1 00:00:07,980 --> 00:00:08,670 Hi everyone. 2 00:00:08,730 --> 00:00:12,549 Welcome to Febrile, a cultured podcast about all things infectious diseases. 3 00:00:12,950 --> 00:00:16,455 We use consult questions to dive into ID clinical reasoning, diagnostics 4 00:00:16,455 --> 00:00:17,865 and antimicrobial management. 5 00:00:18,285 --> 00:00:20,955 I'm Sara Dong, your host and a Med-Peds ID doc. 6 00:00:21,435 --> 00:00:25,185 Today we have a team joining us from the University of Southern California 7 00:00:25,185 --> 00:00:26,865 and LA General Medical Center. 8 00:00:27,045 --> 00:00:30,884 Guiding us will be Hannah Chute, who is a fourth year medical student 9 00:00:30,884 --> 00:00:34,845 at Keck School of Medicine at USC, currently applying to internal medicine. 10 00:00:35,214 --> 00:00:35,995 Hi, I am Hannah. 11 00:00:35,995 --> 00:00:37,165 Thank you so much for having us. 12 00:00:37,405 --> 00:00:41,964 Next we have Dr. Paloma Reta-Impey, who is a first year ID fellow at 13 00:00:42,025 --> 00:00:44,275 USC / LA General Medical Center. 14 00:00:44,425 --> 00:00:45,324 Hi, I'm Paloma. 15 00:00:45,324 --> 00:00:46,375 Thanks for having us on. 16 00:00:46,824 --> 00:00:49,765 And lastly, we are joined by Dr. Brad Spellberg, who is the Chief 17 00:00:49,765 --> 00:00:53,304 Medical Officer at the Los Angeles General Medical Center, one of the 18 00:00:53,304 --> 00:00:55,194 largest public hospitals in the US. 19 00:00:55,224 --> 00:00:57,925 He staffs internal medicine wards, infectious disease 20 00:00:57,925 --> 00:01:00,985 consults, and the antibiotic stewardship service at LA General. 21 00:01:01,035 --> 00:01:05,354 He also maintains an active NIH funded basic science lab that focuses 22 00:01:05,354 --> 00:01:08,985 on novel solutions to combating antibiotic resistant infections. 23 00:01:09,795 --> 00:01:10,995 Hi, I'm Brad. 24 00:01:10,995 --> 00:01:12,315 Thanks for hosting this. 25 00:01:12,884 --> 00:01:13,274 Great. 26 00:01:13,365 --> 00:01:17,624 So we ask as everyone's favorite cultured podcast, if you wouldn't mind sharing a 27 00:01:17,624 --> 00:01:21,574 little piece of culture, just something non-medical that brings you happiness. 28 00:01:21,664 --> 00:01:23,044 Uh, maybe Hannah, I'll start with you. 29 00:01:23,690 --> 00:01:24,050 Sure. 30 00:01:24,050 --> 00:01:25,190 I thought a lot about this. 31 00:01:25,339 --> 00:01:29,600 Um, I don't know if it's poor form to recommend another podcast. 32 00:01:29,690 --> 00:01:30,110 Um, 33 00:01:30,410 --> 00:01:30,589 That's okay. 34 00:01:30,589 --> 00:01:33,440 But something that I've really been, something I've really been enjoying 35 00:01:33,440 --> 00:01:38,160 recently is Home Cooking, um, with Samin Nosrat and Hrishikesh Hirway. 36 00:01:38,330 --> 00:01:42,904 It was originally a lockdown era cooking podcast, but, um, they've kept it 37 00:01:42,904 --> 00:01:48,004 going over time and it's now just about like food and celebrating small joys. 38 00:01:48,304 --> 00:01:50,945 Um, and it's pretty much a warm hug and audio form. 39 00:01:51,034 --> 00:01:51,844 Highly recommend it. 40 00:01:52,115 --> 00:01:52,594 Excellent. 41 00:01:52,835 --> 00:01:53,254 Love it. 42 00:01:53,674 --> 00:01:54,464 What about you, Paloma? 43 00:01:55,579 --> 00:01:55,800 Hi. 44 00:01:56,104 --> 00:01:59,854 Um, so something that I really enjoy outside of medicine is 45 00:01:59,884 --> 00:02:01,384 being in the outdoors and camping. 46 00:02:01,445 --> 00:02:06,935 And I recently got a fantastic opportunity to go out to Joshua Tree National Park 47 00:02:06,935 --> 00:02:08,285 with some friends who were visiting. 48 00:02:08,614 --> 00:02:11,975 Um, and we went during the week and it was lovely and a beautiful experience. 49 00:02:11,975 --> 00:02:16,685 And it was just at the tail end of a, a kind of fading moon. 50 00:02:16,685 --> 00:02:19,234 And so there was a lot of really great nighttime photography as 51 00:02:19,234 --> 00:02:21,454 well, um, to participate in. 52 00:02:21,780 --> 00:02:24,120 Overall support your national park systems. 53 00:02:24,299 --> 00:02:25,230 What about you, Brad? 54 00:02:25,833 --> 00:02:27,093 My kids and my dog. 55 00:02:27,243 --> 00:02:27,603 Love it. 56 00:02:29,163 --> 00:02:32,193 Um, alright, well I will hand it over to Hannah who's gonna 57 00:02:32,193 --> 00:02:33,543 tell us about some cases today. 58 00:02:35,558 --> 00:02:39,938 Yeah, so our first case today is a 58-year-old female. 59 00:02:40,328 --> 00:02:42,668 She has a history of type two diabetes. 60 00:02:42,668 --> 00:02:46,598 Her most recent A1C about eight months ago was 9.3%. 61 00:02:46,658 --> 00:02:52,028 She also has a history of hypertension, osteoarthritis of the hips and right knee. 62 00:02:52,368 --> 00:02:57,438 She's admitted after presenting to the ED from podiatry clinic for worsening 63 00:02:57,438 --> 00:02:59,958 foot ulcer and fevers and chills. 64 00:03:00,723 --> 00:03:03,903 She has had diabetes for about 20 years. 65 00:03:04,563 --> 00:03:09,573 She has inconsistent follow up with her primary care doctor due to social factors. 66 00:03:09,813 --> 00:03:13,833 She works long hours in her family restaurant with longer hours recently as 67 00:03:13,833 --> 00:03:19,053 her two siblings who previously worked alongside her are now both on dialysis 68 00:03:19,083 --> 00:03:21,243 for diabetes related kidney disease. 69 00:03:21,693 --> 00:03:23,253 She's on her feet all day at work. 70 00:03:23,823 --> 00:03:28,878 She first notices a blister at the base of her great toe about six weeks ago. 71 00:03:29,768 --> 00:03:32,858 She's not sure how long that's been present because her arthritis 72 00:03:32,858 --> 00:03:35,318 makes it difficult for her to perform her own foot checks. 73 00:03:35,978 --> 00:03:40,988 She initially presented to podiatry clinic a month ago and received local wound care. 74 00:03:41,468 --> 00:03:45,788 She then presented to clinic a week later with worsening ascending erythema. 75 00:03:46,118 --> 00:03:48,603 X-ray at that time showed soft tissue involvement only. 76 00:03:48,933 --> 00:03:53,943 So she was diagnosed with cellulitis and given a one week course of cephalexin. 77 00:03:54,813 --> 00:03:59,013 She took that full course, uh, but her symptoms continued to worsen and 78 00:03:59,013 --> 00:04:02,823 her ulcer began to exude purulent fluid, which prompted her to return 79 00:04:02,823 --> 00:04:04,263 to her podiatrist once again. 80 00:04:04,983 --> 00:04:09,183 Uh, this time she was sent from clinic to the ED for further evaluation. 81 00:04:10,098 --> 00:04:14,628 Her exam in the ED was notable for 1+ pedal pulses, decreased sensation 82 00:04:14,628 --> 00:04:18,258 to pinprick in a glove and stocking distribution, and a one centimeter 83 00:04:18,258 --> 00:04:21,918 ulcer on the plantar surface of the right foot at the base of the great 84 00:04:21,918 --> 00:04:26,378 toe with erythema ascending to the ankle, no crepitance or fluctuance. 85 00:04:26,838 --> 00:04:30,168 The ulcer probed to bone with associated purulence and abscess. 86 00:04:30,508 --> 00:04:33,838 X-ray was diagnostic of osteomyelitis of the first metatarsal head. 87 00:04:34,628 --> 00:04:39,238 Her wound cultures grew MSSA susceptible to trimethoprim-sulfamethoxazole, 88 00:04:39,418 --> 00:04:42,298 doxycycline, levofloxacin, and rifampin. 89 00:04:42,758 --> 00:04:44,228 Her blood cultures are negative. 90 00:04:44,798 --> 00:04:48,188 She undergoes debridement with ortho, but retains some infected bone. 91 00:04:48,698 --> 00:04:49,538 Okay, perfect. 92 00:04:49,538 --> 00:04:52,688 So, um, I'm just gonna give a summary statement for this patient just 93 00:04:52,688 --> 00:04:56,468 because there's a couple of, uh, moving pieces in terms of her care. 94 00:04:56,468 --> 00:04:59,918 And then I'll use this as an opportunity to kind of jump into the current 95 00:04:59,918 --> 00:05:04,808 guideline recommendations for diabetic foot infections, and, um, talk a 96 00:05:04,808 --> 00:05:08,473 little bit more about some of the pertinent recommendations that are 97 00:05:08,473 --> 00:05:09,973 applicable to this patient's case. 98 00:05:10,453 --> 00:05:13,513 So summary statement for her is this is a 58-year-old female with a past 99 00:05:13,513 --> 00:05:17,113 medical history significant for diabetes, who presented with a six week history 100 00:05:17,113 --> 00:05:21,623 of a non-healing diabetic foot ulcer, found to have MSSA diabetic foot 101 00:05:21,623 --> 00:05:24,143 osteomyelitis now status post debridement. 102 00:05:24,143 --> 00:05:27,383 However, she has, um, retention of infected bone and is 103 00:05:27,383 --> 00:05:28,703 currently on ceftriaxone. 104 00:05:29,583 --> 00:05:32,543 So in terms of the guideline recommendations that exist currently, 105 00:05:32,693 --> 00:05:36,893 so we are going to be going off of the 2023 International Working Group 106 00:05:36,893 --> 00:05:41,033 of Diabetic Foot and IDSA guidelines on the diagnosis and treatment of 107 00:05:41,033 --> 00:05:43,253 diabetes related foot infections. 108 00:05:43,253 --> 00:05:47,753 And this was, um, most recently updated in October of, uh, 2023. 109 00:05:47,753 --> 00:05:51,598 So it's actually, it's celebrating its second birthday today from update. 110 00:05:52,318 --> 00:05:56,578 So kind of pertinent, uh, recommendations in terms of this specific patient's case. 111 00:05:56,818 --> 00:06:01,048 The guidelines do recommend assessing the severity of this infection of a 112 00:06:01,048 --> 00:06:05,518 diabetic foot infection using a proposed classification schema, number one 113 00:06:05,518 --> 00:06:09,388 through four, with one being uninfected and four being a severe infection 114 00:06:09,388 --> 00:06:13,988 with systemic symptoms to describe both the infection itself, uh, plus or 115 00:06:13,988 --> 00:06:16,208 minus the presence of osteomyelitis. 116 00:06:16,208 --> 00:06:20,998 And this is going to help to dictate and guide the initial empiric treatment 117 00:06:20,998 --> 00:06:25,468 regimen, but also the duration and course that patients would typically receive, um, 118 00:06:25,678 --> 00:06:27,758 when treating a diabetic foot infection. 119 00:06:28,238 --> 00:06:33,363 The other main guideline recommendations in regards to once you are able 120 00:06:33,363 --> 00:06:37,083 to kind of classify what type of diabetic foot infection this is. 121 00:06:37,083 --> 00:06:41,223 So going back to their proposed classification schema, this 122 00:06:41,223 --> 00:06:44,773 patient would fall under either a number three or number four. 123 00:06:44,803 --> 00:06:47,923 Number three being a moderate infection, she's got a deep infection 124 00:06:47,923 --> 00:06:49,993 that tracks down into the bone. 125 00:06:50,293 --> 00:06:54,223 Um, you could also classify her as a severe infection based on the 126 00:06:54,223 --> 00:06:58,153 fact that she did have systemic manifestations with both, um, fevers 127 00:06:58,153 --> 00:07:00,073 and chills prior to presentation. 128 00:07:00,073 --> 00:07:02,683 So just for the sake of this case, I'm gonna go ahead and 129 00:07:02,683 --> 00:07:05,173 classify her as a severe infection. 130 00:07:05,533 --> 00:07:09,883 Now from that standpoint, now that we have a classification for her, using 131 00:07:09,883 --> 00:07:11,803 our further guideline recommendations. 132 00:07:11,833 --> 00:07:12,073 Um. 133 00:07:12,688 --> 00:07:16,978 The world is kind of our oyster in terms of what they recommend, um, in 134 00:07:16,978 --> 00:07:23,518 terms of an initial antibiotic selection and also our duration of therapy. 135 00:07:23,518 --> 00:07:28,678 So in terms of figuring out what antibiotics empirically, we wanna treat 136 00:07:28,678 --> 00:07:30,328 a patient with a diabetic foot ulcer. 137 00:07:30,568 --> 00:07:36,868 The guidelines do recommend that any antibiotic that has been shown in 138 00:07:36,868 --> 00:07:41,623 randomized controlled studies to treat both patients with diabetes and, uh, 139 00:07:42,283 --> 00:07:46,723 skin and soft tissue infections can be used to treat diabetic foot infections. 140 00:07:47,023 --> 00:07:50,293 In this specific patient's case because we are going to classify 141 00:07:50,293 --> 00:07:55,513 her as a severe infection, typically we would want to start off with 142 00:07:55,513 --> 00:07:58,433 treating her with an IV antibiotic. 143 00:07:58,733 --> 00:08:01,523 Uh, but there is room within these guidelines. 144 00:08:01,523 --> 00:08:01,823 Um. 145 00:08:02,083 --> 00:08:06,583 And it does explicitly recommend that we can at some point, uh, transition 146 00:08:06,583 --> 00:08:10,903 her to oral therapy as she progresses throughout her hospital course. 147 00:08:11,263 --> 00:08:14,233 And for patients who have a mild diabetic foot infection. 148 00:08:14,233 --> 00:08:17,773 So this would be, there is a signs of infection or inflammation, but 149 00:08:17,773 --> 00:08:19,423 there is no systemic involvement. 150 00:08:19,603 --> 00:08:23,563 The guidelines actually do recommend that you can even start with initial oral 151 00:08:23,563 --> 00:08:27,753 therapy and treat these patients in the outpatient setting and not have to, uh, 152 00:08:27,753 --> 00:08:32,378 require admission, but based on the fact that this patient has a severe infection 153 00:08:32,378 --> 00:08:37,378 in addition to systemic symptoms, definitely warrants admission and, uh, 154 00:08:37,378 --> 00:08:39,628 initial treatment with IV antibiotics. 155 00:08:40,018 --> 00:08:46,108 And so moving on from those guidelines, now that we have a bug 156 00:08:46,108 --> 00:08:51,748 that we're treating and we're treating MSSA, um, the team started her on 157 00:08:51,868 --> 00:08:55,968 ceftriaxone, which I think is a reasonable initial antibiotic for her. 158 00:08:56,208 --> 00:08:59,448 And we can now, as we start to talk about discharge, think about 159 00:08:59,448 --> 00:09:03,258 whether we want to go with a PO option or an IV option on discharge. 160 00:09:03,258 --> 00:09:07,428 Because per our guidelines, these are both valid options for her and 161 00:09:07,458 --> 00:09:10,898 in the setting as she's clinically improving during her hospital stay. 162 00:09:11,168 --> 00:09:16,328 And then the other things to kind of think about for this is, um, for 163 00:09:16,328 --> 00:09:19,988 patients who have severe infection under the guideline recommendations, they do 164 00:09:19,988 --> 00:09:26,158 also recommend in addition to starting antibiotics for an obvious infection, 165 00:09:26,338 --> 00:09:31,138 that patients with severe or moderate infections undergo a surgical evaluation, 166 00:09:31,138 --> 00:09:36,268 whether it be urgent and severe infections or, a little bit later out, um, during 167 00:09:36,268 --> 00:09:40,318 a hospital stay if they have a, uh, a moderate in, are more clinically stable. 168 00:09:40,498 --> 00:09:45,098 So she's now hopefully received some level of surgical source control. 169 00:09:45,158 --> 00:09:49,788 Unfortunately, from her case there is some positive bone margins, but based 170 00:09:49,788 --> 00:09:53,028 on that, even within the guidelines, they do have recommendations that 171 00:09:53,028 --> 00:09:56,638 include positive bone margins versus complete or full debridement 172 00:09:56,638 --> 00:09:58,498 with, uh, surgical source control. 173 00:09:58,678 --> 00:10:03,268 And so in a situation like this patient, it's very reasonable because of the fact 174 00:10:03,268 --> 00:10:08,433 that she has concurrent osteomyelitis, even though she did, um, have some 175 00:10:08,433 --> 00:10:12,093 form of surgical source control that we can go ahead and treat her for a 176 00:10:12,093 --> 00:10:15,093 slightly longer course of antibiotics. 177 00:10:15,303 --> 00:10:20,553 Their recommendations within our DFI guidelines are going to be about three 178 00:10:20,553 --> 00:10:25,523 weeks for osteomyelitis with retained infected bone or if she were to have 179 00:10:25,523 --> 00:10:29,713 dead bone or did not have the opportunity to undergo any surgical debridement. 180 00:10:29,773 --> 00:10:34,993 In those instances, we might want to recommend a longer treatment course, 181 00:10:34,993 --> 00:10:36,673 which could be up to six weeks. 182 00:10:36,673 --> 00:10:39,973 But the nice thing about these guideline recommendations is that 183 00:10:39,973 --> 00:10:42,253 does not specify that it has to be iv. 184 00:10:42,433 --> 00:10:45,553 She's somebody that we could reasonably treat with a po 185 00:10:45,773 --> 00:10:50,093 option on hospital discharge if that was clinically indicated. 186 00:10:51,103 --> 00:10:54,133 And then based off of that, I'll go ahead ahead and hand it over to you, 187 00:10:54,133 --> 00:10:55,483 Dr. Spellberg and your thoughts. 188 00:10:56,413 --> 00:11:03,223 So one of the things that, um, the listeners should take away from the 189 00:11:03,793 --> 00:11:09,013 dementia with psychosis that I'm gonna share with you is that I call 190 00:11:09,013 --> 00:11:11,203 them "schmuidelines", not guidelines. 191 00:11:11,953 --> 00:11:20,018 And if you were to take an electron microscope, put an electron microscope 192 00:11:20,108 --> 00:11:22,538 inside the Hubble Space Telescope. 193 00:11:23,138 --> 00:11:26,228 You still couldn't see how much I care what the guidelines say. 194 00:11:26,708 --> 00:11:27,878 It's that small. 195 00:11:28,268 --> 00:11:33,728 It's not quite zero, but it's super close to zero how much I 196 00:11:33,728 --> 00:11:35,708 care what the guidelines say. 197 00:11:36,218 --> 00:11:38,723 'cause what I care about is what the trials say. 198 00:11:40,088 --> 00:11:45,158 Sadly, the  schmuidelines very commonly make recommendations that are either 199 00:11:45,158 --> 00:11:50,498 based on no data or low quality data, or on the level of evidence that I 200 00:11:50,498 --> 00:11:55,868 call the "because we said so" level of evidence, and I don't think that's 201 00:11:55,868 --> 00:11:57,578 how medicine should be practiced. 202 00:11:58,298 --> 00:12:02,678 So I don't care if you call it severe or mild or moderate. 203 00:12:02,678 --> 00:12:04,298 That stuff's all meaningless to me. 204 00:12:04,868 --> 00:12:08,168 The question is, does the patient have bone infection or not? 205 00:12:08,573 --> 00:12:12,653 And the reason that that matters is because there are trials that show 206 00:12:13,013 --> 00:12:16,853 that longer durations of therapy is needed for bone infections 207 00:12:17,063 --> 00:12:18,713 than for non bone infections. 208 00:12:19,013 --> 00:12:22,283 The bone is not involved, we have randomized controlled trials showing that 209 00:12:22,283 --> 00:12:26,033 five to six days is adequate duration of therapy for a soft tissue infection. 210 00:12:27,173 --> 00:12:32,003 Now, interestingly, if bone is involved, the trial situation is more complex. 211 00:12:32,978 --> 00:12:37,538 The largest two randomized control trials that compared duration 212 00:12:37,538 --> 00:12:42,038 of therapy for osteomyelitis compared six versus 12 weeks. 213 00:12:43,148 --> 00:12:45,638 One of those was a diabetic foot infection trial. 214 00:12:45,638 --> 00:12:50,228 The other was a vertebral osteo trial, and both showed six 215 00:12:50,228 --> 00:12:51,878 weeks is as effective as 12. 216 00:12:51,908 --> 00:12:55,508 So we know you don't need to go more than six weeks for an osteo 217 00:12:55,688 --> 00:12:57,488 without prosthetic joint involvement. 218 00:12:58,613 --> 00:13:04,943 There are three smaller trials in the setting of diabetic foot infections 219 00:13:05,333 --> 00:13:09,683 that suggest that three to four weeks may be adequate with debridement. 220 00:13:09,983 --> 00:13:13,133 Those are small, 30 to 40 patient trials. 221 00:13:14,123 --> 00:13:17,753 To me, not quite enough for me to hang my hat on. 222 00:13:17,843 --> 00:13:23,663 I certainly do think it's not crazy to give four weeks, maybe three, but I 223 00:13:23,663 --> 00:13:27,953 would like a larger trial before I sort of moved in that direction personally. 224 00:13:28,823 --> 00:13:31,683 Um, and then there's the question of IV or PO. 225 00:13:31,733 --> 00:13:34,103 So I'm gonna try to make this as simple as I can. 226 00:13:35,603 --> 00:13:40,913 The bacteria don't actually know the route of administration you 227 00:13:40,913 --> 00:13:43,073 use to administer the antibiotic. 228 00:13:43,538 --> 00:13:48,248 It's not like there's bacteria sitting in this poor lady's bone going, well, 229 00:13:48,308 --> 00:13:52,718 normally if there was this much antibiotic around, I'd stop growing and die, 230 00:13:52,988 --> 00:13:54,728 but you gave the antibiotics orally. 231 00:13:54,728 --> 00:13:57,128 So I simply refuse to stop growing and die. 232 00:13:57,428 --> 00:14:00,698 Those little bugs are smart, but they're not that smart. 233 00:14:01,178 --> 00:14:06,428 Okay, so the only question is, well, I'll say the only two questions. 234 00:14:07,598 --> 00:14:12,848 Do we think we can deliver antibiotic into bone at concentrations 235 00:14:12,848 --> 00:14:14,718 necessary to kill bacteria. 236 00:14:15,548 --> 00:14:20,528 And if so, are there clinical data that validate that it works? 237 00:14:20,828 --> 00:14:23,083 And the answer to both of those questions is yes. 238 00:14:24,008 --> 00:14:29,798 There are dozens and dozens of studies where they took patients who had been 239 00:14:29,798 --> 00:14:33,308 given oral antibiotics and an hour or two later got a bone biopsy or an 240 00:14:33,308 --> 00:14:36,878 amputation, and they ground up the bone and measured the antibiotic levels. 241 00:14:37,388 --> 00:14:41,688 Multiple types of antibiotics can get into bone at levels well above 242 00:14:41,758 --> 00:14:45,758 those needed to kill bacteria when the antibiotics were given orally. 243 00:14:46,613 --> 00:14:51,143 And there is an ungodly amount of clinical data now validating that 244 00:14:51,143 --> 00:14:57,293 pharmacological hypothesis, including 10 randomized controlled trials of 245 00:14:57,293 --> 00:15:03,563 osteomyelitis in which IV only therapy was compared to oral transitional therapy. 246 00:15:03,983 --> 00:15:08,003 In the most recent of those trials, there was no IV lead-in. 247 00:15:08,693 --> 00:15:12,143 Patients were randomized to oral therapy on day one. 248 00:15:12,848 --> 00:15:16,718 In other trials, there may have been 3, 4, 5 days or up to 10 days of IV lead-in. 249 00:15:17,708 --> 00:15:20,738 So the bottom line is there's nothing magical about IV antibiotics. 250 00:15:21,188 --> 00:15:25,328 If the patient could go home, send them home on orals and, 251 00:15:25,328 --> 00:15:27,098 and when do you do that? 252 00:15:28,088 --> 00:15:31,058 When they're hemodynamically stable 'cause you ain't discharging the 253 00:15:31,058 --> 00:15:32,738 hemodynamically unstable patient. 254 00:15:33,608 --> 00:15:36,578 It doesn't make sense if you're going to take this person to 255 00:15:36,578 --> 00:15:38,228 the OR, they're gonna be NPO. 256 00:15:38,558 --> 00:15:42,098 What sense does it make to put them on oral therapy and then make them NPO? 257 00:15:42,638 --> 00:15:45,128 So wait until their surgery is done. 258 00:15:45,668 --> 00:15:46,928 Their gut is working. 259 00:15:46,928 --> 00:15:49,328 If they're vomiting, if they're malabsorbing, that's 260 00:15:49,328 --> 00:15:50,678 not gonna make any sense. 261 00:15:51,248 --> 00:15:55,478 If the pathogen is resistant to all oral options, that's not gonna make sense. 262 00:15:56,093 --> 00:16:00,683 And then sadly in the United States, sometimes we can get people housing if 263 00:16:00,683 --> 00:16:05,093 we put them on IV antibiotics 'cause a skilled nursing facility will take them. 264 00:16:05,363 --> 00:16:07,763 For an unhoused person, that might be a big deal. 265 00:16:08,183 --> 00:16:12,173 So you put 'em on oral, when they're stable, they don't need a source 266 00:16:12,173 --> 00:16:16,553 control procedure, the gut is working, you have a viable option that will 267 00:16:16,553 --> 00:16:20,663 kill the bacteria when given orally, and there's no psychosocial or 268 00:16:20,663 --> 00:16:22,553 economic reason to provide IV therapy. 269 00:16:22,823 --> 00:16:25,013 If that's on day zero, do it on day zero. 270 00:16:25,013 --> 00:16:26,428 If it's on day nine, do it on day nine. 271 00:16:27,908 --> 00:16:28,258 Great. 272 00:16:28,703 --> 00:16:31,433 Um, thank you so much Paloma and Dr. Spellberg. 273 00:16:31,913 --> 00:16:34,913 Our next case actually does involve an unhoused patient. 274 00:16:34,913 --> 00:16:38,153 So some of the issues that Dr. Spellberg just brought up, uh, 275 00:16:38,183 --> 00:16:39,683 will likely be relevant for him. 276 00:16:40,133 --> 00:16:45,683 Um, this is a 37-year-old unhoused male who has a history of polysubstance use 277 00:16:45,713 --> 00:16:48,943 and multiple prior hospitalizations for SSTIs (skin-soft tissue infections). 278 00:16:49,503 --> 00:16:53,853 He presented with acute onset joint pain and erythema for about three days 279 00:16:53,853 --> 00:16:55,683 without any history of recent trauma. 280 00:16:56,368 --> 00:16:59,458 His joint was tapped in the ED and showed 53,000 white 281 00:16:59,458 --> 00:17:01,678 blood cells and GPCs on stain. 282 00:17:01,978 --> 00:17:06,208 Blood cultures grew MRSA in four out of four bottles, susceptible to 283 00:17:06,238 --> 00:17:10,648 linezolid, trimethoprim sulfamethoxazole, levofloxacin, and rifampin. 284 00:17:11,248 --> 00:17:15,838 Uh, A TTE showed a 0.8 centimeter vegetation on his native tricuspid valve, 285 00:17:16,168 --> 00:17:18,243 which was confirmed on a subsequent TEE. 286 00:17:19,278 --> 00:17:21,288 He had no heart failure symptoms. 287 00:17:21,318 --> 00:17:25,428 Only moderate regurgitation was visualized on his echoes, so there was no indication 288 00:17:25,428 --> 00:17:27,198 for cardiac surgery in his case. 289 00:17:28,368 --> 00:17:32,328 He endorses alcohol use about three to four beers daily. 290 00:17:32,688 --> 00:17:36,168 Um, occasional cannabis, smoking about once a week, and IV 291 00:17:36,198 --> 00:17:39,108 drug use, most recently, two days before his presentation. 292 00:17:39,778 --> 00:17:42,448 He's not currently employed, but previously worked in construction. 293 00:17:42,868 --> 00:17:44,668 Born and raised near Bakersfield, California. 294 00:17:44,963 --> 00:17:47,093 No recent travel or sick contacts. 295 00:17:47,303 --> 00:17:49,673 He has a pet dog at the encampment where he's living. 296 00:17:49,973 --> 00:17:54,113 No surgical history, no known allergies, and he does not take any medications. 297 00:17:54,753 --> 00:17:57,963 He undergoes washout of the knee with ortho and his blood 298 00:17:57,963 --> 00:17:59,463 cultures clear by day five. 299 00:18:00,033 --> 00:18:02,433 Um, he is seen by addiction medicine while he's in the 300 00:18:02,433 --> 00:18:04,083 hospital and started on methadone. 301 00:18:04,323 --> 00:18:07,683 He's clinically much improved and now would like to leave the hospital. 302 00:18:08,073 --> 00:18:14,523 Um, so I think that this case is example of kind of where we don't have great 303 00:18:14,523 --> 00:18:18,693 guideline recommendations in terms of, you know, consensus of opinion, as Dr. 304 00:18:18,693 --> 00:18:23,493 Spellberg had mentioned, due to a lack of really robust trials and evidence to 305 00:18:23,493 --> 00:18:28,063 help guide us, with some of these more complicated, um, endocarditis cases. 306 00:18:28,273 --> 00:18:32,788 So I'm just, there's a lot to unpack with the, um, AHA 2015 307 00:18:33,118 --> 00:18:34,648 infectious endocarditis guidelines. 308 00:18:34,648 --> 00:18:37,448 So I'm gonna touch upon some of what I think are pertinent guideline 309 00:18:37,448 --> 00:18:41,458 recommendations for a, a more complicated case like this one. 310 00:18:42,038 --> 00:18:44,628 So with this, just a summary statement for this patient. 311 00:18:44,628 --> 00:18:47,958 So we have a 37-year-old male with a history of IV drug use who's 312 00:18:47,958 --> 00:18:50,958 presenting with acute, non-traumatic right knee pain and found to 313 00:18:50,958 --> 00:18:56,718 have right-sided MRSA infectious endocarditis with septic knee arthritis. 314 00:18:57,048 --> 00:19:02,368 What I'm gonna talk about is gonna be focusing on the recommendations for MRSA 315 00:19:02,498 --> 00:19:07,048 endocarditis, but there is a little bit of nuance even within that, which I'm not 316 00:19:07,048 --> 00:19:10,348 gonna get into too much, but I'll at least touch on the, the key points for that. 317 00:19:10,598 --> 00:19:15,308 So for the 2015 AHA Infectious Endocarditis guidelines, they 318 00:19:15,308 --> 00:19:20,433 recommend initial treatment for MRSA infectious endocarditis of using 319 00:19:20,433 --> 00:19:26,443 either, um, IV vancomycin at 15 mgs per kg divided, over Q 12 hours. 320 00:19:26,533 --> 00:19:31,973 Or we have some data that supports the use of daptomycin, typically at higher doses, 321 00:19:31,983 --> 00:19:36,423 usually around eight mgs per kg as a reasonable alternative to, uh, vancomycin. 322 00:19:36,603 --> 00:19:41,543 But the dosing has not been formally parsed out through rigorous studies. 323 00:19:42,016 --> 00:19:45,706 Daptomycin has actually been approved for right-sided endocarditis for 324 00:19:45,706 --> 00:19:50,056 both MSSA and MRSA, but it has not been approved for left-sided 325 00:19:50,106 --> 00:19:52,881 infectious endocarditis, per the FDA. 326 00:19:52,911 --> 00:19:55,641 That being said, this doesn't really apply to this gentleman because 327 00:19:55,641 --> 00:19:57,351 he has a right-sided endocarditis. 328 00:19:57,711 --> 00:20:02,181 The guidelines also do say that for certain patients, you do have to select 329 00:20:02,181 --> 00:20:06,831 for them, but for patients who have uncomplicated right-sided infectious 330 00:20:06,831 --> 00:20:11,556 endocarditis, that does not include MRSA 'cause mrSA is one of their criteria 331 00:20:11,556 --> 00:20:15,286 that they use to define a complicated right-sided infectious endocarditis. 332 00:20:15,346 --> 00:20:19,636 In patients with uncomplicated, there is a decent amount of data 333 00:20:19,636 --> 00:20:24,406 that supports shorter durations of antibiotic courses, sometimes even 334 00:20:24,406 --> 00:20:28,186 as short as two weeks, but typically recommending between two and four weeks. 335 00:20:28,426 --> 00:20:32,836 And there is some data that has been shown over the years, which is not 336 00:20:32,836 --> 00:20:37,606 explicitly commented on in the guideline recommendations themselves, but show that 337 00:20:37,606 --> 00:20:44,911 there is some option for a transition to PO antibiotics for uncomplicated 338 00:20:44,911 --> 00:20:46,831 right-sided infectious endocarditis. 339 00:20:47,041 --> 00:20:51,211 That being said, this patient does not hit those criteria, so, um, 340 00:20:51,271 --> 00:20:53,341 that's not really an option for him. 341 00:20:53,341 --> 00:20:57,181 And IV is going to be kind of our initial starting point for this gentleman. 342 00:20:57,461 --> 00:21:03,576 So in terms of the recommended duration per the AHA guidelines for MRSA 343 00:21:03,596 --> 00:21:07,076 infectious endocarditis, it is variable and it's going to hinge on whether we 344 00:21:07,076 --> 00:21:11,306 think that this is a complicated or an uncomplicated infectious endocarditis. 345 00:21:11,306 --> 00:21:15,026 And so for this gentleman, due to the fact that there is a presumed 346 00:21:15,116 --> 00:21:19,586 metastatic site of infection in that septic arthritis of the knee, that would 347 00:21:19,586 --> 00:21:25,191 qualify him for what we would consider a complicated infectious endocarditis. 348 00:21:25,191 --> 00:21:30,371 And that would warrant at a minimum six weeks of antibiotic treatment, if not 349 00:21:30,371 --> 00:21:35,301 more, depending on the patient's overall clinical response and stability prior 350 00:21:35,331 --> 00:21:37,941 to cessation of antibiotic therapy. 351 00:21:38,361 --> 00:21:40,821 Another thing I think is important to touch on that does get talked about a 352 00:21:40,821 --> 00:21:45,071 little bit in the guidelines, is the use of OPAT for patients like this. 353 00:21:45,071 --> 00:21:50,531 They say that patients who are at low risk for complications of IE, specifically 354 00:21:50,531 --> 00:21:55,151 septic emboli and heart failure, who have, and they specify it, reliable social 355 00:21:55,151 --> 00:21:59,626 and home support, easy access to the hospital should complications arise, the 356 00:21:59,626 --> 00:22:04,156 ability to have regular visits from home infusion nurses and regular clinician 357 00:22:04,156 --> 00:22:06,286 visits to closely monitor clinical status. 358 00:22:06,286 --> 00:22:09,466 These patients should be considered for enrollment in 359 00:22:09,466 --> 00:22:11,356 outpatient antibiotic therapy. 360 00:22:11,746 --> 00:22:15,856 They also don't explicitly comment on this, but patients who do have 361 00:22:15,856 --> 00:22:20,526 a history of IV drug use that is not a contraindication to doing 362 00:22:20,766 --> 00:22:22,876 outpatient therapy for them. 363 00:22:23,056 --> 00:22:27,016 And the guidelines do recommend that patients who do have a history of IV 364 00:22:27,016 --> 00:22:31,366 drug use should be referred to a drug use cessation program, whether it 365 00:22:31,366 --> 00:22:35,386 be addiction medicine and considered for medication assisted therapy. 366 00:22:35,626 --> 00:22:38,746 Um, and on that note, I will hand it over to Dr. Spellberg because I know there's 367 00:22:38,746 --> 00:22:42,586 a lot to unpack with with this one, and I'm sure you have a lot of thoughts on it. 368 00:22:42,952 --> 00:22:47,782 Um, so I neglected to say for the last case, there is one set of guidelines that 369 00:22:47,782 --> 00:22:51,742 I actually believe in 'cause I helped to found the organization that writes 370 00:22:51,742 --> 00:22:53,422 them, and it's called Wiki Guidelines. 371 00:22:53,602 --> 00:22:57,712 And the reason that I like Wiki guidelines is that the charter of the 372 00:22:57,712 --> 00:23:03,457 organization says you can only make a recommendation if there is reproducible 373 00:23:03,457 --> 00:23:08,227 i.e. more than one prospective controlled study that demonstrates the thing 374 00:23:08,227 --> 00:23:12,127 should be done, uh, one of which has to be a randomized controlled trial. 375 00:23:12,127 --> 00:23:16,147 So you only make a recommendation when data demonstrates that it's 376 00:23:16,147 --> 00:23:17,407 known to be the right thing. 377 00:23:18,157 --> 00:23:22,987 In the absence of that level of evidence, what Wiki guidelines do is provide 378 00:23:23,707 --> 00:23:28,387 a clinical review, a discussion of options of pros and cons of various 379 00:23:28,387 --> 00:23:33,517 approaches and overtly highlights disagreements amongst the authors so 380 00:23:33,517 --> 00:23:37,057 that people can see where they fall on the spectrum of, of considerations. 381 00:23:37,057 --> 00:23:42,037 Whereas in most typical guidelines, dissenting opinions are shut down and 382 00:23:42,037 --> 00:23:45,377 everyone pretends that they agree with what's written even when they don't. 383 00:23:46,592 --> 00:23:51,032 The osteomyelitis Wiki guidelines overtly states that oral therapy is fine, 384 00:23:51,032 --> 00:23:55,592 including upfront, which is a direct contradiction to the societal guidelines. 385 00:23:55,922 --> 00:23:59,432 That turns out to be one of only two questions that could be answered by 386 00:23:59,432 --> 00:24:03,427 a clear recommendation because of reproducible randomized controlled trials. 387 00:24:04,417 --> 00:24:07,717 The same thing is true for bacteremia and endocarditis. 388 00:24:07,867 --> 00:24:08,347 Okay? 389 00:24:08,347 --> 00:24:13,147 This idea that you need IV therapy for endocarditis, IV is more powerful. 390 00:24:13,147 --> 00:24:13,747 Woo. 391 00:24:14,227 --> 00:24:16,567 No, that's based on nothing. 392 00:24:16,927 --> 00:24:23,787 Well, it's based on historical case series from the 1940s and 1950s with oral sulfa, 393 00:24:23,787 --> 00:24:28,597 not trimethoprim-sulfamethoxazole, just sulfa, erythromycin or tetracycline. 394 00:24:29,372 --> 00:24:32,732 I mean, come on guys, we gotta do better than that, right? 395 00:24:33,092 --> 00:24:38,852 We have three randomized controlled trials of oral therapy for 396 00:24:38,852 --> 00:24:43,712 endocarditis and a pre-post quasi experimental study from France. 397 00:24:44,102 --> 00:24:49,802 The pre-post quasi experimental study was 170 patients per arm, and it was all 398 00:24:49,802 --> 00:24:52,417 Staph aureus and it was mostly left sided. 399 00:24:53,897 --> 00:24:59,297 So, oh, by the way, the second randomized control trial was the Hopkins trial, 400 00:24:59,597 --> 00:25:04,037 which was all Staph endocarditis and admittedly mostly right-sided, 401 00:25:04,037 --> 00:25:11,627 but all Staph and oral therapy was given upfront on day zero in the ER. 402 00:25:11,657 --> 00:25:13,637 There was no IV lead in. 403 00:25:14,657 --> 00:25:17,807 So let's stop pretending that these guidelines are based on 404 00:25:17,807 --> 00:25:21,557 anything other than the "because we said so" level of evidence. 405 00:25:22,127 --> 00:25:26,327 And actually talk about the trial data of which there is a large 406 00:25:26,327 --> 00:25:28,637 amount at this point, including POET. 407 00:25:28,967 --> 00:25:29,777 But POET. 408 00:25:29,957 --> 00:25:34,727 I like to quote Mr. Spock from Star Trek four, or paraphrase him. 409 00:25:35,147 --> 00:25:38,807 POET is the beginning of wisdom, not the end. 410 00:25:38,987 --> 00:25:43,547 There are two other randomized controlled trials, a quasi experimental study, 411 00:25:43,547 --> 00:25:48,077 and about 20 observational studies, all of which show the same thing. 412 00:25:48,407 --> 00:25:50,837 Oral therapy is just fine. 413 00:25:52,037 --> 00:25:54,767 Just use the right agents for the right duration. 414 00:25:55,037 --> 00:26:00,227 As far as the duration, I find it hard to believe that the patient with 415 00:26:00,227 --> 00:26:03,737 endocarditis from the septic joint doesn't have some osteo in the knee. 416 00:26:04,157 --> 00:26:04,667 I'm sorry. 417 00:26:04,667 --> 00:26:07,487 I'm treating that patient for six weeks 'cause I think they have an osteo. 418 00:26:07,967 --> 00:26:10,127 I don't care about the freaking endocarditis argument. 419 00:26:10,577 --> 00:26:14,987 2, 4, 6. There's an osteo, very likely I would treat for six weeks. 420 00:26:15,377 --> 00:26:21,062 If you could convince me that there wasn't an osteo and you could convince me, there 421 00:26:21,062 --> 00:26:24,782 was no vegetation on the left side, and that would take a lot of convincing. 422 00:26:24,962 --> 00:26:28,832 Okay, maybe I would do four weeks, and that's, again, that's based on, I don't 423 00:26:28,832 --> 00:26:30,272 know, I'm admitting, I don't know. 424 00:26:30,302 --> 00:26:33,362 There's no good trials to show us the duration, so let's 425 00:26:33,362 --> 00:26:34,562 not pretend that there are. 426 00:26:35,222 --> 00:26:37,172 So that's kind of my take on this situation. 427 00:26:37,172 --> 00:26:40,652 I would be perfectly fine with oral therapy as soon as the patient was 428 00:26:40,652 --> 00:26:44,792 hemodynamically stable, we've cleared the blood cultures, their gut is working. 429 00:26:45,002 --> 00:26:47,372 We know we have oral options that will work. 430 00:26:47,912 --> 00:26:49,869 Now is there a reason to put 'em in a SNF (skilled nursing 431 00:26:49,869 --> 00:26:50,792 facility) to get 'em housing? 432 00:26:51,212 --> 00:26:55,172 If they do not, if they're literally gonna go back to the street to a tent 433 00:26:55,802 --> 00:26:57,572 and they say, can you get me housing? 434 00:26:57,752 --> 00:27:00,992 Yeah, I might put 'em on IV so I could get 'em into a SNF and buy 435 00:27:00,992 --> 00:27:03,602 them some time for a social worker to get 'em some interim housing. 436 00:27:04,337 --> 00:27:10,787 But we also have data that patients who are homeless who take oral, oral 437 00:27:10,787 --> 00:27:15,017 options will complete their therapy just as frequently as they will with iv. 438 00:27:15,347 --> 00:27:18,647 Here's the other hilarious misnomer. 439 00:27:19,007 --> 00:27:23,747 When we send people home, quote on IV therapy, a nurse comes to the house 440 00:27:23,747 --> 00:27:25,247 every day to hang the antibiotics. 441 00:27:25,427 --> 00:27:27,017 That does not happen. 442 00:27:27,797 --> 00:27:29,927 They get home health twice a week. 443 00:27:30,377 --> 00:27:32,747 The IV bags are left in the fridge. 444 00:27:33,107 --> 00:27:35,267 The nurse hooks it up, the pump infuses it. 445 00:27:35,267 --> 00:27:39,437 That patient is on their own for three days till they see that nurse again. 446 00:27:39,707 --> 00:27:42,677 They're no more likely to complete that therapy than they would be if you 447 00:27:42,677 --> 00:27:47,267 gave them pills and they won't have a plastic tube in their central vein. 448 00:27:47,867 --> 00:27:53,627 It turns out hominids did not evolve with large plastic tubing in their 449 00:27:53,627 --> 00:27:55,502 central veins for six weeks at a time. 450 00:27:55,852 --> 00:27:56,662 It's dangerous. 451 00:27:56,732 --> 00:27:58,157 Stop doing that to people. 452 00:27:58,997 --> 00:28:00,317 Yeah, so that, those are my thoughts. 453 00:28:01,442 --> 00:28:04,322 All right, our last patient, a little bit of a different case. 454 00:28:04,622 --> 00:28:09,662 Uh, this is a 94-year-old woman with history of hypertension, moderate 455 00:28:09,662 --> 00:28:13,952 dementia in the setting of Alzheimer's, chronic kidney disease, osteoporosis, 456 00:28:13,952 --> 00:28:17,882 and some chronic back pain that's treated with occasional steroid injections. 457 00:28:18,362 --> 00:28:20,732 Uh, she presented with acute on chronic back pain. 458 00:28:21,542 --> 00:28:25,232 Rikers and chills three days after one of those steroid injections. 459 00:28:25,632 --> 00:28:29,022 She was found on MRI to have vertebral osteomyelitis without any 460 00:28:29,022 --> 00:28:32,607 epidural abscess noted at the level of that recent steroid injection. 461 00:28:33,637 --> 00:28:38,347 Her blood cultures grew MSSA in 4 out of 4 bottles on hospital day one. 462 00:28:38,737 --> 00:28:42,307 Uh, it was susceptible to linezolid, vancomycin and clindamycin, but 463 00:28:42,307 --> 00:28:44,227 resistant to levofloxacin, rifampin. 464 00:28:44,867 --> 00:28:48,287 Two out of four bottles remained positive on hospital day three. 465 00:28:48,527 --> 00:28:50,357 Subsequent cultures were negative. 466 00:28:50,837 --> 00:28:55,487 An average quality TTE was equivocal with potential thickening of the mitral valve. 467 00:28:55,817 --> 00:28:59,507 She was considered a poor candidate for TEE based on her age. 468 00:28:59,687 --> 00:29:03,257 In terms of her surgical history, she had two C-sections 60 years ago. 469 00:29:03,287 --> 00:29:06,617 She just takes Tylenol PRN for back pain. 470 00:29:07,127 --> 00:29:09,977 She lives with her adult daughter, who's her primary caretaker. 471 00:29:10,427 --> 00:29:12,077 The daughter also works full-time. 472 00:29:12,717 --> 00:29:14,757 The patient has been retired for many years, but used to be 473 00:29:14,757 --> 00:29:15,657 an elementary school teacher. 474 00:29:16,232 --> 00:29:19,772 She does not use any tobacco, alcohol, or other recreational drugs. 475 00:29:20,222 --> 00:29:23,522 She was born in Taiwan, but has now not left the US in about 30 476 00:29:23,522 --> 00:29:25,017 years, and she has no sick contacts. 477 00:29:26,577 --> 00:29:31,887 All right, so this case is, um, a little bit less of a polarizing case 478 00:29:31,887 --> 00:29:37,557 in terms of guideline recommendations and also the ability to both use 479 00:29:37,557 --> 00:29:41,692 PO antibiotics and when we might want to transition from IV to po. 480 00:29:42,082 --> 00:29:46,672 With this we're gonna be discussing the 2015 IDSA practice guidelines 481 00:29:46,672 --> 00:29:50,452 for the diagnosis and treatment of native vertebral osteomyelitis 482 00:29:50,452 --> 00:29:54,002 that was published in July of 2015. 483 00:29:54,052 --> 00:29:57,892 This one we're gonna give a shout out to one of our home institution 484 00:29:57,892 --> 00:30:02,472 physicians, um, Dr. Holtom, who was a expert panel contributor for 485 00:30:02,522 --> 00:30:03,932 these guideline recommendations. 486 00:30:04,372 --> 00:30:07,742 They address a couple of topics that I think are helpful to touch 487 00:30:07,742 --> 00:30:12,692 on, um, specifically in regards to osteomyelitis and when we should start 488 00:30:12,752 --> 00:30:15,592 or stop empiric antibiotic treatment. 489 00:30:15,802 --> 00:30:19,642 So for one of the questions that gets posed is when to start empiric 490 00:30:19,642 --> 00:30:24,187 antibiotics in patients who are presenting with concern for vertebral osteo. 491 00:30:24,397 --> 00:30:28,837 So these guidelines recommend that if the patient is not acutely ill and 492 00:30:28,837 --> 00:30:32,817 they're clinically stable, they do not have signs of neurologic dysfunction, it 493 00:30:32,817 --> 00:30:37,467 is very reasonable to actually withhold antibiotics pending the ability to 494 00:30:37,467 --> 00:30:42,827 obtain reliable culture data, ideally from something like a bone biopsy to 495 00:30:42,827 --> 00:30:44,567 be able to guide antibiotic treatment. 496 00:30:44,747 --> 00:30:49,017 However, if a patient is sick, they are hemodynamically 497 00:30:49,247 --> 00:30:54,077 unstable, they have evidence of worsening neurologic dysfunction. 498 00:30:54,257 --> 00:30:57,747 In those cases, it's very reasonable to treat upfront with 499 00:30:57,747 --> 00:30:59,307 an empiric antibiotic regimen. 500 00:30:59,527 --> 00:31:03,337 And it's also worth noting that for a lot of these, uh, recommendations, the 501 00:31:03,387 --> 00:31:05,997 evidence supporting the recommendation, as Dr. Spellberg has mentioned, 502 00:31:05,997 --> 00:31:10,387 has actually been fairly low just due to the lack of good randomized 503 00:31:10,387 --> 00:31:11,527 control studies regarding this. 504 00:31:11,867 --> 00:31:16,037 So optimal duration for patients when we're treating them for a, uh, 505 00:31:16,067 --> 00:31:22,337 native vertebral, um, osteomyelitis is going to be six weeks of antibiotics. 506 00:31:22,352 --> 00:31:26,852 But they do leave room for either IV antibiotics or a highly 507 00:31:27,362 --> 00:31:30,002 bioavailable po um, antibiotics. 508 00:31:30,002 --> 00:31:33,812 And this does have a strong recommendation just with low evidence behind it. 509 00:31:34,082 --> 00:31:38,942 They also did touch on, um, when surgery is indicated, and so surgery would 510 00:31:38,942 --> 00:31:42,272 be indicated if there's patients who have a progressive focal neurologic 511 00:31:42,272 --> 00:31:47,132 deficit, they have significant spinal deformity or spinal instability despite 512 00:31:47,132 --> 00:31:50,422 adequate antibiotic treatment, or they have persistent positive blood 513 00:31:50,422 --> 00:31:52,642 cultures without an alternative source. 514 00:31:52,642 --> 00:31:58,402 They also use weakening pain, um, as one of the criteria that you should consider 515 00:31:58,402 --> 00:32:05,687 surgery, but they advise against pursuing further surgical interventions if only 516 00:32:05,687 --> 00:32:10,277 the imaging is worsening, but the patient is continuing to improve clinically. 517 00:32:10,667 --> 00:32:15,767 Um, and then for this patient, for MSSA specific treatment, um, we 518 00:32:15,767 --> 00:32:19,802 would want to talk about what options are available to her, and kind of 519 00:32:19,802 --> 00:32:23,242 like our initial case presentation with our diabetic foot infection, 520 00:32:23,242 --> 00:32:24,682 the world is kind of our oyster. 521 00:32:24,682 --> 00:32:29,062 So, ideally we would like to use either penicillin or cephalosporin, 522 00:32:29,062 --> 00:32:32,842 but then we have a lot of other options as well, including both PO 523 00:32:32,842 --> 00:32:37,762 and IV options that can include the linezolid, levofloxacin plus rifampin. 524 00:32:37,762 --> 00:32:41,422 You can do clindamycin, you could do vancomycin, or you could do dapto. 525 00:32:41,672 --> 00:32:45,392 And then in terms of the guidelines, they don't give a specific recommendation 526 00:32:45,392 --> 00:32:49,952 as to when you can transition from IV to PO therapy, but one thing that they 527 00:32:49,952 --> 00:32:56,127 commented on is that a lot of studies have shown that the kind of average time of 528 00:32:56,127 --> 00:33:01,017 transition of IV to PO therapy is going to be, um, around two and a half weeks. 529 00:33:01,017 --> 00:33:04,877 So it's very reasonable, just like with our diabetic foot infections to 530 00:33:04,877 --> 00:33:09,617 consider, treating patients with po courses of antibiotics being provided 531 00:33:09,617 --> 00:33:14,497 that they're bioavailable to continue, uh, treatment courses for osteomyelitis. 532 00:33:14,707 --> 00:33:17,197 And on that note, I will hand it over to Dr. Spellberg. 533 00:33:18,117 --> 00:33:23,247 So I thank you for giving a shout out to Dr. Holtom, who has been one of my 534 00:33:23,247 --> 00:33:27,657 longest standing colleagues, friends, I mean, we survived COVID together. 535 00:33:27,687 --> 00:33:32,157 Um, he is also a participant in the Wiki guidelines. 536 00:33:32,247 --> 00:33:36,197 And these issues are all discussed in the Wiki guidelines as well. 537 00:33:36,572 --> 00:33:39,872 Both the endocarditis guideline and the osteo guideline. 538 00:33:40,202 --> 00:33:45,132 Um, so let me start with something that's more controversial before 539 00:33:45,342 --> 00:33:51,102 I get to the, to me, very simple question of oral duh, um, which is, 540 00:33:51,102 --> 00:33:52,632 do you need to get a bone biopsy? 541 00:33:52,752 --> 00:33:54,732 'cause everybody's always, you need to get a bone biopsy. 542 00:33:54,852 --> 00:33:57,732 Well, the ID docs are always, you need to get a bone biopsy. 543 00:33:58,422 --> 00:34:00,432 The hospitalists are always like, do we really? 544 00:34:00,762 --> 00:34:03,852 And the IR people are like, I'm not doing a bone biopsy. 545 00:34:04,152 --> 00:34:06,432 And the ID people are, no, you have to do a bone biopsy. 546 00:34:06,432 --> 00:34:09,912 And then you go round and round and round and they argue with each other and 547 00:34:10,032 --> 00:34:11,772 usually you don't get the bone biopsy. 548 00:34:12,372 --> 00:34:16,902 And so if you actually look at the literature, the yield of 549 00:34:16,902 --> 00:34:18,522 a bone biopsy isn't very good. 550 00:34:18,882 --> 00:34:19,932 It's kind of sad. 551 00:34:20,622 --> 00:34:26,357 In best case scenario, you'll get a diagnosis about 50 to 60% of the time. 552 00:34:27,147 --> 00:34:31,317 That's not growth of an organism, that's a histopathological diagnosis. 553 00:34:31,887 --> 00:34:35,367 So you're gonna put somebody through a procedure where they're gonna get 554 00:34:35,367 --> 00:34:38,967 some sedation and they're gonna have a needle stuck into their spine and 555 00:34:38,967 --> 00:34:40,857 half the time it's gonna yield nothing. 556 00:34:41,107 --> 00:34:44,887 Now how does that change management is really the question. 557 00:34:44,887 --> 00:34:50,092 Am I doing this to make myself feel better, in which case my suggestion 558 00:34:50,092 --> 00:34:54,112 is take some inhaled ketamine, do some meditation and relax. 559 00:34:54,262 --> 00:34:54,772 Okay? 560 00:34:55,012 --> 00:34:57,202 'cause you're supposed to treat the patient not yourself. 561 00:34:57,502 --> 00:35:01,192 Or am I doing this because it actually helped this patient get better. 562 00:35:01,792 --> 00:35:05,692 And what I have evolved to over the years is it will help this patient 563 00:35:05,692 --> 00:35:08,482 get better if I really have no idea what's causing the infection. 564 00:35:08,902 --> 00:35:12,292 And sometimes you'll get these people that have had weeks to months of 565 00:35:12,292 --> 00:35:15,972 symptoms and you're like, oh my God, what if it's TB? What if it's cocci 566 00:35:16,282 --> 00:35:19,312 and I put the patient on empiric antibiotics and I'm completely wrong. 567 00:35:20,032 --> 00:35:20,512 Okay. 568 00:35:20,812 --> 00:35:26,152 If it's the last few days worsening back pain, fevers, and you're thinking, 569 00:35:26,152 --> 00:35:32,392 this is bacterial, there's nothing wrong with targ-, starting an empiric therapy 570 00:35:32,902 --> 00:35:34,822 and seeing if the patient improves. 571 00:35:35,092 --> 00:35:39,442 If I put the patient on Bactrim, with or without rifampin or levo, with or 572 00:35:39,442 --> 00:35:44,017 without rifampin, and the next day, their fever that they've had for five straight 573 00:35:44,017 --> 00:35:50,647 days is gone and they're like, geez, my back pain is 50% better overnight. 574 00:35:51,367 --> 00:35:51,877 Okay. 575 00:35:51,937 --> 00:35:54,697 They don't have TB, they don't have cocci, right? 576 00:35:55,027 --> 00:35:59,947 You can use empiric therapy and a response to that therapy if you know what you're 577 00:35:59,947 --> 00:36:04,837 treating, if there are baseline signs and symptoms of infection that you can follow. 578 00:36:06,127 --> 00:36:09,937 They clearly respond, then I've spared them a biopsy. 579 00:36:10,057 --> 00:36:13,417 It's not changing my management and I'm just gonna keep 'em on therapy 580 00:36:13,417 --> 00:36:18,037 and complete a six week course if they don't get better, alright, 581 00:36:18,097 --> 00:36:19,897 do I have the right diagnosis? 582 00:36:20,047 --> 00:36:22,807 And now I really do need to argue for a bone biopsy. 583 00:36:22,807 --> 00:36:28,147 I'm sorry, my IR colleague or my neurosurgeon, this patient is now in 584 00:36:28,147 --> 00:36:31,297 danger of progression 'cause I don't know what they have and my empiric 585 00:36:31,297 --> 00:36:34,987 therapy isn't working and you have a much stronger argument at that point. 586 00:36:35,497 --> 00:36:38,947 So I don't think there's anything wrong in someone where you're highly 587 00:36:38,947 --> 00:36:42,607 suspicious that it's bacterial for picking a reasonable empiric 588 00:36:42,607 --> 00:36:45,607 regimen and seeing if it makes the patient signs and symptoms better. 589 00:36:47,242 --> 00:36:49,732 Once you know the organism, it becomes pretty easy. 590 00:36:49,942 --> 00:36:52,642 Let me pick something that's gonna cover this organism. 591 00:36:52,732 --> 00:36:54,442 Now, levo rif. 592 00:36:54,442 --> 00:36:56,252 There are good data for, for Staph. 593 00:36:56,512 --> 00:36:57,562 You do need both. 594 00:36:57,562 --> 00:36:59,032 I would not trust levo alone. 595 00:36:59,302 --> 00:37:01,702 You'd need both to prevent resistance emergence. 596 00:37:02,122 --> 00:37:04,282 It's resistant, so that's not an option. 597 00:37:04,672 --> 00:37:05,752 Bactrim is an option. 598 00:37:05,752 --> 00:37:08,422 There's very good data for Bactrim and osteomyelitis. 599 00:37:08,782 --> 00:37:11,872 Some of that data is with rifampin, but not all of it. 600 00:37:13,702 --> 00:37:14,182 Um. 601 00:37:14,992 --> 00:37:23,842 There are less data, considerably less data for oral cephalosporins, but I 602 00:37:23,842 --> 00:37:26,912 have become a convert to cefadroxil. 603 00:37:26,932 --> 00:37:31,942 I was very resistant at first, but there are people out there that 604 00:37:31,942 --> 00:37:33,952 just loves them some cefadroxil. 605 00:37:34,507 --> 00:37:37,447 When they start talking to you, they'll Jedi mind trick you, man. 606 00:37:37,447 --> 00:37:39,947 They will make you a believer in the cefadroxil. 607 00:37:39,967 --> 00:37:40,687 You know what I'm saying? 608 00:37:41,407 --> 00:37:46,867 And then you're like, all right, and you wincingly try it and then it works. 609 00:37:46,867 --> 00:37:49,027 And you're like, oh, what was I so scared of? 610 00:37:49,027 --> 00:37:53,287 And so we've accumulated, I would say, probably 20 to 30 patients 611 00:37:53,317 --> 00:37:54,577 at this point at LA General. 612 00:37:54,577 --> 00:37:57,067 And we're actually in the process of gathering those data 613 00:37:57,067 --> 00:37:58,477 up to publish a case series. 614 00:37:58,837 --> 00:38:03,442 There are limited case series available today, but we are have become more 615 00:38:03,442 --> 00:38:08,122 comfortable with cefadroxil for MSSA in bone over the last few years. 616 00:38:08,482 --> 00:38:12,772 I don't think it's a crazy thing to do, and I would suggest that at this 617 00:38:12,772 --> 00:38:15,922 point you have a shared decision making discussion with the patient. 618 00:38:16,552 --> 00:38:18,652 I think we can do this with an oral. 619 00:38:18,802 --> 00:38:20,692 There's less experience with it. 620 00:38:20,962 --> 00:38:25,432 We have more experience with an iv, but the IV is less safe, and you 621 00:38:25,432 --> 00:38:28,792 walk them through the pros and cons and make a shared decision making 622 00:38:28,792 --> 00:38:32,212 decision with them, and that's probably how I would care for this patient. 623 00:38:34,432 --> 00:38:37,672 Okay, so thank you for taking the time to discuss these cases with us. 624 00:38:37,672 --> 00:38:42,652 And the reason why we brought these up, um, is to highlight and touch on the fact 625 00:38:42,652 --> 00:38:47,632 that, one, our guideline recommendations don't always have great guidance for 626 00:38:47,632 --> 00:38:51,082 when we can use oral versus IV options. 627 00:38:51,082 --> 00:38:55,012 And when we are dealing with, especially complex patient populations, much 628 00:38:55,012 --> 00:38:58,102 like what we see at our LA General Medical Center, we frequently have to 629 00:38:58,102 --> 00:39:03,452 meet patients where they are and don't always have the ability to provide 630 00:39:04,242 --> 00:39:09,432 IV antibiotics when patients have, whether social or medical factors 631 00:39:09,492 --> 00:39:11,232 that make it challenging for them. 632 00:39:11,232 --> 00:39:16,062 And in those instances, we do have to get creative and find ways that we can use 633 00:39:16,122 --> 00:39:22,822 good evidence-based data to help provide appropriate patient care and get patients 634 00:39:22,822 --> 00:39:26,182 the treatment that they need for the very complex infections that they have. 635 00:39:26,600 --> 00:39:32,480 So I would just say Paloma for me, um, when I have to get complex 636 00:39:32,480 --> 00:39:37,040 and creative is when I can't use oral because oral is my default. 637 00:39:37,970 --> 00:39:42,710 It is clearly less safe to use IV and from 23 randomized 638 00:39:42,710 --> 00:39:46,340 controlled trials of bacteremia, osteomyelitis, and endocarditis. 639 00:39:46,700 --> 00:39:48,650 Oral is not less effective than iv. 640 00:39:49,340 --> 00:39:52,970 So sometimes you can't use oral, and that's when I start thinking, all right, I 641 00:39:52,970 --> 00:39:54,980 guess I gotta become creative around IVs. 642 00:39:55,790 --> 00:39:57,170 I wanna flip the script. 643 00:39:57,620 --> 00:40:00,200 Oral should be the baseline because it's safer. 644 00:40:00,560 --> 00:40:03,080 And again, we're not here to treat ourselves. 645 00:40:03,260 --> 00:40:05,810 If we wanna treat ourselves, we should take some inhaled 646 00:40:05,810 --> 00:40:08,580 ketamine, do some meditation. 647 00:40:08,870 --> 00:40:13,070 I used to say IM benzo, but that hurts. 648 00:40:13,100 --> 00:40:15,590 So just do the inhaled ketamine instead. 649 00:40:15,680 --> 00:40:17,150 Okay, relax. 650 00:40:17,480 --> 00:40:18,860 We're here to treat this patient. 651 00:40:19,130 --> 00:40:21,980 It's not about our anxiety, it's about what's the safest, 652 00:40:21,980 --> 00:40:22,910 most effective option for them. 653 00:40:27,020 --> 00:40:29,180 Thanks to our guests for joining Febrile today. 654 00:40:29,510 --> 00:40:32,480 Don't forget to check out the website Febrile podcast.com, where 655 00:40:32,480 --> 00:40:35,360 you can find our Consult Notes, which are written supplements of 656 00:40:35,360 --> 00:40:39,370 the episodes of links to references, our library of ID infographics, 657 00:40:39,370 --> 00:40:40,430 and a link to our merch store. 658 00:40:41,200 --> 00:40:44,800 Febrile is produced with support from the Infectious Diseases Society of America. 659 00:40:45,190 --> 00:40:48,100 Please reach out if you have any suggestions for future shows or 660 00:40:48,100 --> 00:40:49,420 wanna be more involved with Febrile. 661 00:40:49,720 --> 00:40:50,470 Thanks for listening. 662 00:40:50,620 --> 00:40:52,120 Stay safe and I'll see you next time.