Good afternoon, everyone. My name is Marco Restrepo. I come from San Antonio, Texas, and the session that we will have today is Community Acquired Pneumonia in Hospitalized Patients Where Guidelines Meet Clinical Practice. Today we have placed this session in collaboration with the CDC, and we have two great distinguished speakers, Dr. Valerie Bong and Dr. Barbara Jones. So the whole point here is that whatever we say today is our own personal opinion and interpretation of the data, and should not be recognized as what the guidelines will say. Unfortunately, we didn't have the guidelines ready and finalized in order to be discussed today, but we have two members of the committee, including me, and our chairwoman is here. Therefore, we are monitored by our boss. So please make sure that all the sessions that you have here, and particularly the one that we have today, will be evaluated in your app. With no much to say, we would like to invite Dr. Valerie Bong, who will tell us about the current antibiotic management practices for community acquired pneumonia. Thank you very much, Valerie. Thank you. Thank you very much for that introduction. I invite everybody to log in. into the app and log in to our session. So you can use the audience response questions here. I'll give everyone a minute. Great. So before we get started, thank you, Marcos, for the wonderful introduction. I do have just one disclosure, and that is that I am not, in fact, a palm critical care or any kind of chest physician, which I think is important to keep in mind, which means I'm not quite as cool as all of you in the room. And in fact, if you ask ChatGPT, what is the difference between you all and myself, a hospitalist, I didn't realize just how cool you all were, in fact, keeping a second pair of lungs in your body in case you needed it for rapid ECMO, and some other really disturbing things on here, if you have a chance to take a look. Like, I did not know that that's how you did bronchoscopy. So very, very, very cool. So I am not a palm critical care chest physician. I'm a hospitalist. And so you might be wondering, why am I up here talking to you about pneumonia? And I'm going to go through today some of the basic principles for how you treat the most common forms of pneumonia as we see them. And then Barb and Marcos are going to go into some of the more challenging cases. But the reason that I study pneumonia as a hospitalist is that I'm really interested, actually, in how we as physicians make decisions about how we decide what tests we should use to diagnose someone and use that to determine what the right treatment is. And if I had the time, I'd go into the whole host of complexities that go into making those kind of decisions. And all of these apply for pneumonia. But one of them, of course, that is very important is diagnostic uncertainty. And that kind of drives a lot of how we end up making decisions and sometimes overtreating patients with pneumonia. And so these are all super complex. I'll focus kind of on diagnostic uncertainty today. But my job was kind of to talk about the principles of antibiotic treatment or antibiotic stewardship in community-acquired pneumonia, and particularly how you think about getting the right antibiotic to the right patient for the right dose, the right duration, and the right spectrum. And so when I think about community-acquired pneumonia, I generally think about three moments of antibiotic decision-making. And these might vary depending on where you practice and how often you're seeing a patient. So these come from the point of view of someone who's seen them throughout a hospital course. But most of them apply no matter where you see patients. And that's starting with making the initial diagnosis, which we'll see is potentially the most tricky part of all. And then that moves into deciding on the initial empiric antibiotics based on the best guess of what might be going on with the patient. But then as new information comes in, it's really thinking about reconsidering things 48 to 72 hours later. And I used to actually have a fourth moment of antibiotic decision-making, which was discharge. But if you look nowadays, the length of stay for your typical patient with pneumonia is now about three days. So at about that same time that you're thinking about de-escalation, you're usually thinking about discharge as well, unless the patient is kind of one of these more complicated cases that we'll talk about later. So let's start with that initial diagnosis. And this, I'd love to see, this will be an audience response question, but this is kind of the day in the life of a hospitalist. And I'm sure a day in the life of many of you as you are trying to think about treating a patient. And that's someone comes in, 80-year-old woman, dementia, altered mental status, comes in from a nursing home, comes in alone, unable to provide any history. And you're like, OK, well, at least I'll do a great physical exam. But she talks the entire time, so listening to her lungs is nearly impossible. You know that she has stable vital signs, but she's really not able to tell you anything else. And you might have some nonspecific findings like a borderline elevated white blood cell count, maybe a positive urinalysis, which we know is positive in women who are in nursing homes anyway. And if life were perfect, you'd get a chest X-ray that looks like this, which even me as a hospitalist can read and say that there's something wrong there. But instead, what we often get is something that looks more like this. And it gives you absolutely no information. So let me ask you guys, in this case, if you were trying to treat this patient, what would you do next? Would you provide supportive care and maybe do additional diagnostic testing for pneumonia? Maybe empirically treat with vancomzosin, thinking, well, she's coming from a nursing home. Maybe something more narrow like ceftriaxone. Would you provide some supportive care and maybe check back in on her? Or give up? Medicine was never supposed to be this hard. I'm glad we haven't lost any of you, so at least no one's giving up yet. But there's a whole variation in responses here, and I find that really interesting, and probably because it's true that we don't know the exact right thing to do in this case. Some might say that the supportive care and recheck back in is the right direction, but who's going to ask their colleague to do that, or who's going to have time to do that themselves? What if it's shift change? So there are all these things that go into making that decision really hard. And at the end of the day, the question is also, so what is pneumonia anyway, right? And actually, one of Barb's recent papers that just came out really showed that if you were to ask six smart people in the room, what is pneumonia, you'd probably get six different answers. And in a paper that she just published in Annals, she found that more than half of patients hospitalized and treated for pneumonia had discordant diagnoses between initial presentation and discharge. And then treatment for other diagnoses and expressions of uncertainty were common. So really, it's hard to make the diagnosis of pneumonia, and things change, and there are differences in different places. So this is not a straightforward thing. And in fact, if you look at the sensitivity and specificity of different signs and symptoms of pneumonia, you might find some that have a high sensitivity, but a poor specificity, and vice versa. There's no single sign or symptom that's really going to give you like, okay, great, you've made the diagnosis, this is pneumonia. And so many of these things can also be other things, which makes this really tricky. So we actually tried to come up with a standardized definition in order to apply this as a quality metric across the collaborative that I work in in Michigan, which includes 69 hospitals. And to do so, we tried to at least standardize that, okay, a patient had to have signs or symptoms plus some sort of radiographic criteria. And when we applied this to hospitals across the state, including more than 17,000 patients in 48 hospitals, what we found was that about one in eight were overdiagnosed, or either had no signs and symptoms, or had completely negative chest X-rays and chest CTs. And what we found that was really interesting, if you look at these bars over here, is that the vast majority of the patients, each bar here is a hospital, the vast majority of patients within each hospital received a full course of antibiotic therapy. So even in patients who had no symptoms, had no signs of pneumonia, or had negative chest imaging, they often received full courses of antibiotics. And those full courses were associated with more antibiotic-associated adverse events. And there have been other studies that have shown that if the patient, for example, actually has heart failure, they also end up with a longer length of stay as you're giving them fluids instead of diuresing them, which is what they really need. So there's a lot of diagnostic uncertainty here, and a lot of overdiagnosis. And those at highest risk are those you might expect, just like the patients from our case. So people with dementia, altered mental status, and the older the patient is, the higher the risk is of being overdiagnosed, which makes sense because those are also the patients you might feel the least comfortable with withholding treatment. And there's just that much more kind of uncertainty in their treatment. So moving on from the muddy waters of diagnosis, where it's really hard to study and know what's best to do for patients, I'm going to move on to talking about initial antibiotics. And in this, I'm going to focus on the last guidelines and really what they talk about for empiric therapy. And that's if the patient has a history of MRSA, they should be empirically treated for MRSA. If they have a history of pseudomonas, they should be empirically treated for pseudomonas. And then what you do if the patient doesn't have one of those histories but has recently been hospitalized and received IV antibiotics really depends on the severity. If the patient has non-severe pneumonia, you should withhold kind of broader-spectrum treatment but obtain cultures to guide escalation of therapy. Whereas if the patient has severe pneumonia, you should add MRSA and pseudomonal coverage and then obtain cultures to de-escalate therapy. And this, in case people forget, is the definition of severe pneumonia. So patients with septic shock, respiratory failure, or meeting three minor criteria. So we actually looked at this and looked and saw, you know, how often is it that patients are getting kind of discordant empiric antibiotic therapy? And here we focused on non-ICU patients with pneumonia. And again, those kind of 69 hospitals across the state of Michigan that I mentioned earlier. And what we found is that if you actually applied those criteria, 95 percent of them did not need anti-pseudomonal or anti-MRSA coverage. And you can see here, that's what the blue represents. With that small area, the red, representing patients who should have gotten both. And you can see the anti-MRSA and anti-pseudomonal is a tiny, tiny piece of that pie. But what people actually get looks more like this. And basically, 32 percent of patients receive unnecessary anti-MRSA or anti-pseudomonal therapy, the vast majority of whom receive both. And those numbers are somewhat better, but similar if you look at VA hospitals. This data is courtesy of Dr. Matthew Goetz and Dr. Makoto Jones, who found that about a quarter of patients without risk factors for anti-MRSA or anti-pseudomonal therapy end up receiving it. And Dr. Jones has showed us before that adding anti-MRSA therapy to standard therapy is actually associated with harms for patients, including an increased risk of death, kidney injury, C. difficile, VRE, or gram-negative rod infections. So now that we've talked about what to do in the beginning, I want to move on briefly to talk about reconsidering a little bit later. And that's because it's actually easier at that time point. You know, when patients first come in, the risk for them is usually higher, and your diagnostic uncertainty is less. But over time, that risk decreases as you see that they're improving, and your diagnostic certainty increases as you rule out other diagnoses or see how they respond to treatment and get culture results. Yet what we see in real life is that there's a profound diagnostic momentum where diagnoses made even under great uncertainty are rarely overturned, which we saw with that 90% of patients still on antibiotics, even if they're misdiagnosed. And then we know for antibiotics that treatment momentum also exists, where therapy is often continued beyond when it's actually needed or even when we have information to inform de-escalation. For example, when we looked at excess antibiotic duration for pneumonia, what we found is that about two-thirds of patients receive an excess antibiotic duration, and that each excess day of treatment is associated with an increase in antibiotic-associated adverse events. And interestingly, about 93% of that occurs at discharge, now that our length of stay for patients with pneumonia is so short. So the question everybody wants to know is, I just said that there's a lot of excess duration. Well, what is the right duration for pneumonia? And as with all things in medicine, the answer is it depends. But these are some good rules of thumb for most patients with kind of uncomplicated pneumonia. And that's for outpatients. The evidence is a little bit harder to come by. There are less trials that take place in the outpatient space, but likely three days is likely safe. For inpatients, we actually have clinical trial data that shows that if the patient stabilizes by day three of treatment, that three days of therapy is safe. And then prior clinical trial data that shows that if the patient has no more than one vital sign abnormality by five days, that five days is safe. And then patients in the ICU are generally excluded from trials, although there might be some small numbers scattered about. But I think the same kind of criteria could apply if patients stabilize quickly. But then if there are complications or other things, treatment needs to be individualized and thought about more complexly because those patients are not really included in trials. And so I think the take home from this is really that for at least non-ICU inpatients, more than 90% of those can receive three to five days. We found in our data that about half of them are eligible for three days, and the other half are eligible for five days, with a small minority falling into neither of those buckets. And then as we think about duration, we should also be thinking about oral antibiotic options. And although fluoroquinolones are great drugs for pneumonia, this has generally been something that on a national stage, at least from a stewardship perspective, we've been trying to move away from due to collateral harms, including adverse events, C. difficile and antimicrobial resistance. And so some of the oral options that can be used include oral cephalosporins, amoxicillin in the right cases, or amoxclav. And just taking this all together, if you look at antibiotic overuse at discharge, nearly 60% of patients with pneumonia have overuse at discharge, a rate that varies across hospitals. And we're actually studying strategies to help hospitals improve in a cluster randomized trial that we have going on right now in the state of Michigan. So in summary, you know, clinicians make decisions under great uncertainty and experience complex influences rarely related to evidence, and in some cases it's because we don't have the evidence, like how, like what is pneumonia? And there are really three moments to optimize antibiotic prescribing in pneumonia. The diagnosis piece of it, which is hard due to uncertainty, and the fact that it often becomes a catch-all diagnosis when you don't have a better diagnosis to provide, but one of the recommendations I have is to reconsider those mimics and don't let diagnostic momentum happen if you have a new diagnosis a couple days later. Empiric therapy, I think a good rule of thumb is that anti-MRSA and anti-pseudomonal therapy is way overused, and it's associated with harm for patients. And then when it comes to discharge and duration, most patients can get three to five days of antibiotics and really trying to move away from those fluoroquinolones. Thank you for that, and that's my contact information there if people have questions. Thank you very much for that very, very good presentation, and thank you for making my life much easier for this presentation. So the next step is challenges of antibiotic selection. So over the next few minutes, what I'm going to try to show you is a stepwise approach that we have learned from the recommendations from the guidelines and how this could help us manage patients in an organized fashion. So for this, I'm going to show you the seven steps. The first step is how sick is the patient? So if the patient is not very sick, as we know, we can send the patient in the outpatient setting, could be managed at home, and then if the patient is sick, we need to decide to put him in the hospital. So the tools that we can utilize to decide whether the patient is not that sick is the CURB-65 or a little bit more complex PSI score that has 20 parameters. Only one of the parameters in the CURB-65 includes a laboratory marker. The others are all clinical parameters. However, once we decide that this patient will require hospitalization, the ATS, IDSA, major and minor criteria will help us define whether this patient should go to the war service or should be admitted to some higher level of care. And this is why the guidelines change the name to it is not just the room where the patient is at, it's how sick is the patient? Because sometimes, and we saw it during COVID times, our hospitals became super comfortable managing very, very high flow oxygen levels on the floor, PCU, even on the regular floor with noninvasive mechanical ventilation. So the management of critically ill or severe pneumonia patients move only those reserved for vasopressors like the major criteria or those that require mechanical ventilation. So the key here are the minor criteria to allow us to determine this patient is getting sicker or is sick enough that I should put him on a high resource utilization placement. At the time, I have to make an effort to identify what are the most likely pathogen. And the reason why is because if we don't try to identify the pathogen, it will be very difficult to decide how to narrow the antibiotic, how to direct the antibiotic therapy at the time of the decision making. And then the guidelines from the ATS group got together and many of the people are here in the room that also recognize the importance pre-COVID time of the recognition of immunocompromised host that is not included in the guidelines or patients that are critically ill where you have to expand to do viral testing. So in here, every time that you're dealing with a patient that will require to go to the floor, we have this set of testing. But nowadays, if you don't get tested for RSV, COVID-19, and influenza, almost they didn't see you. But why is this happening? So we knew this from the pre-COVID time that the viruses are occupying a large proportion of the patients that end up in the hospital with community-acquired pneumonia. Therefore, this is why the selection of antibiotics and the duration of antibiotic is a little bit more question nowadays because if we have 100 patients and in 60, we cannot find the bug, and then we have only 33 that we can find the bug. Among those, the majority are viruses. Why do we need to really cover a lot of these patients with regular antibiotics or even prolong the antibiotics unnecessarily for these patients? So this is why the rapid testing come up suggesting that we can do for all this panel of viruses, but at the same time, the utilization of some identification of atypical bacteria such as chlamydia or mycoplasma, not including Legionella. However, there is another panel that is the pneumonia panel that has everything that moves and that can really cause community-acquired pneumonia, including the bacteria. So it is a possibility to really expand the identification of these pathogens. So as Valerie, Dr. Vaughan, presented very, very nicely, is the identification and the suspicion that initially with the HCAP, I'm sorry, with HCAP, it made it so bad that the utilization of, over-utilization of antibiotics started to really chase every single MRSA or every pseudomonas risk, but in reality, the risks are very, very well-defined. And they are defined mainly by the prior contact with MRSA or pseudomonas aeruginosa in a well-defined group of patients that tend to have these comorbidities such as bronchiectasis, severe COPD, they are in touch of the tracheostomies, and these are the patients that come in and out of the hospital in contact with antibiotics. Now it's very interesting to really see this recently published paper in JAMA that utilized this computerized provider order entry, and the whole idea with this was trying to make sure that with the combination of the standard spectrum of antibiotic selection was with the computerized order entry, feedback and education versus the regular stewardship police in my hospital. Maybe yours is much better than mine. But the comparison was that with this methodology, they were able to reduce the number of extended spectrum antibiotic days they utilize in these patients. And if we look at in detail here, everything that you do is better. In the baseline, in the intervention, no matter where you are, it's better. But you were able to reduce vancomycin, you were able to reduce the utilization of broad spectrum antibiotics against pseudomonas. However, it was no impact on length of stay on mortality. So whatever you do at that time is not really affecting the other two variables. But the time to antibiotic escalation was also impacted with the utilization of the computerized order entry. If we are not doing anything like this in our hospitals, I think this is a big chance for improvement in our settings to really identify these things that go beyond the regular stewardship programs that we do. The step number four is the selection of the appropriate antibiotics. And here the key is that antibiotics in this sense are usually what Dr. Avon mentioned is depending on where you are. And in this case, the regular antibiotics that have been tested for patients that are not in the ICU setting with non-severe pneumonia includes the combination of a beta-lactam plus a macrolide, a single fluoroquinolone, or the combination of a beta-lactam plus doxycycline that is sometimes utilized depending on the resources. But this study recently published from Canada with antibiotics within 48 hours, it shows that the beta-lactam plus macrolide, respiratory fluoroquinolones, and beta-lactam plus doxy were much better than single monotherapy. And this is important, guys. Why? Because we receive all this data from Europe suggesting that we just can't do well with a single beta-lactam. But be careful. The macrolide seems to be adding something. And numerically higher mortality when the beta-lactam was there alone. Now, this paper was recently published. It's a randomized controlled trial of claritromycin in addition to a standard of care. And the interesting part of this randomized controlled trial was that it has community acquired pneumonia plus sears, meaning that many of the patients may present with a syndromic phenomenon of sepsis, but with a clear defined interstitial and pulmonary infiltrates, I'm sorry, and symptoms. And what they saw was the primary composite outcome was much higher achieved if the patients were receiving Claritro versus not. And the patients also had a better, lower chances of developing sepsis. But when you look at all the composite outcomes and the secondary outcomes, there is a consistent trend here that you can reduce the time of brocalcitonin improvement, symptoms, SOFA score, et cetera, but again, no impact on mortality, at least not in the 20 and 90 days that they look at. So here we can suggest that the claritromycin in addition to standard of care increase early clinical response and attenuates the inflammatory burden of patients with severe. And many of these patients were not truly severe because the curve 65 was 2 in the median number of these patients. So step number five, selection of appropriate dosing. This is important, guys, particularly with older patients that may require the adjustment of these medications. And these are the included selection of antimicrobial agents recommended by the guidelines with the combination therapy of the macrolides that are intended to cover the atypicals, including Legionella. The betalactans are intended to cover all the core pathogens. Therefore, the combination that is also included in the fluoroquinolones as monotherapy for patients that are not in the ICU setting. In patients in the ICU setting, combination therapy is preferred and maybe prefer the combination with a macrolide. Now step number six, I call it the D3, that is daily assessment, de-escalation, and direct therapy. And this could start really, really early if you have one rapid diagnostic testing, or it could start once you got the results from all the laboratory testing that you ordered, including sputum samples and blood cultures. And here we go back again, what are the tools for this? Now let's see the evidence that has been recently reported. In this study from Spain, a randomized controlled trial, the multiplex real-time PCR versus the conventional microbiological testing showed no differences in outcomes. It was not able to reduce the duration of antibiotic therapy. When you look at here the duration, it's interesting that the duration is 10 days versus 11 days, so much longer than what we usually use in the United States. However, the time to switch from IV to PO was shorter if they used the multiplex PCR, and the time to reach an etiological diagnosis was faster, way faster than waiting almost one and a half days for the answers, with no impact in mortality and not the other outcomes. So unfortunately, they were not able to reduce the antibiotics, but they got to the answer faster. Now, this other manuscript that was published this year from Norway had a diagnostic stewardship on the syndromic molecular testing, and what is important here is that they wanted to really test the intervention of the standard of care plus rapid syndromic molecular testing versus standard of care. And what it shows is that the patients that received treatment were more likely to be the provisional of the pathogen-directed treatment if they were in the intervention arm compared to the standard of care arm. At the same time, the pathogen-directed treatment was also improved by the utilization of the rapid testing. Now, the contract is here, is the superiority parallel open-label multicenter trial of 294 patients with non-severe community acquired pneumonia, and they have the PCR testing against the standard of care, and it was unable to narrow the antibiotics. So what do we do? Two negative, one positive during the past year. I think the message here is it's good to know the answer faster, but you need to make a decision. What are you going to do? If you're going to be able to really redirect the therapy or narrow the antibiotics or remove the antibiotics that are completely unnecessary, patient getting better, viral, positive, there is no need to really continue these antibiotics for a long period of time. You may be able to really assess the clinical stability and be able to move the patient away from unnecessary extra doses of antibiotics. Now, this is why we need to be assessing how good is the patient responding to the current therapy. So this is why we need to move more like on a video. What happens today that didn't happen yesterday? What happens today every single day? Because if the patient is telling you, I'm getting better, then you are going to decide for how long I'm going to treat these patients, because at least in my hospital, as soon as you get better, we switch from intravenous medications to oral medications, and you are one day away of going home. Therefore, you can really move out of the hospital very well. However, more than half of the patients do not get clinical stability in the first three days. So it is not a platform that is a standalone platform. But when we look at data from the United States, people are taking almost 10 days of treatment for hospitalized patients, so too long. But you ask all my faculty, for how long you treat, oh, five days, seven days. When you look at, they're never like that. They're at least seven days. And why do I know? It's because all my residents write, today is day five of seven. So they say, like, what, are you stopping day of five? No, you're writing five of seven. So this is why these studies come up and say, OK, can we apply for non-severe patients, not in the ICU, with severe community acquired pneumonia excluded out of this thing? And they say, OK, maybe a beta-lactam therapy alone. Be careful, guys, what I show you. And what they saw was that there was no difference in all the outcomes there. However, you needed to reach clinical stability. So if you're healthy and you get better, then probably whatever we give you is OK. But if you're really sick, it might not be the case. Now, we have other tools, like procalcitonin, that have shown that antibiotic utilization could be reduced, and we can remove antibiotics. However, no difference in antibiotic initiation and use, with no impact of length of stay or mortality. So bottom line here is, it's good when it's high and it goes down, if the patient is getting better. So you still have to look at the patient. You cannot say, OK, I'm just going to follow the procalcitonin, and then whatever is happening to the patient, I don't care, because the procalcitonin is supposed to be the answer. But in this study, recently guiding the utilization of CRP and procalcitonin in a randomized control fashion, we were able to, the number of antibiotic days was reduced from seven to four days in the CRP group, and the five and a half of the procalcitonin group. So given an opportunity that's saying, if you look at the results and you pay attention to the results, they might give you a hint on what you need to do. And I think that's the bottom line of the whole story, is if you order a test, please, please, look at the results and do something with it. If you don't do anything, why did you order the test in the first place? OK, so with this, take home message here. I just showed you seven steps of selection of antibiotics, including the severity assessment to decide where the patient should be at, the microbiological studies to allow you to identify the most likely bug, the specific risk factors, the appropriate selection and dosing of antibiotics, and the possibility to really do these daily assessments in order to properly manage these patients. Now with this, I would like to give you this last quote. Every action has an impact. Choose wisely the impact you want to have. Thank you very much for your attention, and we will have the questions at the end. Now I'd like to invite Dr. Barbara Jones, who will be presenting effective implementation of CAP treatment. Thank you. You've got to put the timer right there, otherwise they won't pay attention to me. Thanks so much. I'm Barbara Jones. I'm super excited to talk to you about implementation today. My talk is a little bit more meta, and I have no audience response, but I have some questions for you. So I do have some things to disclose. Nothing officially, but I am funded by the VA, the CDC, and the Gordon and Betty Moore Foundation for my research. So I am hoping to describe uncertainty of evidence. You've heard a lot about uncertainty here. We're going to talk about it more. Review the purpose and process of guideline development, and then provide ways to conduct what I've been calling implementation under uncertainty. How many of you guys have direct patient care here with patients you see, you see pneumonia in your... Okay. And how many of you guys also create pathways or are involved in your hospital programs to improve quality around pneumonia? A few less. Okay. I'm thinking... I've targeted a few things just to tailor for both of those audiences. So I'm kind of addicted to analogies. So I have two for you today. One, hopefully you haven't heard too much before, but is that medicine is music. So how many people play music? A couple. All right. All right. There's crothers. I can always count on you. How many of you play classical? All right. How many jazz? Anybody play jazz here? Okay. Great. So these are two very different types of music, but all musicians have to combine... There's knowledge of musical structure and then context to anticipate the next note or chord to play, kind of like medicine, right? Then there's classical music, and the theorists call this type of music composer-driven. So whenever you see a Mozart piece, the notes do not change. They are the same every time, over generations and hundreds of years. And they call that planned or prescriptive. Meanwhile, there is jazz music, and every time Miles Davis played a chord or a piece, it changed. So that's what they call performer-driven, or emergent and adaptive. And both of these types of music require expression and mastery. So classical music, you don't change the notes, but there's a lot of expression, volume, pace, and all of that stuff. But then with jazz, you're actually changing the notes. Okay. So in order to practice really good medicine, you need to be good at both of these types of things. So I would use oncology as kind of a Mozart example. You really have a lot of time, typically. You almost never give somebody chemotherapy without getting a tissue diagnosis, right? So they call that composer-driven. And precision here means coordination and pretty tight adherence to your treatment protocol. Meanwhile, infection, a lot of times, especially with pneumonia, we're treating before we get a diagnosis. And so there's action under uncertainty, and that's performer-driven or emergent. And precision here means something different. It's anticipation, attention, flexibility, and adaptation. And you've heard a lot of the word nimble lately, right? And a nice quote from Wynton Marsalis is that, you know, it's not that there aren't any rules in jazz. It's not just a matter of playing any old thing. There's a language. It has its own grammar and vocabulary. There's no right or wrong, but some choices are better than others. And that's similar to kind of infectious disease, right? Okay. Analogy number two. Evidence is like getting to Everest Base Camp. And this is something David Adkins, the VA Director of Health Services Research, said a few years ago. And his point here was that we've done all this great evidence generation, but we really haven't even done the work that goes to actually summiting to patient care, improving patient outcomes. And what I like to point out is pretty much all the deaths on Everest happen kind of above base camp, right? That's where the rubber really hits the road. That's the sharp end. And before I was a pulmonologist, I actually worked as a volunteer in the Everest Base Camp Clinic. And this is a picture. And I like to point out, to extend this analogy a little bit farther, this is the end of the season. So you see all the tents in the background? And the evidence, or evidence, Everest Base Camp is actually very shifty, and it melts over the whole season. So by the time you are kind of at the end of the season and ready to climb, all of the tents are literally like sort of shifty, and people don't really want to set them up again. So they're all sleeping in these kind of weird angles. And there's actually kind of a lot of it. Has anybody been to Everest Base Camp? Nobody? Okay. It's kind of gross, actually. There's a whole lot of people waiting to acclimatize. You have to wait six weeks for your body to get prepared. And then you're just sort of waiting around for a weather window. And there's a lot of planning. There are a lot of plans, but there's not a lot of action. So there's a lot of like ennui. And so that I like to think of as our evidence base. It's pretty shaky. There's a bit of ennui. And we are actually getting better at the disease model in pneumonia. But most guideline recommendations are still actually based on pretty shaky evidence. So we are shifting our paradigm in lung infection. And this is a big deal. It's really exciting. We're going from a simple model of literally a sterile, passive compartment where we used to think humans had no bacteria in them, right, to actually a much more complex model where there's an active complex ecosystem. And there's a role of the host, right, quite a bit more than what we used to think. But this model is still challenged by a lot of heterogeneity and poor generalizability. We have, as we have talked about already, bad diagnostic tests. So a lot of diagnostic uncertainty. There's variation in our patient population's host response, the pathogens. And also there's underrepresentation of sick patients in our clinical trials. And that means that most of what we accept as standard of care is supported only by low quality evidence. But the implementation of recommendations time and time again when we do this, it improves patients' outcomes. And that's kind of an interesting phenomenon. Every component of those guidelines doesn't really seem to have a lot of evidence. But when you implement them as a bundle, they improve care. So I call this implementation under uncertainty. And just to touch on clinical practice guidelines, we've actually come a long way with those two. So clinical practice guidelines in the 1980s were recognized by the Institute of Medicine as having some problems. Basically, it was typically a bunch of guys who would come to board meetings at a conference, kind of like this one, and sit around the table and look over the papers and say, what do you do, Bob? And Bob would say, I think this seems reasonable. And then they would actually create expert opinion guidelines, right? And those would then get pushed into the field. And sometimes they become like performance measures, right? And clinicians are sort of stuck with these guidelines that oftentimes are informed by the interests of the guideline committee. And so the Institute of Medicine, since about the 1980s, really worked hard on improving the process of guideline development. And now we have very strict criteria. So when you see the word guideline, that means something very different from, let's say, an expert review or expert opinion or guidance. That is a blend of evidence synthesis and the clinical experience. And this is just a diagram of how ERS follows the GRADE methodology. And there are clear requirements. So first, you have to have an explicit scope and purpose. You have to have substantial stakeholder involvement, including patient representation. You have to have rigorous development. This is very important. A third party of evidence synthesis methodologist team actually conducts the evidence synthesis that's independent of the clinical experts. And then you have clarity of presentation, applicability, and very importantly, editorial independence. So there's conflicts of interest that are disclosed and reviewed and vetted before a panel is conducted. And the point of clinical practice guidelines is, you know, their purpose is to translate these research findings into recommendation that are relevant to individual patient care, but clearly not for implementation of a one-size-fits-all approach to patient care. And so how does this look? You know, you guys have all been kind of taught the evidence-based medicine model, right? You've got their evidence, expert opinion, then you generate some guidelines, and that should improve practice and outcomes. And the traditional approach to implementation, there are some assumptions. There are assumptions that evidence is certain. Healthcare systems are static. Populations are homogeneous. And therefore, there's an emphasis on fidelity. You know, you want to just carry out. And the role of the clinician here is if you have certain evidence, you really trust the guidelines, they totally work for your population, is to just carry it out. But there's problems with this when you don't have evidence certainty. And so David Chambers, an implementation scientist, calls this embracing dynamism. And this is when you have a shaky evidence base and your guidelines are imperfect. You have a healthcare system that might be dynamic. You have populations that are heterogeneous. And you have change that is central, actually, to the evolution of evidence-based practice. So the emphasis here is not on fidelity so much. It's on adaptation and individualization. And it's on playing jazz. So the role of the clinician here is quite different. It's to face those guidelines and to really think of them critically and think about whether they actually apply to your patient. And then the role of system leaders, like people who develop pathways, is to actually take a look at the deviations and pay attention to when clinicians don't actually think that those guidelines fit and to learn from that. So some examples, I think I will kind of cut this a little bit shorter since we have gotten some really nice basic principles of the recommendations. But one way to think of this as a clinician is every recommendation that you see from a guideline, think of the strength and evidence quality and those evidence syntheses and how good those are and whether the methodologist graded that as a high quality or moderate or low. And then think about factors that strengthen that recommendation. Look at those clinical trials and see what patients they enrolled, stuff like that, and factors that weaken the recommendation. So an example we talked about here is in the 2019 pneumonia guidelines. There was a recommendation basically against broad-spectrum antibiotics for patients with CAT and only using locally validated scores. And that was actually a strong recommendation, but there are still factors that can strengthen or weaken that recommendation based on your patient. And this is kind of how it looks with, when I think about this from the VA system perspective, is we actually have been tracking broad-spectrum antibiotics across the VA system for about 10 years. And this is, we noticed there was lots of widespread variation at the end of 2019. And we were looking at this, and you can see in this map of the United States, all of those little bubbles are VAs. And the dark blue means that over 50% of those patients got anti-MRSA or anti-pseudomonial therapy as empiric treatment. And then the white bubbles show that less than 10% of those patients at this hospital got those antibiotics. So we could actually leverage that variation and examine outcomes. And Dr. Vaughn already highlighted this paper that we did to really look to see if there was any benefit of anti-MRSA therapy. And we couldn't find any. And then we came back to look at, well, okay, this paper, in addition to a bunch of other papers, led to that 2019 recommendation against broad-spectrum antibiotics. And how are we doing now? And it looks like we are de-adopting broad-spectrum antibiotics, but still over 20% of our patients are actually getting this, either anti-pseudomonial or anti-MRSA therapy empirically. And that's still kind of a problem. So what do we do to try to change that behavior? We have implemented some decision support tools, but we actually do this with a very light touch. We tend not to try to default too much. We actually provide information using these clinical decision support tools. We show them their population's risk, and then we provide them risk assessment tools to enhance their kind of comfort with kind of recalibrate the risk of resistant organisms in their patients. And then we actually give them recommendations if they want to use broad-spectrum antibiotics. But if they deviate, we do actually pay attention. And I helped Intermountain Health also develop some decision support, and we were also trying to capture deviation as well. The Nat Dean has spent a long time trying to develop guideline and implementation through electronic decision support. And one of the key principles is that clinicians are always allowed to deviate. They can override those recommendations, but when they do that, we pay attention, we ask them why they deviate, and then we actually study that. So when I step back and really think about the rules of Improv and pneumonia care, they're kind of less about the specific antibiotic regimen or whatever. They're actually more about these five things. Is that five? Yeah. The first is get the correct diagnosis. As we talked about, there's a lot of diagnostic uncertainty. We have to continue to question it, especially if we receive patients in their ICU or receive them on the hospital wards, question that diagnosis. Assessing host susceptibilities. I always try to ask my residents, why do you think this patient got pneumonia? What set them up for that? Because it isn't always just luck. There is usually a host susceptibility, and some of those host susceptibilities we really should address. And then the other really big thing is assessing the clinical response. As Dr. Restrepo has highlighted really nicely, really there shouldn't be a set duration of antimicrobials for anyone. Really we should be considering when to assess the clinical response. And at three days, take a look at your patient and see if they're doing well. And then consider how long their therapy should be after that. The other big thing for me is managing beyond antibiotics. So for lung infection, antibiotics have taken up a lot of oxygen in the room. And I actually think there's so much more that we can do for our pneumonia patients. Managing respiratory failure and sepsis really well, old kind of classic things like moving the patient, mobilization, those are really key things. And then the fifth big thing is plan for recovery. Come up with a follow-up contingency plan. We have real short lengths to say in our hospital patients now, which is fantastic. But what do they do? Do they have a primary care doctor to go to? If they don't feel well or they continue to not do well, you have to actually create a contingency and follow-up plans for your patients. So in summary, the evidence supporting guidelines, I would say for management of CAP are quite imperfect. But despite this, when you provide them to clinicians to support bedside care, it pretty much always improves outcomes. And so clinicians though, this doesn't mean they should follow algorithms. It should mean that we individualize our patient's care and on patient factors with the critical view of the quality and generalizability of the evidence. As they say in jazz, you have to know the rules before you can break them. And when providing support to clinicians and system leaders, we really should focus on supporting the key principles, providing transparency and flexibility, and then the Holy Grail, really learning from deviation when the clinicians don't think they fit. And so kind of back to that analogy number two, this is a schematic of all the bodies on Everest. When somebody dies on Everest, they just sort of leave the body, right? And now they're starting to melt because of global warning and it's very disgusting and kind of scary. But these are all the bodies on Everest. And really the mortality rate for climbers on Everest is actually about 1%. And I would say that pneumonia patients have a much higher risk. They are much more higher risk than mountaineers. And our pneumonia hospital mortality rate is about 10%, 30 day mortality. And clinicians and patients, we're really on the sharp end of these evidence-based practice and guidelines. And we really have to remember that each of these recommendations, we have to think about whether they really fit for our patients. And we should always do what's right for the individual patient. And as William Osler said, the good physician treats the disease, but the great physician treats the patient who has the disease. So I will leave you with that. These are my two little jazz playing mountaineers. Thank you. Well, thank you very much. We have 10 minutes to complete this challenging case. So next time when I have six weeks, I will have to adapt to Everest. I will have expanded all my vacations for two years. So this is the story on a 48-year-old woman with history of hypothyroidism on levothyroxine presents with seven days of progressive shortness of breath, dry, severe cough, and subjective fevers. She had a sick contact. Her daughter has similar symptoms and the recent contact with a child diagnosed with influenza. Throughout the night, she has multiple episodes of cough and urinary incontinence. The patient received five days of amoxicillin clavulanic acid that had from a prior infection. In the morning, she started feeling short of breath and home-based pulse oximetry revealed an SpO2 of 84% and a respiratory rate of 40 breaths per minute. She is taken to the emergency department and at that time, her oxygen saturation is 85% and it required initiation of oxygen therapy at two liters. The physical exam shows that blood pressure was normal, heart rate was elevated, and the respiratory rate was tachypneic. She had decreased breath sounds on the left lung with dullness and crackles. Her laboratory findings consistent with leukocytosis, lymphopenia, and normal lactate. This is the chest X-ray of this patient and a shot of the left lobe. Now, I hope this is certain that this is pneumonia, otherwise we'll be in big trouble with this case. Okay, so the question for this patient we hope to have a certainty about the pneumonia diagnosis is, would you admit this patient to the hospital? So I would like Dr. Valerie Vaughn, who is a hospitalist, is going to have to tell us whether you will take, depending on the answer of this question. And most of you say yes. What do you think? No. Definitely. Why? Why do you say so? Why do you think these people are correct? Do they have the right diagnosis? Yeah. Right diagnosis and she's sick. She needs oxygen. Vital signs aren't good. Very good. So the next decision is whether you're going to put this patient, when you assess this patient in the ward service, you're going to think this is non-severe, this is severe. What is this? What would you say? Her age? Her age? Her age, 48. Only hypothyroidism as the past medical history on levothyroxine, apparently well controlled. So based on Dr. Vaughn's and all of your recommendations, this patient was admitted to the hospital. She was placed on the ward service and her oxygen level was increased from two liters to five liters. She had the persistent cough, the shortness of breath, and the persistent hypoxemia. The SpO2 now is 92% and the respiratory rate, 35 breaths per minute. She was started on ceftriaxone plus acetromycin. That looks according to what we heard, even if the guidelines are bad, like Dr. Jones said, that was the recommended therapy. Any of you will have chosen something different? Say so or? Okay. That was good. My ophthalmologist wouldn't have chosen something different. Okay. Now, on hospital day two, the patient continued to have severe cough with urinary incontinence, persistent shortness of breath, respiratory rate remains in the 30s, SpO2 90, and now her oxygen was increased to 10 liters per minute. The fluid test was negative and the viral respiratory panel was a send-out test. So this is now her chest X-ray. From baseline two, day three, this is the progression of the disease. If you are not familiar with reading X-rays, believe me, it's worse. Hospital day three. The patient was transferred to the ICU, but not because they thought that they were going to intubate the patient. It was because they were concerned that the patient was progressing too fast and they didn't have any beds in PCU. So the kind of progressive care unit or intermediate care unit was not available at that time. Overnight, she continued to have desaturation and she was placed on high-flow nasal cannula with an FiO2 of 65% and 40 liters per minute. Her cough persisted, leading to poor oral tolerance. So I would like to ask the panelists is, guys, what's going on? Why is this not going according to what we just heard during the past hour? What's wrong? Barbara, please. I'd like to get an ultrasound of her left chest. You need an ultrasound in addition to the CT scan and the chest X-ray? Oh, I didn't see the second CT. Oh, a second CT in three days? Does she have an emphyema? That's a good question. That's a good question. Emphyema was not observed on the initial CT scan, but the CT scan was not repeated on day three. Do you guys think it's the right place to go? Well, also, what microbiology do we have? So far, the fluid test was negative. Blood cultures are negative. The sputum cultures were not able to be provided, but the patient had very, very dry cough, but nothing else was coming up. So that's, so far, what we have. But the panel was tested. The panel was sent out. They didn't do it in this hospital. What were you going to say? Legionella test. Legionella test. I believe it was not done. MRSA. MRSA. Am I saying the nurse was done and it was negative? Intubate. You will intubate this patient. Okay. So, day four. Oxygen requirements went up to 70% on 60 liters. Corticosteroids were started. So I would like to ask our panelists, what do you guys think about these corticosteroids were started? Is this the right approach? Will you have done it? It's a little bit late, four days. What do you think? Poor choice? Good choice? Bad choice? Raise your hand who thinks it's a good choice. Okay. You were in my lecture yesterday, and I'm just kidding. Yesterday was a post-graduate course. So what do you guys think? Barb, they don't agree. You said, oh, corticosteroids, yes? At day four? Yes. Really? It's a little late, but I don't know that there's too much harm in it. Yeah. Now, the viral testing showed up mycoplasma pneumoniae. Mycoplasma pneumoniae? Like a lower pneumonia? What do you guys think? Valerie? We were taught in medical school that this was an interstitial pulmonary infiltrate, a typical pneumonia, walking pneumonia. You could be walking with a pneumonia with no problems. Yeah. Radiographic findings don't always correlate with the organism. Okay. Did you listen to that? Radiographic findings do not always correlate, and this is why we should not rely 100%. But now, antibiotic-directed therapy was doxycycline added to acetyl. The reason why is because in this hospital, fluoroquinolone is a bad word. Bad word. Don't say fluoroquinolone, because the police of the antimicrobial stewardship committee become really, really upset with you. What do you guys think? I'm just happy she's on azithro. Good. But she was not responding for four days on azithro. I still want an ultrasound of her chest. Ultrasound. Okay. CT scan was done, and it showed no empyema, no pleural effusion, but it was a CT scan follow-up. They didn't do an ultrasound. Oh, okay. So what do you guys think? Doxycycline plus azithro? Dr. Wandering, huh? He says, give me a break. What happened with the old bad word, fluoroquinolone? He could have azithro resistance. He could have azithro resistance. And that was the rationale for the infectious diseases consultant at that time and said, I think we should add another agent or change the agent to doxycycline. But everyone was very, very concerned, saying, but azithro is a good choice. It could be still there. And the anti-inflammatory effect that we saw in the other studies, what was happening with that? So here, at this time, the question is, would you change antibiotics at this point? Doxy plus azithro. Cephriaxone was removed. Mycoplasma pneumoniae. Oh, no, no, no, on top. No, just one. One is more than enough for this patient. We're happy that it was only one. OK. So the answer is, most of you will change. What would you change it to? What did you say? MRSA coverage. Hey, that is very interesting because I presented this case in our pulmonary critical care division and the people say, it has to be MRSA. And I said, it was not MRSA. MRSA was not here. It was not able to be found anywhere. Sputum cultures were negative later on. No MRSA. Never received vancomycin. Only on the first shot in the emergency department because with a CT scan, you need to get a vancomycin dose. So hospital day five. Clinical improvement. Now require low oxygen. FiO2 40%. 30 liters per minute. Cough started to improve. Hospital day six. Tolerated exercise without desaturations and the coughing spells got better. And she was discharged home to complete 10 days of antibiotics. Dr. Vaughn, what do you think about these 10 days of antibiotics? Is this good? Is this bad? It's probably longer than she needed. She got better. OK. These are the edge scenarios where it's hard to know. Two days ago, she was on 40% of oxygen in 30 liters. Is that OK? Mycoplasma is an intracellular agent, no? This is nothing that we can really eradicate very, very quickly. So most of the recommendations at least, what are the recommendations? From the guideline experts. Mycoplasma? Mycoplasma. Mycoplasma, I thought it was longer. At least seven days, but seven to 14. Seven to 14 days. OK. So last time when I mentioned the 14 days of antibiotics in my hospital, I was put on probation. OK. So guys, this is the story of my sister-in-law. She was visiting us and became so sick. My wife came and said, what have you been doing all these years? Studying pneumonia? Help her. Please do something. So she got better. And her daughter also had mycoplasma. So the key of the whole story was that mycoplasma apparently was happening a lot during this summertime with many kids. And the pediatrician was the one that told us and said, you need to alert about mycoplasma. Then I looked really, really smart telling the doctor, please doctor, order PCR testing for mycoplasma that happened to be positive in this case. So does the guideline fit all the patients, Barb? This is like we would like to make sure that we close this thing saying, is the guideline a good recipe or do we need to think still? And this is something that a doctor has to really come up afterwards and make some decisions that are important when even there is some not perfect guidance at the moment. What would you think? My answer? Yes, please. Yes. Jazz music? With jazz music. Depends. Okay, guys, so it's 5.03. I really apologize. We spent three more times of your evening, beautiful evening in Boston. Thank you very much for your time. Jazz music.

community-acquired pneumonia

hospitalized patients

diagnostic uncertainty

antibiotic overuse

empiric treatment

narrow-spectrum antibiotics

guideline implementation

personalized treatment

clinical progress

patient heterogeneity