SCCM Resource Library-Making the Most of the Clinical Toolbox: Improving Outcomes in HABP and VABP

Video Transcription

All right. Well, I think we'll get started here. I just want to welcome everyone to this program. I'm Maren Coliff from Washington University in St. Louis.  And with me on the podium here, we have Debbie Goff from The Ohio State and Richard Wundering, who's from Northwestern University in Chicago.  And we're going to have a session on nosocomial pneumonia, titled Making the Most of the Clinical Toolbox.  Really, in some ways, following up on the talks that we had earlier this morning in the same room.  The disclosures, you have those available to you, as well as all the information on all of us. And we've got a couple of polling questions that we're going to go through quickly.  First one is, how confident are you currently in your ability to select empiric antibiotic therapy for patients with HAP and VAP? All right.  I'm going to turn it over now to Rich Wundering, who's going to talk to us a little bit about the epidemiology, micro, and clinical consequences associated with HAP and VAP.  Good afternoon. These are my disclosures that you can see. So nosocomial pneumonia is important. This is recent epidemiologic data from the CDC looking at acute care hospitals.  And what you can see is that pneumonia causes 25% or more of the nosocomial infections in everybody's hospital.  If you add the tracheal bronchitis or lower respiratory tract infections, maybe even a little bit more.  And it's really a major player with surgical site infections, GI infections, urinary tract infections, making up many of the other ones, and particularly in the intensive care unit.  What is disturbing about their data is the fact that between 2011 and 2015, the rates of pneumonia remained unchanged despite significant reductions in urinary tract infections and  surgical site infections. Now one of the themes that you may hear today is that we actually have done some important work in preventing pneumonia.  And we think that some types of pneumonia are actually less frequent. But in fact, the multidrug-resistant pneumonias may be increasing.  Part of the reason for that is this data that looks at the number of patients with nosocomial pneumonia who are immunocompromised.  And what you can see on the upper graph is that any immunocompromising condition is increasing.  And so these are patients who are more susceptible to pneumonia and have worse outcomes from pneumonia.  And that's actually despite HIV not playing as big a role as it did in the past. So we have many new chemotherapy drugs, much more use of new monoclonal antibodies that  are immunocompromising. And frankly, patients with immunocompromising conditions are surviving longer.  And so they're making up a greater percentage of our population in the hospital, including in the intensive care unit.  Now just to put this in perspective, we're going to present a case that will continue through much of the discussion. This is a 64-year-old man with emphysema and heart failure.  He's had multiple admissions in the past year for exacerbations of both. He's currently hospitalized for CHF and pneumonia, was treated with ceftriaxone and azithro,  getting 40 milligrams of prednisone for five days for his COPD. And he's admitted to the MICU on hospital day five.  So after admission with a new fever, increasing respiratory distress, and need for mechanical ventilation. And his chest x-ray shows a new right lower lobe infiltrate.  There's a little residual in his left lower lobe. That was the original concern for community-acquired pneumonia.  So the question, the poll here is, this patient's on the ventilator. Saturation is 94% on 50% oxygen. He's got a low creatinine, a very low creatinine, and he's not hypotensive.  How would you manage this patient? Start miripenem, vancotobra, send tracheal aspirin for culture, and start piptazo and vanco. Perform BAL, start piptazo and vanco.  Or perform BAL and MRSA-PCR, and then start miripenem.  All right. So interesting distribution, mainly around the two options. Surprisingly, we got 18% who would do the BAL and MRSA-PCR.  I think probably the one answer that is not correct is actually one. All of our guidelines would suggest you need to get some kind of culture.  And maybe the question fooled you in that way. But we need some kind of respiratory culture in order to do good antibiotic stewardship,  to be able to de-escalate no matter what antibiotic you started. And we'll go into things that may influence your decision about some of the others as we go through this symposium.  Now one of the interesting things that has changed is illustrated by this study. It was a study looking at improving compliance with guideline treatment for HapVap.  And they looked at all pneumonias who came to the intensive care unit. And so 413 patients, a multicenter study.  One of the most interesting pieces of data is actually ignored and not really even discussed much in the paper.  And that is only 10% of patients had no risk factors for MDR pathogens. So we used to have a guideline that said, if you have no risk factors, you can use narrow  spectrum antibiotics. That's really a very small minority of patients, especially in a medical ICU. Maybe some of the surgical ICUs, you can get by with this.  And only about 10% actually got pathogen-directed therapy, so that they had a culture that they could do this.  The other interesting thing from this study, and this is what's becoming more and more obvious in many institutions, is that if you look at the number of patients who have  ventilator-associated pneumonia versus those that have HCAP or hospital-acquired pneumonia that requires ventilation, it's actually an even split.  So we think we're decreasing VAP rates, but we're seeing much higher rates of hospital-acquired pneumonia that require intubation as part of their management.  And then there's a significant proportion of patients who have pneumonia but can get by with non-invasive ventilation or high-flow oxygen therapy as well.  So in increasing rates of ventilator or ventilated HAP patients, we also have this issue of what to do with HCAP. We've decided to get rid of that definition.  This is a huge study from New York City hospitals with 280,000 patients. And community-acquired pneumonia is clearly the most common cause of pneumonia in a hospitalized patient.  VAP is actually the least common of the four categories. But what you see here is that the old definition of HCAP is associated with a higher mortality,  greater length of stay, greater risk of readmission. So even though we've thrown away that term, those patients haven't gone away.  We just need to figure out a better way to define them. And I'll come back to that in a minute. The pathogens are actually less controversial. They vary somewhat.  This is one study that looks at a very large population. And what you see is that Staph aureus, particularly MRSA, is a big player.  And Pseudomonas, and then a variety of Enterobacteriaceae, Klebsiella, Enterobacter E. coli, usually are some of the top three.  And then you've got some other issues, say Stenotrophomonas or Acinetobacter, that have particular importance for your empirical antibiotic therapy.  And if you look at what the CDC and many of the other organizations that are trying to address the issue of antibiotic resistance, there's three main groups of pathogens that  we worry about. One is Pseudomonas. It's the leading cause of opportunistic infections. It's going to be in almost everybody's hospital.  So this is ubiquitous in the water, probably in the food that you're eating right now. And it doesn't cause infection unless you've been exposed to antibiotics.  But everybody has it. It's a great propensity to create biofilms, get on plastic and stay, and a high instance of resistance.  So our hand drug-resistant pathogens are disproportionately Pseudomonas. The Enterobacteriaceae species, and I'll just warn you they're changing the name on us again,  so it'll be called Enterobacteriales, I think, is the latest thing. But they're a group of organisms. They're enteric organisms. They kind of pass things back and forth.  But there the concern is that they have resistance issues. They've always been a cause of pneumonia, probably always in your hospital.  Which particular pathogen may vary, Klebsiella versus Enterobacter, but the resistance issues  with ESBLs and now increasingly carbapenem resistance are something that many of us face. And then the real concern is Asnetobacter.  In institutions that have this, it's developing resistance to carbapenems, our kind of most  broad-spectrum antibiotic, and it's a very serious issue when you have that in your hospital. Thankfully, it has the greatest variability from hospital to hospital, with some having  very few cases, some having it be one of their most common pathogens. Now the risk factors for MDR pathogens were addressed in the ATSI-DSA guidelines.  For MDR pathogens in general, there's a list of things like prior antibiotic therapy, septic shock, ARDS, hospitalization and acute renal failure.  That's for a generic, multidrug-resistant pathogen. So you would be treating for MRSA, Pseudomonas, double coverage for Gram-negatives. Those are the risk factors for it.  But when you try and tease out, okay, do I need to cover for MRSA? Do I need to specifically cover for Pseudomonas or Asnetobacter? It's not very helpful.  It's prior antibiotic therapy. And if your institution is like mine, I'm not sure we get hardly any patients for sure  who've been in the hospital for a while who haven't seen prior antibiotics. And so it doesn't distinguish between these different pathogens that require different therapy.  Now this is a study from Marin that actually illustrates another issue that's coming up. And they looked at all of their patients with pneumonia on mechanical ventilation.  A third, approximately, are culture-negative. And these are very interesting. Why are they culture-negative?  Is it because we gave antibiotics and they're an easy-to-treat pathogen and so it disappears from culture? Are culture techniques not adequate for some of these?  They also raise a potential explanation in that some of these may actually be viral. And so they had a fairly high instance of respiratory viruses that are nosocomally acquired.  However, if you look at the bacteria, what you see is that antibiotic-resistant pathogens clearly outnumber their antibiotic-susceptible equivalents in this study.  And this is a different thing that is clearly happening in almost every hospital. If you look at non-ICU versus ICU patients, what you're seeing is increasing rates of  resistance in both.  In the non-ICU patients, they're starting from a different baseline here in this comparison study of 07 to 11 versus later. But the resistance is increasing dramatically in both.  And so the non-ICU patients are not necessarily patients who don't have multidrug-resistant pathogens.  So what you're all going to end up having to start to understand, and you don't need to understand these definitions of resistant versus MDR, XDR, or PDR.  But the fact is that these are going to start to enter into our discussions, that we have  patients who are at risk for resistance, and you have to understand your resistance patterns to give appropriate empirical antibiotic therapy.  And now I'll turn it over to Debbie to talk about considerations for antibiotic therapy. »» Thanks, Rich. Well, remember when PDR used to stand for a physician desk reference?  Now it's pan-drug resistance. Who would have thought? So I'm going to talk about consideration of antibiotics for MDR infections. And there's my disclosures.  So we had the case that was reviewed previously. So overnight the team had started PIP-Taso 3.375QA plus VANC. Non-bronchoscopic BAL was performed.  Gram stain did not detect organisms. The MRSA PCR was negative. So what would you do when you round on the patient in the morning? Increase your PIP-Taso to a higher dose.  Switch to muropenem and continue your VANC. Switch to some of the newer gram-negative agents, ceftazidine-AB-Bactam, ceftolazine-Tasobactam,  or just continue current therapy until your culture results definitively tell you what to do. All right. Well, I guess that answers that, 57%.  Continue current therapy until the culture results return. So how many are practicing in a hospital with rapid diagnostic tests? Just raise your hand.  Wow, not as many as we would hope. So you're going to be waiting a long time for your results. That's like four days. Let's hope your antibiotics were appropriate.  So when we look at the guidelines, the 2016 IDSA ATS guidelines for empiric therapy, which is how we're selecting them, we have for gram-positives, the vancomycin or linezolid,  the gram-negatives were anti-pseudomonal penicillins, the cephalosporins, carbapenems in panallergic patients, ACE, Trianam, and then the non-beta-lactams, the fluoroquinolones,  although those are really falling kind of out of favor due to the new adverse events that keep getting reported, aminoglycosides, and polymyxins, although at this point in  time hopefully we're not using those with our newer agents that are safer and have proven to be more effective.  The European guidelines are set up a little bit differently, not organism-based. It's really based on assessment of the risk of multidrug resistance and then if you have  sepsis or no sepsis, whether you use single or dual coverage for the gram-negatives. So when you look at, this is interesting, this was done in a European ICU.  They looked at their four or six ICUs in their hospital and applied the guidelines and looked at the percent that would be appropriately treated or over-treated or under-treated,  two very important things to consider. And it's amazing. The percent over-treated would represent 60%. That's pretty high.  And you know, we preach we need to get it right, right from the start, which drives us to such broad-spectrum antibiotic therapy.  But then to see this, if you apply the guidelines, 60% of the time you're over-treating.  But it's such a dilemma in the ICU because you can't afford to be wrong. So it's not real surprising that it's this high of a percentage, but it tells you there's  clearly an opportunity to do better. And you know, you can only streamline and get the therapy right if you know what the organism is.  So again, I think it advocates for rapid diagnostic testing to help guide the most appropriate therapy quickly. All right. So you know, this is an older study.  Looking at early appropriate therapy, why do we care? Because it clearly impacts outcome. So you look at attributable mortality, if you got it right and got them on early therapy  that was appropriate or delayed, 11% versus 28%. That's a big difference. So the data really hasn't changed.  And again, you know, the longer you're on ineffective therapy, the worse your outcome. No surprise.  So are you in a hospital where you routinely obtain institution or unit-specific antibiograms before prescribing empiric antibiotic therapy?  Yes, no, or you're not sure if your hospital provides unit-specific antibiograms.  Great. So it looks like most hospitals do. And it really should be something that your microbiology lab provides for you. And let's just look at some of the reasons why.  So the antibiogram, you know, if you think of it, unit-level antibiogram. I remember doing our first one in 1999, a little bit long time ago. And we were shocked.  We did it in our medical ICU unit first. And the amount of gram-negative resistance was profoundly different.  And so we realized we were guiding people to wrong therapy using the hospital antibiogram. And now I think it's pretty commonplace.  But you know, the antibiograms, I think it's amazing that we tolerate what we do. You're prescribing empiric therapy, your best-educated guest, off of an antibiogram.  That's one year outdated the minute you get it. That's the best we can do, a year-old data. So you know, you're looking at 2019 data, and then you get it about halfway into 2020.  So it's really about 18 months outdated. And that's what you're using to guide your therapy. So can we do a little better? Yes. Combination antibiograms.  Again, the data is a year old, but it does let you know if you're going to prescribe double gram-negative coverage, what two combinations might provide better coverage.  And that's really important. We implemented that in our medical ICU and surgical ICU many years ago.  It was quite telling because, you know, it's a random opinion-based, what do I put as my second drug. You know, you might like aminoglycosides, you might like fluoroquinolones.  It was opinion-based. So we can do better. And that's what a combination antibiogram does. The ultimate is real-time antibiograms. I mean, think about this.  How long have we had Epic and Cerner? They should be doing something for us besides frustrating us. So they should be able to figure out how to get real-time data.  And it makes sense. Somebody in bioinformatics knows how to do that. If we as clinicians don't demand it, it doesn't get done because clearly it's a lot more work.  But the idea of a real-time antibiogram is it interfaces with the micro lab in real time. So you're getting data of resistance that's actually reflective of the patients in your  hospital in real time. So it's like a rolling antibiogram. There's other ones called syndromic antibiograms.  Courtney Hebert at Ohio State is an infectious disease physician bioinformatics specialist. How cool is that? Her knowledge level is amazing.  And that's what she started studying with our team is can we look at risk factors and prior antibiotic exposure and give you a predictive model of what antibiotic would be best?  How cool is that? I mean, that's taking it up a step. So I think the days of relying on year-old antibiograms, just not optimal care.  So we need to expect more from our micro labs and our IT teams to help us really figure out what is best of care. And that's how we do it.  So I think this is a really great way for microbiology to be moving too. And it's the marriage of micro and IT.  So when you look at a combination antibiogram, if you look on the right of the ICU and just  take like Piptazo, you know, if it's resistant to that and you're going to add a second agent hoping to increase susceptibility, you can see the difference between a fluoroquinolone  and an aminoglycoside. And I think it's real important to do this because, you know, when we work in our surgical  ICU, Tony Gerlach is our PharmD there, you know, surgeons don't really love aminoglycosides. But if you have data like this to say, no, you don't love it, but it's what's best, and  I'll monitor it and watch, that provides optimal care. So you really have to try to do what's best based on your own data. And it will vary from hospital to hospital. All right.  And then this study looked at 290 muropenem non-susceptible pseudomonas from 34 US hospitals. And on the x-axis are the percent resistance to the other gram-negative agents.  So if you look at Piptazo, 64% resistance, muropenem resistant isolates. What percent would be susceptible to ceftolazantazo or ceftazidine avbactam? And look at it.  I mean, those are really good numbers. You're up at 85% and 70%. So when you're looking at a stewardship program and doing this for a really long time, many  perceive them as the program of no, no, you can't have this, nope, you need to call us for prior authorization, no, we're not putting those drugs on formulary because they cost  too much, absolutely insane. So when you look at a study like this and see this percent susceptible to these agents,  and this is your patient with HAP or VAP in the ICU, critically ill and septic shock, you're going to deny them expensive antibiotic therapy? I mean, how? So the data is there.  So you know, your micro lab has to provide susceptibility testing.  But it's kind of counterintuitive to say, well, we're not going to let you have these until you fail everything else. I mean, we already know what that outcome is.  So trying to prioritize the role for these newer agents that clearly have better gram-negative susceptibility is the job of stewardship working together with the ICU clinicians.  They see the highest rates of resistance. So it has to be a partnership in trying to strategize how to use these drugs.  My opinion is the ICUs have a different strategy than non-ICUs. And so it's not just one rule for the whole hospital. No, we're going to restrict these.  No one can use them unless you have the following 20 criteria met, meaning you're never going to get them.  The ICU patient population is the population that needs these newer agents. But you have to be responsible in how you execute that.  So combination antibiogram for Pseudomonas aeruginosa, again, look at the right side the ICU and you can see a single agent.  If you look at the carbapenems and you're going to add a second agent, which one are you going to add? So you see those aminoglycosides keep coming up as the better choice.  And it's really important because those are a tough cell. They're not that fun to use. Okay. I think I went the wrong way with the arrow. I'm sorry.  Like, didn't I just talk about that slide? Yes, I did.  Okay. Sorry. We were up at 5 a.m. for our first talk. So it took me a moment to realize that I had already given that slide. All right.  So this one is the susceptibility to the enterobacteriaceae in respiratory isolates. And I see another common theme.  If you look at multidrug resistance for ceftazidine AV, you get 100% coverage. If you look at CRE, 100% with ceftazidine AV.  Ceftolazine is a little bit better for the pseudomonas, so not too surprising here. But clearly, if you're having a CRE outbreak, you know, it's pretty intuitive here what  antibiotic is going to be your best option. All right. Let's turn now to PKPD. So we've got really four parameters, absorption, distribution, metabolism, and excretion.  In the critically ill patients, these are all altered. So trying to personalize antibiotic dosing is so important.  Jason Roberts has published so many studies on PKPD out of Australia. And I like this because it's a picture. It really describes.  If you have increased volumes of distribution, you know, you see alterations in the C-max, important for aminoglycoside dosing, changes in the area under the curve,  important with the fluoroquinolones, increased clearance. You see decreased time above the MIC. That's how we dose all the beta-lactams.  Or if you have increasing MICs, you know, we get these nursing home patients with altered MICs that are escalated because they've had so much prior antibiotic exposure.  It changes all of the parameters. So the kind of takeaway from his paper is there is no one dose fits all when you're talking  about ICU, and that's really the skill of the ICU physicians and pharmacists is trying to customize dosing of these agents.  So you look at variability of the beta-lactam specifically for volume of distribution. The little circle are healthy volunteers, and the squares are ICU patients.  And every single antibiotic there has a major change. In this study, looking at the insufficient beta-lactam concentration. So they had 80 patients. This is from four Belgium ICUs.  And they looked at, you know, does the first dose get target attainment? And the only one that did was muropenem.  Fifty-seven of the 80 patients were able to obtain time above the MIC greater than four for the dosing interval.  So about 75% of the patients were able to achieve the target attainment for just one drug. So, you know, it clearly is an issue, and individualizing doses is important.  This is from a study in CID that looked at the PKPD variability in the ICU for multiple antibiotics, whether it's at 50% time above or 100%, it varies significantly.  And when they looked at the specific antibiotics, you know, they really didn't see a difference between the 50% or the 100% time above the MIC.  One-fifth of patients in this study did not achieve the minimum target attainment. And if you looked at ideal target attainment, it was less than 50% of patients achieved it.  So this study really showed that it's very difficult trying to figure out how to get the right dose in the ICU patient.  And it's not as simple as just give everybody continuous infusion. You know, they looked at Apache scores, SOFA scores, and it was very variable.  So the study kind of concludes it's a challenge. We need more research, but it's clearly not one dose fits all.  A different study looking at beta-lactams in the critically ill patients, 98 of them with gram-negative bloodstream infections, showed it was the fraction  of the time above the MIC ratio of 1.3 was the significant predictor of positive outcome. And positive outcome was defined as they did not have a change in their antibiotic therapy  and completed the course that they were on and survived. So this was one of our studies, gosh, now several years old, Carrie Bauer and I did  with our ICU physicians looking at, you know, at that point in time, this was back in 2003, I think, the only study to date was Tom Lodese's study  with extended infusion PIP-TASO showing a significant mortality benefit compared to 30-minute infusion. So we were using more cefepime, and no one had ever studied it.  So we decided to study it, and, you know, we found a mortality benefit. And you look at a meaningful stewardship initiative, this was one of them.  You know, we partnered with our ICU physicians, and it's a pain to give extended infusion. It's a big pain for the nursing staff.  And so they really wanted to look at this and do something meaningful. They're like, we'll partner with you and do it, but when we get the results,  if we can't find a difference, stop telling us to do extended infusion. And then we got the results, and it was really amazing. And so this got implemented house-wide.  But other studies have been done more recently. So this is the Association of Outcome and Augmented Renal Clearance in the BLING-2 study.  And they compared different dosing strategies, the continuous infusion versus 30-minute, and really didn't find a correlation.  And so, you know, really concluded there were so many other variables, how critically ill they were, their APACHE score, their SOFA score.  It wasn't as simple as give everybody extended infusion, and they're going to do better. So again, this really concluded that we need more studies,  we need more data, and one dose for all doesn't work. And with that, I'll turn it back over to you, Rich. Thank you.  So we're going to take a little bit closer look at some of these new agents that have come up for treatment of pneumonia. We're actually reasonably happy.  We have at least nine new antibiotics that are in the pipeline or already approved. The two at the top there that were mentioned already, ceftolazone tezobactam and ceftazavibactam,  are actually approved for pneumonia, hospital-acquired pneumonia. The rest are not yet approved, but some of them are actually on the market and potentially available for use.  The two newer agents for nosocomial pneumonia are actually still cephalosporins, beta-lactam inhibitor combinations, ceftazavi.  You recognize the ceftazidine, the abibactam is the additional thing there, a newer class or type of beta-lactamases. And it is dosed at two and a half grams every eight hours.  The ceftolazone tezobactam, you recognize the tezobactam from the piperacillin tezobactam. So the cephalosporin is the new agent there.  And it seems to have increased activity against some of the, particularly pseudomonas. It's also FDA approved for nosocomial pneumonia.  Importantly, and I'll probably try and mention this a couple of times, the dose that you might have learned to use for urinary tract infections  or complicated intra-abdominal infections is too low for pneumonia. Going back to some of Debbie's comments about the ICU is different than the floor patient  and you have to modify this. So the dose that was studied was twice the dose that was approved for intra-abdominal  and urinary, complicated urinary tract infections, three grams every eight hours.  So the reproved study was the study of ceftazabibactam for nosocomial pneumonia. It was a randomized controlled multicenter phase three non-inferiority trial,  the standard kind of FDA study for this. They enrolled more than 850 patients with nosocomial pneumonia. A third were ventilator associated bacterial pneumonia. Early sick patients.  And the predominant pathogens in this study was Klebsiella pseudomonas. They had Staph aureus and then some polymicrobial.  Probably the most interesting aspect of this study was they actually had 100 patients. So more than a quarter actually had at least one ceftaz non-susceptible gram-negative pathogen  on culture. So you're seeing that the combination of abibactam does rescue the ceftazidine in these cases. And the comparator drug was meropenem 1 gram Q8 hours.  This is the primary efficacy endpoints. These are the kinds of endpoints that you see for most trials for FDA approval.  There's a modified intent to treat population that showed equivalence. The clinically valuable population was equivalent.  If you start to break it up, if that modified intent to treat population, you see both VAP and non-VAP had equivalent outcomes. In the clinically valuable it was the same.  So clearly passed the criteria for equivalence to meropenem. And this is the study that got the indication for ceftaz abibactam for nosocomial pneumonia.  If you look specifically at some important common pathogens in the study, what you see is that there was no significant difference between ceftaz-Avi and meropenem for ceftaz-Avi  or pseudomonas. But consistently for both of them, or consistently for ceftaz-Avi, both in clinical cure and  favorable microbiologic response, it was much better for ceftaz-Avi than it was for pseudomonas. The clinical rates for meropenem were equivalent.  The microbiologic showed the same kind of pattern that pseudomonas was a worse actor in this study, even with the meropenem comparator.  So it's an approved drug for use for nosocomial pneumonia. The ceftalizone tezobactam is the aspect NP trial.  Once again, randomized, controlled, multicenter, phase III, non-inferiority, 725 patients with FAP or hospital-acquired pneumonia. So these were all ventilated patients.  The higher dose of the ceftalizone tezobactam, once again, you're looking at the most common pathogens were gram-negative that got into the study.  Pseudomonas was about a quarter of the population. And very few MDR or XDR pathogens here, mainly because of the study design.  So if you were resistant to the meropenem, you couldn't stay in the study. The entrobacteriaceae, on the other hand, were the majority of the patients that were  actually enrolled in the study. And here's the primary endpoint was overall clinical cure. They were equivalent at the test of cure.  Ventilator-associated bacterial pneumonia was equivalent. And hospital-acquired pneumonia actually had worse outcomes for clinical cure than  what VAP did, not statistically significant, and no difference between the two drugs. Once again, looking at per-pathogen kind of cures, what you see is overall no difference,  no difference in the entrobacteriaceae, including the ones that produce ESBLs. And a little bit surprising is that Pseudomonas was equivalent with Ceftolazontazone compared  to meropenem. And once again, the MDR and XDR, you can see the fall off in clinical success rates with those, but no difference between the two drugs.  So these drugs are on the market, or I'm sorry, they are released, they are FDA approved for the indication that we're talking about.  The question that we'd like to pull you on now is, do you have restrictions on the use of these newer cephalosporin beta-lactamase inhibitors in your ICU?  All right, so 71% have some kind of restrictions. Only about 15% have no restrictions on their use. So I am not surprised by these results.  I don't think you'd surprise any of us here. So these new cephalosporin beta-lactamase inhibitors are important new options for difficult-to-treat gram-negative pathogens.  Potential for empiric therapy for critically ill patients who have risk factors or a history of infection with very resistant organisms, XDR, Pseudomonas, or CREs.  And it's important to get an antibiotic and microbiologic history for all of these patients to know which are the appropriate patients for responsible use of these.  And as we've mentioned, these drugs are no different than any of the other beta-lactams that Debbie was talking about. They still need to be optimized.  Clearly ceftolazone-tazobactam should not be used at the dose that was used for urinary tract infections and complicated intra-abdominal infections.  Now, there are other drugs that are on the market, whether they're on your formulary or not. One is miripenem-baber-bactem.  So once again, a familiar drug combined with a new beta-lactamase inhibitor. This was a more complex kind of study.  It's a randomized phase 3 study of miripenem-baber-bactem versus best available therapy for treatment of CRE infections, including hep-bap. So we had 77 patients who were confirmed.  There was a 2-to-1 randomization ratio of miripenem-baber-bactem versus best available therapy.  And high incidence of Klebsiella, 60% almost in the microbiologic intent to treat population. And most of them were KPC-specific resistance patterns.  And what you see is that there's actually a mortality difference between miripenem-baber-bactem and best available therapy.  And clinical cure rate differences, 28-day mortality differences, decreased nephrotoxicity. Now best available therapy for this trial was colistin-based treatment in the majority  of cases. And so that maybe explains some of the nephrotoxicity. It also makes you really question whether a polymyxin-based or intravenous polymyxin-based  therapy should be used anymore. The other important component of this study is that they actually allowed immunocompromised  patients to be in this study, which is something that is excluded from almost all of the other studies.  And the mortality difference that I showed you here is actually driven disproportionately by these immunocompromised patients.  So it's this combination of both resistance and immunocompromise that is the most lethal. Another drug that is on the market that is potentially available that there's starting  to be some data on pneumonia is sofideracol. This is a very interesting molecule. It's actually two cephalosporins linked together by something that grabs iron, a siderophore.  And bacteria love iron. In fact, a lot of their exotoxins are actually designed to try and get iron.  And there's an iron pore that allows this drug to be taken into the bacteria and is not so susceptible to some of the other porin channel mutations.  So this is a potential agent for pneumonia. There's a couple of studies. This is an abstract looking at the phase three randomized double blind study for HAPVAP or HCAP.  It started at the time. HCAP was still a politically correct thing to say. And compared to meropenem 2 grams Q8 hours.  So it's important to point out that this is higher dose meropenem than in all of the other comparison drugs.  And it was shown to be non-inferior to meropenem for 14-day all-cause mortality in comparable clinical cure rates, comparable treatment emergent adverse events.  And if you look at specific pathogens equivalent to this high dose meropenem for almost all of these pathogens.  The other thing that has been studied is the use of inhaled antibiotics. And that has been our kind of therapy of last resort for a while.  There are actually two studies that specifically address this. The first is inhaled amikacin phosphomycin.  These are both of the studies used inhaled agents as an adjunct to intravenous standard of care therapy.  And this study did not show any statistically significant difference in clinical pulmonary infection score, the primary endpoint, nor any differences in the hierarchical secondary  endpoints of clinical cure rates, ventilator ICU free days, or mortality.  This used a delivery mechanism that was designed to deliver the drug to the distal respiratory tract. Same thing was done in this study here.  The inhaled study looking at inhaled amikacin only, once again, it's aerosol in addition to standard of care IV antibiotics.  It's an aerosol delivery mechanism that actually would deliver to the periphery in much higher doses in the 10,000 range for micrograms per milliliter.  But what you can see on the right here is that there was no survival advantage to using inhaled amikacin adjunct.  And so this has led to a little bit of disappointment for many of us who have used aerosolized antibiotics.  I don't think the jury is completely out because in both of these studies, the very highly resistant pathogens, there might have been a little bit of a signal.  But it was studied in much more generic HapBap patients. And so the important thing is that neither of these drugs is going to specifically be on the market. All right.  And I'll turn it back to Marin at this point. All right. All right. What about individualizing therapy to support antimicrobial stewardship and improve clinical outcomes?  We'll go through a few things here, but let's start out with a case. So this is a 35-year-old woman. She's had a motor vehicle accident, closed head injury.  She's in a vegetative state. And so we can debate the merits of treating patients who are in chronic vegetative states.  But the reality in this country is when we're talking about LTACs, we have patients like this that get sent to us.  51 days in an LTAC, there's a trach, weaned to a trach collar, status post multiple courses of antibiotics for various conditions, including urinary tract infections and pneumonia.  And then there's an X-ray done because of a temperature spike. So a common scenario occurring in an LTAC, some LTACs are actually within hospitals or adjacent to them.  We've got eight of them that refer patients to us. And so this is the X-ray, sort of to begin with, if you will. The baseline film for this case. And so what ends up happening?  This patient now, after five days, develops a fever to 38.6, becomes septic looking, respiratory  rate goes up to 24, the heart rate's increased, the blood pressure's dropping, and the respiratory  therapist places the patient back on the ventilator after noting increasing secretions as well. So this is the follow-up film.  Now we see this infiltrate in that left lower lobe that's new compared to the previous film. Something's going on there.  And so the question is, what's the most important consideration for antibiotic selection in a case like this? And it's kind of an obvious answer. This is the poll question.  Go ahead and answer it. But is it the local antibiogram that Debbie talked about, including unit-specific antibiograms,  prior antibiotic exposure, immune status, comorbidities, presence of shock, isolation of prior pathogens, or all of the above?  Hopefully no one will get this one wrong.  Okay. Well, someone did get it wrong. Okay. Go ahead and raise your hand up there. Okay, I'm not going to go there. So 92% picked all of the above.  And yes, we can debate the individual elements here. Some may be more important than others, but the point is there are many considerations  when we're thinking about what to do with a patient like this. And certainly prior exposures of drugs, organisms, all become important.  I happen to work at Barnes-Jewish Hospital, about a 1,400-bed hospital in St. Louis. We have 15 hospitals in our system, and they refer patients to us.  But the point of this slide is that the hospitals are different.  So if I'm down at Parkland Health Center, which is about 130 beds, I'm going to be doing something very differently when it comes to prescribing empiric antibiotic therapy than  I would at Barnes-Jewish Hospital. And that has to do with the fact that larger medical centers are nothing more than collecting  bins for resistance genes, and we know that, and we have data on that. So another polling question here.  Does your unit require automatic ID consultation for the use of broad-spectrum antibiotics, meaning you, as an intensivist, are you able to prescribe these antibiotics, or do you  need to wait until you can get approval?  And I can tell you what my opinion on that is, but we'll wait to see what the responses are here.  Okay, wow. This surprises me. I would not have guessed that. So 80% of you working in an ICU have to get approval before you can prescribe certain antibiotics.  I mean, that blows me away. I mean, Rich, Debbie— No, the other way around. They don't have— Oh, no, they don't. Good. All right. Okay.  Let me go ahead and recalibrate my pacemaker after looking at that. I think I went into VTAC there for a moment, but okay, we're okay.  I feel a little better, but still 20% say that they need an approval. So that's still problematic.  Multidisciplinary critical care, obviously, we all practice that. We all believe in it. It's one of the cores, if you will, when it comes to working in an ICU setting.  We have multidisciplinary teams, and in fact, there are data out there showing that multidisciplinary teams can be beneficial. This is actually one study.  It happens to come from the California Hospital Association and Reporting Task Force, and they just make the simple observation that when they looked at surgical patients in this  particular database from their institutions, that those working in a multidisciplinary care whose care is managed by a multidisciplinary team have better outcomes.  Now that's intuitive to us, but at least we have data supporting that. And when it comes to a multidisciplinary team, and sometimes, you know, we sort of balkanize things.  We look at the intensivists, you know, versus maybe the infection control preventionists or the stewardship people, but the reality is we should all be working together.  This happens to be a study that Jason Burnham published from our institution just looking hospital-wide at patients who received an ID consultation for certain difficult-to-treat  pathogens causing bacteremias primarily. And the point of this is that, yes, you can identify a signal.  When there's some expertise involved, you can see that, for example, patients who have Staph aureus bacteremia, Enterobacteriaceae infections, polymicrobial infections, a positive  blood culture seem to do better. So expertise is key, whether it's you providing it in a unit or someone else.  And Jason's actually extending these results using a tele-ID approach to some of our smaller community hospitals. So let's go to the next polling question here.  Blood cultures in a tracheal aspirate from the patient are sent to the micro lab. So I've already gone through the case with you.  Based on your hospital's antibiogram, what backbone gram-negative bacterial drug would you use in this patient?  So we've already seen the scenario here, multiple prior antibiotics and organisms. Would it be Piptezo, Ceftazidime, Cefepime, Acarbapenem, one of the new agents, or Colistin?  Go ahead and select. And the other thing I'll throw out there is one of those answers is a placebo when it comes to treating pneumonia.  And we'll see if anybody selected it, so, okay. Okay, someone did pick Colistin. So Colistin IV doesn't penetrate well into the lung.  Probably not a great choice here as a backbone drug, even if the organism has in vitro susceptibility to it. It's interesting. Based on the data here, Piptezo, 26%.  Again, we have Cefepime at 20% and Carbapenem's at the number one position, 39%. And that seems to fall in line with what a lot of individuals would agree on.  We've got some recent data like the Moroni study published in JAMA about a year and a  half ago, suggesting that for ESBL bacteremias, Carbapenem's do better than Piperacillin-Tazobactam from a mortality perspective. So let's go back to the case here.  The patient has a GFR of 95, started on Imipenem, 500 milligrams every eight hours, and Vancomycin, one gram every 12.  Fourteen hours later, she's hypotensive, requiring norepinephrine, oxygenation's worsening,  MicroOverLab reports abundant gram-negative bacteria on the gram stain of a tracheal aspirate.  So you've started these broad-spectrum antibiotics, Imipenem and Vancomycin, but now you get this additional data back. So what do you do? There's the X-ray.  It looks like it's getting worse. The patient's not clinically responding. Another polling question here. Do you want to just leave things alone?  Let's just give it some more time, see what happens. Do a BAL. I mean, you've got the tracheal aspirate, but do you not have confidence in it?  Switch the Vanco to Linazolid, even though they didn't report any gram-positives in the sputum. Increase the Imipenem dosing.  We heard about dosing from Debbie to one gram every eight hours. Stop Imipenem, start ceptolazontazobactam, or stop Imi, start ceptazidimabactam. What would you do?  Okay, well, the new agents sort of went out here. That sort of makes sense. In terms of making no change, 4%, you know, we can debate that. About 9% said a BAL.  Again, we've already got a tracheal aspirate showing abundant gram-negatives. So the abundance of answers sort of favor going to a more broad-spectrum aggressive  regimen in this patient who's failing. Do you routinely employ molecular diagnostics to diagnose hospital and ventilator-associated pneumonia?  We sort of got a hand raise earlier, but let's see how many patients in your hospitals actually are managed with these new technologies. Okay, so yes, 24%, no, 76, unsure.  So it's really the minority that are using these molecular diagnostics. These are just from a review article.  Christina Vasquez-Gilamant, who's one of our ID intensivists, has this published. It's on PubMed.  the diagnostics that are available for use in the ICU setting. I'm not going to go through them in detail. The information's out there.  These are either single-test PCR or multiplex PCR, meaning you can test for multiple pathogens.  They're available for blood as well as for respiratory disorders based on syndromic panels, and that information is there.  The key that I want to just throw out there is that the information that you get back is within hours, within a few hours, as opposed to several days to get the organism ID and  susceptibilities back. These are the cleared FDA panels, both on the respiratory side and the pneumonia panel.  The respiratory panel tends to deal more with upper respiratory pathogens. Think of it as being more, if you will, outpatient or community-based.  The pneumonia panel takes into account the nosocomial pathogens as well, along with resistance mechanisms.  And you can see there are several that are now approved by the FDA for pneumonia. I'm going to go through a couple of these quickly, not to belabor them.  This is the BioFire system that can be applied on BAL fluid or sputum. You can see that there's a large array of viruses, like the respiratory panel that you  can identify, a large host of bacteria, including the nosocomial gram negatives, as well as atypical bacteria and a number of resistance genes. So how are these tests useful?  Your tests are useful in identifying organisms, but also in excluding them because of their high sensitivity to allow you then to make more concerted antibiotic decisions.  This is the Curitis assay, again, also looking at a broad range of organisms here on the gram negative, gram positive side, as well as a large number of resistance elements.  So again, you're not getting true susceptibilities, but you're getting the resistance mechanisms in the form of these resistance genes.  If they're not there, that gives confidence in using less broad agents for therapy. And so these new panels can be applied both from a diagnostic stewardship standpoint,  meaning helping to key in on what the organism is. I wasn't thinking Acinetobacter. Now I've got Acinetobacter identified, and I know at my hospital, 70% of them are carbapenem  resistant. Therefore, I need to treat with a specific agent or combination of agents. On the other hand, you've got antimicrobial stewardship that can be augmented by these  technologies. I've got an E. coli present. None of the ESBLs are ticked off. Therefore, I should be able to treat it with a less broad spectrum agent, potentially a  drug like piperacil and tazobactam. Does de-escalation work, whether you're using these types of interventions or the more conventional microbiology? Yes.  There are many studies, including a recent European consensus conference that reviewed all that data.  I'm showing you one systematic review here that was published not long ago, focusing on the fact that de-escalation is safe when it's done in the ICU setting, and it can  be associated with improved outcomes, meaning better survival. When you use fewer antibiotics, broader spectrum antibiotics, there are less complications from those drugs.  There's less emergence of resistance as well. So in terms of some concluding remarks, and then we're going to open it up and address  these questions, I think we've tried to address some of the complexities with treating hospital associated pneumonia and ventilator associated pneumonia.  I think we tried to make the point that early therapy can improve outcomes, but it really needs to be appropriate for the pathogen.  Clinicians should be aware of the new agents that are out there, as well as the new diagnostic tests that may actually help them in terms of guiding their therapy.  And obviously, antibiograms, whether they're unit-specific or real-time, are important, and you have to have that multidisciplinary approach.  Another polling question that you can answer, and while you're answering that, I'm going to actually pick a couple of the questions that you submitted to us and have our panel  try to tackle them. So the first one, why wait for patients to fail before new agents are used? Why not start them earlier? Richard, Debbie, do you either one want to address that?  Go ahead. All right. Well, that's the million-dollar question. I mean, you know, in theory, you want everyone to have adequate coverage right up front.  And we simply don't know the organism. So giving everybody, you know, I think Rich's slide where everybody had a risk factor, only  10% of patients didn't, would mean the majority of your patients would be on the new agents. And we know that everybody doesn't need them. It's very hard.  I mean, you have to, I think each clinician has an algorithm they use. You know, if the patient had just been in the hospital, they've already got multidrug-resistant  gram-negative pseudomonas acinetobacter times two admissions, I'm going to be faster to trigger that than someone who does not. We have rapid diagnostic tests.  That to me is the key to making this decision. Waiting four days is four potential days of wrong therapy.  I think when you try to make the decision of using the newer agents that do cost more money, you've got to advocate for a rapid diagnostic test hand-in-hand with these antibiotics  because you need tools to tell you what the organism is. So that to me is the job of a stewardship team working with the ICU physicians to advocate  for these tests and to help them guide you to the most effective therapy. Because I don't think giving everybody these newer agents up front is the right choice.  So I think that the issue is that risk factor-based treatment will always result in over-treatment. They're just overly sensitive. And so you always end up with over-treating.  Even in the meropenem-vabra-bactam, one of the ways to get in was to actually have a prior culture with a CRE.  And that still was only about 70% of them actually grew that as the cause of their infection. 30% did not have it. I'd be happy to only miss on 37% of carbapenem resistance.  But the flip side is a rapid diagnostic gives you that choice very quickly, very early. So I think we do have to be practical.  We need to be responsible with these very expensive agents. There is some desire to preserve them for the patients who really need them. I'm not totally sure I buy that argument.  But I think that you have to have a higher level of suspicion to use some of these new agents than to be suspicious this is pseudomonas compared to E. coli.  And that gets to this follow-up question that someone asked, which may have to do more with understanding what a registration trial really represents.  The question is, based on the data that you showed, why should we use these new combination agents as opposed to meropenem, since you showed us essentially equivalent findings?  Yeah. I think that really does get back to the whole issue of clinical trials versus clinical practice. So clinical trials, you need to enroll a minimal number of patients.  You need a safety profile on the drug that requires it being given to patients. And you need to use it in somewhat of the setting that you think the drug might be used.  But the fact of the matter is, you are not really studying the population that you would want to use this drug on.  That's why I pointed out that with ceftazidine avibactam, at least they had about 20, 25 percent who were ceftazidine-resistant in that study. And that was ethical and made sense.  The problem is that in those clinical trials, you couldn't study meropenem-resistant.  You couldn't study carbapenem-resistant isolates because you had a 50-50 chance of being randomized to a drug that would be resistant.  So the flip side is these best available therapy trials are also very fraught with problems.  I think the meropenem-vabrabactam fairly convincingly said it's equivalent or superior to colistin.  Whether it's equivalent or superior to ceftazidine avibactam is still up in the air and probably would require way too large of a study to prove that difference.  So I'd look at those as roughly equivalent. OK. We've got another one here. What is the average course of therapy, meaning duration of therapy, when you're using these new agents?  It sort of gets at the broader question of how long do we treat for nosocomial pneumonia. Any comments on that topic? So once again, clinical study versus clinical practice.  One of the things that actually blew up the whole amication inhaled study is the fact that at one point the trial was the patients were going to be declared failures if they  continued antibiotics past a pre-specified time, 14 days. That happens way, way too often. So my point is in somewhere between 7 and 14 days is probably the right.  We don't know exactly what it is. There's some fairly convincing data that 8 versus 15, 8 was equivalent.  My concept is if you're going more than 8 days, you probably have a failing regimen. And you ought to be reassessing potentially changing treatment.  Because to be symptomatic persistently for 8 days means you're probably failing therapy.  Whether switching is going to salvage that patient that is probably very immunocompromised is totally unclear. It's not really been studied.  But we do know that in all of these studies, one entry criteria is failure of prior therapy. And failure of prior therapy has always been associated with better outcome with some of  the newer agents when compared to meropenem. So that's a caveat in clinical trials. The only thing I'd add to that is that if you've got someone with augmented renal clearance,  you know, a 7 or 8 day course you might think is adequate. But in reality, if they're not getting enough drug delivered to the lung, there's some data  suggesting that those patients are more likely to fail and have a bad outcome. So they might benefit from a longer course of treatment.  Or they would benefit from the higher doses and better PK. Exactly. Or even doses that are off label, which many hospitals are very uncomfortable doing, unfortunately.  So one practical question is, how do you address the restrictions that some of these clinicians are facing in our hospitals? What can they do?  I like to use the term protected antibiotics, not restricted. Because restricted just, I think, conveys stewardship programs as being the program  of no, everything's restricted and you need permission. And it just sets up barriers. So if you put antibiotics on the protected list, I think that is our role.  We are there to protect and oversee responsible use of the newer agents. And we know the days of letting physicians just use antibiotics based on their best knowledge  is what has created our insanity we live with today with multidrug resistance. So when people say, well, I don't want to have any restrictions or whatever term you  choose to use, I'm like, but look at where we're at. We can't deny that. We can't just have everybody do what they think is best. Because that does not work.  So someone has to come up with some type of guidance. And our approach is, you work with the people in the unit taking care of the patient.  So how we approve antibiotics in our medical ICU are different than the surgical ICU. Because the needs are different.  And so I'm never going to go tell our bone marrow transplant team, you can't use these agents because we have this global restriction.  It really is individualized and you come with data. So we look at unit-specific antibiograms to go, here are your top five pathogens.  You actually don't have a need for this drug because you don't even have vasonative actor in this unit. So this is not a good match.  And that's what empowers you to make good decisions. Rather than imposing restricted criteria for the entire hospital, it's as, in my opinion,  as silly as trying to use the same dose for every patient in the ICU. You just know it's wrong. Some have augmented renal clearance. Some have renal impairment.  There is no one drug, one dose fits all. And there's not one type of guidance that fits everybody in your hospital.  So when you're in a large university, that is, to me, what's most important, is you work with the clinicians who are caring for those patients in the high-risk units, the MICU,  the SICU, our bone marrow transplant team, to individualize what's going to be best of care in that unit. So we've got two questions on colistin here.  One has to do with when we're facing carbapenem-resistant isolates, colistin is an unrestricted drug. Why shouldn't we use it? And that's the IV form.  And then the follow-up question that's provided maybe by the same person is, why not just use inhaled colistin? So I don't know if you want to try to address those.  I think that based on the meropenem-vabra-bactem study, I think to use colistin for a carbapenem-resistant enterobacteriaceae is probably suboptimal care.  The real issue and the only place that we still use colistin or polymyxin B is for acinetobacter  because we're similar to what Maren mentioned, that 75% of our acinetobacters are carbapenem-resistant.  And there's lots of cocktails that have been tried to use for this kind of patient. If it's an pneumonia patient, we actually feel much more comfortable because we will  use aerosolized antibiotic. We'll use polymyxin B as our standard. And the interesting thing to me is to actually look at patients who have PDR pathogens, pan-drug-resistant  pathogens. The mortality rate is still only 50% in those. And that's because we throw these weird, bizarre cocktails at them in some work.  I think the aerosolized polymyxins are probably the best choice if the patient is intubated. You avoid much of the nephrotoxicity, not all of it.  But to me, that's about the only space that is open for polymyxins at this point, at least in the U.S. healthcare system.  Around the world, it's a much, much bigger issue because of cost. Right. And I would agree 100% with you, but the reality is U.S. hospitals are still using  it for first-line therapy because it's cheaper. So there's a study in CID by Neil Clancy, I think, that looked at the use of polymyxins  across the U.S. now that ceftolazatezo, meropenem-vabra-bactam, ceftazaviar are out on the market.  And unfortunately, there's many hospitals still using it simply because it's cheaper, which is just not right. I mean, that's not what a stewardship program is about.  And I would agree with that because I've visited a number of those hospitals. And we're talking about IV colistin, which is being used for pneumonia, where you have  very poor lung penetration. So OK, good. Another question here. I'm sorry I missed it, but your thoughts on inhaled antibiotic therapy.  It sounds like, Rich, you addressed some of that. At least the data that we have from the two trials suggests that inhaled antibiotic therapy  as an adjunct to IV therapy probably doesn't add much. I mean, the only exception to that rule, as Dr. Wunderink has alluded to, is if you've  got really a pan-resistant organism, there are no other options. You're thinking about an agent like inhaled colistin because there's nothing IV that you can actually administer.  And then we've got a question here. What role in decision making do you believe the rapid diagnostics have in patients with  extensive previous exposure to broad spectrum antibiotics? I think it's significant. I mean, those are the ones you don't know what the organism is.  You want to know because you have so few choices. And you want to get it right. So if you have one of the newer pneumonia panels or if it's a bloodstream infection,  they give you the organism and the marker for resistance. So it really allows you to streamline therapy within 24 hours rather than four days. So I think they're highly useful.  This is probably the last question, but it has to do with dosing. So what strategies do you employ when dosing antibiotics in mechanically ventilated patients,  including the use of off-label dosing? You know, there are examples of meropenem dosing in the clinical trials you presented  that are variable, one gram of meropenem three times a day versus two. What's your recommendation from a dosing perspective?  You know, I think going through all the PKPD studies we did today, there is no one dose fits all.  And, you know, it's kind of a hard one to answer as we're out of time at this point. You just can't have one dose for everybody.  And I think that's where the art of individualizing therapy. There's a great role for clinical pharmacists in the ICU to really help look at that data  and guide therapy, because it is complicated. I think that there are a couple of basic principles, though.  If you're doing a creatinine calculation and you've got augmented renal clearance, you ought to be probably adjusting your dose.  I think the other place where it's very helpful working with PharmDs in the micro lab is when you're sitting at an MIC that's very close to resistance.  That's probably somebody that you ought to be using higher doses on. And you have to realize that many of these drugs, say Piptezo is a workhorse forever,  the MICs were much different back when that drug was approved on the market than what it is now.  And the only thing I would add to that is that with some of these new antibiotic studies and the FDA has sort of put out some guidance, if you will, or black box warnings on this,  oftentimes we reduce the dosing of antibiotics in the setting of patients who have abnormal renal function.  But as that renal function improves, we need to think about increasing the dosing appropriately. And sometimes that doesn't happen. So that can actually influence clinical outcomes.  So one really has to pay close attention to the clearance of these agents. With that, I want to thank everyone for being here today.  I want to thank the individuals on the stand here, Richard Wunderink and Debbie Goff. And again, I hope you enjoy the rest of your meeting. Thank you.

Video Summary

The video titled "Making the Most of the Clinical Toolbox" discusses the importance of appropriate antibiotic therapy in the treatment of nosocomial pneumonia. The speakers highlight the increasing incidence of pneumonia in hospitals, particularly among immunocompromised patients and those receiving certain treatments. They emphasize the need for rapid diagnostic tests to guide empirical treatment and provide real-time data on antibiotic susceptibility. The video also mentions new antibiotics available for pneumonia treatment, such as ceftolizumab plus tezobactam and ceftazidime/avibactam, which offer improved coverage against resistant pathogens. The speakers stress the importance of personalized antibiotic dosing in critically ill patients. The video also discusses the use of new cephalosporin beta-lactamase inhibitors for difficult-to-treat gram-negative pathogens and highlights other drugs on the market, such as mirapenem-vabbactam and schofittraco, for treating specific infections. The video emphasizes the need for individualized therapy and a multidisciplinary approach, taking into account factors such as prior antibiotic exposure, immune status, comorbidities, and resistance patterns. Rapid diagnostic tests and responsible antibiotic use are also emphasized. The video concludes by addressing questions on specific aspects of treatment. Overall, the video advocates for the optimal use of antibiotics to improve outcomes in patients with nosocomial pneumonia and ventilator-associated pneumonia.

Asset Subtitle

Infection, Quality and Patient Safety, 2020

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2020 Critical Care Congress held February 16-19, 2020, in Orlando, Florida, USA.

This program is supported by an educational grant from Merck & Co., Inc.

Learning Objectives

Explain the evolving epidemiology and etiology of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP)
Discuss key safety and efficacy data for newer agents being used for the treatment of HABP and VABP
Develop tailored treatment strategies for HABP and/or VABP that support the principles of antibiotic stewardship
Coordinate with members of the multiprofessional care team to improve timely diagnoses

Welcome and Introductions

Marin H. Kollef

HABP and VABP: Epidemiology, Microbiology, and Clinical Consequences

Richard Wunderink

Considerations for Antiobiotic Therapy for MDR Infections in HABP and VABP

Debra Goff

New and Emerging Therapies: A Closer Look at the Data

Richard Wunderink

Individualizing Therapy to Support Antimicrobial Stewardship and Improved Outcomes

Marin Kollef

Concluding Remarks and Audience Q&A

Marin Kollef

Meta Tag

Content Type Presentation

Knowledge Area Quality and Patient Safety

Knowledge Area Infection

Knowledge Level Foundational

Knowledge Level Intermediate

Knowledge Level Advanced

Membership Level Select

Membership Level Professional

Membership Level Associate

Tag Guidelines

Tag Mortality

Year 2020

Keywords

appropriate antibiotic therapy

nosocomial pneumonia

rapid diagnostic tests

new antibiotics

ceftolizumab plus tezobactam

ceftazidime/avibactam

personalized antibiotic dosing

gram-negative pathogens

individualized therapy

responsible antibiotic use

improve outcomes

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