Thank you so much, Ankita. So my name is Lokesh Dayal. I'm a medical intensivist, and I wanted to talk about a couple of the biggest articles, what I would consider landmark articles this year for the Medical Intensive Care Unit. I primarily practice in the adult medical ICU, and the morbidity that I see almost every single day is community-acquired pneumonia, which is I'm sure the same with most of you. So the reason I picked this topic is because it's so pervasive in our medical ICUs, but also it leads well into the next couple of presentations, which will be on ARDS, as well as ventilator management. So there we go. I have no disclosures. All right, let's start off with the definitions of community-acquired pneumonia, which I'm going to refer to as CAP going forward. It's an acute pulmonary and parenchymal infection outside of the healthcare settings, and severe CAP specifically the reason I'm using the terms from the ATS 2019 Guideline slash IDSA Guideline is because it's part of the inclusion criteria for some of the studies that I'm going to describe today. So severe CAP, it's typically one of the two or both major criteria, which is mechanical ventilation or septic shock requiring pressors. There's also minor criteria, which are all common indicators from sepsis. You can have a mixing and matching, one plus one of the other ones. And then the PSI, the Pneumonia Severity Index, that's a measure of multiple different markers of sepsis severity. And the highest quintile is a score of greater than 130. It's typically used for disposition planning in the emergency department, as well as severity ranking. So the first study I'm going to talk about is about corticosteroids. So I just want to give a review of what the landscape has looked like in terms of our guidelines. Rewinding back to pre-pandemic era of 2017, the SECM and the European guidelines in the CERSI Part 2 recommendation gave a specific dose of hydrocortisone. And they recommended that in hospitalized patients with community-acquired pneumonia. Fast-forwarding two years to the ATS and the IDSA Guidelines, the ones that I mentioned earlier, Question 12 specifically said, do not routinely use corticosteroids in adults with severe CAP. And they actually made that same recommendation for non-severe CAP. So surviving sepsis, two years after that, specifically talks about the patient population with septic shock. And they did recommend IV corticosteroids with the use with vasopressors. So that's where the pendulum has swung over the last four to five years, and this new study will hopefully help guide where to practice, or how you practice with your specific patient subsets of community-acquired pneumonia. So without further ado, the two articles that I'm going to be talking about today, both related to community-acquired pneumonia, specifically most severe forms of it, will be CAPE-COD and ACORN. CAPE-COD is short for hydrocortisone in severe community-acquired pneumonia. And then ACORN is cefepime versus pipercella and tazobactam in adult hospitalized patients with acute infections. As you can see, both of them had very high altmetric scores and had been the topic of many journal clubs this year. Okay. CAPE-COD, this is a study that was done out of France, and it was a multicentered, double-blinded RCT. They were able to enroll 800 patients. And in terms of the PICO question, the inclusion criteria was whether, or the question was, whether or not adults with severe CAP who are not yet in shock, did they benefit from corticosteroids. So the inclusion criteria, which was informed from the ATS guidelines that I mentioned earlier, they included patients that were on invasive or noninvasive positive pressure ventilation. They expanded that to also include patients that were on non-rebreathers and high-flow nasal cannulas, so long as they had a PF ratio. So that's a PaO2 to FiO2 ratio less than 300 on their AVGs. They also included pneumonia severity index greater than 130, and that's only the highest quintile of community-acquired pneumonia. The two interventions here were continuous hydrocortisone, 200 milligrams per day, and this was as a drip given over four days or seven days, and the control was a similar bag, but of placebo saline. All the other standard of care for community-acquired pneumonia, ARDS, were all involved, whether that be antibiotic choice, proning, oxygenation method. That was left up to the clinicians. And then the primary outcome was all-cause mortality at 28 days. So jumping straight to the outcomes, the primary outcome, which was death at 28 days, the hydrocortisone group had 6.2%, and then the placebo groups had nearly double that at 12%. The limitations that are commonly prevent us from using corticosteroids empirically on all of our community-acquired pneumonia patients would be the risk of bloodstream infections, ventilator-associated pneumonias, as well as GI bleeds. In this study, however, they powered their secondary outcomes to specifically look for those, which in this patient population in 28 days was not significant. What was significant, however, was the use of insulin, naturally, in the hydrocortisone group. There was also significantly decreased mechanical ventilation or initiation of vasopressors in general. So this is jumping into the specifics of that. The orange table is going to be the... or the orange line is going to be hydrocortisone group, and the blue line is going to be the placebo group. The top right and the bottom left show mechanical ventilation, and not surprisingly, the bottom right shows the use or the initiation of vasopressors in general. The placebo group had significantly more vasopressor initiation versus the hydrocortisone group. Now let's dig into a little bit of the limitations. Some of them were addressed in the article itself. So there was a lower mortality than expected. This may have been because there were more liberal P to F ratios, which is a little bit more consistent with our new global definition of ARDS, but I think we're going to touch on that with some of the other speakers. The other thing is maybe we were just treating, or we had a little bit of a lead time in our patients that were impending septic shock. So putting the hydrocortisone on prior to them developing septic shock may have been a confounding factor. And the other thing that will limit our generalizability, at least here in the United States, is we often don't use hydrocortisone drips. It's more so intermittent dosing here. So the bottom line that I personally took away from this landmark study was in high-risk patients with severe community-acquired pneumonia, a short course of hydrocortisone may improve mortality. This is regardless of whether or not they're in septic shock yet. This was only one study. There's going to be a major debate tomorrow, or I should say more evidence and more detailed debate on these two lectures tomorrow morning. So I just want to give a plug for them. They're going to go into more than just this one article and delve into the literature over the past several years. Okay, moving to our second study. This is going to be another RCT. This one is out of Vanderbilt and it's called the ACORN trial, Antibiotic on Renal Outcome. I know you guys are looking for where the N came from in that title, and I'd like to think that it's a pneumonic device for neurological outcomes that's associated with cefepime. So in this study specifically, they looked at the kidney outcomes in patients that have received empiric treatment for pseudomonas. The two antibiotics in the study were cefepime and piperacillin-tazobactam. And just as a little bit of a background, there have been observational studies, animal studies, as well as just word of mouth and rumors that there is a hesitancy to use zosyn, piperacillin-tazobactam in patients that have kidney injury. So there've been no major RCTs. This is likely the biggest and first one to compare the two head to head. This is the JAMA summary. Blinding was not done in this study. And that's because the administration of these two antibiotics were vastly different. Zosyn is a longer extended infusion versus cefepime, which is a bolus. So the clinicians that were providing the medications knew which one they were giving. There would be EHR triggers that would identify patients that were potentially candidates for this, essentially anybody who required pseudomonal coverage empirically. This was a, and because of these conditions, they were actually able to enroll 2,500 adult patients. The primary outcome in this was the highest stage of AKI or death at 14 days. And they found no statistical significance between cefepime and piperacillin-tazobactam. They were able to notice in secondary analysis that there was increased delirium. And like I said, that's kind of the N in egg corn in the patients on cefepime. And that was determined with CAM-ICU scores as well as RAS scores. Of note, the antibiotics were all dosed by pharmacy and were renally adjusted. So delving a little bit more into the details of this, this was a pragmatic trial. So clinicians were allowed to A, know what antibiotic they were giving, specifically for the anti-pseudomonal coverage. They were allowed to adjust it. Even if the patient had already gotten a dose of the other arm that they were assigned to, they still continued in the analysis. They were able to adjust antibiotics based on sensitivities or a patient's clinical course. And then to refocus specifically on community-acquired pneumonia, as you can see from the table, intra-abdominal infections were the most common indication for empiric anti-pseudomonal coverage at 612 patients. And then lung patients were a very close second at 557. Of note, which is probably specifically relevant for a question of if Zosyn and vancomycin collaboratively induced more AKI, 80% of patients in both arms, both the cefepime arm and in the Zosyn arm received vancomycin. Like I mentioned earlier, cefepime did have higher delirium. But the MAKE scores, major adverse kidney events at 14 days were not different between the two of them. Some of the limitations of this study, however, were that obviously it was not blinded. And that surprisingly, 20% of patients in each arm didn't end up getting at least one dose of the opposite arm's antibiotic. So if you look at the top two graphs, you'll see by day four, less than half of the patients were still receiving empiric pseudomonal coverage. And that may be just because of sensitivities. It may have been because of provider preference. All of these were elicited. Not a lot of it was reported. But the important thing to remember is the take-home message, which would be that piperacil and tazobactam, when compared to cefepime for empiric pseudomonal coverage, did not result in significantly more AKI, nor a MAKE score at 14 days. Even when used concurrently with vancomycin. So from my perspective, those are the two biggest trials for community-acquired pneumonia. Thanks for joining, and I'll pass it on to our next speaker.

community-acquired pneumonia

hydrocortisone

antibiotic choice

CAPE-COD study

ACORN study