My name is Robert Balk. I'm a professor of medicine at Rush University Medical Center, and I'm going to review with you severe pneumonia in the ICU, severe community-acquired pneumonia, hospital-associated pneumonia, and ventilator-associated pneumonia. I have to advise you of a disclosure with past research grants, advisory board membership, and speaking honoraria from B.O. Maroux, Roche Scientific, and Thermo Fisher, which I do not feel will bias or influence this presentation. Our presentation today will review the definition of SCAP, HAP, and VAP, and discuss risk factors for development. We'll discuss the common causes of SCAP, HAP, and VAP, discuss the guidelines for initial antibiotic treatment, and describe the prognosis and strategies for prevention. Pneumonia and lower respiratory tract infections are the second most common cause of death worldwide, and are the most common cause of death from infection in developed countries. We know that the hospitalization for community-acquired pneumonia is associated with increased risk for mortality, acute respiratory failure, ARDS, and need for ventilatory support, and it is quite expensive. Most patients with community-acquired pneumonia present with cough, purulent sputum, pleuritic chest pain, fever, dyspnea, and they all should have an abnormality on their chest x-ray to suggest pneumonia. Many places are using point-of-care ultrasound in the diagnosis of pneumonia. This may be a great tool in resource-limited countries where they may not have x-rays or CAT scans readily available, but there's a lot of variability based on the capabilities of the operator, not only to perform point-of-care ultrasound, but to interpret point-of-care ultrasound. There are a number of risk factors for pneumonia, and these include alcoholism, asthma, being on gastric acid suppression therapy, any medications that alter one's mental status and ability to protect their airway, having an immunosuppressed condition, prior heart disease, being in an institution, or being elderly. Most of the time with community-acquired pneumonia, we do not find an actual pathogen responsible for the clinical presentation. When we do find one, it's typically a virus, but when we are lucky enough to isolate a bacterial cause, strep pneumonia is still the most common, followed by moroxella haemophilus, and in certain areas and times of the year, Legionella may be prevalent. Since you're getting ready to take a board exam, and the boards often emphasize a history of the patient to direct you towards an answer to get the right response, I put together a list of various clinical scenarios, historical features that might make you think about certain pathogens as the cause of a community-acquired infectious process like pneumonia. There are certain characteristics of the sputum that may also influence your decision as to what antibiotic or treatment to start. Patients who have mucopurulent sputum, you typically think about bacterial causes, but that can be seen in viral or mycoplasma pneumonia. Scant, watery sputum is seen in mycoplasma or atypical pneumonia. The characteristic rusty sputum is suggestive of strep pneumonia, and current jelly sputum, klebsiella pneumonia. Foul-smelling sputum, you think about anaerobic infections, particularly a lung abscess. Importantly, if the patient does not have a tachycardia accompanying their fever, think about viral infections, mycoplasma, psittacosis, tularemia, or legionella. And when the x-ray appears much worse than the patient's clinical presentation, think about viral or mycoplasma disease. We've all recently had experience with SARS COVID-19, a coronavirus infection producing an influenza-like illness that became a global pandemic, frequently associated with severe pneumonia and ARDS, and we learned to treat that with remdesivir and other supportive care. We are definitely on the lookout for the development of severe ARDS and severe hypoxemia, where we will then use lung protective ventilatory support, frequently relying on pronine and even ECMO for very severe cases. We learned that some of these patients have a cytokine storm response, and they will benefit from anti-inflammatory therapy. And some of the earlier variants of the SARS COVID-2 virus did have an association with vascular complication and coagulation abnormality. It's important as we look to define community acquired pneumonia, the broad differential exists, but usually the diagnosis is fairly straightforward, although recent data suggests that maybe one in eight people may be misdiagnosed as having community acquired pneumonia. It's important that we initiate treatment rapidly following guideline recommendations, and we risk stratify importantly to get our sick patients who qualify as severe community acquired pneumonia in the ICU, where they will fare better than if they are initially admitted to the floor and have to be transferred to the ICU. Important to remember that about five to seven percent of patients with an acute community acquired pneumonia presentation also have a concomitant cardiac event at the time, and cardiac events are also fairly common in about 30 percent of patients with community acquired pneumonia who survive will have subsequent cardiac events. To determine severity of community acquired pneumonia, there are various tools that are out there. You've heard about the IDSA-ATS criteria, British Thoracic Society criteria, and CURB-65. The IDSA-ATS look for major criteria, septic shock requiring vasopressors or invasive mechanical ventilation as a ticket for ICU admission. Having more than two of the minor criteria will qualify. Having two or more of the British thoracic criteria will get you a diagnosis of severe community acquired pneumonia. And of course, the CURB-65 can also be used to diagnose patients with severe community acquired pneumonia and need for hospitalization. As mentioned in a secondary analysis of mortality in patients with community acquired pneumonia, if they are admitted to the ICU within three days of the emergency department presentation, those who were initially admitted to the ICU fared better than those who initially were admitted to the hospital floor and then had to be transferred to the ICU. This is where sometimes procalcitonin may be beneficial, not as a tool to initiate antibiotic therapy, but to define severity of disease. And speaking of biomarkers, there are a number of biomarkers which have been propagated as potentially useful in either the diagnosis or management of patients with community acquired pneumonia. Procalcitonin, C-reactive protein, are probably the most commonly talked about and ways to potentially discriminate between bacterial and non-bacterial infection and may have ability to help with predicting severity of illness and prognosis. Procalcitonin may also have the ability to help define the duration of antibiotic therapy. However, in using biomarkers in community acquired pneumonia, do not use them alone to determine the need for antibiotic treatment. As far as important issues in community acquired pneumonia management, the causative pathogen, as we said, is frequently not found. Pneumococcal and atypical pathogen coverage is important, but if you're in an area where there's a high prevalence of community acquired methicillin-resistant staph aureus, be on the lookout for that and you may have to begin treatment empirically. Just like in sepsis, time counts. So earlier initiation of antibiotic therapy leads to better outcome. Be cognizant of antibiotic resistance in your area. And there's growing evidence to suggest that combined antimicrobial management, macrolide plus another agent, has shown benefit in outcome. The ATS gave us some modifying conditions to look for patients who may have strep pneumonia that's resistant to penicillin and sometimes other drugs, and that includes patients who have had a beta lactam within the past three months, people with alcoholism, immunosuppressive illnesses, and importantly, if they had exposure to a child in a daycare. As far as knowing which patients to target for enterogram negative coverage, think about residents in a nursing home, underlying cardiopulmonary disease, or those with multiple medical comorbidities, or recent antibiotic therapy. And when thinking about the outpatient who may have pseudomonas, think about patients with underlying structural lung disease like bronchiectasis, who are chronically on prednisone and corticosteroid therapy, who have had broad-spectrum antibiotic therapy for more than seven days in the past month, or who have malnutrition. When you're thinking about the community-acquired MRSA infection, realize this is a distinct illness. It often produces a severe necrotizing type of pneumonia related to the penton-valentine-leukocyte toxin, and it's important that as you think about your therapy, that you use antibiotics that inhibit protein synthesis to counteract toxin production. And those include clindamycin, linazolid, or rifampin, especially if you're using vancomycin alone for therapy. The optimal timing for the antibiotics, as we said, similar to sepsis, you want to start treatment usually within three hours. There are data showing improved survival with multiple antibiotics, especially when one of them is a macrolide. And the duration of therapy is usually five to seven days in conjunction with a clinical response. And lots of data has come out to support the fact that following guideline-approved therapy leads to better outcome. This is a recent review article from the New England Journal by Dr. File and Ramirez that gives you an algorithm for which antibiotics to start in your patient with community-acquired pneumonia based on their presentation, severity of illness, and whether or not you think there is MRSA or not. But most of our discussion will probably center around the 2019 and 2019 ATS-IDSA community-acquired pneumonia recommendations. And we can briefly go through some of these. You can read these at your own pace. Again, they recommend starting empiric antibiotics for those you diagnose with community-acquired pneumonia, regardless of procalcitonin or other biomarker. You should use some way to determine severity of illness, so you can put the patient in the ICU if that is where they should be managed. There are limited scenarios where you'll want to get gram stain and sputum cultures. And if you deal with a patient with severe community-acquired pneumonia, please get blood cultures. Antibiotic treatment should be based on risk factors, severity, and local antibiogram. As we've just talked, beta-lactam plus macrolide is the preferred therapy. There is no need for routine anaerobic coverage unless you have a lung abscess or empyema. The 2019 guidelines recommended against steroid for non-severe CAP, even severe CAP, and influenza CAP. However, we will revisit this shortly. They did endorse following the surviving sepsis recommendations for physiologic steroids in severe CAP with shock. And they concurred with abandoning the terminology of healthcare-associated pneumonia and, again, emphasize the duration of therapy. As we've mentioned a couple of times, adding a macrolide to our beta-lactam leads to benefits in outcome. And there are a lot of potential reasons for that benefit. It's predominantly related to an anti-inflammatory effect and not necessarily to an antimicrobial property. And this anti-inflammatory property will occur even if the bacteria is resistant to the azithromycin. Recent trials, such as the CAPE-COD trial, have shown that in severe community-acquired pneumonia, giving hydrocortisone for seven days leads to an improvement in survival and a number of other important clinical endpoints. But this was significant enough, combined with other meta-analysis, to now move the needle towards recommendations to give steroids to those patients with severe community-acquired pneumonia and the recent 2024 SCCM guideline gave a strong recommendation with moderate evidence in support of steroid treatment along with antibiotic treatment for the patient with suspected bacterial severe community-acquired pneumonia. And here is that recommendation. It's important that as the patient improves and you can see various characteristics of the improving patient, that you then begin to step down or de-escalate your therapy. And the therapy, as we said, we try to limit to five to seven days when there isn't an adequate clinical response. And these are the various features of improvement that we would see. You may find suboptimal response to treatment in people with liver disease, pleural fusion, multilobular infiltrates, actually having cavitary disease, those who are leukopenic, sometimes with Legionella and gram-negative pneumonias, they are slower to improve. And of course, if you're giving the wrong antibiotic, you may find that your patient had a suboptimal response. As far as predictors of mortality, here are a number of things that you can use to look at your patient and see whether or not they are at higher risk of mortality. Some of the more obvious are those who are hypotensive, who have more hypoxemia, more lobes of infiltrate, but things such as having azotemia, having elevated persistent respiratory rates, and hypothermia may also portend poor outcome. Unfortunately, those patients who are elderly, who survive community-acquired pneumonia, have an increase in mortality over the subsequent one to two years. And we also have already talked that acute inflammation can destabilize atheromatous plex and induce a procoagulant state, and that may be involved in adverse cardiac events that afflict patients who survive community-acquired pneumonia. And we'd be remiss if we didn't talk about prevention of community-acquired pneumonia, and that gets down to the basics of vaccination, influenza and pneumococcal, and smoking cessation. We're now going to switch gears a little bit and talk about hospital-acquired pneumonia. This is where there's a development of pneumonia more than 48 hours after hospital admission. We're excluding those patients who entered the hospital already with a pulmonary infection. We see this in five to 10 per 1,000 U.S. admissions, second most common nosocomial infection, and it's associated with increased need for ventilatory support and increased morbidity, mortality, cost of care, and length of stay. Ventilator-associated pneumonia is a little bit trickier because obviously the patient's on a ventilator for another reason and then has a new or expanding infiltrate two or more days post that admission to the hospital and initiation of invasive ventilatory support. They should have fever, elevated white count, purulent sputum, worsening oxygenation. There are various definitions that are out there, whether you're doing research, whether you're looking to fulfill CDC, some of the CHESS, IDSA, ATS guidelines, or CMS guidelines. I will point out the CMS guideline does not include chest X-ray abnormality. The epidemiology, again, has a prevalence of about 9%. It will increase ICU and hospital length of stay, mortality, time on the ventilator, and cost of care. The symptoms and clinical manifestations of hospital-acquired and ventilator-associated pneumonia are similar, purulent sputum, fever, hypothermia, leukocytosis, and or left shift, new or expanding infiltrate on X-ray, changes in oxygenation, or the ventilatory support parameters. And it's always difficult to know what to make of the positive lower airway culture. Is that reflective of colonization or actual infection, especially if it's not semi-quantitative and obtained by protected specimen brush or bronchoalveolar lavage. Early on with ventilator-associated pneumonia that's in the first two to four days, you're really dealing with the same community-acquired pneumonia pathogens. The later onset ventilator-associated pneumonia and hospital-associated pneumonia are going to have enterogram-negative bacteria like Klebsiella, E. coli, Enterobacter, Acinetobacter, often Pseudomonas, and often Staph. And about half the time, ventilator-associated pneumonia is polymicrobial. The European Respiratory Society put together a nice treatment algorithm that basically assesses risk factors for mortality and risk for multi-drug resistance pathogens. And you can see if you follow the path of low multi-drug resistance and low mortality risk, your antibiotic regimens are much different than those who have a higher multi-drug resistant likelihood or a higher predicted risk of mortality. And then you can sort by having shock or no shock as whether you do single or double gram-negative coverage, and then have the decision of is MRSA coverage needed. And speaking of guidelines, let's go back to the IDSA-ATS 2016 guidelines for HAP and VAP. They do not recommend routine invasive sampling, but would recommend non-invasive sampling with quantitative cultures for HAP and VAP, but it's a weak recommendation, very low-quality evidence. And if you are using invasive sampling, you're using it predominantly because you may want to then stop unnecessary antibiotics. They recommend, again, against using various biomarkers to decide who needs antibiotics. If you think they have pneumonia, start them just like you would in sepsis and community-acquired pneumonia. And the guidelines do not recommend treating for ventilator-associated tracheobronchitis for those who just have some organisms in the airway. They emphasize the importance of hospitals generating a local and even unit-specific antibiogram to help guide the therapy that you would then empirically initiate against those organisms that you have in your unit or that the patient's clinical course suggests that they might have. And they do suggest empiric coverage for Staph aureus and Pseudomonas being at least driven by treatment algorithms. And importantly, they encourage the use of pharmacokinetics and pharmacodynamics rather than just standard manufacturing, prescribing information, so that the right dose of the antibiotic is given to the patient. Some patients have augmented renal clearance and may need higher doses. Other patients are on various support therapies like a continuous renal replacement therapy, plasma exchange, or even getting ECMO, and you may have to adjust your dosing accordingly. As far as risk factors for multidrug-resistant pathogens, the big risk factors is prior exposure to antibiotic therapy, which we see in all but you also will be a little bit more attuned to multidrug-resistant organisms for VAP when the patient has septic shock, ARDS, they've been in the hospital a longer period of time or have renal replacement therapy. And here are the treatment guidelines as far as the different antibiotics, which you can review on your own. They do at least support the use and at least support inhaled antibiotic treatment in addition to systemic antibiotics for certain ventilator-associated pneumonias due to gram-negative organisms that are only susceptible to aminoglycoside or polymyxin. If you're dealing with MRSA, HAP, or VAP, treat with either vancomycin or lenazolid, but remember lenazolid has the ability to be an antitoxin. And if you're treating a staph that you worry about, antitoxin need with vancomycin, you'll have to add rifampin or clindamycin. For HAP and VAP secondaries to pseudomonas, they suggest dosing your antibiotics based on culture and sensitivity data. Use monotherapy if the patient is not in shock or at high risk of death. If they are in shock or high risk of death, use combination therapy. When you're dealing with an ESBL gram-negative, treat based on susceptibility testing and patient characteristics. If you're dealing with a possible CRE, you can treat with IV polymyxin or inhaled colistin or even combine them together. And if you're dealing with acinetobacter, you treat with carbapenem or ampicillin sulbactam. The duration of therapy is suggested at seven days. Recommend again to deescalate as the patient improved. This is where procalcitonin may be beneficial combined with clinical data to guide early discontinuation of therapy. Here's the French data where we got the indication that perhaps eight days is as good as 15 days for patients with ventilator-associated pneumonia and a good clinical response. When short duration therapy may not be appropriate is in the severely immunocompromised population when you're dealing with highly antibiotic-resistant pathogens and if you're using a second line antibiotic therapy. These are some strategies that have been utilized to prevent ventilator-associated pneumonia. You can read through the list and I don't need to read it to you. And then in summary, severe pneumonia is the most common infectious disease cause of death in the United States. Rapid diagnosis, effective triage, timely initiation of antibiotic therapy is important. Follow guideline-directed therapy to improve survival. The data suggests improved outcome with early use of multiple antibiotics for severe community-acquired pneumonia and that includes adding a macrolide. Steroids are likely to improve the outcome of patients with severe community-acquired pneumonia and the role of biomarkers remains uncertain but may be useful for either prognosis or to assist in antibiotic stewardship by shortening the antibiotic duration of treatment. As far as HAP and VAP are concerned, they are common and associated with increased cost of care, increased length of stay, increased morbidity and mortality. Begin empiric guideline-based therapy as soon as possible based on clinical status and known unit hospital antibiogram. Again, with an improvement of the patient, tailor your therapy as you get your culture and sensitivity data and de-escalate treatment based on clinical response. Again, treatment is for about seven days with a good clinical response and know your prevention strategies that appear to be effective to prevent hospital-acquired and ventilator-associated pneumonia. However, it's unlikely we'll ever be able to totally prevent ventilator-associated pneumonia. With that, I will conclude the discussion and wish you good luck with your studies. Thank you.

severe pneumonia

ICU settings

risk factors

rapid diagnosis

antibiograms

prevention strategies