1 00:00:05,810 --> 00:00:06,569 Hi, everyone. 2 00:00:06,600 --> 00:00:10,680 Welcome to Febrile, a cultured podcast about all things infectious disease. 3 00:00:11,180 --> 00:00:14,919 We use consult questions to dive into ID clinical reasoning, diagnostics, 4 00:00:14,919 --> 00:00:16,530 and antimicrobial management. 5 00:00:16,850 --> 00:00:19,950 I'm Sara Dong, your host and a MedPeds ID doc. 6 00:00:20,200 --> 00:00:23,429 I hope everyone is settling into the new academic year nicely. 7 00:00:23,900 --> 00:00:27,550 I just thought I'd put out a quick call for volunteers message. 8 00:00:28,189 --> 00:00:33,200 As a little reminder, Febrile is a pretty small operation and it is always improved 9 00:00:33,210 --> 00:00:35,640 by our guests who come to talk about ID. 10 00:00:35,770 --> 00:00:38,700 I am looking to highlight people on the show. 11 00:00:38,750 --> 00:00:43,980 I welcome any ideas that you have and I am definitely in need of new cases and topics 12 00:00:43,989 --> 00:00:45,540 for us to cover in the coming months. 13 00:00:45,809 --> 00:00:49,910 It is really just as simple as emailing me at febrilepodcast@gmail.com. 14 00:00:49,929 --> 00:00:54,249 If you want to be on an episode, have a recommendation or another idea, 15 00:00:54,419 --> 00:00:58,149 especially for fellows, trainees and junior faculty, I think this is a really 16 00:00:58,149 --> 00:01:00,079 great way to make your work count twice. 17 00:01:00,129 --> 00:01:04,300 If you have a topic that you've previously presented on and it helps support 18 00:01:04,310 --> 00:01:07,300 Febrile to keep us running , and if you're interested, but you don't have 19 00:01:07,300 --> 00:01:09,219 an idea, I can brainstorm with you. 20 00:01:09,494 --> 00:01:11,514 Thanks for letting me make that little plug. 21 00:01:11,904 --> 00:01:12,255 Okay. 22 00:01:12,255 --> 00:01:13,404 So back to business. 23 00:01:13,424 --> 00:01:16,184 We are here with another Febrile StAR episode. 24 00:01:16,214 --> 00:01:20,204 These feature topics and authors from the CID, Clinical Infectious Diseases 25 00:01:20,204 --> 00:01:21,725 journal, State of the Art Reviews. 26 00:01:21,904 --> 00:01:25,044 We've been spending the past few months getting caught up and still have a few 27 00:01:25,064 --> 00:01:26,905 upcoming episodes, including this one. 28 00:01:27,125 --> 00:01:29,894 Today, we have two guest stars here to discuss multidrug 29 00:01:30,005 --> 00:01:31,714 resistant gram negative infections. 30 00:01:32,649 --> 00:01:33,330 Hello, everyone. 31 00:01:33,350 --> 00:01:34,490 I'm Arsheena Yassin. 32 00:01:34,539 --> 00:01:38,530 I'm an ID pharmacist at the Robert Wood Johnson University Hospital in New 33 00:01:38,530 --> 00:01:41,100 Jersey, and I'm excited to be here today. 34 00:01:41,740 --> 00:01:42,430 Hi, everyone. 35 00:01:42,480 --> 00:01:43,990 My name is Mariya Huralska. 36 00:01:44,010 --> 00:01:48,630 I am an infectious disease fellow at Robert Wood Johnson, 37 00:01:48,630 --> 00:01:50,130 and I work with Arsheena. 38 00:01:50,310 --> 00:01:52,150 I'm also really excited to be here. 39 00:01:52,160 --> 00:01:53,920 I really love the Febrile podcast. 40 00:01:54,620 --> 00:01:58,169 As everyone's favorite cultured podcast, we always start off by asking 41 00:01:58,179 --> 00:02:01,459 if you'd be willing to share a little piece of culture or something that, 42 00:02:01,530 --> 00:02:03,340 uh, brings you joy or happiness. 43 00:02:03,589 --> 00:02:06,910 You know, as the weather is getting warm, I actually saw a lot of sunlight 44 00:02:06,910 --> 00:02:10,169 yesterday, so I'm looking forward to being outside more, but the music 45 00:02:10,169 --> 00:02:14,849 is something that I really enjoy and something that I, you know, listen to 46 00:02:14,849 --> 00:02:18,040 on my downtime, whenever I'm coming home from work or on the weekend. 47 00:02:18,100 --> 00:02:21,579 And I like all types of music, depending upon my mood that day. 48 00:02:22,249 --> 00:02:26,259 Yeah yeah it's nice, well depending on when this gets released, it's 49 00:02:26,779 --> 00:02:30,689 flower blooming season outside, even though it's raining for me today. 50 00:02:31,239 --> 00:02:31,919 It's very nice. 51 00:02:32,789 --> 00:02:35,510 Mariya, what about you? 52 00:02:35,929 --> 00:02:39,119 So one of my favorite shows right now that I'm watching with my mom, it's 53 00:02:39,119 --> 00:02:44,369 called Servant of the People, and it's on Netflix, and it stars President Zelensky 54 00:02:44,399 --> 00:02:49,119 from Ukraine and it's about a teacher who goes on a rant about politics and 55 00:02:49,119 --> 00:02:53,249 corruption and his video goes viral and then he becomes president and then he 56 00:02:53,259 --> 00:02:54,889 actually becomes president in real life. 57 00:02:55,669 --> 00:02:56,499 And I just really love it. 58 00:02:56,499 --> 00:03:01,329 It's a very satirical commentary on the disconnect between corrupt 59 00:03:01,329 --> 00:03:03,964 politicians and the people that they're supposed to be serving. 60 00:03:04,064 --> 00:03:06,394 So I really love it and I highly recommend it. 61 00:03:07,399 --> 00:03:07,779 Nice. 62 00:03:08,569 --> 00:03:15,244 So we're gonna walk through a case that also is featured in the review as well, 63 00:03:15,284 --> 00:03:19,734 but just to talk through some of the key concepts that you covered in the article. 64 00:03:19,804 --> 00:03:22,434 So I'll jump in with our case today. 65 00:03:22,474 --> 00:03:28,044 We have an 82 year old female with hypertension, diabetes, CKD, 66 00:03:28,074 --> 00:03:32,044 and a recent ruptured cerebral aneurysm, status post embolization, 67 00:03:32,044 --> 00:03:33,364 so that was about 2 months ago. 68 00:03:33,984 --> 00:03:37,874 She is transferred from a nursing home to the emergency department due to 69 00:03:37,874 --> 00:03:42,404 hypotension and fevers, as well as one week of coughing and pleuritic pain. 70 00:03:43,104 --> 00:03:47,264 She had received five days of piperacillin tazobactam at the nursing facility 71 00:03:47,294 --> 00:03:49,094 without improvement in her symptoms. 72 00:03:49,234 --> 00:03:53,594 And we'll note that that recent admission related to her cerebral aneurysm, she 73 00:03:53,594 --> 00:03:58,899 was admitted for 10 days in the ICU and was overall in the hospital for 18 days. 74 00:03:59,149 --> 00:04:02,789 And so during this time, she was treated for a ceftriaxone resistant E. 75 00:04:02,789 --> 00:04:06,179 coli UTI with seven days of pip-tazo [piperacillin-tazobactam]. 76 00:04:06,199 --> 00:04:10,799 And then in the interim, she has also had one other reported UTI that was 77 00:04:10,799 --> 00:04:12,669 treated with seven days of levofloxacin. 78 00:04:13,129 --> 00:04:18,240 This time she's dyspnic, she's hypotensive, 80s over 40s, heart 79 00:04:18,240 --> 00:04:21,379 rate's 120 and is febrile to 101. 80 00:04:21,380 --> 00:04:21,390 2. 81 00:04:21,500 --> 00:04:25,329 Her oxygen saturation is 86 percent on room air and she has 82 00:04:25,329 --> 00:04:26,879 crackles at the left lung base. 83 00:04:27,719 --> 00:04:31,939 For a little more objective info, her lab showed a leukocytosis 84 00:04:31,979 --> 00:04:38,409 to 18, lactate of 4, and a serum creatinine of 3 from a baseline of 1. 85 00:04:38,410 --> 00:04:38,489 5. 86 00:04:38,489 --> 00:04:43,219 Her chest x ray demonstrates a dense infiltrate on the left side and she's 87 00:04:43,250 --> 00:04:48,429 continuing to deteriorate and now is intubated and requiring a norepi drip. 88 00:04:49,010 --> 00:04:52,829 Two sets of blood cultures and respiratory cultures are cooking in the lab. 89 00:04:53,750 --> 00:04:58,444 So this is a pretty common scenario, the ICU or ED calls you, they're 90 00:04:58,464 --> 00:05:00,684 asking, what empiric therapy to start. 91 00:05:00,724 --> 00:05:04,344 So I was hoping you could walk us through how to approach this type of case, 92 00:05:04,454 --> 00:05:08,944 and then what gram negative targeted antimicrobial you'd want to start? 93 00:05:09,028 --> 00:05:14,297 For us in ID, it's getting a really good history on our patients is really key 94 00:05:14,297 --> 00:05:18,757 because we're thinking about how to tie this into what pathogens we need to be 95 00:05:18,757 --> 00:05:25,157 concerned about, and also how likely this patient is to have resistant organisms and 96 00:05:25,157 --> 00:05:30,117 then be able to tailor our antimicrobials to the pathogens we are concerned about. 97 00:05:30,167 --> 00:05:34,417 When we are seeing these patients that are coming in, and especially 98 00:05:34,417 --> 00:05:37,747 when you are concerned about resistant gram negatives, is really trying 99 00:05:37,747 --> 00:05:40,157 to see where that patient has been. 100 00:05:40,257 --> 00:05:43,977 So some of this was also presented in the case, but really looking to see 101 00:05:44,517 --> 00:05:49,167 what antibiotics this patient has been exposed to, which facilities and exposure 102 00:05:49,167 --> 00:05:53,807 this patient has had, what infections this patient has, had past micro. 103 00:05:54,200 --> 00:05:59,310 When I'm evaluating a patient that's coming in with a suspected resistant 104 00:05:59,550 --> 00:06:04,390 organism infection, there's a systematic way that I evaluate high 105 00:06:04,390 --> 00:06:06,480 risk risk factors, is what I call them. 106 00:06:06,680 --> 00:06:09,100 So, firstly, where's the patient coming from? 107 00:06:09,100 --> 00:06:12,160 Is the patient coming from the community, meaning from home? 108 00:06:12,575 --> 00:06:16,775 or are they coming from another facility and the facility is also important. 109 00:06:16,815 --> 00:06:19,665 So are they coming from a different hospital and they were only in that 110 00:06:19,675 --> 00:06:23,645 hospital for a couple of days or are they coming from an ICU part of that 111 00:06:23,655 --> 00:06:28,305 hospital where they were already trached or ventilated for a month and now they're 112 00:06:28,305 --> 00:06:30,445 being transferred to your hospital. 113 00:06:30,770 --> 00:06:35,240 Or are they coming from a long term care facility, which that in itself is 114 00:06:35,240 --> 00:06:40,030 a pretty strong risk factor for having a resistant organism, especially if 115 00:06:40,030 --> 00:06:42,590 they have foreign indwelling devices. 116 00:06:42,610 --> 00:06:46,320 So a trach is a big one, chronic indwelling catheters, 117 00:06:46,890 --> 00:06:48,780 long term PICC or midlines. 118 00:06:49,130 --> 00:06:52,530 Those are all risk factors for having resistant organisms, 119 00:06:52,840 --> 00:06:54,120 especially in the bloodstream. 120 00:06:54,270 --> 00:06:58,850 I always review the prior culture results, I usually look about a year out. 121 00:06:58,910 --> 00:07:03,885 You don't have to go a year out, but it is important to look at least within the past 122 00:07:04,295 --> 00:07:09,565 30 days, I would say, to see if they've ever been in that hospital and if they've 123 00:07:09,565 --> 00:07:11,325 ever grown anything resistant in the past. 124 00:07:11,895 --> 00:07:17,185 Now that doesn't mean necessarily if they've grown a resistant organism 125 00:07:17,185 --> 00:07:20,795 in the urine, let's say six months ago, that that is the exact same 126 00:07:20,825 --> 00:07:26,265 organism that is presenting in our patient as a cause of her pneumonia. 127 00:07:26,285 --> 00:07:30,725 However, knowing that this patient has grown a very resistant organism 128 00:07:31,285 --> 00:07:34,195 even in the urine six months ago tells you that this patient is 129 00:07:34,235 --> 00:07:37,805 colonized with this organism or could be colonized with this organism. 130 00:07:38,135 --> 00:07:43,805 And so again might push you into starting broader therapy early. 131 00:07:44,450 --> 00:07:49,060 And lastly, travel history, I think could be an overlooked risk factor, but 132 00:07:49,060 --> 00:07:54,630 it's also really important, especially when we're talking about NDM organisms. 133 00:07:55,150 --> 00:07:58,410 So recent travel to India is a really big risk factor that you 134 00:07:58,410 --> 00:08:01,360 don't want to miss finding out about. 135 00:08:01,790 --> 00:08:07,560 Other MDR Enterobacterales have been observed in southern Asia, South 136 00:08:07,560 --> 00:08:10,530 America, and northern Africa as well. 137 00:08:10,950 --> 00:08:16,160 Getting a good travel history, especially within the past month, I would say, um, 138 00:08:16,360 --> 00:08:21,110 and if that patient is then coming in with a severe infection, you want to know the 139 00:08:21,530 --> 00:08:26,965 epidemiology of the resistant organisms to the relevant country that they've traveled 140 00:08:26,965 --> 00:08:31,695 to because that again may increase your pre test probability of this patient 141 00:08:32,065 --> 00:08:33,825 being sick with something very resistant. 142 00:08:34,565 --> 00:08:39,495 Yeah, and then just piggybacking off of the risk factors, the two that the 143 00:08:39,595 --> 00:08:45,705 IDSA's AMR document really highlights is previous antibiotic exposure and 144 00:08:45,715 --> 00:08:47,755 the past cultures, like Mariya said. 145 00:08:47,805 --> 00:08:51,465 And then there are others that have been studied, such as advanced age, 146 00:08:51,495 --> 00:08:54,945 other comorbidities, such as being immunosuppressed, being bedridden, 147 00:08:55,085 --> 00:08:58,395 et cetera, that may put these patients at high risk for infections. 148 00:08:58,785 --> 00:09:01,945 When you look at the studies that were done to look at which risk 149 00:09:01,945 --> 00:09:06,965 factors we can use to really estimate the probability of a patient having, 150 00:09:07,495 --> 00:09:10,855 whether it be a carbapenem resistant Enterobacterales or a difficult to 151 00:09:10,865 --> 00:09:15,015 treat Pseudomonas, they've all been very different, including various patient 152 00:09:15,015 --> 00:09:17,935 populations, various infection source. 153 00:09:18,035 --> 00:09:21,805 So just being aware of the other risk factors that may play a role 154 00:09:21,815 --> 00:09:24,715 in that patient presenting with drug resistance is important. 155 00:09:25,025 --> 00:09:28,895 Locally at one of my previous hospitals, we really tried to see of the models 156 00:09:28,905 --> 00:09:32,405 that were published, how we can use them in our patient population to 157 00:09:32,405 --> 00:09:36,455 distinguish who will have a carbapenem resistant Enterobacterales or not. 158 00:09:36,895 --> 00:09:40,615 And they really sort of varied in how they were able to predict those 159 00:09:40,615 --> 00:09:42,255 infections in our patient population. 160 00:09:42,373 --> 00:09:45,663 As ID fellows, we're usually the ones kind of seeing the patient first. 161 00:09:45,813 --> 00:09:52,203 So when you're seeing a patient who potentially might have a resistant 162 00:09:52,203 --> 00:09:55,373 gram negative infection, especially based on their history, it's really 163 00:09:55,373 --> 00:09:59,653 important to figure out where their source might be because the source 164 00:09:59,703 --> 00:10:05,588 will then change what antibiotics you use with respect to locations. 165 00:10:05,618 --> 00:10:07,958 For example, if you're thinking that it might be a CNS 166 00:10:08,018 --> 00:10:10,468 infection, you need CNS dosing. 167 00:10:10,818 --> 00:10:14,584 If you're thinking that it might be a GU infection, then you need 168 00:10:14,584 --> 00:10:19,034 an antibiotic that has good renal penetration and so on and so forth. 169 00:10:19,094 --> 00:10:22,014 So in this case, she's coming in dyspneic. 170 00:10:22,024 --> 00:10:25,374 She is hypoxic and eventually becomes intubated. 171 00:10:25,434 --> 00:10:28,684 So I'm thinking that it's probably a respiratory source. 172 00:10:29,554 --> 00:10:30,824 We already have a chest x ray. 173 00:10:30,824 --> 00:10:34,654 We know that she has a left infiltrate, and so she gets intubated. 174 00:10:34,724 --> 00:10:38,294 When you're working someone up, it's always really, really important 175 00:10:38,314 --> 00:10:42,034 to get a good sample from wherever you think the infection is. 176 00:10:42,034 --> 00:10:46,454 So if she's getting intubated and she has a lot of secretions, I would either 177 00:10:46,454 --> 00:10:50,539 hope to get secretions to culture at that time or maybe down the line 178 00:10:50,539 --> 00:10:51,819 when she's a little bit more stable. 179 00:10:52,639 --> 00:10:56,659 We already have a CBC and I would want to get a CMP to look at 180 00:10:56,659 --> 00:10:58,119 her kidney and liver function. 181 00:10:58,249 --> 00:11:04,349 That will be helpful also in the future for antibiotic dosing, Say she has an AKI 182 00:11:04,389 --> 00:11:07,009 or shock liver or something like that. 183 00:11:07,009 --> 00:11:10,009 We would want to know that information for the future. 184 00:11:10,904 --> 00:11:14,844 Lastly, you know, when choosing an empiric antibiotic, especially 185 00:11:14,844 --> 00:11:17,884 when it's broad, you want to look at how sick is the patient. 186 00:11:17,924 --> 00:11:21,624 So, you know, is the patient coming in with a diabetic foot ulcer and 187 00:11:21,624 --> 00:11:25,464 you have some time to think about it and maybe even hold antibiotics 188 00:11:25,514 --> 00:11:27,674 before you can get cultures? 189 00:11:27,744 --> 00:11:32,464 Or in this case, she's coming in very sick, intubated almost right 190 00:11:32,464 --> 00:11:34,424 away, and she started on pressers. 191 00:11:34,554 --> 00:11:37,324 We don't have a lot of margin of error in this case. 192 00:11:37,634 --> 00:11:39,454 We can't afford to be wrong. 193 00:11:39,464 --> 00:11:43,624 And so if I were to have a patient like this where I'm asked what I start, 194 00:11:43,654 --> 00:11:49,164 I would be more inclined to allow myself the freedom to go more broad 195 00:11:49,164 --> 00:11:54,014 because again, we don't have the luxury of being wrong in this situation. 196 00:11:55,034 --> 00:11:59,954 Now, specifically looking at when we're choosing an empiric regimen for 197 00:11:59,954 --> 00:12:03,784 our patients, Where we're concerned about multidrug resistant infections. 198 00:12:04,109 --> 00:12:08,039 Here I'm mainly talking about those gram negative infections where 199 00:12:08,039 --> 00:12:13,349 you have resistance to one or more antibiotics in three or more classes. 200 00:12:13,689 --> 00:12:16,549 When we're thinking about these patients, and as Mariya highlighted 201 00:12:16,599 --> 00:12:20,789 , just looking at these three factors, looking at the local epidemiology, 202 00:12:21,269 --> 00:12:26,199 looking at the patient specific risk factors and then also looking at the 203 00:12:26,259 --> 00:12:28,429 acuity of illness for that patient. 204 00:12:28,529 --> 00:12:32,929 So now I'll go into briefly, just more focusing on the local epi. 205 00:12:33,659 --> 00:12:37,509 So when we're looking particularly at multi drug resistant gram negatives, 206 00:12:37,609 --> 00:12:42,739 resistance really varies locally, globally, even within a hospital. 207 00:12:42,789 --> 00:12:46,429 It's really important when you're looking at your patient, where 208 00:12:46,429 --> 00:12:48,359 did that patient infection start? 209 00:12:48,934 --> 00:12:52,884 Because the way we approach that patient is going to be different from whether 210 00:12:53,104 --> 00:12:57,184 they're coming from the community versus coming from a facility versus 211 00:12:57,234 --> 00:13:01,324 someone that's sick in your ICU or the floors, because again, the resistance 212 00:13:01,344 --> 00:13:05,714 pathogens, the exposure that the patient has really varies from that location. 213 00:13:06,239 --> 00:13:11,019 And one helpful tool that we in ID love to use are our antibiograms. 214 00:13:11,019 --> 00:13:13,079 Most hospital has a local antibiogram. 215 00:13:13,609 --> 00:13:17,649 It's not always easy to get antibiograms from a facility or somewhere else 216 00:13:17,649 --> 00:13:18,879 that the patient's coming from. 217 00:13:19,209 --> 00:13:23,559 And if you're so lucky, you may also have antibiograms that are syndrome 218 00:13:23,559 --> 00:13:25,639 specific or even unit specific. 219 00:13:25,639 --> 00:13:27,869 And all of this information is just very helpful. 220 00:13:28,354 --> 00:13:31,854 Because it sort of gives you an idea as how well your agents 221 00:13:31,924 --> 00:13:34,974 are against that particular pathogen you're concerned about. 222 00:13:35,574 --> 00:13:38,734 So let's say we want to cover for Pseudomonas, for example. 223 00:13:39,444 --> 00:13:44,189 And generally, you're thinking about using your backbone drug, cefepime. 224 00:13:44,699 --> 00:13:48,359 You can look at your antibiogram and say, hey, how well does cefepime cover 225 00:13:48,509 --> 00:13:50,349 this pathogen that I'm concerned about? 226 00:13:51,069 --> 00:13:55,029 And depending upon the susceptibility rates in your antibiograms, you may 227 00:13:55,269 --> 00:13:58,819 lean towards choosing cefepime or using something else, depending upon 228 00:13:58,829 --> 00:14:02,039 that susceptibility rates within your antibiogram, if you're able to 229 00:14:02,039 --> 00:14:03,629 get the nursing home antibiogram. 230 00:14:04,089 --> 00:14:08,049 So this is all just very helpful information for us to use when we're 231 00:14:08,049 --> 00:14:11,779 trying to choose which empiric regimen to use for that particular patient. 232 00:14:12,229 --> 00:14:14,739 Just something to note, depending upon your hospital, and I think 233 00:14:14,739 --> 00:14:17,349 this is probably true for most hospitals here within the U. 234 00:14:17,349 --> 00:14:22,209 S., our antibiograms are almost always outdated. 235 00:14:22,279 --> 00:14:25,889 It's usually based on microbiology results from the year prior. 236 00:14:26,284 --> 00:14:31,694 So, for example, at our hospital, we're now creating our 2023 antibiogram. 237 00:14:32,104 --> 00:14:34,434 It's not the most up to date information. 238 00:14:35,264 --> 00:14:39,124 It's helpful, but it's just really important to be aware of some of these 239 00:14:39,134 --> 00:14:41,184 downsides with using your antibiograms. 240 00:14:41,574 --> 00:14:45,974 Also, another thing is that when you're looking at your antibiograms, you may 241 00:14:45,974 --> 00:14:48,104 have changes in certain breakpoints. 242 00:14:48,114 --> 00:14:53,654 So, the Clinical and Laboratory Standard Institutes, they're normally the ones that 243 00:14:53,654 --> 00:14:57,604 review and set a lot of breakpoints for various antibiotics for various pathogens. 244 00:14:58,289 --> 00:15:02,239 But there's often a lag from when they would suggest breakpoint changes to 245 00:15:02,239 --> 00:15:06,389 when that actually happens in the lab, just updating all of those panels. 246 00:15:06,699 --> 00:15:10,469 So when there are changes in breakpoints, it's just really important to communicate 247 00:15:10,509 --> 00:15:14,339 to your micro lab to come up with a game plan on how to report those 248 00:15:14,339 --> 00:15:18,419 susceptibility results and also how to incorporate that maybe when you're 249 00:15:18,419 --> 00:15:20,149 creating your antibiogram as well. 250 00:15:20,669 --> 00:15:24,139 And just briefly talking about specifically looking 251 00:15:24,139 --> 00:15:25,579 at gram negative infections. 252 00:15:25,709 --> 00:15:26,649 Here within the U. 253 00:15:26,649 --> 00:15:26,919 S. 254 00:15:27,424 --> 00:15:31,674 You know, most of the gram negative resistance that we see, it's 255 00:15:31,704 --> 00:15:34,444 usually, you know, ESBL organisms. 256 00:15:34,564 --> 00:15:39,134 So, 2020 CDC data shows about over 20 percent of hospital E. 257 00:15:39,134 --> 00:15:43,204 coli are resistant to third generation cephalosporin and also Pseudomonas. 258 00:15:43,314 --> 00:15:47,484 Those are, you know, two major pathogens that most hospitals would commonly see. 259 00:15:47,784 --> 00:15:52,914 But when it comes to carbapenem resistant Acinetobacter, or difficult to treat 260 00:15:53,044 --> 00:15:56,894 Pseudomonas, so these are pseudomonal strains that are resistant to most of 261 00:15:56,894 --> 00:16:01,524 the commonly used antibiotics . This is often very rare that we would need to 262 00:16:01,544 --> 00:16:06,344 cover empirically for patients, unless you're in an area where there is a 263 00:16:06,344 --> 00:16:09,514 recent outbreak, for example, maybe a nursing home has a recent outbreak of 264 00:16:09,514 --> 00:16:13,564 one of these pathogens, or even locally as well, or if they're just endemic 265 00:16:13,564 --> 00:16:15,074 to maybe the area that you're in. 266 00:16:15,274 --> 00:16:18,064 So, it's really important just know your local epi and also be 267 00:16:18,064 --> 00:16:21,884 aware of trends that are happening within your community as well. 268 00:16:22,434 --> 00:16:25,604 But most of the time, we usually do not have to cover these agents 269 00:16:25,604 --> 00:16:28,854 empirically, unless you have a really strong suspicion for those pathogens. 270 00:16:29,394 --> 00:16:33,244 But other than that, it's really covering those ESBL organisms, 271 00:16:34,014 --> 00:16:37,444 Pseudomonas, and when it comes to CRE, it really depends upon the 272 00:16:37,444 --> 00:16:38,984 area in the United States you're in. 273 00:16:39,404 --> 00:16:43,404 I know the resistance that we see here in New Jersey may be different from 274 00:16:43,424 --> 00:16:47,464 other places within the country, and then also the various strains within the U. 275 00:16:47,464 --> 00:16:47,644 S. 276 00:16:47,644 --> 00:16:49,234 It's mainly KPC right now. 277 00:16:49,564 --> 00:16:51,804 But they're also, this is really changing as well. 278 00:16:52,414 --> 00:16:56,474 And then also, this sort of ties in especially for your travelers. 279 00:16:57,029 --> 00:17:02,629 So, in our example case, just based on her risk factors and her previous cultures, 280 00:17:02,659 --> 00:17:09,139 we decided to cover for Pseudomonas just because she has previous hospitalization, 281 00:17:09,189 --> 00:17:10,759 a recent past antibiotic use. 282 00:17:11,159 --> 00:17:16,059 Also decided to cover for MRSA just based on those risk factors as well, following 283 00:17:16,059 --> 00:17:18,809 the latest IDSA pneumonia guidelines. 284 00:17:19,859 --> 00:17:24,189 And also because she's coming in pretty sick and has past cultures 285 00:17:24,229 --> 00:17:28,049 with ESBL E coli, it was decided to cover for those as well. 286 00:17:28,649 --> 00:17:32,179 And just based on the antibiogram, the empiric regimen that 287 00:17:32,179 --> 00:17:34,619 was chosen was meropenem. 288 00:17:34,784 --> 00:17:39,064 Based on the antibiotic, we're making sure we're covering for susceptible, usually 289 00:17:39,064 --> 00:17:44,124 susceptible, not difficult to treat Pseudomonas and also that ESBL pathogen. 290 00:17:44,294 --> 00:17:50,314 Vancomycin to cover a risk for MRSA and also just adding on an aminoglycoside 291 00:17:50,574 --> 00:17:55,524 to help increase just based on meropenem susceptibility patterns in the hospital 292 00:17:55,754 --> 00:17:59,464 and in the nursing home to really help expand that gram negative coverage 293 00:17:59,464 --> 00:18:01,334 for better coverage of Pseudomonas. 294 00:18:02,399 --> 00:18:07,899 Now, if for example, we chose not to cover and start this patient out 295 00:18:07,939 --> 00:18:12,199 on one of the the newer agents, and here newer, I'm talking about 296 00:18:12,479 --> 00:18:16,039 agents that we'll generally be using for carbapenem resistant pathogens. 297 00:18:16,689 --> 00:18:20,889 And this is mainly because she did not present with past 298 00:18:20,889 --> 00:18:22,879 cultures for these pathogens. 299 00:18:23,319 --> 00:18:28,069 If for example, she, she did, we had a urine culture with a carbapenem resistant 300 00:18:28,069 --> 00:18:33,779 Enterobacterales or she's coming from a facility that has recent outbreak or, 301 00:18:33,869 --> 00:18:38,179 this is very common within their facility to have patients with these pathogens. 302 00:18:39,009 --> 00:18:43,319 Or she's coming, maybe had a recent travel to an area where these pathogens 303 00:18:43,349 --> 00:18:47,939 are endemic, then we would generally have a much lower threshold to start these 304 00:18:47,999 --> 00:18:52,369 patients on one of the more targeted agents to cover those resistant pathogens. 305 00:18:53,449 --> 00:18:57,409 And Arsheena kind of already touched on this, but let's say I have a septic 306 00:18:57,409 --> 00:19:02,029 patient and she's coming in on pressors. 307 00:19:02,474 --> 00:19:03,574 , is being intubated. 308 00:19:03,944 --> 00:19:07,794 Maybe she's coming in from a long term nursing home facility, 309 00:19:07,844 --> 00:19:11,744 but she has no history of resistant organisms in the past. 310 00:19:11,744 --> 00:19:14,504 I've reviewed her micro cultures, I don't see anything. 311 00:19:14,854 --> 00:19:18,214 Or let's say she's really never even been hospitalized. 312 00:19:18,274 --> 00:19:23,349 I really would not be reaching for the newer agents in this case right away. 313 00:19:23,439 --> 00:19:29,219 I would be relying on my local antibiogram that I always carry in my pocket. 314 00:19:29,559 --> 00:19:33,479 And so in our cases, we have choices of antibiotics that we can 315 00:19:33,479 --> 00:19:37,079 use based on whether the patient is in the ICU or whether the 316 00:19:37,079 --> 00:19:38,849 patient is somewhere on the floor. 317 00:19:38,949 --> 00:19:43,799 So in our case, a patient that's in the ICU that I would like to cover for a 318 00:19:43,819 --> 00:19:50,194 severe infection, I would choose cefepime based on our local antibiogram, . but 319 00:19:50,194 --> 00:19:54,094 I still would like to go broad because of how sick she is, tying it back to 320 00:19:54,104 --> 00:19:57,984 what we talked about before, where the margin of error is small and I 321 00:19:58,204 --> 00:20:00,694 can't afford to guess incorrectly. 322 00:20:01,144 --> 00:20:06,784 Yeah, and, especially in these cases where patients have no real risk factors for 323 00:20:06,784 --> 00:20:11,514 resistant pathogens, it's really helpful to use your local antibiogram to see how 324 00:20:11,514 --> 00:20:13,664 well your backbone therapy is working. 325 00:20:14,304 --> 00:20:17,874 For example, your backbone gram negative is the cefepime for your 326 00:20:17,884 --> 00:20:23,784 hospital, and cefepime covers more than 90 percent of your gram negatives, 327 00:20:23,784 --> 00:20:27,174 including Pseudomonas, depending upon how sick the patient is, you may 328 00:20:27,174 --> 00:20:29,914 be okay with using one agent or not. 329 00:20:30,244 --> 00:20:35,054 But it really depends on the patient as to what margin you're okay with, 330 00:20:35,114 --> 00:20:40,004 but let's say you have maybe cefepime susceptibilities are in the 70s. 331 00:20:40,274 --> 00:20:45,074 That's really when you want to consider adding on a second agent 332 00:20:45,084 --> 00:20:48,814 to really increase that gram negative spectrum for that patient. 333 00:20:48,900 --> 00:20:52,780 And then the opposite spectrum of the scenarios, you have a patient coming 334 00:20:52,780 --> 00:20:57,050 in with, let's say, a diabetic foot ulcer and that ulcer's been there for 335 00:20:57,050 --> 00:21:00,730 many weeks and the only reason the patient's coming in is because his sister 336 00:21:00,730 --> 00:21:02,160 said, you're going to the hospital. 337 00:21:02,670 --> 00:21:07,420 Meaning there weren't any preceding signs of sepsis, the patient wasn't 338 00:21:07,610 --> 00:21:11,320 having chills or rigors at home, there wasn't increased drainage, it's 339 00:21:11,320 --> 00:21:15,690 mainly a just situational admission to the hospital for a long term, 340 00:21:16,075 --> 00:21:20,335 probably diabetic osteomyelitis in a patient who's otherwise stable. 341 00:21:20,725 --> 00:21:25,155 Um, but, I review his cultures and I see that previously he's been admitted 342 00:21:25,155 --> 00:21:29,145 for this ulcer before and he's had debridements before and he actually has 343 00:21:29,145 --> 00:21:30,885 grown carbapenem resistant Klebsiella. 344 00:21:31,775 --> 00:21:34,515 Am I reaching for a newer agent? 345 00:21:35,695 --> 00:21:41,075 Probably not, at least not at this stage, because again, the overarching theme 346 00:21:41,095 --> 00:21:42,625 here is that the patient is stable. 347 00:21:42,705 --> 00:21:46,755 He's not having fevers, he's not having chills, rigors, he's hemodynamically 348 00:21:46,765 --> 00:21:51,695 stable, and I have time to wait until we consult our surgical colleagues 349 00:21:51,725 --> 00:21:54,735 so that they can get us really good specimens, and then we can send that off 350 00:21:54,735 --> 00:21:59,400 to the lab and tailor our antibiotics based on what grows this time. 351 00:21:59,760 --> 00:22:03,790 Um, so I may consider not starting anything despite the fact that 352 00:22:03,790 --> 00:22:07,510 I know that he's grown very resistant organisms in the past. 353 00:22:09,390 --> 00:22:14,530 So, I can briefly talk about optimizing the dosing for patients when we're 354 00:22:14,530 --> 00:22:19,590 looking at Gram negative infections, and, the IDSA's AMR document is a 355 00:22:19,590 --> 00:22:22,950 readlly helpful tool based on the resistance that you're seeing to 356 00:22:22,950 --> 00:22:24,420 help choose the empiric regimen. 357 00:22:24,460 --> 00:22:27,710 And also, it has a helpful table there on how to dose these 358 00:22:27,740 --> 00:22:31,060 antibiotics for the resistant pathogens that you're concerned about. 359 00:22:31,810 --> 00:22:36,470 Now, oftentimes, when we have patients and we're starting them on an antibiotic, 360 00:22:36,470 --> 00:22:38,710 it usually involves beta lactams. 361 00:22:38,950 --> 00:22:43,460 And especially in our very sick patients, really we just want to be careful on 362 00:22:43,460 --> 00:22:47,040 how we're dosing to make sure we're using appropriate dose, especially 363 00:22:47,040 --> 00:22:50,950 in our ICU patients where there may be altered volume distribution, their 364 00:22:50,970 --> 00:22:55,170 clearance may be changing, they may be on continuous renal replacement therapy, etc. 365 00:22:55,170 --> 00:22:58,740 So just taking all of these things into consideration when we're dosing 366 00:22:58,770 --> 00:23:02,260 antibiotics and just making sure that we're using the appropriate dose 367 00:23:02,580 --> 00:23:05,910 for a particular patient based on the pathogen we're concerned about. 368 00:23:06,360 --> 00:23:10,180 Now, oftentimes specifically when we're using beta lactams, we can 369 00:23:10,180 --> 00:23:14,830 either give them intermittent, so for example, infuse over 30 minutes, or we 370 00:23:14,830 --> 00:23:16,670 can give it by a prolonged infusion. 371 00:23:16,860 --> 00:23:21,145 So most of our beta lactams, after you give a dose, you have this high 372 00:23:21,185 --> 00:23:25,615 concentration and peak, and usually with that short half life, you may have 373 00:23:25,895 --> 00:23:31,035 a decrease in concentration eventually leading to concentrations below the MIC 374 00:23:31,035 --> 00:23:35,825 of the pathogen you're concerned about, and this may lead to decreased efficacy 375 00:23:35,825 --> 00:23:40,265 of the drug and even regrowth of those organisms and potential resistance. 376 00:23:41,200 --> 00:23:45,010 If we prolong that infusion of the antibiotics, so giving piperacillin 377 00:23:45,080 --> 00:23:49,080 tazobactam instead of 30 minutes over 4 hours, you're having a more constant 378 00:23:49,080 --> 00:23:53,590 concentration in the blood above the minimum inhibitory concentration, and 379 00:23:53,600 --> 00:23:59,090 really it's a way to help enhance the efficacy of that drug, decreasing the 380 00:23:59,090 --> 00:24:01,960 resistance based on specific parameters. 381 00:24:02,160 --> 00:24:05,260 And this is something, especially when we're looking at resistant gram negatives 382 00:24:05,410 --> 00:24:10,600 that maybe have higher MICs, using this prolonged infusion to really help target 383 00:24:10,700 --> 00:24:13,190 those higher MICs are useful tools. 384 00:24:13,870 --> 00:24:18,050 Now, when it comes to clinical outcomes and use of prolonged infusion antibiotics, 385 00:24:18,560 --> 00:24:22,750 mainly it's been retrospective studies that have shown mortality benefits, 386 00:24:22,800 --> 00:24:26,880 particularly in really sick patients with documented Gram negative bacteremia. 387 00:24:27,420 --> 00:24:31,590 It really has not shown in a lot of more retrospective studies. 388 00:24:32,080 --> 00:24:35,690 But just based on the pharmacokinetic properties of the medications, the 389 00:24:35,690 --> 00:24:39,350 international consensus guidelines on prolonged infusion beta lactams 390 00:24:39,350 --> 00:24:43,840 really recommends using prolonged infusion if possible, especially for 391 00:24:43,840 --> 00:24:47,200 those patients where you're looking at resistant gram negatives, especially 392 00:24:47,200 --> 00:24:48,820 in patients that are critically ill. 393 00:24:49,670 --> 00:24:53,250 Now, for in our example patient, that patient will also be started 394 00:24:53,280 --> 00:24:57,280 on usually vancomycin, as you mentioned, as well as aminoglycoside. 395 00:24:57,880 --> 00:25:01,170 And part of the monitoring for these antibiotics, as a lot of 396 00:25:01,170 --> 00:25:04,860 our pharmacists like, will involve therapeutic drug monitoring. 397 00:25:05,310 --> 00:25:10,080 And this involves measuring a concentration of the drug within the body. 398 00:25:10,685 --> 00:25:14,195 And then being able to really calculate to see if your drug is 399 00:25:14,195 --> 00:25:18,095 reaching its efficacy target and also as a way to help decrease toxicity. 400 00:25:18,725 --> 00:25:21,175 So, very commonly in most hospitals, this is done for 401 00:25:21,185 --> 00:25:22,695 aminoglycosides and vancomycin. 402 00:25:23,075 --> 00:25:27,885 Not really done for beta lactams, but it is done in certain centers within the U. 403 00:25:27,885 --> 00:25:28,085 S. 404 00:25:28,665 --> 00:25:32,545 But I do think if you are using a beta lactam in a patient that's just you know, 405 00:25:32,545 --> 00:25:35,055 their, their clearance may be different. 406 00:25:35,055 --> 00:25:39,525 So patients with extremes of body weight, our CF patients, if your 407 00:25:39,525 --> 00:25:43,425 patients are on ECMO or continuous renal replacement therapy, if your 408 00:25:43,425 --> 00:25:46,565 patients are having side effects from some of these medications, for 409 00:25:46,745 --> 00:25:48,955 example, of neurotoxicity from cefepime. 410 00:25:49,460 --> 00:25:53,310 Or, if you're using, you know, you're stuck using beta lactam for a pathogen 411 00:25:53,320 --> 00:25:57,710 with a higher MIC, this may be an area to incorporate using therapeutic 412 00:25:57,790 --> 00:26:00,630 drug monitoring with our beta lactams to make sure we're reaching our 413 00:26:00,630 --> 00:26:04,290 efficacy and as well as safety targets for those particular antibiotics. 414 00:26:05,210 --> 00:26:07,660 And, we're getting more and more resistant pathogens. 415 00:26:07,670 --> 00:26:11,530 We now have a large amount of various antibiotics to use and which 416 00:26:11,530 --> 00:26:14,560 one to use for certain resistance genes will just become more and 417 00:26:14,560 --> 00:26:16,090 more confusing in the future. 418 00:26:16,510 --> 00:26:20,910 But really just involving an ID or maybe a stewardship specialist within 419 00:26:20,910 --> 00:26:24,440 your hospital to really help guide that we're using these drugs for the 420 00:26:24,460 --> 00:26:28,370 appropriate indication, and we're using it for the appropriate pathogen as well. 421 00:26:28,370 --> 00:26:29,410 That's a great summary. 422 00:26:29,630 --> 00:26:34,120 I mean, I think some of the points that you guys made of general considerations, 423 00:26:34,555 --> 00:26:36,985 are obviously good for this case, but they're probably good for everything in 424 00:26:36,985 --> 00:26:39,705 ID, like what's the source of infection? 425 00:26:39,845 --> 00:26:41,505 What bugs do we think are there? 426 00:26:41,545 --> 00:26:45,365 And like Mariya talked about the consequences if we don't have the 427 00:26:45,375 --> 00:26:48,085 correct combo of antibiotics initially. 428 00:26:48,515 --> 00:26:52,355 So at this point in our case, let's say, we have a working diagnosis 429 00:26:52,365 --> 00:26:53,885 that our patient has a pneumonia. 430 00:26:54,325 --> 00:26:59,235 The patient was empirically placed on vancomycin, meropenem, and tobramycin. 431 00:26:59,705 --> 00:27:04,455 We mentioned some risk factors for MDR gram negative infection, so recent 432 00:27:04,475 --> 00:27:06,895 antibiotic exposure and hospitalization. 433 00:27:07,275 --> 00:27:12,115 And after some chart review, you also learn that she has had previous cultures 434 00:27:12,115 --> 00:27:14,285 or colonization with the likely ESBL E. 435 00:27:14,285 --> 00:27:14,905 coli. 436 00:27:14,955 --> 00:27:18,885 You are lucky enough to get a little bit of information from her local nursing 437 00:27:19,095 --> 00:27:23,825 facility antibiogram, which showed that Pseudomonas susceptibility to meropenem in 438 00:27:23,825 --> 00:27:27,735 the ICU is 75 percent on that antibiogram. 439 00:27:27,965 --> 00:27:32,435 So again, another, another place that we're often called, empiric therapy 440 00:27:32,435 --> 00:27:34,035 has been started in this patient. 441 00:27:34,045 --> 00:27:37,605 You have sort of pending partially returned diagnostic results. 442 00:27:37,655 --> 00:27:41,965 And we are asked to help think about how do we adjust the antibiotic regimen? 443 00:27:42,395 --> 00:27:45,975 Can you talk a little bit about some of the cautions or things 444 00:27:45,975 --> 00:27:50,605 to think about related to sort of traditional testing and whether or 445 00:27:50,605 --> 00:27:54,565 not we may have rapid diagnostics that can help impact our management? 446 00:27:55,380 --> 00:27:59,090 Yeah, I can sort of start here, you know, especially when we're starting 447 00:27:59,130 --> 00:28:00,690 broad antibiotics for our patients. 448 00:28:00,720 --> 00:28:02,590 I'm wearing my stewardship hat right now. 449 00:28:03,060 --> 00:28:08,100 It's really important for us to get additional testing, utilizing 450 00:28:08,110 --> 00:28:10,590 rapid diagnostic testing, if you have that available, so you're 451 00:28:10,610 --> 00:28:12,730 able to get your answers quickly. 452 00:28:13,060 --> 00:28:16,040 And this really allows us to be broad when we need to be broad and then 453 00:28:16,040 --> 00:28:19,970 be able to taper and streamline our antibiotics in a timely manner, 454 00:28:19,970 --> 00:28:23,170 so we're not giving these patients unnecessarily broad antimicrobials. 455 00:28:23,720 --> 00:28:28,410 Now specifically looking at our traditional culture methods, right now, 456 00:28:29,000 --> 00:28:32,630 most laboratories in the United States, if you obtain blood cultures, those blood 457 00:28:32,630 --> 00:28:37,860 cultures will then go to lab, has to be incubated, and then maybe within a couple 458 00:28:37,890 --> 00:28:40,190 hours or a day or so may become positive. 459 00:28:40,200 --> 00:28:44,170 And then, the techs are able to do gram stain results, and you're able to see 460 00:28:44,490 --> 00:28:48,140 the gram stain and be able to tailor results based on the gram stain results, 461 00:28:48,141 --> 00:28:50,040 which are negative or gram positive. 462 00:28:50,335 --> 00:28:55,045 Then, that culture is then plated out and then further incubated for growth. 463 00:28:55,155 --> 00:29:00,235 And once there's growth, usually most laboratories use susceptibility testing 464 00:29:00,235 --> 00:29:05,185 panels such as Phoenix or Microscan to do identification susceptibilities. 465 00:29:06,055 --> 00:29:10,335 Overall, for even a susceptible pathogen, it takes about three 466 00:29:10,335 --> 00:29:12,475 days to get ID and susceptibility. 467 00:29:13,525 --> 00:29:16,005 Now just think about that for resistant pathogens. 468 00:29:16,335 --> 00:29:20,655 It's going to be much longer, especially, for example, if you are treating 469 00:29:20,685 --> 00:29:22,785 a difficult to treat Pseudomonas. 470 00:29:23,225 --> 00:29:26,395 So, on day three, when you have all your results returning, then there's 471 00:29:26,395 --> 00:29:30,375 additional testing that has to be done on other antimicrobials, the newer 472 00:29:30,375 --> 00:29:36,185 antimicrobials, and then that again delays that time to final susceptibility results 473 00:29:36,185 --> 00:29:39,655 and really for us to be able to know if we're treating this patient appropriately. 474 00:29:40,045 --> 00:29:44,165 Now, there have been some panels that are updated with some of the newer agents, so 475 00:29:44,165 --> 00:29:48,145 when I say newer, it's really relative, but more of those agents that we use 476 00:29:48,155 --> 00:29:50,205 for carbapenem resistant gram negatives. 477 00:29:50,315 --> 00:29:55,375 So, some panels include ceftolozane tazobactam, ceftazidime avibactam at 478 00:29:55,375 --> 00:29:58,705 this point, and it's really important to know what your micro lab has. 479 00:29:59,275 --> 00:30:02,276 So when you have a patient that's coming in or you're in a hospital 480 00:30:02,286 --> 00:30:05,716 that sees a lot of resistance, just so you're able to really decrease that 481 00:30:05,716 --> 00:30:08,066 time to final susceptibility results. 482 00:30:08,196 --> 00:30:11,946 For us, we, we do have some cases where we do see quite a 483 00:30:11,946 --> 00:30:13,736 number of resistant pathogens. 484 00:30:13,766 --> 00:30:16,706 So we worked with our micro lab to have reflex testing done. 485 00:30:17,156 --> 00:30:21,466 So if there's a pathogen that tests resistant to particular antimicrobials, 486 00:30:21,896 --> 00:30:26,566 certain antimicrobials are automatically tested without us even having to call the 487 00:30:26,566 --> 00:30:31,846 lab and that just helps us with decreasing our time to final susceptibility 488 00:30:31,846 --> 00:30:35,466 results and hopefully decreasing that time to appropriate antibiotic use. 489 00:30:35,691 --> 00:30:39,031 And then to expand a little bit more on what Arsheena said, so she talked 490 00:30:39,041 --> 00:30:45,101 about traditional culture testing and rapid diagnostics is a way that we can 491 00:30:45,151 --> 00:30:51,421 test for possibly resistant organisms and then can get resistance patterns 492 00:30:51,521 --> 00:30:55,511 in these organisms a lot quicker than traditional culture methods. 493 00:30:55,621 --> 00:31:00,421 Like Arsheena said, with culturing, it might take 24, 48 hours or longer 494 00:31:00,481 --> 00:31:05,891 to grow an organism, but with rapid diagnostics such as Accelerate Pheno or 495 00:31:05,901 --> 00:31:11,961 Maldi TOF or Varigene for Gram Positives, we can get those results much quicker. 496 00:31:11,961 --> 00:31:13,261 So one to eight hours. 497 00:31:13,371 --> 00:31:19,101 Our lab, we can get the identification of an organism within three hours, and 498 00:31:19,151 --> 00:31:22,996 we're usually expecting to get some kind of susceptibility results, at least 499 00:31:23,016 --> 00:31:25,076 the earliest ones, within six hours. 500 00:31:25,096 --> 00:31:28,056 So much quicker than with traditional culture results. 501 00:31:28,256 --> 00:31:31,816 And so in these cases where patients are coming in septic, very sick, 502 00:31:31,836 --> 00:31:37,506 intubated, and we're concerned for septic shock, losing time is detrimental, 503 00:31:37,506 --> 00:31:40,736 waiting for cultures to grow, especially if you don't know how broad 504 00:31:40,896 --> 00:31:42,946 you should go with your antibiotics. 505 00:31:43,226 --> 00:31:48,066 So from the infectious disease fellow standpoint, I'm already 506 00:31:48,066 --> 00:31:51,076 calling the micro lab pretty much as soon as I see the patient. 507 00:31:51,076 --> 00:31:54,036 And firstly, I'm telling them, Hey, I have a concern for a 508 00:31:54,036 --> 00:31:55,806 multi drug resistant organism. 509 00:31:55,836 --> 00:32:01,586 Could you please, in addition to the early susceptibility antibiotics on the 510 00:32:01,586 --> 00:32:06,236 standard panel, could you also please add the newer agent as well so that I'm not 511 00:32:06,266 --> 00:32:10,986 losing time waiting for them to then add it on once it does come back resistant. 512 00:32:11,456 --> 00:32:15,676 Yeah, and luckily for us, we have a lot of rapid diagnostic tools that we're 513 00:32:15,676 --> 00:32:19,346 able to use for our patients, and I think this is just going to be more 514 00:32:19,346 --> 00:32:24,166 and more common as we're seeing more resistant pathogens and using more of 515 00:32:24,186 --> 00:32:29,996 these tools, I think it's really important to tie these results with some sort 516 00:32:29,996 --> 00:32:32,736 of ID or stewardship feedback as well. 517 00:32:33,186 --> 00:32:36,706 It's very difficult for frontline providers to understand the 518 00:32:36,716 --> 00:32:40,106 results of these rapid diagnostic tools and how to use them. 519 00:32:40,106 --> 00:32:44,766 So, for example, we have CARBA 5 that's being done for patients where 520 00:32:44,766 --> 00:32:46,626 isolates test carbapenem resistant. 521 00:32:46,956 --> 00:32:53,176 As you can tell, if something comes back, OXA positive, the primary team usually, 522 00:32:53,536 --> 00:32:57,356 they don't understand how they should be tailoring regimens for these patients. 523 00:32:58,021 --> 00:33:01,961 So currently, at our institution, when these results are positive, the 524 00:33:02,001 --> 00:33:05,251 ID stewardship team, the ID fellows are made aware, and we sort of have 525 00:33:05,251 --> 00:33:10,151 a schedule to call the team and make them aware to adjust antimicrobials. 526 00:33:10,531 --> 00:33:14,251 So we're really utilizing the rapid diagnostic tools to decrease that 527 00:33:14,251 --> 00:33:16,041 time to appropriate antibiotics. 528 00:33:16,051 --> 00:33:18,901 And I know like multiple studies that have been done in the past, 529 00:33:19,171 --> 00:33:24,381 really showing mortality benefits in using these tools in this way. 530 00:33:24,871 --> 00:33:28,681 And it's also important when we talk about resistant gram negatives, how to 531 00:33:28,681 --> 00:33:35,146 interpret an ESBL pattern in a isolate of E.coli that is ceftriaxone resistant or 532 00:33:35,216 --> 00:33:38,026 pathogens with inducible AmpC resistance. 533 00:33:38,026 --> 00:33:42,256 Because again, it's, it's something that may be familiar to us in ID, but 534 00:33:42,616 --> 00:33:46,966 the teams will you know, not aware of what the meaning of these and usually 535 00:33:46,976 --> 00:33:50,261 choose something that says susceptible on the panel that's being released. 536 00:33:50,643 --> 00:33:55,113 Later in that day, after antibiotics have been started, we learned that the blood 537 00:33:55,113 --> 00:33:59,433 cultures have returned positive for gram negative bacilli in two of two sets. 538 00:33:59,896 --> 00:34:04,886 The rapid diagnostic results one hour after this showed Klebsiella 539 00:34:04,886 --> 00:34:06,716 pneumoniae with the KPC gene detected. 540 00:34:06,756 --> 00:34:09,976 So the patient was adjusted to meropenem vaborbactam. 541 00:34:10,606 --> 00:34:14,016 So, about two days after this, the susceptibility results confirmed the 542 00:34:14,016 --> 00:34:18,066 organism was resistant to standard antimicrobials, including meropenem, 543 00:34:18,376 --> 00:34:23,246 but susceptible to tobramycin based on updated CLSI breakpoints. 544 00:34:23,246 --> 00:34:27,006 Reflex susceptibility testing was done due to the resistant meropenem 545 00:34:27,036 --> 00:34:31,631 result and showed us susceptibility to ceftazidime avibactam, imipenem 546 00:34:31,631 --> 00:34:34,251 relebactam, and meropenem vaborbactam. 547 00:34:34,371 --> 00:34:38,671 And in addition to these, our respiratory cultures also did show a carbapenem 548 00:34:38,721 --> 00:34:40,201 resistant Kleb pneumoniae as well. 549 00:34:40,251 --> 00:34:42,071 The patient has defervesced. 550 00:34:42,341 --> 00:34:45,711 They are extubated over the course of the next 72 hours. 551 00:34:45,771 --> 00:34:49,871 And so now we are being asked, well, what should we do for a duration of therapy? 552 00:34:50,646 --> 00:34:54,946 Okay, so I can I can get started on kind of monitoring the patient first. 553 00:34:55,256 --> 00:35:00,436 Well, when we start the broad spectrum antibiotic, so mero-vabor in this case, 554 00:35:00,886 --> 00:35:05,896 we always want to make sure that we monitor and see signs of improvement 555 00:35:05,956 --> 00:35:08,106 as in most infectious diseases. 556 00:35:08,136 --> 00:35:11,396 So in her case, her fever curve improved and most importantly, 557 00:35:11,396 --> 00:35:13,066 she was able to be extubated. 558 00:35:13,186 --> 00:35:17,486 So, in our case, we picked the site of infection correctly. 559 00:35:17,766 --> 00:35:20,631 We picked the right antibiotic and very quickly she was 560 00:35:20,631 --> 00:35:21,951 able to come off of the vent. 561 00:35:22,031 --> 00:35:25,771 However in other cases, especially in let's say intra abdominal 562 00:35:25,771 --> 00:35:30,561 infections, which become a lot more complicated situations where duration 563 00:35:30,561 --> 00:35:34,791 of therapy is not defined and it's really dependent on source control. 564 00:35:35,041 --> 00:35:39,131 In those instances and or in cases where patients are intubated on top 565 00:35:39,131 --> 00:35:43,161 of that and can't tell you any signs and symptoms, you're stuck kind of 566 00:35:43,161 --> 00:35:48,231 monitoring things like, again, fever curve, but also sometimes lactate 567 00:35:48,261 --> 00:35:49,911 and procalcitonin can be helpful. 568 00:35:49,911 --> 00:35:53,331 Although those markers can be a little bit controversial and they're more 569 00:35:53,371 --> 00:35:56,271 taken in the context of the patient. 570 00:35:56,641 --> 00:36:01,931 So in this case, she's getting better and duration of therapy. 571 00:36:02,281 --> 00:36:07,586 It's important to understand that with resistant gram negatives, IDSA 572 00:36:07,616 --> 00:36:12,546 does not recommend extending duration of therapy just based on the fact 573 00:36:12,546 --> 00:36:14,226 that the organism is resistant. 574 00:36:14,316 --> 00:36:18,216 What's most important in terms of duration is, is the patient getting 575 00:36:18,226 --> 00:36:23,156 better, and is the patient responding to the antibiotic that we've chosen. 576 00:36:23,681 --> 00:36:28,641 Another key part of your review and really all of these state of the art reviews 577 00:36:28,641 --> 00:36:35,601 that I wanted us to end on is how to use multidisciplinary approaches to not 578 00:36:35,601 --> 00:36:39,971 only manage patients in the hospital, but also to help ensure they have a safe 579 00:36:39,971 --> 00:36:41,791 transition to the outpatient setting. 580 00:36:42,426 --> 00:36:46,296 So in our example in this case, the patient is ready for 581 00:36:46,296 --> 00:36:47,886 discharge back to her facility. 582 00:36:47,896 --> 00:36:51,826 It's about hospital day five, but you get a call that the facility 583 00:36:51,856 --> 00:36:54,426 does not have meropenem vaborbactam. 584 00:36:54,426 --> 00:36:55,816 They're not sure if they can get it. 585 00:36:56,196 --> 00:37:00,786 So maybe as you talk about how you might handle the situation, you could 586 00:37:00,786 --> 00:37:05,636 give us some insight into who is part of this multidisciplinary team that 587 00:37:05,636 --> 00:37:10,226 is trying to help the patient get to a safe discharge from the hospital. 588 00:37:11,416 --> 00:37:16,196 So from the clinical side, when we've said as consultants, okay, we would 589 00:37:16,196 --> 00:37:21,076 like for this patient to go on this newer agent, probably the very first 590 00:37:21,076 --> 00:37:25,886 people that we're consulting is, of course, case management, and I mean, 591 00:37:25,886 --> 00:37:29,906 we always have our ID pharmacist on board with us, but I think those two 592 00:37:29,906 --> 00:37:34,866 people early in the discharge process are really important because, you have 593 00:37:34,866 --> 00:37:39,336 to make sure that the place that you're sending this patient to on this newer 594 00:37:39,336 --> 00:37:45,191 agent or any really broad agent spectrum agent is available at the facility. 595 00:37:45,481 --> 00:37:50,141 And so the social worker and the case manager, and in some cases, ID 596 00:37:50,141 --> 00:37:53,701 pharmacist can help ensure that when the patient gets to the facility, 597 00:37:53,951 --> 00:37:57,691 there is no delay in treatment because the antibiotic is or isn't available. 598 00:37:58,061 --> 00:38:03,411 Additionally, we always want to send patients on an antibiotic that is 599 00:38:03,411 --> 00:38:05,311 given the least amount of times. 600 00:38:05,761 --> 00:38:10,481 If anybody's had to take antibiotics multiple times a day can appreciate that, 601 00:38:11,251 --> 00:38:15,111 in theory, it doesn't sound like a big deal, but in practice, it can be very 602 00:38:15,111 --> 00:38:19,251 challenging, especially for patients who already have other comorbidities going on. 603 00:38:19,671 --> 00:38:23,391 So we really try to minimize the amount of times that the patient 604 00:38:23,441 --> 00:38:25,111 receives the antibiotic per day. 605 00:38:25,151 --> 00:38:27,961 Less frequent dosings are favorable. 606 00:38:28,221 --> 00:38:32,651 There are studies that have found that OPAT regimens that are dosed once or twice 607 00:38:32,701 --> 00:38:37,881 daily are closely associated with better adherence, than more frequent regimens. 608 00:38:38,541 --> 00:38:44,641 And then, of course, whenever possible, we always try to consider oral agents. 609 00:38:44,971 --> 00:38:51,911 Now, in very resistant organisms, that's almost never an option, but if we can, 610 00:38:52,021 --> 00:38:57,491 we always consider sending the patient on an oral agent to minimize complications 611 00:38:57,921 --> 00:39:02,841 from PICC lines or midlines that may further downline cause more infections. 612 00:39:02,841 --> 00:39:06,651 Yeah, just just piggybacking off of the multidisciplinary team it's 613 00:39:06,661 --> 00:39:11,191 really important to get ID involved, especially early in these cases 614 00:39:11,191 --> 00:39:15,341 to really see and help determine the duration of antibiotics. 615 00:39:15,351 --> 00:39:21,416 So, does that patient really need an additional 7 days of these agents outside 616 00:39:21,426 --> 00:39:25,116 at a hospital and really determine what the correct duration is and if 617 00:39:25,116 --> 00:39:26,856 those patients can switch to oral. 618 00:39:27,376 --> 00:39:31,566 And then also to, especially if you're going to be on, for example, 6 weeks 619 00:39:31,566 --> 00:39:35,856 of antibiotics after discharge, really making sure that we have the appropriate 620 00:39:35,856 --> 00:39:40,186 labs are done and someone is following that patient outside to make sure 621 00:39:40,186 --> 00:39:43,366 that you're having no toxicity and you're having clinical improvements. 622 00:39:44,356 --> 00:39:48,446 And, the usual monitoring, especially for most antibiotics 623 00:39:48,446 --> 00:39:51,296 is usually weekly CBC and CMP. 624 00:39:51,296 --> 00:39:55,666 if you're giving maybe vancomycin, also therapeutic drug monitoring is needed. 625 00:39:56,056 --> 00:40:00,431 So, I really think it's key to, to really have a broad team involved 626 00:40:00,431 --> 00:40:02,661 when discharging these patients to make sure all of that is 627 00:40:02,661 --> 00:40:04,681 really communicated on discharge. 628 00:40:05,251 --> 00:40:09,671 And other members, if you have these in your hospital are OPAT liaisons, 629 00:40:10,001 --> 00:40:13,521 your transition to care pharmacist that can work magic to help you get 630 00:40:13,521 --> 00:40:16,741 some of these antimicrobials that you really need for your patients 631 00:40:17,361 --> 00:40:19,371 at home, or even at a facility. 632 00:40:20,256 --> 00:40:26,716 Looking at various formulary options, and again, just involving case management, 633 00:40:26,716 --> 00:40:30,466 social work, and also the bedside nurse is going to be the one that's educating 634 00:40:30,466 --> 00:40:35,186 that patient and their family member on how to, if it's an IV antibiotic, how 635 00:40:35,186 --> 00:40:38,046 to administer that antibiotic, because most of the time, if they're going 636 00:40:38,056 --> 00:40:41,846 home, they'll likely be administering those antimicrobials themselves. 637 00:40:42,606 --> 00:40:45,436 When we do have these patients admitted to the hospital, I do 638 00:40:45,466 --> 00:40:48,616 think this multidisciplinary approach also holds through. 639 00:40:49,266 --> 00:40:54,346 So when we have these patients, especially that have these resistant pathogens and 640 00:40:54,396 --> 00:41:00,226 intra abdominal infection, it's really important to get a multidisciplinary team 641 00:41:00,226 --> 00:41:04,916 to really help ensure you have source control, because especially when we're 642 00:41:04,926 --> 00:41:10,766 reaching for, agents such as, ceftazidime avbactam, the more likely that patient 643 00:41:10,766 --> 00:41:13,786 still has that remaining source, the more likely that patient is going to develop 644 00:41:13,796 --> 00:41:15,896 further and further resistance later on. 645 00:41:15,906 --> 00:41:19,216 So I think just having that multidisciplinary approach involving 646 00:41:19,606 --> 00:41:24,356 key stakeholders, that's important for that patient care, helping appropriate 647 00:41:24,811 --> 00:41:31,161 antibiotic use in the hospital, appropriate source control if needed, and 648 00:41:31,161 --> 00:41:33,091 then appropriate discharge is really key. 649 00:41:34,126 --> 00:41:37,306 I want to add to what Arsheena just mentioned. 650 00:41:37,366 --> 00:41:42,336 So, source control, especially in situations where source 651 00:41:42,336 --> 00:41:43,756 control may never be achieved. 652 00:41:43,856 --> 00:41:49,296 So, a good example is in a patient who has an LVAD infection, and that LVAD is a, is 653 00:41:49,356 --> 00:41:55,621 destination therapy, and has, let's say, a drive live infection with an organism like 654 00:41:55,621 --> 00:42:01,321 Pseudomonas, where the more antibiotics you give this patient, the more 655 00:42:01,321 --> 00:42:03,151 resistant the Pseudomonas will become. 656 00:42:03,571 --> 00:42:06,541 So, I think it's really important to start planning early in these 657 00:42:06,561 --> 00:42:10,961 kinds of situations where source control is, may not be feasible. 658 00:42:10,971 --> 00:42:16,501 What, what will be the plan once that Pseudomonas becomes so resistant 659 00:42:16,541 --> 00:42:18,501 where there are no options available. 660 00:42:19,266 --> 00:42:22,966 And, of course, involving the patient as well and making the patient 661 00:42:22,966 --> 00:42:27,671 understand, there may come a time where we may run out of antibiotics. 662 00:42:28,221 --> 00:42:31,991 And so these are one of the times where you want to involve the patient, the 663 00:42:32,001 --> 00:42:37,871 surgeon, ID, the pharmacist, so that we have a plan for when that time arrives. 664 00:42:38,896 --> 00:42:39,276 Awesome. 665 00:42:40,096 --> 00:42:43,196 And then I just want to open it up just to see if there's any other 666 00:42:43,196 --> 00:42:44,896 closing thoughts that you guys have. 667 00:42:45,306 --> 00:42:48,976 Thank you so much , it's a huge topic that we can't always condense 668 00:42:48,976 --> 00:42:52,766 into these episodes, but I think you've given people really valuable 669 00:42:53,126 --> 00:42:54,646 initial steps to get started. 670 00:42:55,546 --> 00:42:59,776 So closing thoughts would be that treating multi drug resistant gram 671 00:42:59,776 --> 00:43:04,016 negative infections is certainly challenging, but it's exciting that 672 00:43:04,056 --> 00:43:06,096 we have new agents that we can use. 673 00:43:06,136 --> 00:43:11,966 It's encouraging, but I think it's really important to understand the 674 00:43:11,966 --> 00:43:14,356 appropriate time of when to use them. 675 00:43:14,746 --> 00:43:18,346 , it's really important to understand that just because these newer agents 676 00:43:18,426 --> 00:43:22,936 are novel, we shouldn't be afraid to use them, especially if we have 677 00:43:22,936 --> 00:43:27,236 strong risk factors, strong indications to reach for them, and especially 678 00:43:27,236 --> 00:43:28,856 if the patient is very, very sick. 679 00:43:29,296 --> 00:43:32,016 So don't be afraid of them, but also use them thoughtfully. 680 00:43:32,941 --> 00:43:36,161 And just adding to what Mariya said, just really considering the whole 681 00:43:36,161 --> 00:43:43,441 patient, their risk factors, how ill they are, your local epi, to really 682 00:43:43,441 --> 00:43:46,811 determine which one of these agents to start, because now we have several. 683 00:43:47,191 --> 00:43:50,141 And then also really utilizing, I think, rapid diagnostic testing 684 00:43:50,141 --> 00:43:53,951 has really changed how we will be approaching these patients. 685 00:43:53,981 --> 00:43:56,411 Really just taking advantage of those. 686 00:43:56,776 --> 00:44:01,716 If you have them to really be able to modify therapy in an appropriate manner 687 00:44:01,726 --> 00:44:05,806 based on the resistance, based on the results . And then also just adding the 688 00:44:05,806 --> 00:44:09,526 duration should really just focus on the clinical improvement, how that patient is 689 00:44:09,526 --> 00:44:15,066 doing versus just maybe this is resistant pathogen, we need to treat them longer. 690 00:44:15,716 --> 00:44:20,306 And then also just involving a multidisciplinary team, and be 691 00:44:20,306 --> 00:44:24,186 able to facilitate those patients leaving the hospital safely and 692 00:44:24,186 --> 00:44:27,546 hopefully being able to prevent them from having further readmissions. 693 00:44:28,416 --> 00:44:32,276 And just closing thoughts, this was an exciting article that we 694 00:44:32,276 --> 00:44:34,036 did with some amazing co authors. 695 00:44:34,036 --> 00:44:35,406 I just wanted to give them a shout out. 696 00:44:35,406 --> 00:44:38,326 So shout out to co authors, Drs. 697 00:44:38,326 --> 00:44:42,866 Jason Pogue, Deepali Dixit, Robert Sawyer, and Dr. 698 00:44:42,866 --> 00:44:43,446 Keith Kaye. 699 00:44:45,196 --> 00:44:47,666 Thanks to Arsheena and Mariya for joining today. 700 00:44:47,706 --> 00:44:51,016 You can find their article linked in the episode description and Consult Notes 701 00:44:51,016 --> 00:44:55,726 from CID entitled State of the Management of Infections Caused by Multidrug 702 00:44:55,726 --> 00:44:57,526 Resistant Gram Negative Organisms. 703 00:44:57,966 --> 00:45:00,146 Don't forget to check out the website, febrilepodcast. 704 00:45:00,146 --> 00:45:03,276 com, where you'll find the Consult Notes, which are written complements to 705 00:45:03,276 --> 00:45:06,736 the episodes with links to references, our library of ID infographics, 706 00:45:06,876 --> 00:45:08,126 and a link to our merch store. 707 00:45:08,826 --> 00:45:12,556 Febrile is produced with support from the Infectious Diseases Society of America. 708 00:45:12,726 --> 00:45:15,576 Please reach out if you have any suggestions for future shows or want 709 00:45:15,576 --> 00:45:16,886 to be more involved with Febrile. 710 00:45:17,246 --> 00:45:18,076 Thanks for listening. 711 00:45:18,296 --> 00:45:19,716 Stay safe and I'll see you next time.