I'm going to give you a sort of brief review of severe pneumonia in the ICU, and we're going to try and cover severe CAP, HAP, and VAP. I think it's been long enough now that we can actually say that healthcare-associated pneumonia is not something that will be talked about on the board exam. So it's been since 2017 that the IDSA came out and said, we're eliminating that. So I apologize. I don't have a lot of questions for you in this talk. We went over some of those. I put a lot of information here, and I'm going to try and go quickly to cover it. I'm going to review some of the definitions of severe community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, and discuss the risk factors. We're going to talk about guidelines for initial antibiotic treatment. Remember this, just like you heard in sepsis. Guideline-based is the way to go to get good outcomes, and that's probably what's going to be on your board exam. We're going to bring up a brief discussion of macrolides and steroids. Steroids I'll highlight, because that is also a moving bar. I'm not sure that's going to come up except under the category of somebody with septic shock, if that is part of the pneumonia. But we'll discuss some of the evidence in brief fashion, and I'll probably lead you to more discussions, which is in the longer presentation that you have as part of your syllabus, and describe the prognosis and strategies for prevention of at least severe community-acquired pneumonia and ventilator-associated pneumonia. When we talk about community-acquired pneumonia, this is one of the most common respiratory infections throughout the world, and in the U.S., it is one of the most common causes of death from infection. When you talk about hospitalized community-acquired pneumonia, that's about 40% of the community-acquired pneumonia population during COVID. It was even more of a population of people. And realize that 5% of community-acquired pneumonia ends up as severe. Those are people in your ICU. They have increased risk for mortality, acute respiratory failure, ARDS and need for ventilator support, and it costs a lot of money. There's a lot of risk factors for pneumonia. Some of these may be a little bit controversial, but most are pretty well accepted. Being on inhaled steroids, so you're asthmatic, you're COPD patients. People on gastric acid suppression, especially PPI use. The new guidelines may call that into question a little bit, especially for nosocomial-acquired pneumonia. They didn't seem to see an increase unless in the guidelines you were combining your PPI with enteral nutrition, and then you had increased likelihood. Being altered in your mental status, whether from opioids, benzodiazepines, being on immunosuppressed agents, having heart disease, being institutionalized, being old, and don't forget the importance of micro-aspirations. So anybody who has problems with swallowing, your Parkinson's patients, things like that, people with altered mental status. Pneumonia is one of those topics that we all know. We all recognize, we all treat, and probably, if you look at current data, we're probably over-treating a lot of people, especially with antibiotics, because truth is, we don't often find an actual pathogen, especially a bacterial pathogen. When you do find bacterial pathogens, most of the time it's going to be strep pneumonia, and it may be atypical, especially in your area. If you have things like Legionella, you'll know when that is going on. Most of the time, at least with hospitalized community-acquired pneumonia, you're probably dealing with a viral pathogen, as the EPIC-CAP study showed, and in fact, human rhinovirus being one of the most common. In season, influenza will pop up. We all played the COVID game. It may come out on the boards, because remember, it's four years ago, so there probably will be some studies on that. Strep pneumonia is still your most common bacterial pathogen, but I'll call your attention to this pie chart, 62% of the time, with an intense effort to find a pathogen, you don't find a pathogen in what we think is community-acquired pneumonia. Nonetheless, we have great guidelines from various societies all over the world. I'll emphasize some of those. This is a nice review article that was in the New England Journal last year by Feil and Ramirez that talks about the progression from CAP to severe CAP, the various manifestations that you have in at least clinical, laboratory, radiographic abnormalities that you may see, and as you move along and get to more severe community-acquired pneumonia. It's important that you recognize patients with severe community-acquired pneumonia. There's a lot of guidelines out there. Most of us in the U.S. use the IDSA, ATS, severe CAP guidelines. They're older, but I think they still bear fruit. Obviously, if they have septic shock requiring vasopressors or invasive mechanical ventilation, I think we'd all agree that's severe. But having more than two of elevated respiratory rate, elevated BUN, low ratio of partial pressure of arterial oxygen to FiO2 ratio, confusion, multilobar infiltrates, leukopenia, hypothermia, hypotension requiring aggressive fluid, and thrombocytopenia, those would manifest somebody with severe community-acquired pneumonia. The British Thoracic Society just say two of these three, the elevated respiratory rate, which on a board exam, pay attention to that respiratory rate. That may be a good clue for you, and we sometimes gloss over that, especially on clinical rounds where everybody's 20. When they tell you somebody's got a respiratory rate of 30, pay attention. Even a mild elevation in BUN should get your attention in the community-acquired pneumonia population as, could this person have severe community-acquired pneumonia? And that also manifests in the CURB-65 calculation, all designed to help you put the patient in the right spot. If they're severe, they should go to your ICU. And if they don't go to your ICU right away, end up going to the floor and getting transferred to the ICU. Those community-acquired pneumonia patients have a higher mortality than if they went to the ICU in the first place. So location, location, location, like your realtor will tell you. And procalcitonin, while it won't help you decide who has community-acquired pneumonia, who may benefit from antibiotics or not, it may help you that if they have a high procalcitonin, maybe you should think about putting them in your ICU. As far as management issues of community-acquired pneumonia, we've already seen that most of the time you don't know what the pathogen is. The usual coverage is going to be for pneumococcus and maybe atypical pathogens. But if you know you're in an area with a high amount of MRSA, then you ought to consider, do I have to expand my initial coverage to at least think about that? Treatment is empiric, guideline-directed, and that will lead to improved outcomes. You should, again, like you just heard from John, time probably counts. There were metrics in the past that at least CMS people implicated to say, this is how we separate good and bad quality care by whether you got your antibiotics in quickly. The unfortunate thing is it got the ER giving everybody levofloxacin before they even had a chest X-ray. So still due diligence, evaluate your patient, and if you think they have pneumonia, start your antibiotics. And we know there's a lot of antibiotic resistance, so pay attention to what you're doing. But in community-acquired pneumonia, the addition of macrolides has been shown to improved outcome for those with severe community-acquired pneumonia. So we'll talk about that in a little bit. And this is a nice little algorithm that came from the Phile Ramirez review article that helps you look at your patient who is admitted with severe community-acquired pneumonia and decide, do they have risk factors for pseudomonas, for MRSA, and then you can pinpoint whether to give standard antibiotics, expand your antibiotics to cover for MRSA, expand your antibiotics to cover for multidrug-resistant organisms and pseudomonas. So it actually breaks things down fairly easily, helps you with some antibiotic stewardship and your decisions. Now that reflects ATSI-DSA. The rest of the world, you can see all their societies, came out with guidelines for severe CAP, and they make some interesting observations. They tackle the topic of, do we have to get sputum on everybody, and look at that to help direct what you do. And they actually said, with very low evidence, only get your sputum if they had to look at what's going on in the lower respiratory tract. If you're going to use multiplex PCR testing for things like viruses or sophisticated bacterial studies, otherwise just use your standardized guideline therapy. They tackled the topic of high-flow nasal oxygen, which I think we are all using at this point in time, as opposed to a regular cannula. They actually tackled the topic of the macrolides, and they suggest the addition of macrolides, not fluoroquinolones, to a beta-lactam. In fact, they would even say, if you're starting a fluoroquinolone, you can even add a macrolide to that to get better outcome. And do they use PCT to decide about antibiotics? No, but they may use it to shorten the duration of the antibiotic course. And certainly, if you think the patient has influenza and you're doing PCR to suggest that, you should treat influenza with ozotamivir. The topic of steroids, we're going to defer to if we get further on. It depends on when your guideline basically is published. That's the new answer. Using prediction scores to look for resistant organisms. There are a number of them out there. They would suggest thinking about using one of those, and we had an algorithm that worked just as well. And an important topic, especially in those who we talk about micro-aspiration, do you need to cover with an anti-anaerobic antibiotic? And the answer is, in severe community-acquired pneumonia, as well as regular community-acquired pneumonia, you do not need to cover for anaerobic infections. Here's the data on adding a macrolide in mild community-acquired pneumonia. Probably no benefit. In severe, there is a benefit to adding a macrolide to your beta-lactam. It will reduce mortality. And this happens even though the bacteria, if you do actually grow it out, may be resistant to the macrolide. So it's not working necessarily as an antibiotic. It's working as an anti-inflammatory agent. It may be working, if there's gram negatives, to interfere with quorum sensing, with being able to look at bacterial adherence to biofilms and other things. And it will even work in addition to steroids, if you have administered steroids to your patient. So the anti-inflammatory effect is different than the anti-inflammatory effect you get with corticosteroids. I guess in the future, there are efforts to try and come up with a macrolide agent that's not an antibiotic, but is anti-inflammatory. And we'll talk about steroids. So here's a recent trial as of 2024, 15 studies, 3,200 patients from 11 countries, hospitalized. Not all severe CAP, but mostly severe CAP. Different steroid preparations. This is why this literature is so difficult to actually put together. But the addition of hydrocortisone to patients with severe community-acquired pneumonia was found to reduce all-cause mortality, particularly in younger patients, decrease the need for mechanical ventilation, need for vasopressor support, reduce hospital length of stay, ICU length of stay. And the downside is really hyperglycemia with steroids, maybe a little hypernatremia. No increase in secondary infections, GI bleed, adverse cardiac events. And most of the studies are not looking at prolonged neuromuscular weakness, unfortunately. The Cape Cod study, also another big study that was done in France, looked at steroids versus placebo, severe community-acquired pneumonia, with the caveat they had a marker of inflammation with elevated either CRP or procalcitonin. And here again, they found significant improvement in survival, and it was very safe. The only thing that really was different was you had to give more insulin to the pneumonia patients treated with steroids versus placebo. So I'm not sure what to tell you on the board exam. This is all new stuff. I hope they don't go, do you give community-acquired pneumonia steroids? I would say that is a no, but for severe, you might want to say yes. And here's the confusion. Here's a recent sort of summary of steroids for community-acquired pneumonia, and the answer is, depends on whose guideline you're looking at and when it was published. So if you look at the most recent publication, that would be the SCCM guideline for the use of steroids in severe community-acquired pneumonia. It was a strong recommendation with moderate evidence. And since we're at the SCCM, I think we'll give that some at least consideration here. But you see, the ATS didn't even recommend it because they really was done way before all these new articles, and the European Society, it's a conditional use with low evidence. For your community-acquired pneumonia, sometimes you don't see the good response. Think about what else is going on. So patients with liver disease, pleural effusion. If there's pleural fluid, tap it, make sure it's not an empyema. So if you have that option. People with cavitary disease, think, could they be going to a lung abscess, or is it just a patient with staph, especially MRSA, causing the cavitation? Certainly if they're leukopenic, make sure you didn't give the wrong antibiotics. So discordant therapy associated with poor response. The other thing to remember as we wrap up community-acquired pneumonia is even after you survive community-acquired pneumonia, if you look at elderly patients over 65, their long-term outcome for the next two years is associated with increased mortality, and an increase in myocardial infarction and other cardiac events, presumably related to the inflammatory process of the pneumonia itself on plaques in the existing coronary arteries. So we're going to switch gears now and talk about hospital-acquired pneumonia, which develops in a hospitalized patient who's been there for over 48 hours. That helps eliminate what's been incubating from the community by the time the patient was admitted. It's the second most common nosocomial pneumonia, or nosocomial infection. It increases the need for ventilatory support, increases morbidity, mortality, cost of care, and length of stay. One more difficult thing to define is ventilator-associated pneumonia. So there's various definitions. Most would agree that it's a new or expanding infiltrate happening more than two days after invasive mechanical ventilatory support. There should be clinical features that suggest a pneumonia. It becomes difficult because these people are already on a ventilator, so they already probably had something going on in their lung. They may have abnormal clinical findings, so you're looking for change. I know the new CMS VAP definition is not x-ray based. It's based on changing your FiO2 or your PEEP requirement in conjunction with clinical manifestations. But nonetheless, they are not throwing out x-rays, and they are not throwing out in the definition what you're culturing. It's the fact that you started antibiotics, and you have these ventilator changes along with clinical findings. The epidemiology of ventilator-associated pneumonia depends on when it develops. Within three to four days of being on the ventilator, you probably have community-acquired pneumonia-type organisms. After five days, you probably have the microbiome of what the patient has, as well as what your unit has. That's where you're going to see more multidrug-resistant organisms and more multiplicity of organisms. Most would agree that a ventilator-associated pneumonia increases ICU and hospital length of stay, increases mortality, although it's tough to come up with what is the attributable mortality from just the new pneumonia. Definitely increases time on the ventilator and costs of care. As far as the antibiotic therapy, again, we're looking to guidelines. Here's the European Respiratory Society recommendations from 2017, which pretty much mirror the ATS-IDSA guidelines. You look and see, how sick is your patient? Is there a low or high risk for multidrug-resistant organisms? If there are low risks for both, you can use antibiotic monotherapy with common agents. On the other hand, if they're higher risk, then you ask yourself, are they in shock or not in shock? The more shock you have, the more need to have dual-gram negative anti-pseudomonal coverage, with or without MRSA coverage. Your MRSA coverage may be dictated by what goes on in your unit. Some will use, do any of you use nasal cultures for MRSA when you admit somebody to your ICU? It's an Illinois-type thing. We get that, and it may help you. If they are positive, you're more likely to want to give them MRSA coverage. Or on the other hand, if they're negative, you may stop your empiric MRSA coverage. As far as guidelines from the IDSA and ATS for 2016, which have been out there now eight years, so probably are testable, hospitals should know, and you should know, your local antibiogram, hopefully your unit antibiogram. You're going to begin empiric treatment informed by where you think the patient's risk factors lead you, and your known antibiotic susceptibility, because you should know your antibiogram. You will base your empiric coverage of staph aureus and pseudomonas based on the treatment algorithm we just saw. And importantly, if you have the ability to do pharmacokinetic pharmacodynamics, this way you give the right amount of the drug to the patient, because some people have augmented renal clearance, some people have expanded volumes of distribution. Sometimes you're using things like dialysis, ECMO, other support strategies that may impact your antibiotic availability. Emphasize the seven days. I think the one study has made a huge mark, and nobody has really gone with a large-scale trial to try and cut it down, but people are trying to move the bar more to the left. Remember to de-escalate rather than fixed duration of initial treatment, if patients are improving. You can think about procalcitonin combined with clinical data to help you shorten the to help you shorten antibiotic courses. Notice we did not say to initiate antibiotics. And don't use things like the clinical pulmonary infection score to help you discontinue antibiotics. Now importantly, who do you not want to do short-course seven days of antibiotic therapy? So if you start wrong, you can't count those days. So initial inappropriate antibiotic therapy, if they're severely immunocompromised. If you've got highly antibiotic-resistant pathogens, such as Pseudomonas, the carbapenem-resistant Acinetobacter, and Enterobacteriaceae, probably not going to get along that well with just seven days of antibiotics in those groups. And if you're using one of these second-line antibiotic therapies because of bad resistance, probably should go longer than seven days. Back to the steroids, here's the SCCM 2024 guideline. And I just threw that out because we throw in the sepsis, we throw in the ARDS, and here's the community-acquired pneumonia, just to reemphasize that. And then finally, we'll talk about prevention of ventilator-associated pneumonia. There's a whole host of things. I am sure you are all familiar with your ventilator-associated pneumonia prevention bundle that you're using. The biggest thing in that bundle is get the endotracheal tube out. So if you don't have to intubate somebody, that's a good way to start. But if you can get them off the ventilator, even sometimes transitioning from invasive ventilation to non-invasive ventilation will facilitate reducing your ventilator-associated pneumonia in your hospital. So it's a lot to cover in a short period of time. But remember, severe community-acquired pneumonia is one of the most common infectious causes of death that we deal with. It's important to have rapid diagnosis, effective triage, timely initiation of antibiotic therapy, and use guideline-directed therapy to help improve outcome. Data suggests that you will have improved outcome by using a macrolide with your empiric therapy. I'll put in there, steroids are likely to improve the outcome of patients with severe community-acquired pneumonia. And the role of biomarkers is still uncertain, but may be helpful in antibiotic stewardship by allowing you to stop antibiotics sooner in those who are clinically better. As far as HAP and VAP are concerned, they are associated with increased cost of care, length of stay, morbidity, and probably mortality. Again, begin empiric, guideline-based therapy as soon as possible, and you have guidelines to help you with that. Tailor and de-escalate treatment based on the clinical response. Ideally you can treat for seven days with a good response, and remember, preventive strategies are likely to be effective, but not likely to totally eliminate ventilator or hospital-associated pneumonia. With that, thanks for your attention, good luck on the boards, and have a good day.

Severe Pneumonia

ICU

CAP

HAP

VAP

Antibiotic Therapy