SCCM Resource Library-Antimicrobial Optimization in the ICU: Treating HABP/VABP in the Critically Ill Patient

Video Transcription

patient program entitled Antimicrobial Optimization in the ICU, Treating Hospital-Acquired and Ventilator-Acquired Bacterial Pneumonia in the Critically Ill Patient.  This program is provided by SCCM and by ProCE, and I'm Zachary Schwartz with ProCE. We're so delighted to have you here.  We're especially delighted to have our two expert faculty joining us, Dr. Christopher Bland, who is a clinical professor at the University of Georgia College of Pharmacy,  and Dr. Tatiana Calvano, who is program director in the internal medicine residency at the Madigan Army Medical Center in McCord, Washington.  Full information on their disclosures were presented in the slide scrolling before this presentation and they're also listed here.  Now, before we start off this question, let's ask a few, before we start off this presentation, let's ask a few questions to learn a bit about you, our audience.  If you are in practice, what is your degree type? Are you a nurse, nurse practitioner, pharmacist, physician, physician assistant, other health care professional?  The polls are open. Please vote.  Okay, I think we have enough results. Let's close the poll and see the results. So you can probably see that most of the audience here is pharmacists, but we do have some physicians  and nurse practitioners and physician assistants as well. We're going to also move on to a few pre-survey questions, which we're using to establish a baseline.  So these will be to see what you know before the session begins. So to read off this first question, I'll turn it over to Dr. Calvano.  Hello everyone, and thank you so much for being with us today. We'll start with the first question.  You receive a rapid diagnostic call for a patient who has been intubated 72 hours requiring minimal vasopressor support.  Bronch was performed earlier in the day, and now microbiology is calling as they have detected Acinetobacter baumannii with OXA48-like gene.  What is an ideal first-line empiric regimen to initiate? A, high-dose ampicillin-sulbactam with polymyxin B, B, high-dose extended infusion meropenem  with that tigacycline, C, high-dose ampicillin-sulbactam with minocycline, or D, minocycline with cefeterocol. Great. And the polls are open, please vote.  Okay, I think the votes have slowed down enough that we can close the polls and show the results.  Now we're not going to discuss these results, but this will be good information for our faculty as they do their presentation, because we're going to be coming back to each of these  questions at the end of the presentation to see what you've learned. So without discussing, we'll move right on to the very next question, which I'll turn  over to Dr. Calvano to read for us. We have a patient who is being transferred from the floor to the ICU with worsening respiratory status, secondary to hospital-acquired pneumonia.  Cultures have grown difficult to treat resistant Pseudomonas, and what is the first-line treatment for this resistant organism?  A. Seftaz-Evibactam, B. Seftolazantezobactam, C. Sefitercol, or D. Imipenemsilostatinibrelabactam. Great. And the polls are open. Please vote.  Okay, we had a lot more people voting this one, so let's close the polls and look at those answers. You can look at those as faculty, but again, we won't discuss this. We'll move  on to the very next question, and that is question three. Which drug characteristic is the best predictor for removal during CVVHD, continuous venous  hemodialysis? A, low molecular weight, B, high degree of protein binding, C, high volume of distribution, or D, low renal clearance?  Okay, we have enough results, let's close this poll.  Let's have a quick peek at those. And again, we're going to come back to these all at the end of the session. And now onto our final question. This is question number four.  An ICU patient, hospital date 20, with a documented sulfa allergy develops a new oxygen requirement. Four liters of oxygen via nasal cannula and is febrile to 102 Fahrenheit.  Respiratory culture demonstrates growth of stenotrophobonus multifilia. Medical history is significant for acute myeloid leukemia. What would be likely the next step in management  assuming confirmed susceptibility to choices below? A, this is consistent with colonization, do not treat. B, ceftaz-avivactim monotherapy.  C, cefeterocol and minocycline combination therapy. Or D, minocycline and levofloxacin combination therapy.  Okay, just a few more seconds, make sure everyone gets a chance to vote. Yeah, I think we have enough. So let's close this final poll and see what those results are. Excellent.  Now, of course, we want to hear your questions as well. So anytime during this program, please do submit your questions using the field on the left of your screen.  We'll get to as many as we can at the end of the program. So with that, it is my great pleasure to begin this presentation, turn things over to our first presenter, Dr. Bland.  All right, excited to be here. And I hope everyone at SCCM is having a great beginning to their meeting. Very excited to present, even though the two of us look like  we may not know each other, we've known each other for years and actually worked together in the same hospital and took care of a lot of these critical care patients  together for a number of years in my days when I worked for the military and we were both in Fort Gordon, Georgia. So Tatiana, without further ado,  why don't we go ahead and dive into these cases? What do you think? Sure, thank you so much, Chris. I'm absolutely thrilled to be here with you.  And this is going to be a case-based approach with focus on multidisciplinary approach. So putting our heads together with pharmacists, infectious disease physician,  critical care physicians and the rest of the healthcare team. So our first case is a patient,  69 year old male with poorly controlled diabetes and obesity who presented with worsening shortness of breath over five days. He was found to have hypoxia at the time of admission  and required supplemental oxygen via high flow nasal cannula. He's been declining clinically with escalating oxygen requirements over 24 hours from admission.  He tested positive for SARS-CoV-2 and was admitted to the ICU.  And so initially he was afebrile.  He was normotensive with some tachypnea and tachycardia as you can see, and he was satting only 89% on 30 liters of high flow nasal cannula.  Labs indicated leukopenia and lymphopenia which is not surprising. Procalcitonin was normal at that time and he had significant elevation in inflammatory markers.  And so he was intubated within 24 hours from presentation to the hospital and was treated for severe COVID in a critically ill patient with remdesivir, dexamethasone and teslizumab  in addition to supportive therapy. At that time, there were no indications for antibacterial therapy.  However, he's had prolonged hospital stay which is not unusual with these patients over the last four weeks and has intermittently been febrile with episodes of hypotension  during which he was evaluated for infectious ideologies of these syndromes and received short courses of broad spectrum antimicrobials.  No clear ideology of infection was identified during any of those times. And now about four days ago, this patient was febrile and appropriately received multiple cultures  or multiple cultures were obtained and had imaging for evaluation for source of infection. And at that time, he was found to have catheter-related bloodstream infection with MRSA.  The line was removed. He didn't have any evidence of vegetations on TEE and he rapidly cleared his bacteremia and is currently treated with vancomycin and improving clinically.  But at the time he was evaluated for fever, a tracheal aspirate culture was obtained and that grew stenotrophomonas multifilia. It was susceptible to TMP-SMX,  levoploxacin and minocycline which was what the lab tested it for. And this patient has a sulfa allergy with history of anaphylaxis.  At this time, he didn't have any evidence of purulent respiratory secretions. He was on CPAP intermittently via trach with continued improvement in respiratory status  over the four weeks from his initial diagnosis of ARDS at the time of admission. And his daily chest x-rays actually have been improving  with improvement in those ground glass capacities and no evidence of any consolidations or infiltrates.  So what would you do at this time?  A, start TMP-SMX as this is the drug of choice for treatment of stenotrophomonas multifilia. B, no need to initiate treatment for stenotrophomonas  at this time as this is consistent with colonization. C, start minocycline for treatment of VAP due to stenotrophomonas multifilia. Or D, start Piptezo for treatment  of ventilator-associated pneumonia due to stenotrophomonas multifilia.  And please answer.  Yeah, Tatiana, I'll be interested to see kind of how this goes. We're gonna have a nice discussion on this one, but this is an interesting one.  I'm interested what our audience here a lot, one of the cool things about doing something like this at an international meeting  is we get to see a lot of different ways of practicing and ways we see different scenarios. So I'm excited to see what our audience has here for us.  And I think we have enough results so we can close the polls and show the results. Great, thanks. Well, look at that. So Tatiana, I'm really excited. It was very definitive.  No, I'm just kidding. We've got multiple options here. And I think this is perfect because it was like a perfect split.  You know, when you look at this, Tatiana, we find this all the time, right? This stenotrophomonas, it will grow in the respiratory tract all the time.  And so to treat or not to treat, to quote Shakespeare, actually, I think he said something else, but what do you think about this one?  What are your thoughts when you look at this case and what do we wanna talk about here at this point? Yeah, and this is a tough one. Thank you all for answering this question.  There's so many different factors that we need to consider when determining this. So distinction between colonization and infection is particularly important.  Obviously, we know that there's potential harm of antimicrobials with their adverse effects and there's antimicrobial resistance,  but also this particular organism can cause severe disease, as we know, particularly in certain patient populations. So steno has historically been viewed as a colonizing organism.  And still is associated with colonization, particularly in these patients who have prolonged ventilatory dependence or people who have chronic lung disease.  And Chris, we really wouldn't even be talking about this that much and considering it if steno was susceptible to some of the things that we routinely prescribe  for our very ill patients as empiric regimens.  So we are really left with this risk benefit analysis and clinical decision-making, which is the story of our lives.  So we put our heads together and try to figure out what the best thing is in each scenario. And so we have to consider the clinical syndrome that the patient is exhibiting.  And this is tough with some of our patient populations, especially with profound immunosuppression where they might not really have the syndrome that's typical.  But this particular patient really didn't have evidence of pulmonary infectious process at this time. We know that the patient is at risk, but the imaging has been improving,  his respiratory vent settings have been improving and he's only been on minimal vent settings and no purulent respiratory secretions. So in this particular setting,  it's reasonable to not treat this infection and to say, or not consider this as an infection and consider it as colonization. There is some data on Stenotrophomonas colonization  and that demonstrate that there's no change in clinical outcomes. However, these are variable definitions of colonization versus infection.  Variable patient populations, so we still have to make sure that we take into account the risk to that particular patient of not treating this.  We will find ourselves in this situation more and more actually with different organisms because we are using lower respiratory PCR more commonly  and we are more likely due to the sensitivity of the test to detect colonization and even oropharyngeal contamination.  So this will be an ongoing discussion and I'm glad I have you to put my heads together  to make these tough decisions.  Yeah, I'm thinking back. I'm gonna go ahead and move on here and talk a little bit about Steno. Yeah, it's one of my favorite organisms to really talk about.  We've done some research here on it, but yeah, Tatiana, I think, you know, critical care physicians, pharmacists, ID physicians,  you know, are really having these discussions a lot more. Like you said, with our technology, the ability to detect is great, but at the same time, the ability to detect something  also means we have to deal with that. And so we're seeing this a lot with Steno, you know, C. difficile is an organism we're dealing with this as well.  And so Steno is an interesting bug. It's an aerobic non-fermenting gram-negative bacillus. And, you know, from a colonization standpoint,  it happens a lot in your chronic CF patients, long-term mechanical ventilation. You know, this case, we tried to make that point. You know, this person has been here a long time  and probably been exposed to a lot of different antibiotics that quite frankly have no activity against this organism. And that's what ends up happening.  Sinotrophomonas, I think it's kind of underrated in the sense that it has a number of resistance mechanisms that are intrinsic to that organism. And it can acquire some as well,  but it just is not susceptible to a lot of different options that we have. And so it has some virulence factors, tends to occur in these long-term respiratory patients  or hematologic malignancies. And so it's something we're having to deal with more and more, especially because as we're starting to find resistance to our frontline drug,  which has historically been trimethylamine sulfamethoxazole  is definitely increasing in pockets of the country. We produced some research a few months ago that we published that found, at least in the Southeast United States,  we are definitely seeing more trim sulfa resistance. And so when you start getting past that and levofloxacin and minocycline, that's where you're really starting to get  at some difficult territory. So I will do, you know, one of the things, Tatiana, I know you and I are passionate about educating, you being a program director and me being at UGA.  And one of the things I want to put for our audience is there's a great two documents that we're going to talk a lot about today that we want to reference  so that you have this after this talk. And IDSA has had some guidance documents that they have published that are online. One of those is for non-fermenting gram-negative broads  like stenotrophin monase that we're talking about here. So this is a table that's really drawn from that. And really what this comes down to  is that if you've got trimethrin, sulfamethoxazole or levofloxacin or even minocycline,  for mild infections, monotherapy is okay. But when you start to get to moderate to severe infections, a lot of times you're going to start using combination therapy.  And when you get to drugs like cefeterocol or Ceptaz, really plus-AVBactam more than minus, the document really focuses on it not as monotherapy, but when you're using Resteno  for a moderate to severe infections combo therapy, there's not a lot of data for these Ceptaz, AVBactam  or cefeterocol, because when you look at some of their studies, it's in the numbers, like especially cefeterocol, you're talking about five patients  all in the cefeterocol arm of the study. So we're really limited on that data. So we're still really limited on these options. If we're going to use for a severe patient,  it's probably going to be a combination of these therapies. So fortunately, a lot of times it is a colonizer, but when we do treat, it does get tricky  because there's just not a lot of options that are available. So Tatiana, let's jump back into this case here. You want to take it from this point further? Yes, of course.  So now some time has passed, and unfortunately the patient is rapidly worsening clinically, and now he's having escalatory ventilatory settings  and difficulty with oxygenation and ventilation. And he now has pulmonary infiltrates, fevers, leukocytosis, and purulent respiratory secretions.  And so due to ARDS and barotrauma-associated pneumothoraces and need for chest tubes and continued respiratory failure, he's now on ECMO.  His renal function, thankfully, is still intact. Now you know this patient has had extensive exposure to broad-spectrum antimicrobials during his six-week hospital stay,  and he's declining clinically. And so you need to initiate empiric antibiotics in this critically ill patient. What factors do you take into consideration?  A, your institution's antibiogram and local resistance. B, patient's prior exposure to antimicrobials and patient's prior colonization and infection history.  C, suspected etiology of infection and pharmacokinetics, pharmacodynamics of available therapeutic agents, or all of the above.  And please answer.  Yeah, again, hearing this, Daniel actually, in the Q&A, Tatyana made a good point that they were a little concerned on our last case because the patient was immunosuppressed  on TOSI and steroids. Yeah, I agree. That's definitely a concern. We would want to walk through that more. We did have an identifiable source of infection, that Lyme infection,  and so we're hoping that was the cause. But yeah, that's a great point is that, especially in the era of COVID,  you know, these things get very complicated.  Yes, and we lose a lot of sleep when we make these recommendations. I remember you told me that when you first came to Eisenhower. You're like, I lose sleep every night, Chris,  when I stop antibiotics. It's tough. It's tough. Yes. We definitely have enough answers and we can show the results for this poll.  All right. Oh, look at that. We gave them an easy one.  Yeah, you know, there's a lot goes into that. That's great. You know, I mean, that's true, but let's be real, Tatiana. What are you really going to give this patient?  What do you think you're going to treat them with? Yes, and I knew you would ask that. And, you know, obviously as an ID doc, I'm always asked that.  You know, yes, it's good to put our heads together and go through this clinical reasoning exercise and consider all of these factors, but what do I actually order in the EMR?  And so we know that this patient has had extensive exposure to broad-spectrum antimicrobials throughout this very long hospital stay. He has had known infection with MRSA,  and we know he's colonized with steno or has had an infection with steno. And clearly now he does have VAP. He's met all the clinical criteria  for diagnosis of ventilator-associated pneumonia, and he's at risk for resistant gram-positive and resistant gram-negative organisms and nosocomial pathogens such as steno.  And he's also at risk potentially for molds and some of these atypical infections in the setting of immunosuppression  with immunomodulatory medicines for treatment for COVID. And so obviously I would recommend collecting  as much data as possible with culture data and also other microdata with the respiratory PCR  via tracheal aspirate and blood cultures. And so in my particular region of the U.S., we are very, very fortunate that we have little resistance compared to some of the other areas.  And my antibiogram in my own facility is absolutely beautiful. I commend them for their stewardship  initiatives all the time, which is probably the result of those efforts. And so I would  I would start vancomycin, piptazo, and levofloxacin. In this situation, we had a levosusceptible steno, and we don't know if that's potentially playing a role. And  based on our antibiogram, this would be reasonable. And I know that in many of your facilities,  you would choose a completely different empiric regimen. And then, Chris, you know, this patient  is now on ECMO. And I always worry about the antimicrobial sequestration in the setting of ECMO. Is this something I should worry about? Well, we should educate on that. Yeah, it's  yeah, I think it's interesting you put, you know, levofloxacin, there's a lot of debate on second, you know, anti-pseudomotor drugs. But in reality, you're right. It's because this  person's steno was there previously. Makes a lot of sense for that as an agent. A lot of people  listening to this are, they wish they had your antibiogram. That's for sure. We do too, because  we definitely have some resistance here. So the ECMO, somebody said, why not an aminoglycoside?  Yeah, I mean, definitely that your antibiogram supported that. I think that would be a reasonable  option. So the ECMO definitely is a concern. You know, I've had more questions about this in the  last couple years due to COVID. And just really looking at, you know, patients that end up on  ECMO and they're on other antibiotics for other reasons. But really the three characteristics I think most about are drug sequestration, then also increased volume of distribution,  altered drug clearance, because these are all occurring simultaneously in our patients. And so  the lipophilic drugs are definitely the most susceptible. So a good key pharmacology point  is if a drug works at a target site of action that is intracellular, such as a ribosome with  macrolides or DNA gyrase, like a quinolone, then that tells you that drug probably is lipophilic  because it has to pass through a lipophilic layer to get to its target site of action.  And then increased volume of distribution, you think about all the different volume that's being  increased in these patients with extracorporeal volume and tubing binding, and then also drug  clearance. And so really when you look at the different drugs, I tried to look at some of our  more common use drugs. Beta-lactams for the most part are minimally sequestered. Ceftriaxone, because of its high protein binding, we definitely see that it is bound up some.  Aminoglycosides tend to be minimal. Azole antifungals for sure have significant drug sequestration. So I always say with these, the data changes rapidly and that there are new case  reports or case series that are published very often. So if I have a particular case, what I  would strongly recommend is going to the primary literature, doing a PubMed search, and really  seeing what's out there at the time. Because as we know, newer data, especially in the era of COVID,  and sometimes that research has not been the best, but it is something we look for whenever we have  the opportunities to evaluate this. And so that's something that we do. So yeah, it's definitely  something on our mind and something that's being asked for. I strongly believe, Tatiana, that we  are moving towards an era where there's going to be more therapeutic drug monitoring, just quite  frankly, because really a lot of these are educated guesses. And especially on our beta-lactams, even  though they're minimally sequestered, these patients can also have, you know, augmented renal clearance. And so when you start putting all these factors together, it really helps to  have a level, which is great when we have a drug like Banker or aminoglycoside, not so great when  we're having our beta-lactams. So let's move on to number two here, a gunshot wound to the chest  or abdomen. Definitely see that in my area of the country from time to time. I know you see it  everywhere, unfortunately, but why don't you go a little bit more detail into this case?  Sure, thank you. So we have a 37-year-old female who was brought to the hospital after sustaining  multiple gunshot wounds to the abdomen and chest. She was intubated initially in the field and  immediately underwent surgical interventions and only received Cefazolin perioperatively during  that time. Luckily, she recovered very well and she was extubated on hospital day six, but unfortunately on hospital day 12, she was febrile up to 103 with leukocytosis  and purulent respiratory secretions. So you obtain imaging and visualize right middle lobe and right  lower lobe consolidations, and now she's requiring some supplemental O2 via nasal cannula. And so you diagnose this patient with hospital-acquired pneumonia.  And you apply the same principles in selection of empiric antimicrobials, obviously taking into consideration the clinical syndrome, what the anticipated microbiology is, what your  antibiogram is, who our host is, and what the barriers to certain antimicrobials are, as well  as pharmacology. You collect all of your culture data and you start vancomycin and Piptezo empirically.  Yeah, so this is kind of a scenario that happens at a lot of institutions, right? But now we're  heading into really an era where we're starting to see more of these diagnostic platforms used.  And so a lot of different syndromic testing, whether it's blood or, you know, sputum and  now in pneumonia panels, you know, I've listed a number of these here, both the platform names,  both Brandon, kind of generic and how they work. And some facilities I've found are not even aware  that they have these technologies, Tatiana. I mean, we did a survey several years ago that found  that people weren't even aware what the name of their system was and how fast it worked, etc.  So a big take-home point I would say is, A, find out at your facility, do you have any rapid  diagnostic platforms? And B, really you have to integrate this with antimicrobial stewardship  for success to happen, because any technology is great technology when all parties that are  really important to know that technology exists, if that's not there, then really it may even cost  money. So one thing I will say is that the multiplex PCR does have a pneumonia panel. And so just to talk a little bit about that panel in particular, overall, as you said before,  we're still trying to figure out like how to integrate these very well into practice. And so  the PPA and the NPA, as far as, you know, their sensitivity, specificity as well of these  different organisms are very high, and they will find them if they're there. And so that's why the  key is to not only have the result of this rapid diagnostic, but how are you communicating that  result to the clinician at the bedside that's caring for this patient? Because they may tell you that, you know what, yeah, we had this particular organism grow, but the patient's  afebrile, their white count's normal, the circumstances in which this was done were not  ideal. So really for this, the important thing is to know is it is very sensitive and specific, but it has to be correlated clinically with the patient and how they're doing.  And so when you get this pneumonia multiplex PCR, right, there's pseudomonas in the sputum.  And a couple days later, the culture results actually demonstrate pseudomonas aeruginosa  with resistance to peptazo, cefepime, levofloxacin, or TOBRA. Tatiana, you ever seen one of these  isolates before they exist? Sadly, yes. Yeah, unfortunately, right. So let's talk about options  for treatment. So this goes right back to this guidance document by IDSA, really dividing these  into multi-drug resistant pseudomonas aeruginosa, and then what we call difficult to treat  resistant pseudomonas aeruginosa. So multi-drug resistant, you know, a lot of definitions out there.  The classic one we see is resistance to one or more antibiotics within three different classes,  for which we would expect to see susceptibility. And I put quinolones up there. We lost them in a  lot of places years ago. So a lot of times that's one of the least reliable of these. And we see a  lot of resistance to the quinolone class. Then you got your difficult to treat, and that's where we  get, I call them the pirate strains when there's R's, right, all the way down the susceptibility  report. So you see things like astreonin, meropenem, and these are very, very, as the name says,  difficult to treat. So the question is, what do you do in the scenarios where you need to treat  maybe one of these difficult to treat resistant organisms? So we're still gaining a lot of  knowledge and experience with some of these newer agents. And I would say that there are a number of  people on this call that maybe have never even used one of these agents. So in general, we've  got ceftolazantazobactam, emirele, ceftazabactam, and sofideracol. The best data so far, and that  the guideline or the guidance document supports, is ceftolazantazobactam. It really does have  excellent anti-pseudomental activity. It's been studied in a large randomized trial, the AspectNP  study. But keep in mind, it's at a three gram every eight hour dose. Emipenumrelebactam also  has some published data, but overall not as much as ceftolazantazobactam. And then ceftazanabactam,  a little bit more limited evidence, showing good susceptibilities. It has decent, but not as much  as say ceftolazantazobactam. And then sofideracol is kind of at the bottom there because we're  still, it's still the newest agent of these, where we're trying to determine its ultimate role within the treatment of some of these DTR pseudomonas isolates. You want to give an  update here on case two? Yeah, so despite all of our efforts, unfortunately our patient is now  worsening clinically and has hypotension, is on pressors, and evidence of acute kidney injury.  And due to aggressive volume resuscitation and volume overload and continued worsening renal  function, decision is made to start the continuous venovenous hemofiltration. And so, Chris, I'm so  glad that you're my brain trust and only text away, and that I can talk to you and figure out  what to do in these situations. And as we both know, and most of you on this webinar, there's data out there that supports adjustment of dosing of antimicrobials for CRRT,  depending on the flow rates. But there's also literature out there that suggests that we are  underdosing our patients with these modifications of antimicrobials in the setting of CRRT. And so,  Chris, what are your thoughts regarding that? Yeah, so CRRT is something we are using much more frequently. When I transitioned to my position here, I work within a community health  system, about 700 total beds, but 300 within my facility. And definitely in our ICU patients, we are doing more CRRT. And this is very, I don't want to say puzzling or frustrating,  but for our critical care pharmacists and ID pharmacists that are involved in these cases,  it can be frustrating because finding, you know, there's lots of review articles that  are published, a couple of them we've got listed here on our references, which are excellent. The  biggest thing I would say is we're looking at modes, we're looking at frequency, you know,  is this a continuous versus, you know, sometimes we do these intermittent kind of like a slow, low efficiency dialysis. If you're doing continuous, the effluent rate is probably  the biggest thing I'm looking at. And that effluent rate is going to determine not only  the drug clearance, but, you know, that's really the major determinant of how much of these drugs  are going to be removed. Because as we know, if you get into some of these really high effluent  rates, you start to see creatinine clearances essentially that are almost replacing somebody's  renal function. And so you're really getting back to doses and frequencies that are going to be near  kind of normal renal function with some of these patients. And, you know, when you look at what,  what are the different types of, you know, drugs that are affected, the time dependent,  concentration dependent drugs really can all be affected. Penicillin, cephalosporins, parapenems,  I mean, for most of these, the half-life is already, you know, short and somebody gets an end-stage renal disease, well, then it's much longer. But then as you start to ramp up the  effluent rate within these continuous forms of dialysis, you are increasing that patient's risk  for underdosing. My students sitting with here with me right now watching this, and we had a  case last week where someone was tremendously underdosed on their cefepime because they had  gone on CRRT and essentially that needed to be upgraded to a higher, more frequent dose because  now they're removing a lot more drug. There's a lot of interruptions with CRRT that can result in  a risk of drug accumulation. So I would say this is definitely, you know, when somebody's on this,  we are looking at this literally 12-hour shifts almost to see, okay, where are we with the CRRT?  Because depending on what's going on with the patient, you don't want to assume that they're  being on it for 24 hours and there's not any issues. So there's a lot more removal of drug,  you know, drugs like vancomycin that are high molecular weight, they start to get removed more  than we normally would. And so it's very, very helpful when you've got drug levels to be able  to make these situations. And sometimes we will choose an option where I can do some therapeutic  drug monitoring. But outside of that, this is another thing like ECMO where really it's going  to the current literature that patients, that we can use for our patients to help determine these  decisions. Because it is, especially with the newer agents that I just talked about, there's  very little information on those. So we're always checking the updated literature to be able to make  an informed decision about these patients. So it's a lot of frequent monitoring and a lot of  literature searching that goes in to these recommendations. Is that kind of your experience,  Tatiana? Yes, very much so. And we engage in these exercises of clinical reasoning all the time. And  luckily, I'll talk pharmacists on rounds as well as critical care physicians and infectious disease  physicians as we make these decisions and make quick adjustments a lot of times. Definitely.  Well, let's go ahead and move on to our final case as time is getting close. So this is a burn  patient with an inhalational injury and a prolonged hospital stay. So Tatiana, how about this one?  Sure. So this is a 44-year-old with 45% total body surface area burns that he sustained  during a gas explosion in his house fire. And he's been hospitalized for nine weeks now. And so during his hospital stay, he's already had history of carbapenem-resistant  tenterobacteriales, catheter-related bloodstream infection. He's had MDR, acininobacter,  bumani, ventilator-associated pneumonia, and also a history of candidemia. And all of those were  treated successfully, and he's recovered from each one of those episodes over the last nine weeks. And now he has new fever, leukocytosis, and purulent respiratory secretions with  concern for ventilator-associated pneumonia. And so this is another tough one, Chris, right?  Yeah, these are all easy, you know? It's rough. Yeah. I mean, you know, I look at a case like  this, and you know, I can see you and I working together, you know, when I round in the ICU for  12 years previously, and we would just try to figure, okay, oh man, we've got, you know,  what are we going to do with this regimen? So let's talk about what are some of our potential  options for this patient. So a couple things I want to put in here is what do you do with like  these Klebsiella pneumonia carbapenemase patients, so these KPCs? So we're starting to be able to  detect some of these organisms from our rapid diagnostic platforms. So some, a number of these  are here, like maripenibabirbactam. This one is somewhat favored by the IDSA panel. Septazidime  avibactam, if you suspect carbapenemase, can be given in combination with estreonam. Then you got  imipenibirbactam, and then sofideracol. And so right now, the preferred option in these KPC,  typically these are going to be your E. coli and your Klebsiella species. Just want to put this  slide here to make this point, is that that's where a lot of these novel beta-lactamase inhibitors,  such as vabirbactam, avibactam, and relabactam, come into play specifically for KPCs. Now for  Acinetobacter baumannii, this is an organism that is really, in my view, very difficult, because  a number of the newer agents that have been FDA approved really do not have great activity  against Acinetobacter. So when you talk about the term CRAB or carbapenem-resistant Acinetobacter,  for mild infections, we're really looking at amsulbactam, and really it's just a sulbactam.  Sulbactam is the component that has activity against this organism. There are a number of different alternative options, minocycline, tigacycline, polymyxins, really polymyxin B  outside of the urine or colistin within the urine, or sofideracol. Now there's a newer option that is  currently under review by the FDA called durlapactam sulbactam, and what role it will have,  unlikely to know. We never know what's going to happen with these drugs until they're approved,  but we will see. Moderate to severe infections, really the panel recommends two or more drugs.  Generally, high-dose amsulbactam is recommended as part of that combination therapy, even if not  susceptible. It's interesting when you look into the mechanism of resistance for amsulbactam with  Acinetobacter, there is some debate how much of it actually is beta-lactamase production versus, say, an altered penicillin-binding protein. So with these rapid diagnostics,  they're not necessarily going to detect the altered penicillin-binding protein. So high-dose  amsulbactam is still kind of our go-to drug as part of a regimen, even if not susceptible. The  nice thing is we do know susceptibility because we actually look at it. So there's no recommendation for nebulized antibiotics or pneumonia specifically to this within the guidance,  and again, we list our resistance mechanisms there that are there, and so there's a lot of them.  Acinetobacter at one point had demonstrated, I remember reading a New England Journal review  years ago, to like 46 different genes. I mean, it's just tremendous, and really among the newer  agents, there aren't a lot of these that have come out that really have dependable activity  against this drug. The one, the options we've got listed here, for a number of those in the  audience, or in the virtual audience, I should say, listening, is that they don't use amsulbactam  9 grams every 8 hours. That's a big dose, and most people are used to the 3 grams Q6, something  like that, but actually as part of a CRAB regimen, the higher the dose is actually what we recommend.  Again, trying to get enough sulbactam to actually have activity. Minocycline, higher doses of this  as well, 200 milligrams every 12 hours, and of the tetracycline drugs, this one has the most data for treating our carbapenem-resistant acinetobacter species. Tigacycline, there are  some concerns over some boxed warnings and mortality. It is an alternative to minocycline, keeping in mind, tigacycline does not concentrate very well in the bloodstream,  and then the polymyxin-meropenem-extended infusion, you can consider as part of a combination therapy. It's a consideration, but there are a number of carbapenem-resistant  isolates out there, and as a fit or a call, there actually was after we, it always happens,  right, Tatiana, we turn in our slides and something's published, right? That's just kind of like how it works, but there actually was a paper just released in antimicrobial agents  and chemotherapy. I highly recommend people read it, along with the editorial by a good friend of  mine, Emily Heil at the University of Maryland, that talks about sophitercol's role, and a lot  of what we see within this is, again, very few patients, some definite resistance can occur on  therapy, so for that reason, sophitercol really is recommended as a combination therapy if you're  going to use it, but again, it's going to be more when other things are not an option, and because this is a critical care audience, I think it's really important to remember  that this is a three-hour infusion, and so for those patients that require this antibiotic, you're talking about nine hours a day where that line could be taken up depending on your  compatibilities, so I think that's a really, really important point when you're looking at that drug from the practical aspect of administering this as an option in an ICU setting.  All right, so I think we're done here with these cases. I think we're going to go into our questions and kind of see how our folks, let's see what we learn, right, Tatiana?  Yeah, so we get a rapid diagnostic call, patient's been intubated, receiving some vasopressin support  minimal, bronchoscopy was performed earlier in the day, and now microbiology's calling, saying hey, they got an Acinetobacter, and they are detecting this OXA48-like gene,  so what would be the first line regimen that you would recommend? Let's see what our audience has  here. This would be a tough case for sure, but yeah, Acinetobacter is just one of those organisms that there just truly is not, you know, a lot of these newer agents like that  we've talked about do not have activity against this. Polls are open, people are voting, we're  going to keep it open a bit longer to make sure everyone gets a chance. Yeah, definitely, give  everybody a good, we had a great participation here. Tracy had a question, in these cases we're  leaning towards Banxosin as our first empiric regimen, are any sites going to a Banxcefepine  to try to decrease the risk of maybe some proposed synergistic AKI with Bancomycin? We've  talked about that, it's not, Zosyn is quite the drug, right, people get used to it, they prescribe  it a lot. I haven't seen that as much. Tatiana, have you seen that at all? Yes, I actually have,  so when the susceptibilities on the antidiagram is equivalent, when they are equivalent, then we consider that, and so somebody earlier mentioned was the diaphragm injured, and that  would be one of the factors to take into consideration with the prior case with gunshot  wounds to the abdomen and to the chest, and so we look at all of those, what are the risks for  anaerobes, and I think it's reasonable to not cover anaerobes if it's pulmonary source only  without a lung abscess or a concern for anaerobes for a different etiology, so I think it's  reasonable to consider, and it's always a controversial discussion, as Dr. Dobbs mentioned.  Yeah, exactly, yeah, yeah, and so that's a great question. One thing I would point out is that there  could be some major changes in the next few years with vancomycin, and this is a discussion for  another webinar, maybe next year, Tatiana, but vancomycin like the daptomycin lenazolid  are much more affordable now, and so there is a push, we're presenting some data actually in Lisbon  headed up by our group and Jamie Wagner that is looking at that as because of the cost savings  potentially. It's going to be interesting to see if bank remains a first-line drug, but I see in  our poll, to stay on task here, most people, yes, high-dose amylobactam with metacycline, I agree  that would be our next, our go-to as far as, you know, we try to keep our high-dose amylobactam, and then, you know, polymyxins, a lot of adverse effects, somebody on pressors,  metacycline definitely has some decent data, that would be a reasonable approach. So our next  question, next poll question, a patient's being transferred from the floor of the ICU, worsening  respiratory status due to a, what looks to be a hospital-acquired pneumonia from a DTR pseudomonas.  So what would your first-line treatment be? Do we have ceftazab bactam, ceftolzantazobactam,  sofideracol, or imipenemsilstatin relabactam? There is a question from someone that says, what side effects are you seeing with high-dose amylobactam for CRAB? Honestly,  it's pretty well tolerated. I haven't seen a lot of bad adverse effects or stopping the drug.  Tatiana, have you had any? No, I haven't seen that either. We always worry about risk of AIN,  or risk of altered sensorium in these individuals who already have many reasons to have altered  sensorium. And our antibiotics are often blamed and culprits in some of those. But I have to say  that I anecdotally have not seen clinically all of that, despite my concerns. It makes my renal  adjustment on the three grams, can you see it? Somebody's got to really convince me they have  renal insufficiency to do that, you know what I mean? But anyway, all right, our polls, are we  good? There we go. So yeah, so ceftolzantazobactam every eight hours, definitely are the recommended  drug from the guidance document from IDSA, has a lot of clinical data out there. Ceftazav, I agree,  there would be some, you know, use for that potentially, but probably not over ceftolzantazobactam  if you're able to test that and have that ability. Okay, so question three, what drug  characteristics the best predictor for removal during CBBHD? So we've got A, low molecular weight,  B, high degree of protein binding, C, high volume of distribution, or D, low renal clearance.  So Ashley, one of my former graduates, sorry to embarrass you, Ashley, she's a wonderful, awesome future critical care pharmacist, says we've seen an increased incidence of COVID-19  associated pulmonary aspergillosis in our critically ill patients. Is your institution adding on antifungal coverage when your COVID-19 patients have a worsening pneumonia?  Are you waiting for positive cultures for treatment? That is a great question, she was trained well, not by me, I'm kidding. Tatiana, what are y'all doing there for these patients?  So very rarely have we added empiric anti-mold coverage. For our patients, we have been,  again, very fortunate that we haven't seen a lot of invasive mold infections, but it is always a  concern and we are always getting, you know, beta-D-glucan and galactamannan and looking for  some of those findings, lack of clinical improvement on antibacterials and, you know, obtaining as much data as possible. I have to say in a handful of cases, have I added this  in the setting of rapid clinical decline and, you know, concern for this, but not routinely.  Yeah, I would, all I would say is one word, ditto. That's exactly what we have done. Not common,  but it has been done on occasion, especially in these very, very sick, critically ill, ventilated patients. So Ashley, thank you for your question. All right, so everybody put low  molecular weight. Yeah, exactly right. So that's going to be a drug that's going to be removed a  lot. High degree of protein binding, not so much, and the others are not correct because it'd be  the opposite. Okay, so let's move on to our last poll question here. So an ICU patient day 20 of  her stay with a documented sulfa allergy develops a new oxygen requirement, four liters O2 nasal  cannula, and it has a T max of 102 degrees Fahrenheit. Respiratory culture demonstrates stenotrophin monosmaltophilia growth. Their history is significant for AML. What would  likely be the best next step in managing their, this patient, assuming you have confirmed  susceptibilities? So we've got A colonization, do not treat, B ceftazidime abibactam monotherapy,  C cefetiracol and minocycline combination therapy, or D minocycline and levofloxacin combination therapy. So we'll, we'll open the polls up here and, uh, for one of my favorite  organisms to talk about. Um, so Tatiana, wouldn't it have been nice if we could have done this from  Puerto Rico? Yeah, it would have been wonderful. Um, we will have an opportunity to do something  similar soon. I think that's a great idea. Uh, Puerto Rico I've been to one time and had a  wonderful time. Uh, it was a beautiful place. So hopefully we'll get to go there at some point.  Um, yeah, so our final poll is in and it looks like minocycline and levofloxacin. Yeah, I agree  that, you know, if you got those agents and you've got confirmed susceptibility problem is you got a  sulfa allergy here, you would definitely want to use that if it was available, trim sulfa, but if  not, we're going to go, uh, with our minocycline and levofloxacin combination therapy. So, uh,  with that, I know we got, we'll, we'll hang on here for, I know we're right at the top of the  hour. We respect people's time. Thank you, Tatiana. Uh, that was a lot of fun. We should do that again  soon. Um, but, uh, we, we will have some time for any further additional questions that we've  tried to answer these throughout, but if there are any more, we'll hang on here just a second.  Thank you, Chris. And to the team. Yes. ProCE, SCCM, the Society of ID Pharmacists. Thank you.  Uh, it was a great, great, great opportunity and a great team to make this happen behind the  scenes. There's a lot of people behind the scenes making sure this is running well and we appreciate  it. Yes. And thank you all for being with us and participating and answering the questions.  It's been fun. Yeah. Thank you, Dr. Bland and Dr. Calvano. I don't see any additional  questions except one asking when will slides be available. They'll be available very soon on the  ProCE site. So everybody keep your eyes peeled there. Um, unless you have any closing remarks,  I can finish this, finish this out here. Okay. I think we're good. Great. Well, thank you all  so much. Enjoy the rest of the SCCM program. And most of all, thank you to the audience for your  great questions and thank you to Dr. Bland and Dr. Calvano for a great presentation. We'll see you on the next webinar soon.

Video Summary

The webinar discussed the treatment of bacterial pneumonia in critically ill patients, focusing on the use of antimicrobial agents. The presenters presented several case scenarios and asked the audience to choose the appropriate treatment options. The cases included patients with hospital-acquired pneumonia, multidrug-resistant pseudomonas infection, and ventilator-associated pneumonia. The audience was asked to consider various factors, such as the patient's clinical condition, resistance patterns, and drug characteristics, in making their treatment decisions. The presenters also discussed the use of rapid diagnostic tests and the challenges of treating infections in patients on continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO). The webinar emphasized the importance of considering the specific factors of each case when making treatment decisions and highlighted the need for close collaboration between healthcare professionals in optimizing patient care.

Asset Subtitle

Pulmonary, Infection, Pharmacology, 2022

Asset Caption

The goal of this activity is to improve the knowledge and competence of health care providers about the diagnosis, treatment, and management of HABP/VABP in critically ill patients. Learning Objectives: -Describe the role of rapid diagnostics in HABP/VABP caused by MDR gram-negative infections -Appropriately use new antimicrobial agents for both empiric and targeted therapy in MDR gram-negative HABP/VABP -Identify strategies for managing critically ill patients with unique clinical scenarios, such as augmented or diminished renal clearance -Implement effective approaches to antimicrobial stewardship and minimizing TTET This program is supported by educational grants from AbbVie and Merck Sharp & Dohme Corp

Meta Tag

Content Type Presentation

Knowledge Area Pulmonary

Knowledge Area Infection

Knowledge Area Pharmacology

Knowledge Level Advanced

Membership Level Select

Tag Ventilator Associated Pneumonia VAP

Tag Nosocomial Infection

Tag Antibiotics

Year 2022

Keywords

bacterial pneumonia

critically ill patients

antimicrobial agents

hospital-acquired pneumonia

multidrug-resistant pseudomonas infection

ventilator-associated pneumonia

rapid diagnostic tests

continuous renal replacement therapy

extracorporeal membrane oxygenation

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