Okay, everyone, welcome to Community Acquired Pneumonia, New Frontiers in the Oldest Disease. We'll have three speakers today, and we're planning on having questions at the end. So please stick around, and then we can kind of quiz everybody after all three talks. So our first speaker is going to be Dr. Dixon. Thank you, Kirsten. Thank you all for joining us. Thank you for the invitation to speak. Happy to meet with you all in Honolulu. I am Bob Dixon. I'm a faculty member at the University of Michigan. I have no disclosures. I do have many acknowledgments, and I'm going to start with them. I will do my best to identify the individual lab members and collaborators who generated the data I'm about to share with you, but didn't want to shortchange this. I am speaking on the topic of pneumonia and the respiratory microbiome. I'm going to do this in two parts. First, I'm going to give you an ecological understanding of pneumonia. I'm going to argue that our conventional way of thinking about pneumonia pathogenesis, where we think of just host factors or bug factors, is inadequate, given our contemporary understanding of respiratory microbiota. That's going to be abstract and theoretical. And then I'm going to talk about anti-anaerobic antibiotics and pneumonia. In contrast, this one's going to be concrete and directed. I'm going to use this pulpit to preach at you that we should really knock it off with a zosyn. That's the one takeaway I'm going to leave you with. Making the pharmacist happy. Excellent. From the top. So on this topic of an ecologic understanding of pneumonia, so it's 2023. If I were giving this talk in 2007 when I graduated from medical school, it would be very short because here was our ecologic understanding of the lungs. The normal lung is free from bacteria. This is what I was taught in medical school. And I was informed that essentially the presence of microbiota in the lower respiratory tract was synonymous with infection. That's what infection was. And I thought in clear sterility and infection, I also thought of the immune response as dichotomous. It's basically dormant or DEFCON 1 all out. Something has happened since then. So if you search PubMed for lung microbiome, what you'll see is this explosion of interest in publications. And it was driven by something that happened around 2010, which was methodological. We started using culture-independent techniques for characterizing microbial communities, so microbial ecology tools, to study respiratory specimens. And found that it's much more interesting than just the presence or absence of pathogens. That's what we use clinically with culture-based techniques. When we're using these community-based techniques, we find diverse, dynamic communities that seem to be more interesting the closer you look at them. It's been a very eventful decade and a half. It's also been confusing. With apologies up front, I'm going to summarize all of that work in about five minutes with this slide. And I'm going to jump from conclusion to conclusion. My email address is easy to find. I'll put it in the last slide. If there's anything you want more information on, please just email me. But what do we know about lung microbiota in 2023? Well, for one, they are indeed detectable in health, even in healthy asymptomatic volunteers undergoing research bronchoscopies. But they are very, very low in biomass. So by this point, there have been more than 30 studies of 800 healthy subjects, every one of which has detected bacterial DNA in the lung specimens of these volunteers. To give you a sense of how low biomass they are, on the right here we have the bacterial burden. So the quantity of bacterial DNA detected in oral rinse from healthy volunteers. Here it is in bronchiobital lavage fluids, about 100-fold lower. And that in turn is about 100-fold greater than what we see in our negative background controls. So the bacterial DNA is there. It's sparse. And remember, it's spread over an enormous surface area. So very, very low biomass. This is also true in our animal models. So this is bacterial DNA burden from homogenized lung from mice. The advantage of this is that it's excised surgically. So you don't have to go through the pharynx. And indeed, the lowest quantity is still higher than we find in all of our background controls. So there are bacteria there. It's not just DNA. We know that at least many of these bacteria we find are viable and metabolically active. We know that if you grow them out using a diverse array of microbiologic conditions, different media, different oxygen tensions, different nutrient availability, you can grow out many more than you just get from the clinical micro lab that is using selective media justifying pathogens. Leo Segal and his group at NYU has done very elegant work comparing the identity of bacteria found and the bacterial-derived metabolites present in the alveolar space and shows that they're very congruent. So at least some of these bugs are actually viable and metabolically active and doing stuff. Where do they come from? They're derived from the aura pharynx. And I qualify that's in health and in humans. So in health, in critical illness and other conditions, I can tell you that there are other sources of lung microbiota. In other animals, they don't have a reservoir of pharyngea gravitationally above their lungs. So it's a bit different. But this shouldn't surprise us. So we've known for decades that aspiration, by which I mean microaspiration, subclinical aspiration, is actually the norm. It's not the exception in humans. If you put radiotracer in the upper respiratory tract and then you image the lungs later in the day, you will find that even in healthy asymptomatic volunteers, you can find evidence of microaspiration. This is quite different than clinical aspiration or macroaspiration that we're all familiar with clinically. And so this is not a never event. This is probably ubiquitous. And it may even be physiologic. We'll talk about that more later. Highly variable across individuals. This is a source of biologic heterogeneity across our patients and across healthy people that isn't captured when all you're doing is heterogeneity of the host genome, things like that. Spatially uniform in health. Now, this is different in advanced lung disease. So if you take explanted lungs from patients with cystic fibrosis or other chronic lung diseases, you can find spatial heterogeneity. But among healthy volunteers, we've done bronchoscopic studies and found that, by and large, you're self-similar within the same patient, the same volunteer. One way of thinking about this is that the lung microbiota in my right lower lobe are more similar to my left upper lobe than they are to your right lower lobe. It's not as if there's a uniform anatomic microbial community. And it's self-similar and it looks, frankly, like your pharyngeal microbiota. Dynamically, they are transient in health and resident in disease. So like I mentioned, there's this constant aspiration pressure that even healthy individuals have, maybe from sleep, maybe from snoring, maybe from just stuff going down the wrong pipe. But if you've got intact mucociliary clearance, you've got intact host defenses, you quickly clear them. We know this from animal experimentation that it's pretty short-lived. In contrast, we all know clinically the phenomenon of colonization tells you that when you have advanced lung disease, you do have resident reproducing bacteria that stick around for a long time. They are altered by exposures. Experimentally, co-housing, if I take mice from different vendors, they have completely different lung microbiota. If I co-house them within a day or two, they start to converge. Within a week, they're indistinguishable. That takes longer with lower gut microbiota. Environment, we've done work with horses. Leo Segal has done work with volunteers, showing that you can find environmental microbiota detected with environmental sampling present in the lower respiratory tract. Experimentally, if we give healthy animals antibiotics, we change their lung microbiota. And my lab has been very interested in oxygen, therapeutic inhaled oxygen changes respiratory microbiota. And this is a topic for another day, but that seems to be complicit in lung injury. So germ-free mice are actually protected from oxygen-induced lung injury. So it's modifiable. It's consistently altered in disease. So if you compare lung microbiota from healthy volunteers from people with either chronic lung disease, chronic airway disease, or acute illness, they are different, and they're different in a disease-specific fashion, which makes sense if you think about the ecologic differences across conditions. They're predictive of clinical outcomes. This is very consistent across numerous conditions now. These are just three results from my laboratory group, but in idiopathic pulmonary fibrosis. For all three of these, the Y-axis is going to be the clinical outcome, the X-axis is going, and then what you're going to see is them divided by their lung bacterial burden. So if you stratify patients by high, intermediate, and low bacterial burden, how do they do according to clinical outcomes? Having more bacterial DNA in your lungs, and I should mention in all these cases, these are patients without clinical evidence of infection. You would never think clinically this is a patient with a pneumonia. Having more bacterial DNA in your lungs is a bad thing. So in this case with IPF, David O'Dwyer, and now in three other cohorts have all found that it's predictive of either mortality or disease progression. Lung transplantation, Michael Combs has shown that among healthy lung transplant recipients 12 months after transplant, just getting a surveillance bronchoscopy, lung bacterial DNA burden predicts subsequent onset of rejection. He has new data showing that once you have rejection, it predicts mortality, and it seems to also indicate if you're going to benefit from azithromycin or not. And then finally, among critically ill patients, a partnership with Louis Abbas from the Netherlands, if you look at mechanically ventilated patients, who again, don't have clinical evidence of pneumonia, the more bacterial DNA we find in the lower respiratory tract, the longer they're on the ventilator, and the less likely they are to survive. So it's prognostically important. And it's immunologically important as well. So in terms of correlations with healthy mice, healthy humans, and diseased models and patients, the variation we see in lung microbiota correlates with variation we see with lung inflammation, suggesting that it's not, like I was taught, this dichotomous, the lungs are either off or on, like dormant or complete all guns firing. But rather, it's dynamically calibrated according to the microbial exposures. We're talking about pneumonia. So how do we bring this ecologic understanding of the respiratory tract to bear on a disease model of how pneumonia occurs? So if you're like me, when you were taught about pneumonia, you were taught that it comes down to host factors and bug factors. If someone develops pneumonia, what was the immune deficit? What was the breakdown in bacterial killing and clearance that allowed this to happen? Or a bug factor, what is the virulence factor in strep or pseudomonas that made this possible? I'm going to argue that that's inadequate to explain pneumonia, given what I just told you, given that we understand that there are respiratory microbiota, even in the lungs of healthy humans. We now need an ecologic understanding of pneumonia. So how do we get there? It's not the way we used to think about it. So if I asked for an ecologic understanding of pneumonia before, that's not a coherent question. That's like saying, give me an ecologic understanding of space. There's no life there. It's just invasion from without. That's not an ecologic idea. Pneumonia, I think, is more like this, so an algal bloom. So I'm sure you're familiar with the idea that some ponds look fine, clear water, and then overnight, they can have this catastrophic ecologic collapse. And these algae that were present there before, suddenly completely take over. You have this drop in community diversity. You have this dominance of a single bug that, in this case, was there the whole time. I don't think that's well understood as a host factor, bug factor problem. It's more of an ecologic factor. What changed about the ecosystem that allowed this explosive growth of one member of that community? So to develop an ecologic understanding of pneumonia, we need to develop our first principles for the ecology of the respiratory tract, and that's what this looks like. So any community, the city of Honolulu or the microbiota in your lower respiratory tract are defined by three ecologic factors. Immigration, elimination, and then growth conditions, which you can think of as differential growth rates of the community members. So if the population of Honolulu is different today than it was 10 years ago, it must be because of one of those three things. Either people moved into the city that weren't there previously, people moved out or left, or the people living in Honolulu are reproducing at differential rates. Does that make sense? The same thing is true ecologically for the respiratory tract. So in terms of the lungs, immigration is, I already told you, largely micro-aspiration. We think subclinical aspiration from the pharynx to a lesser degree inhalation of bacteria, because we know that air is not sterile. In terms of elimination, it's those familiar ways that we fight and prevent infections, cough, mucocarial clearance, and innate and adaptive host defenses. And in terms of what determines who thrives and the differential growth rates of community members, the same things matter in the lung that matter anywhere else. Nutrient availability, what's the oxygen tension, temperature, pH. These things are variable across lungs and across patients. And those are going to inform community structure the same way they would in a pond. What we've learned in the last decade is that as you progress from health to disease, you move from your ecosystem being determined by the left side of the screen, namely this dynamic balance between immigration and elimination with very little residents and resident bacteria turning over, to the right side of the screen where it's more determined by the ecology and the reproduction rates of the members. Right? So you can think of it in terms of airway disease. We already know that people are chronically colonized with staph or pseudomonas. What that suggests is that there's a specific species that's very well adapted to that specific environmental growth conditions of that patient's airways. We've learned with the sequencing identification that happens earlier than we previously appreciated. You don't have to have culture-identified colonization to see that signature of chronic airway disease. But in health, we tend to be on this balance of immigration elimination. So what's interesting about pneumonia is how abruptly you go from one to the other. You go from this transient dynamic ecosystem to one that's completely overridden by strep pneumo, pseudomonas, staphylococcus acheris. In terms of how to develop this ecologic model of pneumonia, we can break it into parts. So, of course, what we were taught about host factors still applies. So if you have impaired mucociliary clearance, if you have some defect in your innate and adaptive host defenses, that's going to impair elimination and make you more susceptible to pneumonia. Immigration's a little more interesting, though. So if you think about it, our working model of how strep pneumo works is not really the way we model it in mice. In mice, you develop a very large batch of strep pneumo, squirt it into healthy lungs, and you call that pneumonia. That's not a very faithful capitulation of what's happening in our healthy human subjects, right? They don't aspirate a gigantic inoculum. It might be that one of the more exciting ideas from the past decade is that that subclinical microaspiration that we think is happening all the time in most of us may actually be protective. So why do I say that? So this is a really cool paper done by Ben Wu and Leo Segal a few years ago, Blue Journal. They took healthy mice, and they did episodic aspiration of human pharyngeal microbiota. So they're taking those benign anaerobes, by and large, that you find in the upper respiratory tract of humans, squirting it into mouse lungs, and then seeing, did that convey any kind of protection in terms of subsequent pneumonia challenges? So this is the cocktail of microbiota that they instilled, and they checked them at these various time points, and they challenged them. They both characterized their immune response, and then they challenged them with pneumococcus and saw if they were susceptible to it. A couple things that are really remarkable here is how quick those bugs are killed. So you don't give mice pneumonia by putting these benign pharyngeal anaerobes into their lower respiratory tract. They kill them quite quickly. But there's a persistent immunologic protection, and if you challenge these mice with streptococcus one day later or 14 days later, they're protected. So that benign pharyngeal aspiration may actually be helping to calibrate that immune response so that it's appropriate. It may be serving a sort of sentinel role, right? If you have to dial up or down your immune responses, you may want to know what's up there and what the source of the aspiration and subsequent potential pneumonia is going to be. The other thing that I think we've sort of elevated our understanding on is the right side of the screen of environmental growth conditions, and I think in terms of understanding why pneumonia happens and how it happens so catastrophically, so abruptly in certain patients, we need to think about nutrient availability, top of the list for what determines bacterial community structure. So I think about this figure a lot. I'm sure anyone who's studied ARDS has seen it a million times. This is from Lorraine Ware and Michael Matthei's review 25 years ago. And it shows quite nicely the difference between a healthy alveolus and an injured alveolus. Now, I give talks to microbiology audiences, and when I show them this, and I'm telling them what lung injury and ARDS is, they say, you know, the right half of that figure looks like a culture flask, and they're right. That looks much more hospitable to bacterial growth on the left side. Ecologically, healthy alveoli are really inhospitable for bacteria. There's just nothing for them to eat, aside from the intuitive things like macrophages and cilia. There's just very little in terms of it's not like the gut that we're shoving carbon into all the time. There's very little for bacteria to metabolize in the healthy lung environment. As soon as you have any kind of injury, local or systemic, and you have a leak of protein-rich edema into the alveolar space, suddenly you have nutrient availability. You have something that the bacteria can gobble up and chew and reproduce with. So to try to interrogate this and understand how true this is and how relevant it is, we developed a model that basically directly asks, is that true? Does it actually, does the right side of the screen more promoting a bacterial growth than the left side of the screen? So we use an ex vivo culture approach where we use sterilized BAL fluid as culture media. So we can use this with BAL fluid from volunteers and healthy human subjects, or we can use it from mice. And we basically lavage the lungs, compared injured lungs to uninjured lungs, sterilize that fluid, and then spike it with staph, pseudomonas, strep pneumo, and see does it grow better or worse, depending on how injured the host was and what was in there. And the short answer is it matters. So this is a hyperoxia model of lung injury. This is just the sterile saline control. This is lavage fluid from mice who were not treated. These are lavage fluid from mice who've gotten hyperoxia for three days, which causes lung injury. And you can see that staph does a whole lot better growing in the lavage fluid from injured mice. What is it? Is it someone taking the foot off the brakes, so inactivation of host defenses, or stepping on the gas by providing nutrients that the bacteria can grow with? We're more excited about the latter because of this series of experiments, so Jen Baker is a very talented grad student of mine, compared, used metabolomics to compare the metabolites, the carbon detected in BAL fluid from healthy mice on the left, injured mice on the right. This is a volcano plot that's supposed to look like a volcano erupting in both directions, where you see what's enriched in one, what's enriched in the other. What's remarkable is there's nothing enriched in healthy lungs. This, I think, visually is telling you what I already told you, which is healthy lungs don't offer a lot for bacteria to eat. In contrast, you do have this explosion of available metabolites, carbon sources, in injured lungs. And every one of these is potentially growth-promoting to bacteria, so we're interrogating that now to determine what specific factors of the injured lung environment are promoting bacterial growth. So that's my snapshot view of how to think ecologically of the respiratory tract. Now, as I mentioned, I'm going to preach at you. We're going to talk about anti-anaerobic antibiotics and pneumonia. So I'm a microbiome guy. I need to think, I love to think only about what's above the diaphragm, but I have to think about what's below the diaphragm as well. That's where most of the bacteria in our body are. I suspect, I think many of you are clinicians, and you've heard these pearls at some point in your life, if not pearls, just things said. Aspiration pneumonia is caused by anaerobic bacteria, and in facing a patient who's got a pneumonia, you're not sure what's going on yet, let's just give them Piptozo, there's no harm, we can always de-escalate later. I am going to try to debunk both of these. So starting from the top, this pearl that I was certainly taught and perpetuated, that aspiration pneumonia is caused by anaerobic bacteria is out of date and wrong. So it was based on studies, older than I am, from the early 1970s, using, and they were lumping together patients who had plain old community-acquired pneumonia, but lung abscesses and pyema, which we would now consider separate processes. When we use contemporary studies, epidemiologically, looking at pathogens in pneumonia, we just don't find many anaerobes at all. And when you specifically look for aspiration risk factors, does that cause a differential growth of anaerobes and respiratory specimens from patients with pneumonia? The answer is no, even in patients with what we would bill clinically as aspiration pneumonia, do not grow out anaerobes when you go looking for them. If you're like me and you're molecular and you want to know what the sequencing shows, Georgios Kitsios' pit has done work comparing patients with plain pneumonia, aspiration pneumonia, and found really no difference in the sequencing-detected presence of anaerobes in the lower respiratory tract. So it's just not true in terms of microbial etiology that aspiration pneumonia is driven by anaerobes. You might think Dixon's just being a contrarian. This is actually guideline adherent. So for quite a while now, ATS and IDSA have said in the inpatient setting should patients with suspected aspiration pneumonia get anaerobic coverage beyond standard empiric coverage? And the answer is no for this reason. So it's just outdated. You don't need to cover anaerobes if you have a concern for aspiration pneumonia. But how about this one? Let's just give them Zosyn. There's no harm. We can always deescalate later. I think this is a very dangerous concept. And I think it's because in our hearts, we don't think antibiotics hurt people. We think that the risk is abstract, theoretical, and distributed. Like maybe it's increasing drug resistance, but that's spread over a population. But I got a sick patient in front of me, and they're going to derive benefit from this or harm if I don't treat them, right? I'm going to argue against that. So I mentioned I have to think about the gut. There's all kinds of ways that gut microbiota inform lung biology. And when you do decide to give anti-anaerobic antibiotics, by which I mean Piptazo, Unison, Clenda, Flagyl, the common anaerobic antibiotics, with a single dose, you knock down 99.9% of all of those benign commensals in the lower gut. So you are devastating those gut anaerobes. And those are protective. We know all kinds of ways they're protective. So they provide colonization resistance against potential pathogens, things like C. diff and VRE. My group studies this. Translocation of gut bacteria, you've termed translocation of relatively benign commensals to a bunch of angry gram negatives. Calibration of systemic and alveolar immunity is very hot right now. They are literally giving fecal microbiota transplants to prime patients' immune response so they can get immunotherapy from melanoma. We know that the gut microbiome informs your systemic and your alveolar immunity. And finally, the gut microbiome is a metabolic organ. It makes over 400 detectable compounds that make it into the blood and have potent effects on end organs. So for all of these reasons, we might want to be thoughtful before we say, hey, give them a dose of Zosyn and kill those anaerobes in the lower gut. The gut microbiome is an organ. It has a function and a dysfunction. When anaerobic antibiotics are given, they cause a type of organ failure, and I would argue we're just beginning to understand the metabolic, immunologic, and clinical consequences of this. So this has become the main focus of my group right now. I have a very talented trainee, Rishi Chandraj, who asked this question. So he said, because in multiple animal models, when you deplete gut anaerobes, they have a worsened susceptibility to pneumonia. Do we see any evidence of this in observational human data to suggest the same? So we looked at mechanically ventilated patients who are at high rates of pneumonia, high risk for VAP. 3,000 of them at the University of Michigan. Essentially all of them, to a rounding error, received antibiotics in the first 72 hours. You can't be on a ventilator at our hospital and not get antibiotics in the first three days. But of those, about two-thirds did get anti-anaerobic coverage and a third did not. So we're talking about just the most commonly given drugs here were Zosyn versus Cephapim. So Piptazo versus Cephapim. Cephapim doesn't touch the anaerobes. And asked, do they differ? And they differ dramatically. They differ in their VAP-free survival, their ventilator-free survival, and their overall survival. So this 30-day survival is a six-point absolute difference in mortality. But you should be saying, well, this is just observational data. It's surely confounded. There was some reason that docs decided to give some of those patients Zosyn and some people Cephapim. So maybe it was just confounding by indication. So we modeled it in mice. On the left, it is an infectious model, Klebsiella pneumonia. And if you treat them with Zosyn, they have impaired bacterial clearance. On the right, it's a sterile model. So hyperoxy-induced lung injury. We turn a sterile, this is four days of hyperoxia. We turn a nonlethal model into a lethal model by pre-treating them with Piptazo. So you can't blame confounding for that. That's two different models. We found the same delta here. You could say, well, that's just those guys in Michigan. That's just one center. This group from the Netherlands recapitulated our analysis with a much broader cohort. So this was not just mechanically-ventilated patients. It was 16,000 patients in Dutch emergency departments and found the same survival delta. So a strongly significant same-hazard ratio. People who got anaerobic coverage did worse than people who didn't. And what we're looking at now is this. This is, if you are a nerd for methods, this was a gift from the heavens. So there was a 15-month shortage of Zosyn. So for 15 months in 2015, 2016, they took it away from us. The world kept spinning somehow, but what you can see is it dramatically altered our prescribing practices. So the orange line here is Zosyn. It was 20 to 30% of all antibiotic doses in our hospital. On a dime, it went to close to zero, and it was replaced by cefepime. And then on a dime, we went right back to it, right? So if you're a methods person, this is just an amazing opportunity to ask, causally, did it make a difference, right? And we have 7,000 patients who didn't have a good indication for anaerobic coverage. They didn't have an abdominal abscess, right? These are all patients who didn't have a firm indication for anaerobic coverage. And the only determinant for whether they got Zosyn or cefepime was calendar date. Did they fall within the window of that shortage? And what did we find? The exact same delta. So 5% increased mortality among the patients who got Zosyn compared to cefepime. And it didn't matter how we, with sensitivity analyses, how we tried to adjust different models, it was very consistent. So this is very concerning to me, and this is why, instead of talking about over the horizon, what are we going to do about the microbiome in the future, I'm saying we should consider the microbiome right now. We are constantly, without good indication, destroying an organ, the gut microbiome, and it probably has profound consequences on the outcomes for our patients with pneumonia and other conditions as well. That is the end of that topic, and I am, again, very grateful for the time and opportunity to speak to you, and I'll move on to the next speaker. Thank you. All right, I am the next speaker, so all of my slides are loading. My name is Kirsten Cota, and I am a primarily a critical care and emergency medicine pharmacist at Mayo Clinic in Rochester, Minnesota. But I recently got 40% time for infectious disease. So I am the stewardship pharmacist for all of our ICUs and our emergency department. So on that note, my section is talking about the impact of antimicrobial resistance on CAP and what the data for novel antibiotic agents are in the treatment. So for a quick summary, we were actually better at understanding what was growing in people's lungs before we had antibiotics. It turns out when your treatment modality is keep them in the hospital and watch them, when they die, you can culture what is left of their lungs. As we moved into the post-antibiotic era and we moved into having outpatient antibiotics available, you can see that our actual retrieval of understanding the microbiology of CAP in patients in the 80s took a deep dive. The overall trend, though, was pretty similar. Streptococcus pneumoniae is one of the main bacteria that we see in community-acquired pneumonia, followed closely by other strep species and Haemophilus influenzae. With Staphylococcus, Klebsiella, and other gram-negatives, an atypical is kind of increasing in prevalence, just as we were able to actually detect them. When we look at the current landscape of the microbiology of CAP, we are really obtaining true positive cultures in about 30% of CAP cases. So this means that 66% of CAP cases, at least in this study by Gadsby and colleagues last year, showed that you had strep pneumo, Haemophilus influenzae, Staphylococcus aureus, Pseudomonas, and atypicals. And in all the other cases, it was other bacteria, viral or unknown. And blood cultures were positive in only 5% to 8% of cases. So at the current juncture, we are treating an infectious etiology that we don't really know what's exactly growing from the patient. When we think about the classics, though, and what the emergent drug resistance looks like, I'm just going to break it down fairly quickly based on the bacteria we know about. So strep pneumonia, there's two primary concerns with resistance in Streptococcus. This is going to be macrolide resistance, which across the United States has increased. So it's above 25% in most of the country, which means that what was previously a gold standard first line only single drug antibiotic is no longer appropriate for the management of CAP on an outpatient setting. And we also worry about the increasing incidence of penicillin and beta-lactamases, as well as the penicillin-binding proteins. For fluoroquinolones and tetracyclines, there are a few genetic modifications that can happen that Streptococcus pneumonia across the United States doesn't have as much of a problem. So we do actually still have a lot of functional antibiotics that we can give patients for strep pneumo. Penicillins, third-generation cephalosporins, fluoroquinolones. I mean, I would never give Linazolid to one of these people, but you could. Tegacycline also I would never do, but you could. And then ceftaroline. Moving on to Haemophilus influenza, this is going to be beta-lactamases as our primary concern for inducing resistance, as well as the introduction of efflux pumps. You have some DNA generator mutations that can occur and hamper your fluoroquinolones. But again, across the board, our primary workhorse antibiotics for CAP are still effective for Haemophilus influenza. Staphylococcus aureus, obviously, methicillin resistance is our main concern, especially in a community population, where identifying which patients are those at risk for MRSA becomes the challenging question. This is mediated by MEKA resistance and alterations in penicillin-binding protein, too. But again, we do still have functional antibiotics for MRSA in a community setting. Linazolid, vancomycin, ceftaroline, some of the novel antibiotics I'll be talking about a little bit later. When we look at our atypical bacteria, this is armicoplasma, chlamydophylla, and legionella, really macrolide resistance is kind of on the horizon for these three, with the exception of chlamydophylla. And we still have tetracyclines and fluoroquinolones for these various agents. The other kind of specter would be the enterobacterialis and the increasing incidence of ESBLs in the community. And so your concern here is that you're going to have an increasing incidence of resistance to our workhorse third-generation cephalosporins that we primarily rely on for most of these patients. And as you get into the carbapenemases, efflux pump and porin mutations, AMP-C existence in some of these bacteria, we do have options. They become less and less palatable for empiric community-acquired pneumonia use given how broad they are, but there are still options for CAP. So when we're thinking about kind of the specters of empiric CAP treatment failure, right, our workhorse guideline-recommended outpatient antibiotics for most people are going to be perfectly adequate, except in three situations. MRSA, pseudomonas, and those ESBL producing enterobacterialis. It's very challenging because the risk factors do not overlap across the bacteria, so there's not really one patient who is clearly at risk for all three. It becomes, it's very individualized. There are important regional differences in the rates of pseudomonas and MRSA in CAP, as well as the various enzymes that the local enterobacterialis are producing. The baseline location of patients can be a challenge, right? A 30-year-old coming in with CAP is going to look very different from a 75-year-old coming in with CAP. And then our definitions of risk factors vary across study of the studies that currently exist. So this is kind of where the real challenge is with drug resistance in community-acquired pneumonia. You say, all right, what about the guidelines? Unfortunately, not that helpful. So we've seen that a one-size-fits-all categorization of risk for multi-drug resistance doesn't really work. But the recommendation is, all right, well, if you grew MRSA or Pseudomonas in the last year, you can empirically cover. If they were hospitalized in the last 90 days and they got IV antibiotics, you could cover MRSA and Pseudomonas. And then locally validated risk factors, which doesn't really mean that much, right? If you don't have the ability at your hospital system to have a large assessment of what your microbiology looks like and what your patient population looks like, who's at risk, that's not really a very helpful statement. So we may say, I wrote about novel diagnostic techniques. Is there a better assessment of somebody's risk of having a resistant bacteria? This is a study by Falsey and colleagues that looked at the nucleic acid application test that was intended for use on sputum versus lower respiratory tract samples. It's very sensitive, but the specificity is not quite as satisfying. And as Dr. Dixon just educated all of us on, lungs aren't sterile. They're not a sterile source. And so when you're using this nucleic acid application test and you're finding DNA of Pseudomonas in a patient, does it mean they're actually infected? It's not clear at this point. There's a lot of data that's ongoing for the actual clinical utility in broad spectrums of these tests. I would say the current state is that the negative predictive value is going to be more valuable to us than the positive predictive value. This study in particular looked at patients that came into the hospital with a concern for acute respiratory infection or cardiopulmonary illness. And you can see that across the final discharge diagnosis, about 30% had CAP, but many of the patients had other respiratory failure syndromes. And so if we took this test on a patient that had heart failure and we had Pseudomonas DNA and we gave that person a seven-day course of Zosyn, we're going to have a lot of, it's going to lead to a lot of unintended consequences. So at this point, I would say the nucleic acid application tests are an exciting future step, but routine incorporation to practice, we're still learning how to do that. One correlation that came out of this study was that if the bacterial volume seen on that test was greater than 10 to the 6th or 10 to the 7th copies per mil, it had a better correlation with an elevated procalcitonin, which we're likely all familiar with. Elevated procalcitonin has some validity in determining if the patient has bacterial pneumonia versus say COPD or heart failure as their reason for heart failure. So we all remember HCAP, or some of us might remember HCAP, which was this horrible generic criteria that said everybody's at risk for Pseudomonas. Give them all double coverage with gram negatives and then add MRSA coverage. So this led to a horrible loss of antimicrobial stewardship. And HCAP has now gone out of the guidelines. So the question is, what about this drug-resistant pneumonia cap? How do we differentiate these? Amati and colleagues this year published this really excellent review of essentially the data that's been done for what are the clinical characteristics of the patient that should make you think about, do I need to cover Pseudomonas or MRSA in a situation where they hadn't grown in the previous year? So for generic comorbidities, for MRSA, we've got the list up there, and for Pseudomonas really it was having COPD or bronchiectasis put them at potentially higher risk. For previous exposures, if they had infection or colonization with either agent, did receive antibiotics in the last 90 days, they were hospitalized in the last 12 months, and then for Pseudomonas the patient had a chronic tracheostomy, they were potentially at higher risk of recovering that as a bacteria of cause of illness. For demographics, the very young and the very old for MRSA, male gender for Pseudomonas, the presence of tube feeds for both skilled nursing facility and smoking use for MRSA. And then from a severity of illness standpoint, severe CAP, particularly those post-influenza have a much higher risk of MRSA as the organism causing the problem. And for Pseudomonas, those with more severe respiratory failure are the ones potentially at risk. But again, this is not a one-size-fits-all, and we can't take every patient that has one of these risk factors and say, I'm going to cover MRSA and I'm going to cover Pseudomonas in this person. So the DRIP score was created where a hospital did just what the guidance recommend, and they looked for their locally validated risk factors, and they found excellent prediction in their own data and in their own models of the likelihood that a patient was coming in with a drug-resistant pathogen. However, like every model that we build, when you apply it to a much broader population, the accuracy tends to decrease. And so Rothberg and colleagues in 2022 looked at 138,000 dataset of patients from 177 hospitals across the country that had blood bronchial and sputum cultures collected on hospital day one. They used 80% to derive the model and 20% to validate on it. And they looked at 43 overall variables to devise their CAP antibiotic resistance model or CARM. And 12 were found to be significant. What you have here is a comparison of the overall R-curve of prediction of cultured drug resistance based on these scores. And you can kind of see here that my mouse is not showing up. All right. So the overall CARM score for resistant to any empiric CAP therapy had a better correlation than the DRIP score on its own. And if you look at the graph on the right, it held true as well when they compared it on overall CCHS data as opposed to just a validation cohort. So this is a potential solution if your hospital system does not have the resources to look and see what your specific locally validated risk factors are. They have publicly published this calculator. And the 12 variables of interest are gender, smoking status, nursing home residence at baseline, hospitalization in a prior year, if they grew an organism resistant to CAP therapy in the prior year, paralyzed, COPD, pressure ulcers, bad functional status, and then ICU requiring a ventilator and vasopressors. And just as an example, I did some experimentation as I was putting the talk together. If I had a 30-year-old male patient who was in the ICU on a ventilator and required vasopressors with concern for pneumonia, they estimated roughly a 10% risk of that patient having a drug-resistant pathogen. And I would say for me personally as a stewardship ICU pharmacist, I would probably be comfortable still giving that person regular CAP therapy in the absence of intravenous drug use or recent influenza or something that would profoundly increase my concern for a drug-resistant pathogen. So again, if you don't have the resources to do a deep dive on your local risk factors, this is a potential temporizing measure that gives you a little bit more to go on and who to empirically cover broadly than the guideline recommendations. We'll breeze through current outpatient treatment recommendations from the guidelines. I think everyone's very familiar with this, amoxicillin, doxycycline. I don't know a place in the country that has macrolide resistance less than 25% for strep pneumo, but if you do, good for you. As patients have more comorbidities at baseline, we broaden therapy out a little bit. We add the clavulanic acid and a macrolide or doxycycline. We go to cephalosporins, respiratory fluoroquinolones. And from the inpatient standpoint, for non-severe pneumonia, we've got a respiratory fluoroquinolone, beta-lactam and a macrolide, and then we would add that MRSA pseudomonas coverage if the patient met those risk factors. For severe pneumonia, so this would be shock, mechanical ventilation, or three minor criteria which are listed in the guidelines and there are various measures of severity of illness, then you would consider doing the beta-lactam and a macrolide or a fluoroquinolone, and again adding MRSA pseudomonas coverage if the risk factors exist. One note, the guidelines do not currently recommend doxycycline for the inpatient coverage of atypicals. However, there is reasonable data that suggests that doxycycline is an acceptable treatment of Legionella. And so if you're at a site that's restricting fluoroquinolones out of concern for increased C. diffuse, doxycycline is a reasonable add to your third-generation cephalosporin for a patient in the ICU. So then getting into the new drugs. So there are three approved ones that I'm going to talk about quickly here. The first one is Lifamulin. So these were studied in the LEAP trials. This one is a plurimutalin that binds to peptidyl transferase centers of 50S ribosomal subunits. It's effective against MRSA, gram-negatives, and atypicals, with a note that it's bacteriostatic except maybe bactericidal against mycoplasma. And it has excellent penetration into pulmonary fluid. The approval study for this one identified when compared to moxifloxacin, it was non-inferior to demonstrate both early clinical response as well as an investigator-assessed clinical response at 10 days post-therapy. And you can see that both for any polymicrobial infection and then our two main players, strep pneumo and Haemophilus influenza, it appears to be a very reasonable choice. Ometacycline is our next drug. You may know this better as skin and soft tissue infection, but it is also approved for community-acquired pneumonia through the OPTCS trial. This is a chemically-derived version of ometacycline, technically called an aminomethylcycline, and it binds to that 50S subunit and inhibits protein synthesis. It's effective against MRSA, some ESBL-producing enterobacterialis, and I'll get into that a little bit later, and atypicals. And again, it's also approved for skin and soft tissue infection. And if we remember tegacycline as, oh, it's the great new super-broad tetracycline, it's going to be great, and then people that had pneumonia died more when we gave it. So this has better pulmonary penetration than tegacycline, which is why it ended up getting FDA approval for the pneumonia indication. And then our final new one is delafloxacin. So this is a novel fluoroquinolone that has improved cellular penetration, and it's more stable against mutations in topoisomerase and in DNA gyrase. It has activity against pseudomonas, MRSA, atypicals, and anaerobes. And compared to levofloxacin in particular, it has a much lower likelihood of acquired gram-positive resistance. So it would be a reasonable fluoroquinolone to use in a staphylococcal infection. And similar to our other two agents, in the assessment of early clinical response as well as at end of treatment, you had a non-inferior response versus amoxifloxacin, with a note that in COPD and asthma patients, they actually had an increased likelihood of achieving early clinical response and an increased likelihood of achieving end of treatment response. So potentially a target population for us to consider for this drug. However, I wouldn't be a stewardship pharmacist if I didn't care about money. Our dosing is up there. It's fairly straightforward. Dose adjustment is also fairly straightforward. But I'd like to bring your attention down to the fourth row of my table. The average wholesale price cost of a five-day course of each of these drugs is absurd. Amoxifloxacin is $1,600. Ometacycline is $3,600. Andelafloxacin is $850. So I cannot in good conscience stand up here and tell you that for the majority of patients that have community-acquired pneumonia, when our workhorse backbone drugs are good for essentially all of them that don't have those risk factors for resistance, I would not recommend any of these agents as a first line. I think it is not economically appropriate, and they haven't demonstrated clear benefit over what our current general recommendations for the average patient is. However, it is pretty exciting that we now have three agents that are oral that can be given outpatient for somebody with MRSA pneumonia. So I think there is a role for these antibiotics in the right population. And I'd like to clarify that ometacycline, remember when I said it kind of covered ESBLs? So they did a large assessment of about 6,000 cultures of ometacycline's efficacy. And they saw that ESBL-producing E. coli had good efficacy against. But the efficacy against ESBL-producing Klebsiella and other gram-negatives went down. So personally, I would not recommend ometacycline empirically in a patient that I knew had an ESBL history, unless I had the actual susceptibility testing from my lab. So it's potentially an option in that situation, especially if you've got a patient that, you know, perhaps they're on a chronic ventilator, and they come into the hospital every time they have a pneumonia because they need the IV antibiotics. So there could be a niche population for these drugs that will allow us to reserve ICU and hospital beds for patients that don't require them, but can still treat some of these resistant bacteria. And then again, the Delafloxacin does also cover Pseudomonas. So it's another agent, another oral anti-pseudomona agent for our arsenal. Yeah, that's kind of what I just said. All right. So that's the end of my section. So again, resistance in CAP is rising in our traditionally understood bacteria, but the majority of our workhorse antibiotics are still very effective and should continue to be first-line recommendations. We do have an increasing incidence of that ESBL Enterobacterialis Pseudomonas in MRSA and community-onset pneumonia. So refer back to either your local risk factors for drug resistance or some of the more generic resources that exist for us. I can't talk today. That exist for assessment. And then finally, there are some excellent novel antimicrobial agents for CAP, but they have an extremely niche usage due to cost. So that is the end of my section. And our final speaker is Dr. Ray. Thank you. So this is what I'm going to talk about over the next 20 minutes or so, that is prevention of community-acquired pneumonia. I am Animesh, and I hail from, you know, a government hospital and medical school in the heart of the capital of India, that is New Delhi. Thank you very much for having me here. So I have no specific financial disclosure, and these are my lesson objectives, which are mainly threefold. I'm going to talk about some of the established modalities for preventing CAP in adults, and I'm going to talk about mainly the target population and how effective the individual modalities are. So just briefly, the different modalities I'm going to talk about, they are going to be the vaccination against the common respiratory tract infections. I'm going to talk about cessation of exposure to irritants, mainly smoking cessation, a little bit about air pollution, some general measures, face masking, some role of breastfeeding, and one or two special cases. So just to set the ball rolling, why are we, why am I talking about community-acquired pneumonia? It is actually a very common cause of hospitalization. I am sure most of us know that. It's actually the most common cause of death worldwide, and US alone, more than two million people get hospitalized every year due to community-acquired pneumonia. Now if you need to prevent community-acquired pneumonia, we need to know the risk factors. Now these are, some are non-modifiable, like age, and some are modifiable. So the common risk factors, they may be chronic lung diseases, there may be conditions increasing risk of aspiration, some immunocompromising conditions, smoking, alcohol, associated lifestyle factors. Influenza is a common cause of community-acquired pneumonia. It also may be, may predispose to the development of Staph aureus infection, so it's a very common cause, and some mitogenic causes like instrumentation and drugs. Now when we talk about risk factors, it's good to know about risk factor stacking, what it essentially means that some risk factor, typically smoking, it not only increases the risk of pneumonia, but it can also cause a few diseases, COPD, heart failure, lung cancer, which itself can give rise to pneumonia. So there is kind of stacking of risks, and it actually compounds the risk of developing community-acquired pneumonia. Now if you need to prevent community-acquired pneumonia, we need to also know the individual microbes. So what are the common microbes causing pneumonia? So it depends on where you are. In US and Europe, if you leave aside the common causes, common cases where the pathogens cannot be detected, you can see the most common causes are the red sectors and the green sectors, which are respiratory viruses and bacterial pneumonia. The two most populous countries of the world, there it's a little different. So the light green sector, which are mainly bacteria, out of which septic occurs pneumonia, are a common cause. So worldwide, respiratory viruses and bacterial infections, streptococcus pneumonia, are common causes. So that kind of introduces the need for vaccination against these common organisms. Talking about the first vaccination, that is influenza vaccine. I'm sure a lot of us, we use influenza vaccine on our patients, or we ourselves have been vaccinated. Now do they work? Well, it does. ICU admission and death. If you can see the forest plot, the diamond at the bottom, you can see it to the left of the line of no effect, which shows that ICU admission deaths, they are decreased. When it comes to hospitalization due to pneumonia or due to hospitalization due to influenza-like illness, well, the evidence is not that robust. So influenza vaccine, what it does is it not only reduces incidence of influenza, it also reduces mortality, it reduces incidence of severe influenza. And as far as heart disease patients are concerned, it also decreases mortality and major cardiovascular events in patients with heart disease. So if you know a cardiologist, a cardiologist would be very interested in vaccinating their patients with influenza vaccine, and that's the reason why it is so. So influenza indication says anybody more than equal to six months, they should be vaccinated and there are some high-risk groups, extremes of age, pregnancy, nursing home residents, asthma, and some other diseases. So these are the high-risk groups, but ideally they should be given to anybody more than equal to six months. Now if you are using influenza vaccine, it's good to know that there are some forms of influenza vaccines. They may be inactivated vaccines, recombinant, or live attenuated. So where I come from, mainly inactivated influenza vaccines are being used. And if you see to the right of the screen, so depending on where you're practicing, Northern Hemisphere or Southern Hemisphere, there are two types of vaccines, Southern Hemisphere vaccines and Northern Hemisphere vaccines. So India, where I'm practicing at, Southern Hemisphere vaccines, they're recommended. And also the bottom part of the right screen, it actually shows that influenza vaccine also needs to be given at a particular time of the year. So just before the monsoon season or the influenza season kicks in, you're supposed to give the influenza vaccination. So in New Delhi, it is usually April, May, when you want to vaccinate your patients. Moving to pneumococcal vaccine, as I've said, pneumococcus is one of the commonest cause of bacterial pneumonia. In USA, it might be responsible to 5% to 15% of cases of community-acquired pneumonia. And the number may be higher from some countries in Europe. What is important about pneumococcus is that it has got the propensity for causing invasive pneumococcal diseases, some complications like empyema, meningitis, endocarditis, and so on. And what is important is that the in-hospital mortality, which is considerable, 12% to 15%, it in presence of bacterium actually kind of doubles. So bacterium pneumococcal disease patients, they fare much worse than non-bacterium patients. So coming to pneumococcal vaccine, do they work? Again, yes, they do. Invasive pneumococcal disease, and PP stands for pneumococcal pneumonia, the incidence is much less in individuals who are vaccinated by pneumococcal vaccine. The data for death due to pneumonia or death due to specifically pneumococcal pneumonia, again, the evidence is a little less robust. What are the indications? So anybody more than 65 years of age or younger with some predisposing medical conditions, heart disease, lung disease, liver disease, alcohol use, or some immunocompromising conditions like HIV malignancy, or some having increased risk of meningitis like CSF leak or prior invasive pneumococcal disease. So these are the patients where you would like to give your pneumococcal vaccine. And again, the pneumococcal vaccines may be, you know, it may be a protein conjugate vaccine or a polysaccharide vaccine. So previously, PCV13 or PPSV23 were being used, but with the advent of PCV15, the number actually refers to the serotypes covered by the particular vaccine. So with the advent of PCV15 and PCV20, these are commonly being used, and the current guidelines also talk about their use over and above the earlier vaccines. Moving on to COVID-19 vaccine, well, the pandemic is formally over, but we keep getting cases of COVID-19. Worldwide, it has caused more than 7 million deaths. So we have lived through that, so I need not speak about that. What is important is COVID-19 vaccination is still very relevant, and, you know, the indication in U.S. is more than equal to six months. Where I'm coming from, it is usually more than six years, and it has been shown by this network meta-analysis that COVID-19 vaccines work, and it can prevent both COVID-19 illness as well as severe COVID-19 diseases. The final vaccine is the RSV vaccine, so this is a new inductee. Now, RSV is a little less appreciated than influenza, but it's good to remember that it can cause outbreaks of respiratory infection during winter seasons, especially in some high-risk groups. Elderly individuals are commonly involved, and if you would see the Kaplan-Meier curve, you can see the graphs diverging, showing that the RSV patients might fare worse than influenza patients. So RSV is definitely a killer, and the high-risk groups which I talked about are, you know, besides elderly, it may be infants, patients having persistent asthma or other cardiopulmonary diseases, nursing home residents, and so on. So as of 2023, USFDA, they have approved two vaccines, one adjuvanted, the other non-adjuvanted, and you know, these can be used in individuals, elderly individuals or other individuals who meet the eligibility criteria. So again, the Kaplan-Meier curve, they actually show the divergence, showing that these RSV vaccines work. So the four vaccines I talked about, it's good to know about them, but it's also good to know the real-world scenario where the vaccine coverage is definitely less than optimum. So if you would see the violet line in the middle, which shows the uptake of influenza vaccines in adult patients, so barely touching the 50% mark. So five out of 10 individuals who are eligible for influenza vaccines, they don't end up getting it. For higher-risk groups, the brown line, it's a little better, 60%, but still, 40% individuals are not being given the vaccines that they deserve, and similarly for pneumococcal vaccines, you know the number, they are again very, very modest. Now moving from vaccine to smoking, now tobacco is a killer, and smoking is actually the commonest form of tobacco consumption, and smoking kills, and how it kills is causing pneumonia is one of them. So it kills a large number of people, including the 1.3 million people dying due to second-hand smoke. What is important to realize is that none of the smoking products, they are safe, and there is nothing called a safe level of exposure. So if somebody is smoking, then he has the increased risk factor for developing its consequences, including community-acquired pneumonia. And this was proved by an old study, more than 20 years back, it was shown that smoking increases the risk of pneumonia, and there's a dose response to it. If you would see the bar diagrams, those who are smoking more than 24 cigarettes, they have higher risk vis-a-vis those smoking, say, 1 to 14 cigarettes per day. I'm not sure whether you can see the box on the right. This talks about the risk of cigarette smoking and the risk of tuberculosis. Long story short, cigarette smoking also increases the risk of tuberculosis, and there is a dose response to it. And what more, in the same study by the Neote and his team, it was shown that after quitting, if 10 years have elapsed, then the odds ratio of developing pneumococcal disease or pneumonia, they substantially decrease. Two messages, one is smoking can cause pneumonia, and if somebody quits smoking, then the risk of pneumonia comes down, albeit a little slower, and it would take almost a decade before the risk comes back to baseline. How can smoking cessation be done? So this is easier said than done. Most adult cigarette smokers want to quit, and there are some elaborate programs to do so. However, fewer than 10, they actually manage to quit. And one of the common reasons being is less than 50% of the adult smokers who meet health professionals, they are not advised to quit smoking and how to go about it. So this is something, again, which reflects on us, and this is something that we as health professionals can make a difference about. Number of smoking cessation options, pharmacological, non-pharmacological, I won't go into the details, but it would be suffice to say that all of them works if they are used as a part of standard program. A little bit about hand hygiene and pneumonia, now hand hygiene, it has traditionally been linked to diarrheal diseases, through oral route, diarrheal diseases, especially in school children, especially in people having weakened immune system, but it's also, you know, interesting to note that hand hygiene can also reduce respiratory illnesses, like say colds, up to the tune of 21%. So a number of, you know, a number of studies have been done over the years which shows the benefit of, you know, hand washing or hand hygiene in preventing pneumonia. So we have got two meta-analyses, one was done almost 20 years back and the other more recent. So it was shown that these, again, are studies predominantly done in children less than five years and school-going children, it was shown that hand washing can substantially decrease the incidence of community-acquired pneumonia. What about face masking? Well, face masking has been one of the, you know, the commonest symbols, commonest modalities that have been used during the COVID-19 pandemic and during the pandemic we had also put together a meta-analysis which was published and what we saw was that the number of studies showed that face masking can help in preventing pneumonia, but then again there were a lot number of studies which also were kind of equivocal. So we can see the diamond at the bottom touching the line of no effect. So the reason on probing what we could understand was that all of these studies which were randomised control trials, there was contamination of the control arm because a lot of the individuals in the control arm, they themselves, you know, took up masking even though it was not, you know, put up as a part of intervention. So again, long story short, face masks can help in prevention of community-acquired pneumonia. So these are the, you know, the diamonds. Finally about air pollution and pneumonia. So around 50% of the world population, they use biomass and they are actually exposed to the hazards of household air pollution, air pollution which can be divided mainly into, you know, household air pollution and ambient air pollution. So as you can see, combined they cause around 6.7 to 7 million deaths per year. In fact, if you look at the numbers, so it kills more number of people than HIV, tuberculosis and malaria combined. So air pollution is a killer and, you know, one of the methods in which it kills is by causing community-acquired pneumonia. Now air pollution prevention, so where I come from, air pollution is again is a significant problem. So the government, you know, in LMICs, they know how to go about it and there are various methods of preventing air pollution. For example, you know, decreasing vehicular emission, more stress on renewable energy and planting more trees. But again, just realize that most of these measures, though effective, they take a long time to take effect. And finally, you know, there are recommendations by WHO to address household air pollution as well. Few words about breastfeeding and pneumonia. Now this is mainly for children. So it has been seen that breastfeeding, it affects newborns, how? By inducing immune maturation, how? By promoting a healthy gut microbiota. And as can be seen from this meta-analysis, that exclusive breastfeeding can lead to decreased incidence of community-acquired pneumonia in, you know, in infants and children up to two years. Right. Finally, a little bit about good health habits and pneumonia. So does a healthy diet, rest, exercise help? So as per this study, which was published from UK, a hospital-based study, it was seen that, you know, some form of diet like increased consumption of coffee, tea, fish, and fruits, they may be beneficial in preventing community-acquired pneumonia as compared to, say, increased consumption of red meat, which increase the risk of pneumonia. Finally, special cases, so Legionella, we know that it can cause infection through infected water sources. So disinfection of water supply, and in case of Legionella longbeachii, which is found in some parts of the world where, you know, gardeners are exposed because of the prevalence in soil. So in these cases, washing of hands and, you know, masking to avoid inhaling dust may be helpful. So I would like to sum up by saying, you know, the cornerstones for preventing community-acquired pneumonia would be vaccines. It would be smoking cessation. There are roles of hygiene and pollution in preventing community-acquired pneumonia. And finally, some role about exclusive breastfeeding and general measures, healthy lifestyle in, you know, in prevention against community-acquired pneumonia. I would like to end with that. Thank you so much for your patient hearing.

community-acquired pneumonia

prevention strategies

vaccination

influenza

pneumococcus

RSV

COVID-19

smoking cessation

hand hygiene

air pollution