Thank you guys for coming, and hopefully more will straggle in, and we can do some voting. And welcome, and thank you for braving it here on a beautiful day in Hawaii in the afternoon. So this is always when the winds come up. So the surf is different, so you can come in here and get some rapid fire cases. So today we're gonna talk about clinical challenges with patients with both HAP and VAP, and hopefully over the next 60 minutes we'll present a couple different cases. So the idea is we'll present a case, have a couple difficult questions associated with the case, let you guys vote and give some input, and then we'll hear from our esteemed panel who I'll introduce in a second. And then you guys hopefully can come up as well and have a discussion at the microphone, so we'll keep this as interactive as humanly possible. Our hope is to get through about three cases, and just know that our questions here really don't have a right answer. They're kind of designed to not have a right answer, and get some opinion, see some of the differences we have in how we practice medicine across different specialties. But ideally we're gonna hit, at least for the most part, empirically-targeted antimicrobial therapy. We'll look a little bit on diagnostic issues and treatment decisions based on those issues, and then some of the differences in the HAP-VAP treatment guidelines as well. So we'll introduce everybody, I'll do it briefly, but they're welcome to give more when they speak. So Christina Crothers is coming from the University of Washington and the VA Health System. Barbara Jones from the University of Utah. Charles de la Cruz from the University of Pittsburgh, and I'm Christian Sandrock from the University of California. None of us have, or none of you have disclosures, I assume. The only disclosure I will say is I was involved in a number of different antimicrobials in the clinical trial portion and drug development portion, or drug and safety monitoring for a few of these, whether it was Shinogi, Pfizer, AbbVie, and a few others. So that's the main thing. So I'll bring this up now. So if you guys have your phones out, we'll spend a second here. So I know we've gotten pretty good with the polling side of things, and you can work on getting some of that polling done. Each of the questions, just so you know, as we go through them, the QR code will pop up as well in our discussion, but you can start here with the QR code as well. So, okay. So first case, which we will torture you with. So 73-year-old gentleman who's currently in hospital day 21 and has 50% total surface area burns when he was working with a little bit of methamphetamines in his trailer, and they caught on fire, and subsequently now has these burns. Been in the ICU for a while in the burn unit. He has an endotracheal tube in place, so they haven't quite moved to a tracheostomy. Is on a cyst control, mechanical ventilation, volume cycled in general, and doing quite well on that. Of course, had acute kidney injury with his original burn, and subsequently is on renal replacement therapy. We'll say it is sled for now. And as usual, is on rounds a few hours before rounds. Everything seems to happen at around 3 a.m., whether it's increased somnolence or fevers or whatever it might be. But at about 3 a.m., develops a fever to 38 degrees Celsius, or 38.6 Celsius. RT in nursing reports some thick copious secretions. There's a little bit of hypoxemia and an increase in oxygenation needs, so the FiO2 is bumped upwards. An ET aspirate is obtained, and we can talk about whether you like your ET aspirates or not that far along. But ends up having three plus PMNs, three plus gram-negative rods. He started meropenem and tobramycin for therapy. And we're gonna just, I'll put a plug in for good stewardship. So whoever the doctor was on this case, noticed no gram positives on the gram stain. He used the gram stain old school and didn't start vancomycin, which is nice. Culture grew acinetobacter baumannii, and unfortunately it's resistant to most of the major classes. So beta-lactam such as, advanced beta-lactam such as piperacillin, cephalosporins, including cefepime, and ceftaz, carbapenems, such as meropenem, imipenem, and so forth, and the four quinolones. So again, a highly resistant gram-negative acinetobacter. And here's the X-ray, which you can see as well, showing just kind of a patchy infiltrate, nothing too terrible, and pretty normal of what we would see in the ICU in general. And, oh, I went ahead a little too fast, I'm so sorry. Hopefully we'll get there. We'll see this question, ah, here we go. So you're now faced with a carbapenem-resistant acinetobacter baumannii, or what we would call CRAB, ventilator-associated pneumonia. So which of the following therapies would you initiate? And I realize many of you may choose different therapies than are listed up here, so we're just kinda getting a few in place. But essentially, you can see some colistin, some fidericol, C is arabicycline, and D is sulbactam-durlabactam, which is a newer antimicrobial, if you're familiar with that. So we'll get a couple votes in here and see where you guys are at. And hopefully then we'll hear from our lovely panel, see what they think, and if you guys have other questions, we can come up along those lines. So, all right, getting pretty good with 11 votes. That's about where we're at, or 12 in general. So hopefully if I hit the next one, it'll show it. Okay, so about 46% colistin, a little bit of fidericol, a little bit of arabicycline, and then 23% sulbactam-durlabactam or SOLDER. Oh, pretty nice, that's higher than I expected for SOLDER. So interesting, okay, so perfect. So with that being said, I'll look to our lovely panel and see any thoughts you guys have. If you had a carbapenem-resistant acinetobacter in your ICU or ventilator-associated pneumonia, any differences you'd try, anything you'd start with? Well, I guess my thinking in this case, I did vote for colistin. I think I was thinking that he didn't sound all that sick. I don't know how he has changed clinically. I didn't hear that he was hypotensive, and there was this little bump in his oxygenation, and he had this endotracheal aspirate, so I'm like, does he really have a resistant acinetobacter pneumonia? And so it would be great to know if there was any quantitative cultures and how he's clinically doing, but thinking that I was gonna reserve sort of some of these more novel antibiotics in case that he was, start with sort of a more first-line, second-line therapy, and reserve some of these more newer antibiotics in case he really deteriorates again. So that was sort of my thought process, I think, but also wondering about maybe adding potentially often we think about covering with a second agent. Yeah, I mean, I think based on our experience, mostly with what we use, I also pick colistin, because we have more experience in our institution with it with regards to sort of breakthrough cases like this initially. And that was what I voted too, but my first reaction to this question was, oh my God, I'm gonna call ID and talk to my pharmacist and talk to my infection control colleagues, because this is the kind of decision that just shouldn't be made individually. This is definitely a team effort. This came from somewhere. Everyone needs to know about it and have a collaborative approach, and it really does depend on your local kind of ecology. So that was my first reaction to the question. Yeah, and I would say actually that I wouldn't even have to call ID. They would have auto-consulted. Yeah. As part of their antibiotics stewardship program. Yeah, and I think you can see already, at least probably the same for you guys at your institution. So if I recall, and definitely Solder, those two would automatically, there are automatic ID consults at our facility, not even just an approval. ID's gonna be seeing them, so I think that would get you there. And I think that highlights the point. You know, we have a lot of decisions, and I think you hear from the panel. One is how sick is this person, right? So if they're really sick, do we really have to use, I'll use an ID term that's not awesome, but the bigger guns or the things that are sort of in reservation that we have for later down the line, is that much more appropriate? Do we use something that's an antimicrobial, but we're pretty familiar with like colistin, and if things don't quite turn around, we can always move on to something else, or do we start and hit them a little bit harder and more appropriately, particularly when they're relatively stable, right? Very often we're gonna see patients in rounds, increased oxygenation needs, increased secretions and so forth that sort of drive that. So I think you can sort of mention that. Anybody, while we're here, anybody from the audience have any comments? We can either microphone or yell if you want. This is my joy from being from New Jersey originally. Yelling is kind of part of our cultural experience, so feel free to yell if you want. But anybody else do something different? I know we have, not everybody has arabicycline, some places have tygocycline. Some may choose not to treat at all in these cases, which I know has happened in the past. A lot of bronchial hygiene and hypertonic saline and so forth. So anything different? Okay, all right, perfect. So we'll see, we'll hop on to the next one here, which hopefully is good. So the second question, we're gonna go a little bit differently. And by the way, when we talk about sofideracol, or excuse me, when we talk about colistin, it's very interesting. You know, obviously we're here in Hawaii, which is really hard to miss, but if we're to go all the way halfway around the world and visit Europe, colistin has a much stronger presence than it certainly does here in the use for ventilator-associated pneumonia. And one of the agents up there, cellbactam, duralobactam was recently, their study was published a few months ago. The FDA gave approval. Their actual control arm had colistin as the mainstay of therapy with a carbapenem. So it's interesting because there is no standard of care for CRAB and what combination we have, so colistin plays a big role in many facilities as you saw. So kind of the point of highlighting that, which is great. So all right, so let's assume, we'll go different. Let's assume that ID came by and they said, you know what, we're gonna start sofideracol. We're not gonna listen to your colistin recommendations as a group, we're gonna start some sofideracol. So would any of you do dual therapy? So based on, as Dr. Carthers mentioned, kind of stable, a little bit increased oxygenation needs, not too sick. This is an ET aspirate, so not a BAL or not a deep airway sample with quantitative cultures. Would you actually, would any of you do dual therapy? So we'll see and vote what you guys think. This is always a lot harder. I'm curious to see what you guys pick for this. All right, so we'll hop ahead. Okay, one more second. Ah, see, the numbers are going up. This count is kind of like, you know, the step count on your phone. You want it to keep going higher, but at some point you have to give up. So, which is there, all right, 17, perfect. Okay, so let's see. All right, so almost split evenly. Okay, interesting. So I'd love to hear more. So would any of you guys try dual therapy at your institutions? Would you wait and see how sick they were? Yeah, because I think he, this person also was on trobomycin, so I'm not sure, you know, whether there's sort of a failure with growing the crab. So, you know, likely we won't get approval for a second agent. We might bag one and then keep the other like trobomycin to add on this. Okay, so kind of start with one, if not getting better or not clinical improvement after a day or two, transition to two. Okay. Yeah, well, actually, I mean, I was looking at some of the IDSA guidelines in this and they have like these updated sort of, it's really like expert opinion statements, but they do recommend dual therapy. Like if you're going to, if you're going to commit to treating it and say it's the pathogen that's causing the pneumonia, they do recommend dual treatment. So, and one of their first line sort of dual agents that they would use with all of them is ampicillin and sulbactam because of the sulbactam component. So, but that doesn't, that's not sort of consistently recommended certainly in the ATS IDSA sort of HAPVAP guidelines or if you look on up-to-date. Yeah, yeah, okay, yeah. And I selected yes also, although severity of illness really plays into this. And so this would again be a collaborative discussion with the infectious disease folks at my community. Okay, well, that's good. We have actually, we'll get to the other therapies and patient worsening, which is good. So I think that's, I mean, it's great. You heard the highlight here, which is really that guidelines are somewhat inconsistent, right? So the IDSA guidelines, which were updated, I think the most recent update was in April of this year, right, in 23, something along those lines. So in April 23, sort of recommending dual therapy for Acinetobacter, even in their recommendations, they said there is no standard, there is no right way for VAP, but dual therapy is probably recommended, but the ampicillin and sulbactam should be one of the mainstays in many of those cases. But the second agent, if you do a dual therapy, can be widely used. But it's kind of that full commitment, right? If you think this is an infection, you're gonna treat it accordingly and go both ways. We don't see that across all the guidelines. So I think that's a nice highlight. Would anybody do anything different? I have one question. Oh, perfect. Last time, when I worked with Epidermco, they almost have a heart attack. Yeah. Because of the data that shows they had a link to a higher mortality, and then they say, well, we're very concerned that you might end up killing the patient instead of really helping the patient. What would be your call for this study? Yeah, so what Marcos is mentioning was a study that was credible CR that was predominantly a European-based study that looked at patients with all coming infections, but there was definitely bloodstream infections, HAP-VAP, that had a higher mortality in the cephideropal arm when compared to others. And when you looked at the subset of those with acinetobacter, that's where the mortality difference arose. And that was compared to best available therapy, which was often two or three drugs, including colistin and carbapenem in both. So any thoughts for you guys with that data? This would not be an antibiotic that would be offered in my community. I mean, I think it's hard to know because I think those numbers were quite small in that study. So is it a chance finding or is it true? I think we need more data, but there is that warning now, so. Yeah, yeah, it was interesting. For the US, it wasn't part of their approval process. So it's in the safety data analysis. In Europe, it was part of the approval process. So they don't recommend it for bloodstream infections, which is very interesting. But in ID week last year, and there were a couple open label and mostly open label studies, not retrospective studies, looking at acinetobacter and that outcome difference that they saw in the credible study was not there. So you often see the IDSA making some recommendations that if they're not hypotensive and unstable, it might work. So this is the challenge we often have. So Marcos raises a good point. You may actually see ID having a heart attack or pharmacy having a heart attack. And this is besides price, which is the usual way they have chest pain. It's usually with price, but it may not be priced this time. So, okay, all right, interesting. So, all right, cool. And that's why, thank you for picking that up. I kind of forgot, but I picked Sofitopal for that reason, the controversy over the credible CR. So that helps a bit. All right, so the next one is, if you said yes to dual therapy, which are half of you, or let's just say all of us are saying it, what would you initiate as your second agent, right? So if you, let's assume you don't have Calistin on board, would you do Calistin second? Or if you already had Calistin, what else would you use? And Dr. Crowther's kind of gave a little bit of a hint. That's the- Yeah, because it wasn't moving. It wasn't moving. What's that? Yeah, yeah. Maybe. It might've not been. I might've changed that. Ha, ha, ha. And again, no right answers here, which is the, it's kind of like my daughter asking me questions about her homework. There's never a right answer. Okay, perfect. All right, so let's see what we got here. Okay, oh, a nice mix, okay. So at least a third of you going with the Ampsol-Baptam, which is interesting. All right, any, and we can just open this up. It was really the discussion of dual therapy in VAP or in HapVap. Is there any, when we look at Acinetobacter, we sort of talked about Calistin being the main, maybe a good cornerstone in someone who's not too unstable. Is there any other agents you would, combinations you guys like in particular for Acinetobacter? Or is it more, again, I know it's a group discussion with ID and others, but. Yeah, I mean, I think Tigecycline would have been a, like, or a Minocycline, or Tigecycline would have been another alternative sort of second agent or another therapy. And I think there was a recent study with Solbactam, Thrombactam also showing benefit in, I forget what it was called, in Acinetobacter pneumonia. So I think all of these are potential viable options. Yeah, yeah, and I've seen some people do combinations, which make sure which backbone they use, right? Either Calistin or one of the Bactams, plus something else, if so, depending on what's available and. Yeah, our, my community Minocycline is one of our cornerstones with the Episil and Solbactam. Perfect, okay, all right. Anybody else do anything different out there? Brave enough to come to the microphone? Which is good argument. Yeah. Yeah, so what would you, so the hard part is, again, with Acinetobacter, right? If you look up there, AMP Solbactam, so AMP obviously doesn't have activity against Acinetobacter, but Solbactam does, and it's variable. And to get just Solbactam susceptibilities, most micro labs don't have it. So Solbactam, Duralobactam, which is a newer agent that just came out, that was the ATT&CK study, which actually showed a mortality benefit, although Colistin was the, it was both arms had imipenem, but Colistin was the other agent in the control arm. That showed a mortality benefit, but only about 60 some odd patients. That one is actually interesting, but there is no really good susceptibility testing, and there's some discs that are coming out. Tygocycline, I know Tygocycline, Ravacycline, Minocycline, we do get some on that, which is great. And then the MIC testing for Colistin, I guess we could say is, what, troubling at best, in many cases for these agents. So that's the part that's often hard, is we have to get advanced testing, and that may take us outwards of, I don't know, what does it take at your institution? Probably for us, about six days. If we, because we'll have our first panel, we'll come, that's about three days, and then another two plus days for a panel to come out. So by then, we've often made the decision clinically. So hard question, but I would say, let's say it's Minocycline-susceptible, and we think most of the isolates in the institution are Solbactam-susceptible, so. So that would pretty much leave everything kind of still open, but it's a good point. This is the hard part, is if we have an MIC, and we know it's low, that's really great, but often we don't have those MICs available. So, okay, perfect. Here's the next question. So now this, we kind of got to this question in our discussion panel, but we'll see if, and we've highlighted this already, so this may be a very quick one. So the patient's showing signs of distributive shock, so now unstable, right? So we have one where it's just increased oxygenation, secretions, fever. Now we're actually saying they're unstable. So lower MAP, minimally responsive to fluids, lactate's bumped upwards, right? So is there any agent in cornerstone of therapy that you would use or not use for that matter? So, and we kind of highlighted this as well. So if you recall, Marcus kind of made some good points about why we might avoid that one. And then certainly Ampsolbactam, we talked about the Tigacycline, the Ravacycline, and the Colistin. So is there any, if you're thinking bacteremia, bloodstream infection, is there anything you guys definitely want to have as one agent for sure? And again, we'll assume we don't have susceptibilities just to make it easier or more torturous. So we're good in there, so. OK. Yeah, interesting. Tygocycline, Amstel-Bactam. OK. So this one is an interesting one, which is good. You guys actually had a little bit more of a discussion. You guys have any thoughts about the results? And we talked about the Amstel-Bactam, right? So that one being one of the mainstays in the IDSA guidelines suggesting it, although others do not. Anything else? Well, I mean, I guess I was thinking I already had him on colistin and Amstel-Bactam, and he's getting worse. Yeah, exactly. I kind of didn't highlight that. If he's getting worse, I think you're kind of done. Since I didn't want my pharmacist to have a heart attack, I chose Tygocycline. Yeah. Which is always a bit harder, so. But I don't know. I guess the question would be, if this was the initial presentation, like, what was your first choice? Yeah, and that's probably, I probably didn't word the question perfectly. So I would say, if we assume it's the initial presentation, yes. Yeah, I mean, I think it's interesting if you look in the IDSA guidelines, and there are a lot of differences. A lot of the pharmacy guidelines, as well, pharmacists take Tygocycline or Ravacycline, and surprisingly, it's not cost. It's very often, you know, those agents tend to move out of the bloodstream into the tissues. So you often have one or two log higher tissue concentrations than bloodstream concentrations, which is why, in theory, the cyclines, Tygocycline, Ravacycline, and Minocycline are not preferred for bloodstream infections. Now, do we have clinical outcome to say that's a problem? Not necessarily, right? So the pharmacy guidelines will stay away from that. The IDSA guidelines really want Amisulbactam, and high dose is a cornerstone. And then you'll see some of the European guidelines where Colistin should always be used. So again, it's just this mismatch, which is hard. But I think you raise a good point. If we're starting from complete scratch, we're not failing current therapy, including Amisulbactam, usually the IDSA guidelines will recommend Amisulbactam, but we haven't really gotten there with other ones, as well. And I think this is our last question. I'll be done torturing you after this, I promise. So, and we'll look at the time. So let's assume the patient never really got to that point of hypotension and so forth. But they're on day eight, and like most of our patients, they're back to baseline. Everything is great. I know there'll be some pro cons in the ensuing days about Procalcitonin. And this patient is on renal replacement therapy, so we'd probably get yelled at if we got a Procal at our institution. But we got one anyway, and it returns at 0.5, so nice and low. The CRP is nice and low. So what would you guys do next? Would you continue therapy for a total of 14 days? Continue therapy for a total of 10 days, just stop at day eight, because they've gotten better? Or would you just repeat cultures and you use your cultures to terminate therapy? So clearance, which this is, again, probably more of a pharmacy stewardship question, but the guidelines say one thing. Our general bedside practice is often very different. Let's say I've already been improved at day eight, so yeah, all right, so perfect. So most people, about half of you would terminate therapy, which is great. It's an antimicrobial steward, that we love to see, so that's perfect. Even though they recommend, you know, sometimes therapy, even dual therapy for upwards of 14 days. In the older guidelines, many of us, Pseudomonas, Acinetobacter, and others are stopping early, but I'd love to see how are you guys practicing at your facility. Would you continue, stop? What would you guys think? Yeah, usually we would stop. I mean, assuming that they didn't go through the hypotension episode. If they did, then you may have to reconsider what were the antimicrobial coverage to lead them to get better from that standpoint. So if it didn't go through that, then I think eight days would be more than enough, given all those clinical findings. Yeah, I mean, I think generally for HAP and VAP, sort of a seven-day treatment course is sufficient, particularly showing, find the clinical improvement, and as Charles pointed out. So for you guys, regardless of organism, seven to eight days, that feels pretty comfortable. If improvement, no hypotension. Yeah, I think sometimes Pseudomonas still raises some questions, some discussion about whether it needs longer. Okay. And I would say the same. I have an aggressive antibiotic stewardship setting, so they wouldn't let me do 14 days, probably. But one thing I would be really clear about is what the radiograph looks like, if there's any necrosis, and then also if they're mobilizing. So on top of all the antibiotics we're talking about today, there are reasons that people get bad. And I want to identify those reasons and then try to reverse the patients, kind of really restore their lung health. And that includes getting them out of bed, doing chest mobilization. So that would be a real cornerstone at this point, making sure that the environment that allowed that infection to develop was actually restored to more lung health. Okay. Perfect. So what we're saying is there should be a choice E, which is fire the current administration and get one in place that will provide funding for physical therapy and all the things we need in the ICU, which I think would be really helpful for most of us. So perfect. All right. Any other? So this is probably, I think this is the end of case one. Any other issues? You guys have any questions? If there's an audience about case one? That's right at the, yeah. Actually, I'll let you guys answer, pro cal. Yeah, it's at the border, I think, right? So you want to see a much lower one. So I'm assuming that it was higher before. Yeah, I didn't actually give you where it was, but it's right at the cutoff. For us, 0.5 is right on the bridge of normal, not normal. Usually, it's so minimally elevated. I don't know. For us, we don't get super excited. If it came back 12, we'd be like, okay, now we have a problem. And especially with sort of the clinical improvement, so yeah. Anybody else do anything different? Any other questions? Okay, good. All right, we'll get away from the torture of Acinetobacter. Maybe we start with the bad case first. This is why it's good. Can I ask a question? Yeah. So next week, the patient feels bad again. What happens? Yeah. Did you stop doing everything, or did you not do it? Not for a year or whatever with a very highly resistant body? So what do you guys think? Say a week later, the cycle repeats itself. Febrile, new infiltrate, leukocytosis. What would you guys think? I mean, I guess it's thinking about do we have source control? Is there sort of some kind of something that's seeded that maybe is ongoing? Are they continuing to have poor lung health? They haven't been mobilized. I mean, I think he had a trach, right? So he's going to kind of be persistently having a risk. So I think I'd be worried that is this recrudescence of Acinetobacter? It could be something else. So I think you also have to do the broad search for infections elsewhere and other causes of fever as well and not just assume it's the same thing. Dr. Jones, you had mentioned looking for the root cause, right? So how do you do that in your hospital? So I think I'm even getting back to Marcos' question. Like if it happens, right? And we were sort of taught they're like, I guess, never events. But in our reality, they're definitely events. How do you guys go through that for a bedside patient? That is a great question. So I'm at the VA. And so we have a pretty standardized infection control program across all VAs. And it's a reportable event. That is something that we report to the NHSN. It's taken really seriously. And one of the things we always go through is whether people are actually following the VAP prophylaxis bundle. One of the things I feel like personally I see a lot that we are not doing is keeping the head of the bed at 30 degrees and constantly going back in and putting the place in. And then just getting the patient really good mobility. And there's also an oral care element. There's questions about that. How much oral care is the right amount? And how much does it actually prevent HAP and VAP? But some form of following that VAP bundle definitely is associated with that prevention. So that is kind of what we're doing at our institution. And really looking for the underlying structural issues that are lending the patient. In addition to the trach, does that patient need more aggressive airway clearance? That's another thing I see a lot of is airway clearance sometimes falls off. There are a lot of barriers to implementation of really good airway clearance. One respiratory therapist takes a vacation and then we forget that the airway clearance is important. And so that's something that I as an attending feel like I'm kind of constantly a little champion of airway clearance. And this usually triggers infection control too. Depending on if this patient has this multidrug resistant organism, our infection control folks and ID folks would be interested to find out are there other cases? How did they get there? Because of the patient's exposure that led to that. Now that we're in Hawaii, we have all the beautiful little food trucks around, little shave ice trucks. We actually have an infection prevention truck sitting in our burn unit because they pretty much are there all the time for these problems. So that's exactly right. So in the interest of time, we'll try to get these last two a little bit shorter. But hopefully they won't be as annoying, so to speak. All right, this is case two. 54-year-old gentleman has a traumatic brain injury. Otherwise pretty straightforward. Has a GCS at three, EBD in place, intubated inside the neurointensive care unit. It's only hospital day six, so pretty early in their neurohospital course. They develop a fever, right lower lobe infiltrate, increased secretions. BAL is performed in this case. And you can see the gram stain there is sort of a mixed picture. Some gram-positive cocci, gram-negative bacilli, and gram-negative rods along with some PMNs. It is sent for molecular testing, which we can talk about in a second, which is great. Admission MRSA screening, just so you guys know, a few days ago was negative. And the results from the molecular testing show Klebsiella aerogenes, which actually is carrying three different resistance. A CTX, which is basically an ambler class A. An NDM, which is an ambler class B, metallobetalactamase, usually conferring carbapenem resistance. And an OXA48, which can confer certain carbapenem resistance. A pseudomonas, which appears to be fully susceptible. And then a Staph aureus, which does not have MEK-A and is MSSA. So now you have a BAL, which again is done. And it has three organisms on molecular testing. So the first question we sort of have is this patient's only hospital day number six. Appears to have a VAP. Really no past medical history. No history for drug resistance. We have a molecular test that suggests a mix of organisms. So which of the following would you believe? Which would you cover? And which is one that would worry? So it looks like we got pseudomonas somehow separated in B and C, which is interesting how that sort of happened out. So let's assume A is Staph aureus, B is pseudomonas, D is Staph aureus and pseudomonas, and E is all three. And actually C should be Klebsiella. That should be K, erogenes. So the Klebsiella one is C. Somehow that got cut off. All right. Well, thank you guys for your patience, which is good. So let's see. A, Staph aureus, B, pseudomonas, three to Klebsiella erogenes, which has resistance features, D, just the Staph and pseudomonas, and E, all three of them. And this is the hard part with the molecular testing, which I'll ask you guys all about in a second. Perfect. All right. So let's see. We've got a couple coming in here at the end. Perfect. Okay. So a mix of all of them. So all three. Okay. So this is always the hard part. So I don't know. I know at my facility we do not have molecular testing. We've talked about it before. None of you guys have the pleasure of having this as well. So what the heck do we do with this data, and how would you guys handle that data, which is at increasing frequency across facilities with sputum or BAL cultures? I mean, we don't have it in our facility, and so I guess if we did, it would really require a lot of exposure and practice in what it means. And so assuming that there's actually a sputum culture or tracheal aspergillus. So if this is BAL culture cooking and sensitivities are pending, I would certainly cover all three in the beginning. Okay. Okay. We do have access to that now in our facilities. Oh, great. So we actually use it in parallel with cultures on every endotracheal aspirate and bronchoscopy. And I actually have found it useful and also really important to always get it in parallel with the culture. But mostly we're using it for negative predictive value, not for positive predictive value. So if we don't see anything, it really is useful in helping us not start, you know, antibiotics unnecessarily for those patients that many of them, we're not really sure if they have an infection. So that's been where we use that. I think what I feel, I don't have this panel either at RVA. And I think what I am sort of uncertain about, I guess, in this case is that he's sort of hospital day six. And I guess I wasn't expecting him to have a very resistant. But so I don't know if I need to cover the resistant Klebsiella at this point yet or not. Just because you see it there, does it mean you cover it until you see what your cultures are? Yeah. Is there a quantitative result available on the panel or anything else that would guide you to know if you need to treat that? And then also my thought was on the, you know, on Staph aureus, like his initial swab was negative. We are at day six and you do see gram positive cocci on the stain. So if he was, so given that and that, you know, we're worried that he's, if he's, particularly if he's more sick, I would empirically cover for MRSA while we're waiting for the cultures to come back. Okay. Perfect. Yeah, I think that's the key. So it sounds like if I hear you right, if we have a patient who doesn't have a risk factors for a multidrug resistant organism, but we find one on molecular testing, that's always the challenge. So it sounds like severity of illness might drive some of that. And if they're not that severe, you may actually not treat that. Sounds like, okay. Interesting. Anybody else, anybody else do anything different? Treat this accordingly. Okay. I think the next question is a pretty straightforward one, which hopefully is the one we had. So, and this is more interesting. So this is actually whenever you ordered a molecular test. So the question is, more importantly, do you guys actually have a molecular test at your facilities? So let's leave it that way. We'll even ask, would you even have a molecular test at your facilities? More importantly, would you have ordered it? Meaning, do you even have it? So that's not the question I thought I had, but anyway, thank you for your patience. So we're changing them on the fly. It keeps you awake. So yeah, this is a different question. So the question is whether we have it or not? Yeah, exactly. We can just skip this one. Yeah, we'll skip that one. I think that was a good idea. We like that. Okay, perfect. 50-50. So even better. We can move on. So, okay. This is probably the better question, given the sense of time. So as you mentioned, cultures in parallel, which is always key, right? So you obviously got the molecular test. The fellow also sent a quantitative culture from the BAL. So this returns 8,700 organisms of the Klebsiella. So you didn't think it was there. It comes back. And we'll say this is a straight BAL, so we'll use that as the cutoff. And which of the following therapy would you initiate? So in this case, it's 8,700, so kind of close. And would you actually do therapy? And would you not? And if you did, which of the ones would you sort of start? So A, sophitercol B, meropenem. C, astrein M, and ceftazavibactin D, colistin, or E. Hey, it's 8,700. It doesn't reach 10 to the fifth. We're not going to go there yet. And no risk factors. And let's assume their severity of illness is what we had before, which is essentially febrile, infiltrate, increased sputum production, but not unstable. and ceftazavibactin. OK, nice, which is one of the mainstays for metallobetalactamase in the guidelines. OK, good. Any of you guys, any thoughts? Would you guys actually treat this? It looks like one in five people said they wouldn't even treat it. So how about the three of you? Would any of you guys not treat this? If so, what would you choose? Yeah, I said no treatment because it's less than the guideline recommendation for the quantitative analysis. I know it's close. There's many other causes of fever. It could be atelectasis. OK, yeah. I mean, I guess that's what I said as well. And I'm assuming it didn't grow staph or pseudomonas or anything else either. This was the only positive result. So yeah, I think I would be trying, as Charles said, looking elsewhere. And then if nothing else and he continues to be febrile, then reconsider that decision. All right. Yeah, this is why we get quantitative cultures. Yeah, sort of to verify what we're doing, which is very helpful. OK. And let me ask. So the molecular test showed three organisms. If, say, for example, on this it came back with three organisms, this is a BAL. Obviously, hopefully, it's done appropriately. It's going out. It's wedged nicely. We're getting a beautiful sample back from the alveoli. If you get multiple organisms, do you believe, in many cases, that's a crappy BAL? Or poorly done technique? Or do you believe that that's actually polymicrobial? I don't believe it's a crappy BAL because I trust my fellows. Oh, you trust your fellows. I see a few in the back. I don't trust them at all. We do great lavages because otherwise we beat them up if they don't. But it is possible to have multiple pathogens involved. Do you have to treat all of them is a very hard question. If you have a small population of a single organism, do you have to just wipe everything out? And I think this gets back to our model of disease. And sometimes it's important to preserve some of the microbiome that you had originally. So I'm pretty careful, actually, if I really think that it's a subpopulation. I think this question highlights the use of quantitative culture, and not many places actually do that, right, even with BALs. You probably have to ask, and so to see if this, you know, people do that, otherwise you would have the sort of arbitrary quantification, right? Yeah, the plus-one, plus-two, plus-three kind of quantitative, which is always hard. Yeah, then you have that big discussion with stewardship as a colonization or infection, right, which kind of helps. Okay. And do any of you guys do blind BALs, or are they all bronchoscopic? At the county hospital, we used to have, like, overnight, the RTs could do the mini-BALs, but generally during the daytime, we do do a quantitative BAL. Okay. Yeah, I mean, we've generally found that it's helpful for sort of the quantitative cultures for then sort of directing us to look elsewhere if it doesn't sort of meet the threshold for pneumonia. Got it. Okay. Yeah, ours is mostly research for mini-BALs. Okay. Got it. Yeah. Yeah, it's actually mostly a blind BAL that's RT-guided unless, you know, with rounds we decide to do it differently, which is why I bring up the polymicrobial issue. That happened a few years ago when one of our fellows looked, and about 50 percent of our blind BALs came back with more than one organism. And we did a re-education with the blind BALs, and it actually dropped to a single organism more dramatically. So in those cases, in that case, it was actually more technique, and the fellow both figured it out and showed the good technique, which is perfect. Okay. Great. So that somehow got to the messed up one. So do you guys actually have molecular testing, or in this case, and or, we'll throw in BAL with quantitative culture net facility, or is your only option the old school ET aspirate? Which by the way is not necessarily invaluable. So if you get, as we looked at before, if you get no gram negatives, no gram positives, or no organisms, that negative predictive value is excellent. Can I ask this question in the title one, so maybe you guys think VAP did not evolve? That's what I understood from the title. Or I think the question may be, it may not be VAP, right? 8,700, yeah. Oh, you don't think it is VAP? No. So 8,700 organisms that not, you know, kind of close to that 10 to the fifth. But at the beginning of the case, you didn't say that the patient had VAP. I did, but then that was based on molecular testing and clinical findings, but then the cultures showed 8,700. Right. So, so no, slight, slight torture, which is good. Okay, perfect. So, okay, so about half of you have some options for quantitative culture or molecular testing and the other half not. So, okay, perfect. So this one we probably don't need to spend much time on given our time. So, okay. Any, so if we finish up that case, any other questions? Things we missed? Controversies you'd like to know about more? Diagnostics is always a hard point. So I assume all of you, and we talked beforehand, everybody at least has a viral respiratory panel option, right? With some atypicals, that's pretty routine, I think, in most places now. And we're talking about bacterial molecular testing, but I think the viral molecular testing we all have. Yeah, I mean, I think one point is that the aspirates versus sort of BAL is still a question. I think there's a big debate still because it's not, you know, to do a full clinical bronchoscopy, it's not usually routine to get regular samples. We always do it whenever something's going on bad, right? Just try to find something. And so the question is, does tracheal aspirates replace, for example, full BAL? And there's some studies using sort of metagenomic sequencing, and for true pneumonias, they're pretty similar. But if it's not pneumonia, then it's discrepancies. And so I think a lot of work still needs to be done to figure out whether we could translate tracheal aspirates fully. Hopefully, we can. That way, you know, we can do it much easier and more generalizable. But I think that those are still in the works, right, as you know. Another issue with endotracheal aspirate is timing is everything. So the quality of... probably lower positive predictive values since you've got colonization. Yeah, I remember my older critical care faculty saying, every time you intubate, get that ET aspirate. You're there, it's clean, get it done. And I did have one other question, going back to prevention. Do any of you use subglottic suction endotracheal tubes? I don't know that. Okay. No, me neither. Yeah, I think there's a trial going on now. I think one of my colleagues is doing that. Yeah, interesting, because I know that that's getting a lot more press, but everybody I talk to, not many people use them, so it's an interesting discussion. Okay. All right, last case three, and thank you again for your guys' patience. I'm gonna cough right when it happens. So case three, 57-year-old gentleman with a CVA. He was on hospital day 11. Of course coughing right when it happens. Improving with speech therapy and physical therapy. Excuse me. Still getting, feeding through his NG tube. Nursing staff finds him alter, increased bronchi, increased oxygenation needs with high flow. He goes, okay, you know, perfect timing. Thank you. And then a leukocytosis and a right lower lobe infiltrate. So all the fun things you would see. This is what happens. This is when my wife tells me I just talk too much. So basically all the stuff that we kind of would see with your classic cap on the floor. So here's the first question that we have. So he has a poor cough, cannot produce enough to give a sputum sample. So given that this is potentially a hospital-acquired pneumonia on the floor, which of the following would you guys do? So would you intubate him and try a bronchoscopy and get a BAL? Would you do the best you can and get a sputum culture at the bedside? Would you intubate and just do an ET aspirate? Because it's a fresh sample that we talked about or not even bother with the culture. Thank you. Preventative VAP. Yeah, that was cough medicine. You want to try subglottic suction? Yeah, I know, exactly. I need some subglottic suctioning. It's terrible. We're not going to intubate you, so. Right. I don't know. Once the vocal cords pass. Should we do a bronchoscopy? Yeah, please do. I remember we did them on each other as fellows. I'm not really interested in having another one. Oh, wow. It's like a rite of passage, which we're like, OK, now we need to get to know one. And the worst part, like everything, is the prep. The taste of the lidocaine is always the worst. Oh, god. OK. All right, let's see where we're at here. So OK. So some would attempt a sputum culture at bedside. 25% wouldn't even bother, which is pretty good. And then 30% would intubate and do a bronchoscopy with the BAL. So I turn to our esteemed colleagues here, based on the guidelines and treatment and diagnostics for HAP and VAPRD different. So any thoughts you guys have? What do you think about the idea of getting samples versus not in this case? And if we do get a sample, which is the best route? Well, my choice would have been to try and see if he could maybe get an NT aspirate. It sounds like he was maybe his mental status wasn't so great. He's not able to cough. That could have been an approach to do. But I would not intubate him and do this unless he had a clinical need, like that his respiratory status was deteriorating and getting intubated was in his goals of care, in which case then you could do bronchoscopy. Or actually, sorry, an endotracheal aspirate I would do in that case, because it would be a clean endotracheal tube, as we just talked about. So my choice was D. I wouldn't attempt a diagnostic culture. Because I believed you that he was not producing sputum. Yeah. No, that's good. I like it. My choice was B because I didn't believe you. And I tend to be pretty aggressive about this. But a sputum culture with a grain of salt. So really try, which for me means ask, talk nicely to your RT, and really try to get an induced sputum if you can. Because he had a bronchi on exam. And he's got a CVA. So he may just not be able to coordinate. So RT may be really useful here. And then knowing, though, that it's a sputum culture. So it's not a direct visualization of what's in the lung at all. But it can sometimes be useful. So I usually try to get them if I can. OK. Perfect. So any thoughts with, if I remember right, with the guidelines, the HAP side of things they don't recommend pursuing culture often. So it sounds like at least in certain cases, you're going to feel pretty, I wouldn't say strongly. That might be words in your mouth. But you feel pretty strongly at least trying to get it if we can get it reasonably. So that's worth something. OK. All right, perfect. Anybody else, other thoughts? Different ways you would do it? I would say in our institution, most of the times we probably would never get a culture in this case. We might have tried to work with RT. But if we do, it's pretty difficult. And I think the A and C, we really wouldn't follow very much. They may end up getting intubated as their GCS declines or they have a second aspiration event or something. That's another story. But certainly in those cases, we wouldn't really intubate someone for a sample, per se, on the floor. But they often get there on their own other ways. OK, perfect. Next one. So which antimicrobial would you initiate? So kind of relatively straightforward and not too serious. Curious to see which ones you guys would pick. Aye, aye, aye. I definitely need to bronch. And this is more just to see what you get. Every institution has different therapy. You might do none of those in general. All right, so 40% cefepime vanco, or what we would call the vancopime, and the other half piperacillin-tazobactin vancomycin, or the vancocin. So the good combos, which is great. And then at least a little bit with piperacillin-tazobactin alone. I'm happy to see no one using a carbapenem. Very good stewardship. Thank you, which is good. So any thoughts on this? Any different? I know the guidelines mention a little bit about the HAP patients having a lower likelihood of MRSA, which obviously you could leave the vanco out. Any thoughts around that? My actual choice wasn't on here, because I would have started them on standard spectrum, so probably ceftraxone and azithro. So, what used to be the older, early VAP recommendations, right? Okay. Perfect. And depending on whether there's, like, MRSA swap here, I guess we didn't have that result. back, you know, one of the antibiotics and do empirically, say, piperacillin or cefepime or something like that. Yeah, exactly. So, yeah, if the MRSA swab is negative, definitely, you know, the vancomycin's out. And I wanted to avoid zosyn after going to Bob Dixon's talk yesterday, in fact, if you were there, and talking about the data sort of with the, showing the anaerobic coverage as zosyn compared to cefepime, having worse outcomes in patients who were started on zosyn. So that did sway my choice some. So that's good. So we can check the box that does, you know, attending chest change your clinical practice. That's good. Yeah. And that reason, too. That's a very good point. Yeah. That's a good point. And I think that's, you know, we sort of joke with our learners, but, you know, we'll be on rounds, and everybody, we're a very cefepime-heavy facility, right? Much less peptazole, but we'll often joke, you know, they were started on vancopime. Why? They're sick. What are they sick with? They're just really sick. How do you know they're sick? They're in the ICU sick. And there's never really a thought about how they target, but I think that's, that part is very important. So. Yeah. And I think yesterday, too, there was also a discussion about how, well, the ED started it. They must have had some reason to start it. You know, something that we don't know kind of thought process. And then I think it was Kirsten Corr who was talking about that, her data, and that she said they had then talked to the ED attendings who thought, oh, well, the team will de-escalate it. We're just starting this now as sort of the, you know, initial step and they can de-escalate. But it's like, it's harder to de-implement when somebody has already started it and you receive them. Yeah. I work with a couple of qualitative research leaders who have interviewed people with, you know, on antibiotic choices and de-escalation and residents and attendings. And it's typically, regardless of the patient's clinical status, it's always to continue the antibiotics. So, because they got worse or because they got better, it's still a good reason to continue the antibiotics. So, de-escalation is very difficult. Yeah. You can see how stewardship earns their job, right, which is always a good thing. So, okay. Perfect. And I think, you know, it's an interesting trend, which we don't have here. The only comment I'll make with, and part of the reason for the piperacillin-tazobactam is there is something called a SAR, you know, standard antimicrobial ratio, which pharmacies worried about that is publicly reported now. So, if you ended up doing, for example, I'm going to make this up, cefepimumetronidazole, right, to get some anaerobic coverage versus just piperacillin-tazobactam, pretty much would cover very many of the same things, similar effectiveness. One is two antibiotics. One is one. So, it actually looks like your stewardship is worse with the cefepimumetronidazole. Maybe cheaper, maybe a safer option, but from what's recorded and publicly reported, it looks worse. So, you're seeing, for lack of a better term, some games being played where piperacillin-tazobactam is sometimes preferentially reused, which worries me, given the discussions we had yesterday and your mentioning of the acute kidney injury with it. So, all important, but okay. So, this might be the last question, and then we can probably free you and put you guys on parole. So, on, I think it's the last question, on hospital day three, or excuse me, on day three of the antibiotics. So, we start antibiotics. Let's just assume that most of you guys picked manc and cefepim, which is great. Three days goes by. The patient's better. Their GCS is better. They're back to the baseline. They're off high-flow nasal cannula, now on six liters nasal cannula. Still a little bit of bronchi, still a little bit of a right lower lobe infiltrate. Pulmonary hygiene has been instituted, and they're doing the best they can. Procalcitonin comes back nice and low and in the normal range. So, what would you guys do at this point? So, we now don't have cultures. Let's assume we didn't get cultures, and nothing came back. So, we have no cultures. We have three days of antibiotics. We have a normal procal, and the patient's better and back near, close to baseline. So, would you continue therapy for a standard seven to eight days and just call this a VAP? Would you do 14 days? Would you do 10 days? Or would you just say, you know what? We did three days. This probably was an aspiration event. I'm going to go ahead and stop antimicrobials at this point. Close to 20, so we only have a minute. All right. Nice. Look at that stewardship. Beautiful. All right. So more than half say discontinue antibiotics. That's what we like to see. As we know, marriages, politics, jobs are all negotiations, as is stewardship. So very often, it's, let's stop the Venco today. We'll stop the cefepime tomorrow kind of discussion, which doesn't always work out. How would you guys handle this in most cases? I assume you guys were in the discontinue camp, maybe? I did say discontinue, because I guess I was questioning whether he really had a hap in the first place with how quickly he improved. I was a little bothered still by the wrong guy in right lower lobe. Like, if he had been left lower lobe, I'd have been like, oh, he's just got some atelectasis. So that made me pause a little bit. But I guess I was reassured by the procalcitonin. Like, it wasn't the only thing that was driving this, though. So I voted to discontinue, and I think then keep a close eye. Yeah, I had to discontinue as well. But if you said, like, the patient had risk factors for pseudomonas or has grown pseudomonas or multi-reductive resistance, I might have a longer course. Yeah. If cultures are positive, probably seven to eight days in most cases. I like what Christina said, and watch. So this is one thing. watching that clinical status. So it's easier, and we're always subconsciously looking for things that can make things easier for us because we're overloaded. But to have, instead of the stop date or the duration, to actually be nimble is actually really challenging, but it's definitely probably better than what we have been previously doing with the antibiotics and pneumonia. So when we round and discuss what antibiotics as a plan, we try to make an effort to really explain why we picked the choices we picked, what's the rationale, and for how long. That way we have this kind of interaction every day during the rounds, right? So in a way, we're trying to steward ourselves within a team. And the last question, do you guys spend time discussing what would be your trigger for restarting? I mean, we stop at day three, and this idea of watching, which I love because most of us think the hospital closes at six, right, when radiology and GI medicine, everybody goes home, we forget we're still in the ICU. So do you discuss on rounds often what the threshold might be for restarting, which I think is often missed? Yeah, I think that's often sort of the afternoon rounds to kind of go through with our team and sort of say, what are the ifs, ands, what are the things we're worried about for this patient, and what do we sign out? So a new fever, sort of worsening oxygenation, sort of worsening of their mental status, again, like things that might prompt you to say, oh, is there an infectious process going on or something else, obviously, too, but no, it's all infection, right? And so that thinking, OK, in that case, maybe we need to restart the antibiotics that we just stopped, repeat cultures if they've been off for a little while. I'm glad you mentioned, what do you talk about on rounds? Because one of my goals as an attending is to actually try to not talk so much about antibiotics. Because I think in infectious disease, we spend about 80%, 90% of our time talking about antibiotics and 10% talking about physical therapy, family relationships, getting the patient out of bed. And so I've actually really tried to shift that. And one of my huge people that I rely on is our pharmacist. So I was actually curious how many of you guys have ID pharmacists, or not ID, just pharmacists in the ICU that round with you, multidisciplinary, OK, awesome. So I think about cognitive load a lot. And that is a huge form of cognitive offloading. If I trust my pharmacist, most of these responses, I basically say, I don't know, I think I should probably talk to Ben about that. And then we can actually then focus on the other critical care issues that are more of our job. So that's kind of my personal approach. Great point. Because the antibiotic costs a lot. You spend 10 minutes on it, and you spend literally 30 seconds on their distributive shock. There's something fundamentally wrong with that, right? Exactly. That's perfect. OK. Well, thank you guys. Thank you for putting up with the questions.

hospital-acquired pneumonia

ventilator-associated pneumonia

clinical challenges

molecular test

Klebsiella aerogenes

Pseudomonas aeruginosa

Staphylococcus aureus

diagnosing infections

treatment decisions

multidisciplinary collaboration