:16,200 --> 00:14:19,460 So if you had stopped at gram-positive rods, I would say, Hmm. 158 00:14:19,490 --> 00:14:23,700 Is this Rhodococcus, you know, Streptomyces, NTM. 159 00:14:25,190 --> 00:14:31,580 Um, but when you say gram-positive branching and beaded, kind of forced to think Nocardia. 160 00:14:32,500 --> 00:14:35,700 So I guess, Pathology did a great job at that. 161 00:14:35,710 --> 00:14:39,010 And like, you know, helped us out there saying, okay, all right. 162 00:14:39,010 --> 00:14:46,670 So if we narrow it down from all of the broad differential diagnosis to, there is a 99% chance, this is Nocardia. 163 00:14:46,670 --> 00:14:48,610 The 1% we still have to wait for the culture. 164 00:14:49,150 --> 00:14:54,340 In transplant patients, I have come to learn that you should expect curveballs and plan ahead for them. 165 00:14:54,640 --> 00:14:59,860 So I would say, okay, I'm comfortable knowing that this is Nocardia, so we can plan our treatment around. 166 00:15:00,710 --> 00:15:06,740 So in solid organ transplant and immunocompromised patients, honestly, Nocardia is not that common. 167 00:15:07,310 --> 00:15:10,910 The incidence is less than 4%. 168 00:15:11,600 --> 00:15:17,600 Um, our patient lives in the United States, Southwest, where the incidence of Nocardia is higher. 169 00:15:17,630 --> 00:15:20,210 So, which is why this makes it more likely in her. 170 00:15:21,170 --> 00:15:23,300 And there are other risk factors that you need to consider. 171 00:15:24,590 --> 00:15:32,030 She's a lung transplant patient, and heart and lung transplant patients are at higher risk of compared to liver and kidney for Nocardia infections. 172 00:15:32,810 --> 00:15:34,610 She is six months post transplant. 173 00:15:34,610 --> 00:15:42,920 So she kind of fits the timeline where the highest chances of having, um, Nocardia infections are one to two years post-transplant. 174 00:15:43,610 --> 00:15:48,380 Um, though, the bacteria doesn't read the guidelines and the timeline. 175 00:15:48,380 --> 00:16:03,020 So it's still possible that you can see it a little earlier, you can see it after two years, you can see to the later point in life, especially if they have recently been treated for rejection and they had, you know, augmentation in their immunosuppression. 176 00:16:03,470 --> 00:16:08,500 So certain immunosuppressants also increase the risk factors for Nocardia, I would say. 177 00:16:08,950 --> 00:16:11,200 There have been various case control studies done. 178 00:16:12,115 --> 00:16:32,545 A large one here in the USA and another one from Europe that in solid organ transplant patients that identified that the risk factors include high doses of corticosteroids, um, a high serum concentration of calcineurin inhibitors and prior CMV infection, like in the past six months. 179 00:16:33,475 --> 00:16:39,295 In addition, older age, prolonged ICU stay at also considered to be risk factors for nocardia infection. 180 00:16:40,135 --> 00:16:51,565 So this is specific to solid organ transplant, but remember like other stem cell transplants, leukemics, lymphoma, patients receiving monoclonal antibodies like rituximab and infliximab. 181 00:16:51,805 --> 00:16:53,755 They are also at risk for Nocardia. 182 00:16:54,275 --> 00:17:03,995 Especially I think with infliximab, they have, there have been reports where there, um, Nocardia infections in like patients being treated for rheumatoid arthritis. 183 00:17:04,595 --> 00:17:06,785 So consider other immunosuppressants while you're at it. 184 00:17:08,075 --> 00:17:11,315 Typical clinical manifestations of Nocardia. 185 00:17:11,825 --> 00:17:16,895 Um, I would say the primary site of infection is the lung, you know, you inhale it. 186 00:17:16,955 --> 00:17:18,815 So that's why it's going straight to your lungs. 187 00:17:19,415 --> 00:17:27,345 Um, and in some cases there is cutaneous involvement, either alone, so the isolated cutaneous involvement. 188 00:17:27,680 --> 00:17:41,770 If there is trauma, um, and you know, people who are into gardening and landscaping, where you just have a single nodule and hopefully it stays contained there, or it could be from hematogenous spread from the primary site to the skin. 189 00:17:42,310 --> 00:17:45,040 So you could have that, uh, pulmonary infection. 190 00:17:45,040 --> 00:17:46,690 And then of course, CNS infection. 191 00:17:47,230 --> 00:17:59,495 Um, Nocardia seems to have affinity for the brain and, due to the tropism, there are a predominant number of cases in solid organ transplant that have disseminated nocardia infections. 192 00:18:00,695 --> 00:18:05,545 When it comes to diagnosis, I would say we absolutely need it on culture. 193 00:18:05,785 --> 00:18:08,495 Growth on culture is a must to help in diagnosis. 194 00:18:09,185 --> 00:18:20,045 In cases where it is not growing on culture, um, consider molecular testing like PCR testing, or like a 16 s RNA um, testing, where you can send it to a reference lab. 195 00:18:20,705 --> 00:18:30,495 I actually honestly saw a similar case where the patient was initially diagnosed with organizing pneumonia, because it didn't grow on culture for weeks. 196 00:18:31,165 --> 00:18:32,245 And the treatment. 197 00:18:32,575 --> 00:18:38,645 The treatment is completely different because they get steroids for organizing pneumonia versus nocardia treatments. 198 00:18:38,735 --> 00:18:40,085 So it's something to think about. 199 00:18:40,335 --> 00:18:49,945 While you're waiting for the culture, is first of all, get adequate samples, send the skin biopsy for cultures, send the BAL culture, whatever specimen you can find that's a source of infection. 200 00:18:49,945 --> 00:18:51,055 You send it for culture. 201 00:18:51,055 --> 00:18:55,625 Let the microlab know, communicate with the micro lab because they're your best friends. 202 00:18:56,115 --> 00:19:00,055 Tell him you're considering nocardia so they can do a modified acid fast stain. 203 00:19:00,415 --> 00:19:02,335 They can incubate it for longer. 204 00:19:02,755 --> 00:19:10,375 Cause sometimes it might grow soon or sometime it might choose to grow 3-4 weeks later so they can hold your specimens and incubate them for longer. 205 00:19:10,555 --> 00:19:15,805 Also there's a role where they can consider certain selective media to help nocardia grow faster. 206 00:19:16,195 --> 00:19:20,945 So communicate with them about your potential diagnosis and that will help you. 207 00:19:21,325 --> 00:19:22,555 And then we're coming to imaging. 208 00:19:22,755 --> 00:19:24,375 Imaging for nocardia is important. 209 00:19:24,915 --> 00:19:35,745 What you described, uh, in our patient's CT scan, where you said she had a right lower lobe consolidation with a two centimeter nodular lesion and peripheral cavity. 210 00:19:36,135 --> 00:19:36,555 So. 211 00:19:37,530 --> 00:19:50,500 Almost typical for, um, nocardia and other infections also unfortunately, but an irregular nodule, large mass, like a third of them have cavitation, can easily be considered to be malignancy. 212 00:19:50,950 --> 00:19:54,070 Um, that's what you typically see on a CT chest. 213 00:19:54,350 --> 00:20:03,550 Remember, not just with nocardia infections, I would also say with fungal infections and non TB mycobacteria, remember to stage your infection. 214 00:20:03,550 --> 00:20:04,665 So, you know the severity. 215 00:20:04,665 --> 00:20:11,385 So staging of disease involves imaging of the chest, sinuses and brain to understand the extent of involvement. 216 00:20:11,805 --> 00:20:21,375 So in this case, you know, just to see if the patient has no CNS symptoms, no headaches, vision problems, we can start with a CT brain and, and then ask for an MRI brain. 217 00:20:21,735 --> 00:20:23,865 Um, or you could just get the MRI first. 218 00:20:24,135 --> 00:20:24,615 Cesar Berto: Perfect. 219 00:20:24,765 --> 00:20:30,355 So actually a more careful review of systems of these patient reveals some intermittent headache. 220 00:20:30,810 --> 00:20:39,240 Patient underwent a brain MRI and it show a well-defined very small ring enhancing lesion in a temporal lobe with minimal surrounding edema. 221 00:20:39,570 --> 00:20:46,110 So knowing this, how could these affect your management and what changes could you recommend? 222 00:20:47,070 --> 00:20:47,430 Shweta Anjan: Okay. 223 00:20:47,430 --> 00:20:55,425 So what we know now is that there is lung, skin, and CNS enrollment. 224 00:20:55,875 --> 00:21:05,745 So this patient definitely has a disseminated process, likely disseminated nocardia, because there's involvement more than more than two sites. 225 00:21:06,355 --> 00:21:11,995 This can be life-threatening with the high mortality rate, mortality as high as 20%. 226 00:21:13,195 --> 00:21:15,145 So we would need to act fast. 227 00:21:15,445 --> 00:21:21,685 One, establish from a neurosurgery standpoint, how safe is the edema and the lesion. 228 00:21:21,785 --> 00:21:28,345 with a typical ring enhancing lesion would mean, um, could also be toxoplasma but get neurosurgery involved. 229 00:21:28,455 --> 00:21:30,975 Is there any role for an intervention? 230 00:21:31,485 --> 00:21:33,635 Is there something to evacuate or drain? 231 00:21:34,035 --> 00:21:38,265 And is there anything to be done for the surrounding edema and inflammation? 232 00:21:38,835 --> 00:21:47,570 So starting there, I believe this patient is on vancomyvin and cefepime empirically? 233 00:21:48,670 --> 00:21:51,210 Cesar Berto: Vancomycin and cefepime empirically. 234 00:21:51,210 --> 00:21:51,470 Yes. 235 00:21:51,470 --> 00:21:51,820 Correct. 236 00:21:52,350 --> 00:21:52,680 Shweta Anjan: Alright. 237 00:21:52,800 --> 00:22:02,220 So we're thinking most likely this patient has Nocardia, but until I know more, I might also want to cover for NTM. 238 00:22:03,360 --> 00:22:08,760 But the good thing is that the treatment for nocardia sort of covers some, some NTM also. 239 00:22:09,450 --> 00:22:17,850 So the first line of treatment from nocardia, like the backbone has to be a sulfonamide, like Bactrim (trimethoprim-sulfamethaxazole) so you start off include Bactrim in your regimen. 240 00:22:18,330 --> 00:22:29,010 And then in addition, the other first line options are the drugs you can add would be, you know, imipenem, Amikacin, linezolid, depending on the severity of disease. 241 00:22:30,120 --> 00:22:35,130 So, if it is just cutaneous, you can get away with monotherapy with Bactrim. 242 00:22:35,550 --> 00:22:44,960 If it was limited to the lung with imaging confirming that there's no brain or sinus involvement, you can also get away with monotherapy with Bactrim. 243 00:22:45,620 --> 00:22:48,380 In our patient, we actually know she has disseminated disease. 244 00:22:48,380 --> 00:23:02,585 So I would say combination therapy, um, depending on what she can tolerate, I would say bactrim, imipenem and if the symptoms progress or don't improve within a week, also add amikacin IV and monitor her. 245 00:23:03,965 --> 00:23:11,765 Now, this is the best case scenario, but what do you do in terms of Bactrim allergies or, you know, patients who are intolerant to Bactrim? 246 00:23:12,455 --> 00:23:24,055 Um, if they have a serious allergy to Bactrim consider desensitization, but even after that, if patients are intolerant to it, then you would have to consider treatments, such as linezolid. 247 00:23:24,055 --> 00:23:28,525 So you can try imipenem and linezolid, which has proven to be effective multiple times. 248 00:23:28,915 --> 00:23:40,475 In fact, linezolid is a great, great drug with the bioavailability being a hundred percent, ease of administration, there are both IV and PO options, you know, transitioning would be easy. 249 00:23:41,045 --> 00:23:44,195 It achieves good CNS and lung tissue concentration. 250 00:23:44,195 --> 00:23:45,095 So it will be perfect. 251 00:23:45,575 --> 00:24:07,085 The only problem is the duration of treatment and toxicities, you'd have to factor in because when you're thinking about treating nocardia, you're thinking about prolonged treatment and with linezolid, you would have bone marrow suppression, thrombocytopenia, peripheral neuropathy, you know, serotonin syndrome to consider. 252 00:24:07,550 --> 00:24:10,700 It it's a good option, but a short-term option. 253 00:24:10,730 --> 00:24:14,900 You would still need something else to complete the duration of treatment. 254 00:24:15,740 --> 00:24:24,960 So empirically, um, I would choose bactrim, imipenem, but without amikacin, depending on how the patient progresses. 255 00:24:25,610 --> 00:24:28,220 Imipenem would also cover some NTM. 256 00:24:28,760 --> 00:24:36,740 Um, and if there's a strong feeling that this is probably NTM, you could also add a macrolide, uh, while you wait for the final culture. 257 00:24:37,730 --> 00:24:40,280 So while we're managing this patient empirically. 258 00:24:41,200 --> 00:24:50,800 You do need to emphasize on the cultures because a species identification and anti-microbial susceptibilities are absolutely necessary. 259 00:24:51,730 --> 00:24:54,700 The species of nocardia vary by geographical region. 260 00:24:54,820 --> 00:25:02,740 So the species that's predominant in Europe is not predominant in the U S and even within the U S every state has a predominant species. 261 00:25:03,220 --> 00:25:04,840 So you would have to know that. 262 00:25:05,580 --> 00:25:11,640 And every species differs in terms of pathogenicity and antibiotic susceptibility. 263 00:25:11,770 --> 00:25:15,940 We have empiric treatment, but there are certain species of nocardia. 264 00:25:16,150 --> 00:25:22,930 I would say the dangerous ones are, um, N.farsinica, which almost always causes disseminated disease. 265 00:25:23,410 --> 00:25:28,330 It can be resistant to Bactrim, imipenem, third-generation cephalosporins. 266 00:25:28,690 --> 00:25:40,840 And there's also N.pseudobraziliensis that's also can be resistant to Bactrim and N.abscessus sometimes, um Nocardia abscessus has variable sensitivity to. 267 00:25:41,665 --> 00:25:43,285 Um, imipenem and Bactrim. 268 00:25:43,405 --> 00:25:48,445 So like knowing these things, it's very important that we get down to the details. 269 00:25:48,565 --> 00:25:54,325 Like what is the species, what the antibiotic susceptibility, and then we can narrow our treatment from there. 270 00:25:55,135 --> 00:25:55,525 Cesar Berto: Great. 271 00:25:55,735 --> 00:26:05,255 So the culture was obtained by the team and it was finally identified by the micro lab as Nocardia abscessus, which was sensitive to imipenem and sensitive to bactrim. 272 00:26:05,695 --> 00:26:09,475 So the patient was transitioned to imipenem and bactrim as per ID recommendations. 273 00:26:10,555 --> 00:26:15,775 Um, so in this particular case, how long would you, would you treat this patient? 274 00:26:16,285 --> 00:26:17,035 Shweta Anjan: Okay, that's great. 275 00:26:17,155 --> 00:26:20,815 That's great that we had Nocardia abscessus and it's sensitive to imipenem, bactrim. 276 00:26:20,865 --> 00:26:21,505 So we're winning! 277 00:26:21,685 --> 00:26:23,725 So talking about a disseminated disease. 278 00:26:23,725 --> 00:26:33,010 So I would say a minimum of six months, six to 12 months is what the guideline says, but I would say at least six, more likely 12, push towards 12. 279 00:26:33,640 --> 00:26:37,330 Even the 12 months would depend on clinical progression. 280 00:26:37,690 --> 00:26:40,660 So this patient will likely become your best friend. 281 00:26:40,670 --> 00:26:42,760 So you need to know everything about them at this point. 282 00:26:43,420 --> 00:26:48,240 Um, because this patient's going to be followed by you in clinic for the next 12 months. 283 00:26:48,600 --> 00:26:54,610 So for ease of communication, make sure you have emails and phone numbers, um, and a way to get ahold of labs. 284 00:26:55,070 --> 00:26:58,070 She's going to need clinical monitoring. 285 00:26:58,160 --> 00:27:02,240 I would say at least 1, 3, 6 months after diagnosis. 286 00:27:02,810 --> 00:27:09,580 Um, for both for drug toxicity, and also repeat imaging, you know, repeat the MRI of the brain, the CT chest. 287 00:27:09,580 --> 00:27:11,830 See where you're at with radiological resolution. 288 00:27:12,580 --> 00:27:17,680 After completion of treatment, she may or may not need secondary prophylaxis. 289 00:27:18,280 --> 00:27:24,790 Um, but you would still need to follow up with imaging at least at six months and 12 months post stopping treatment. 290 00:27:25,600 --> 00:27:25,960 Cesar Berto: Great. 291 00:27:26,110 --> 00:27:30,580 So in the case of this patient, uh, he remains on therapy and was able to tolerate it. 292 00:27:31,310 --> 00:27:46,705 One of the things that we wanted you to expand a little bit more, it's the impact of uh, PJP prophylaxis, um, usually on bactrim and in this case, the patient was on Atovaquone, in terms of the prevention also of, of Nocardia infections, 293 00:27:47,305 --> 00:27:48,865 Shweta Anjan: Alright, and that's a good question. 294 00:27:49,435 --> 00:27:51,915 So your patient here was on atovaquone. 295 00:27:52,335 --> 00:27:57,345 Bactrim does have a role, so Bactrim use for PJP prophylaxis. 296 00:27:57,375 --> 00:28:01,245 The dosing's either a single strength daily or double strength three times a week. 297 00:28:01,975 --> 00:28:05,605 It does have a role in primary prevention of Nocardia. 298 00:28:06,175 --> 00:28:08,605 However breakthrough infections have been reported. 299 00:28:09,355 --> 00:28:23,870 And this has been an ongoing debate about, you know, is it because of the dosing, that the dosing for PJP prophylaxis is insufficient to ensure complete primary prevention of Nocardia? 300 00:28:24,620 --> 00:28:35,710 Um, and there are studies that show patients who have these breakthrough infections on Bactrim for PJP prophylaxis, the isolates can still be susceptible to Bactrim. 301 00:28:36,145 --> 00:28:41,035 And then there are a few instances where they're resistant to Bactrim, so that would explain the breakthrough infection. 302 00:28:41,695 --> 00:28:53,505 Um, but I would say yes, when possible, and if the patient tolerates it, um, Bactrim for PJP prophylaxis is still preferred, um, and will definitely offer some protection against nocardia. 303 00:28:54,255 --> 00:29:07,920 Again, the data on, both dosing and duration of Bactrim for primary prevention and secondary prophylaxis for nocardia is, um, limited, I would say. 304 00:29:08,010 --> 00:29:13,320 We don't really have, you know, any head to head trials or prospective studies in this area. 305 00:29:13,740 --> 00:29:18,600 Most of our information is from retrospective studies and case reports. 306 00:29:19,270 --> 00:29:37,350 In fact, there are, I think there's a study from Mayo clinic from a few years ago where they looked at recurrence rates in patients while they were on secondary prophylaxis and there was still a 5% recurrence rate on their secondary prophylaxis of Bactrim, single strength daily. 307 00:29:37,740 --> 00:29:44,400 And they identified the risk factor for those recurrences, mostly lung transplant, patients, chronic lung problems. 308 00:29:44,970 --> 00:29:48,660 Um, and if for some reason they received less than six months of treatment. 309 00:29:49,860 --> 00:30:01,485 So even on the single strength daily, you know, they can still have recurrence, I think that might be why our AST guideline recommends Bactrim double strength daily for secondary prophylaxis in these patients. 310 00:30:01,905 --> 00:30:03,465 But there is no data to back that up. 311 00:30:04,350 --> 00:30:04,560 Sara Dong: Yeah. 312 00:30:04,590 --> 00:30:24,890 Cause I feel like this question, it always comes up when there's a case of nocardia and I think emphasizing that you can still have it regardless of the isolate is susceptible or if they're on daily prophylaxis is such an important point because I think sometimes, when teams call us, they sort of say like, oh, well there's no way it could be X, Y, and Z, because they're on prophylaxis. 313 00:30:25,190 --> 00:30:30,980 And it's the same with fungal disease, that we use that as a piece of information, but can't really take something off the table. 314 00:30:31,670 --> 00:30:32,660 Shweta Anjan: No, absolutely. 315 00:30:32,660 --> 00:30:33,860 That's always a problem. 316 00:30:34,610 --> 00:30:40,210 I would say a take home message for nocardia is that it does not respect fascial planes. 317 00:30:40,410 --> 00:30:40,830 Okay. 318 00:30:41,250 --> 00:30:42,810 Like, it's a very disrespectful bug. 319 00:30:43,200 --> 00:30:52,110 It can spread right to your lungs, you know, it can go, go to spread to the chest wall from its primary site of infection. 320 00:30:52,410 --> 00:30:54,250 So no respect for fascial planes. 321 00:30:54,270 --> 00:30:56,070 There is hematogenous spread. 322 00:30:56,670 --> 00:30:58,170 Like who does that? 323 00:31:00,595 --> 00:31:08,725 Sara Dong: Uh, I think that's most of the case we have, I wanted to make sure there weren't other pearls or things that we should keep in mind with Nocardia. 324 00:31:08,745 --> 00:31:17,230 I feel like we talk about it a lot and we see it occasionally, but, uh, at least for me, I feel like the cases are actually somewhat spread out. 325 00:31:17,350 --> 00:31:18,100 Shweta Anjan: No, that's true. 326 00:31:18,100 --> 00:31:22,810 Like, um, like as I said before, like our incidence in solid organ transplant is low. 327 00:31:22,890 --> 00:31:32,310 But there's a good chance that you might see an increase, especially now that there's an increase in the number of transplants overall, increasing the number of lung transplant. 328 00:31:32,310 --> 00:31:36,390 So there are a lot more immunocompromised people in our community. 329 00:31:37,545 --> 00:31:39,315 Um, and also global warming. 330 00:31:39,855 --> 00:31:53,265 Like it or not, it's going to become a big infectious disease problem with the rise of temperatures and providing this like favorable environment for all these bacteria, fungi and parasites to grow and multiply. 331 00:31:53,655 --> 00:31:56,265 Um, you're going to see a lot of these infections. 332 00:31:57,375 --> 00:32:11,275 Sara Dong: Well, thank you guys so much for coming on the show and talking about Nocardia, but also thinking this is a really nice case to think about brain and skin and then brain and lung, and a lot of the combos that we see on ID consult. 333 00:32:11,295 --> 00:32:15,225 And of course, cavitary lung lesions, which are one of my favorite ID differentials, so! 334 00:32:17,355 --> 00:32:20,135 Shweta Anjan: Yes, thank you for having us, Sara. 335 00:32:20,545 --> 00:32:22,235 Cesar Berto: Thank you! 336 00:32:22,685 --> 00:32:26,555 Sara Dong: Thanks again to Shweta and Cesar for joining Febrile today. 337 00:32:27,005 --> 00:32:31,605 Our usual disclaimer, that all presented patients on this podcast are inspired by patient experiences. 338 00:32:31,845 --> 00:32:36,015 The cases are constructed or significantly altered, and de-identified for learning purposes. 339 00:32:36,555 --> 00:32:48,845 Please, don't forget to check out the website, febrilepodcast.com, where you will find our Consult Notes, which are written complements of the show with links to references, our library of ID infographics, and a link to our merch store. 340 00:32:49,270 --> 00:32:54,530 So please reach out if you have any suggestions for future shows or if you just want to be more involved with Febrile. 341 00:32:55,000 --> 00:32:55,840 Thanks for listening. 342 00:32:55,870 --> 00:32:57,700 Stay safe and we'll see you next time.