Medicine in New Orleans, based at the branch campus in Baton Rouge. What I'd like to do in this presentation is to take a series of scenarios that occur in the intensive care setting that are either due to an infectious disease or to a complication of an infectious disease. And I've chosen all of these because of the likelihood of them showing up on a high-stakes exam. The first case is a 38-year-old man recently diagnosed with HIV infection. He has a CD4 count of 43, but he's not on antiretroviral therapy. And he presents to the emergency department acutely ill with a seven-day history of fever, shortness of breath, and bright red blood perectum. His temperature is 39.2 with a blood pressure of 92 over 56, and that's orthostatic. Other than diffuse lymphadenopathy and scattered crackles in both lungs, his physical exam is unrevealing. Chest X-ray shows bilateral interstitial opacities. Laboratory data are noteworthy for pancytopenia, a sodium of 126, a potassium of 5.8, a chloride of 84, and a bicarbonate of 19. The blood culture is drawn in admission and reported three days later as being positive. On the basis of all of this information, the most likely pathogen causing this man's presentation is streptococcus pneumoniae, mycobacterium tuberculosis, nicardia asteroides, or histoplasma capsulatum. The relevant things about this guy's story include his HIV infection, the fact that he's having a GI bleed, that we see that he's got pancytopenia, implying perhaps some kind of a bone marrow infiltrated process, and lab work that would be consistent with adrenal insufficiency. And if we look at the two pathogens most likely to do that on this list, it would be TB and histoplasmosis. TB doesn't usually grow in a blood culture in three days, but histo can. And this was a case of histoplasma bloodstream infection in an HIV-infected man, leading to adrenal insufficiency. There are several situations in the world of infectious disease that present as endocrine emergencies. And one of those is adrenal insufficiency on an infectious basis. Granulomatous processes like TB and fungal infections like histo have a propensity to involve the adrenal glands. And when they do, they can present as adrenal insufficiency. We've seen it in our HIV population of people who are treated for histo, get sent home and come in a few days later with intravascular volume depletion because of previously unrecognized adrenal insufficiency. In medical school, we usually learned about adrenal insufficiency due to Neisseria meningitidis infection in the Waterhouse-Friedrichsen syndrome with bilateral adrenal involvement and loss of the adrenal gland function. And in HIV-infected people, particularly when CD4 counts get to be below 50 cells per millimeter cubed, the risk of CMV affecting the adrenal glands. In the world of cardiology, one of the important challenges is how do you manage endocarditis with regard to valve replacement? The most recent iteration of the endocarditis guidelines gives some pretty good reviews about this. And I'd like to just give you what I believe are the high points. First of all, information about the vegetations. The guideline lists more than 10 millimeters in diameter, particularly when there is mobility of the vegetation is being the important findings. And in terms of location, it's the anterior leaflet of the mitral valve. Recurrent emboli, particularly when they occur after therapy has been stored, it may be an indication. On the other hand, in somebody who comes in with a small embolic lesion before antibiotics, a trial of antibiotics is indicated. It is refractory heart failure. So if the heart failure can be managed with medicines, there is no reason to take the valve out. And then the entity of persistent bacteremia. Recognizing that with Staph aureus, bacteremia for more than 72 hours is considered prolonged, but it's within the natural history of Staph aureus bacteremia for taking up to five to seven days. So in an individual who doesn't clear their blood culture for Staph aureus at five days, one might ask, is that just the natural history of Staph aureus? And does it require valve replacement? And then finally, fungal etiology is an indication to remove the valve. A classic teaching three decades ago is that there was no role for cephalosporins in the treating of enterococcal infections. And our most severe enterococcal infections is enterococcal endocarditis. Recently, we've come to recognize that ceftriaxone and cefetaxime work in a different way than the penicillins in that they tend to saturate the penicillin-binding proteins number two and three at a level that penicillin can't do. And this produces a synergistic bactericidal effect in enterococcus faecalis. That's not been demonstrated so well in enterococcus faecium. Because of that, there are two situations where there may be a role for cephalosporins in enterococcal endocarditis. One of those is in prosthetic valve endocarditis with penicillin-susceptible enterococcus and where the patient has impaired renal function. That's gonna be given along with ampicillin. The second is enterococcus due to vancomycin-resistant enterococcus faecalis. And it divided out in the guidelines into whether there is high-level resistance or not high-level resistance. But a role for either ceftriaxone or cefetaxime in that scenario. In medicine, the questions don't change, just the answers do. And that really applies into the world of microbiology where we frequently get new names for old bugs. There's some applicability of that in the world of endocarditis. And the first bullet are the two new names for what we used to refer to as the nutritionally deficient streptococci. The classic teaching was that these streptococci were usually penicillin-resistant, which required two drugs and treatment as though they were enterococcal pathogens. The old strep bovis associated with colon cancer was recently renamed as streptococcus galiliticus. It expresses the same group D antigen that enterococcus does but it can be distinguished from enterococcus by a chemical test. There's an understanding that whenever strep galiliticus appears in a blood culture, that there's a need to look for underlying mucosal disease in the colon like colon cancer to be sure that colon cancer isn't the cause for this organism which can see valves and lead to endocarditis. A 38-year-old homeless man who lives in a tent in a homeless encampment in downtown Los Angeles presents in August to the emergency department with an illness that began five days earlier which was fever, headache, sweating, and nausea. Over the past 24 hours, he began experiencing shortness of breath that was rapidly progressive. His epidemiologic history is notable for a recent hiking trip in a tick-infested wooded area adjacent to a dairy farm and on which he came across a dead rabbit. He does occasional work in the mailroom of a governmental building. On physical exam, his temperature is 101, his heart rate's 128, and respirations are shallow at a rate of 32. There's a discreet macular rash on the trunk with a few petechiae. Laboratory data are notable for a hemoglobin of 16.8 and a leukocyte count of 2,700. He is lymphopenic and his platelets are 86,000. Serum transaminases are three times the upper limit of normal and serum creatinine is 1.72. Chest radiograph reveals a generalized bilateral alveolar filling process with a normal-sized cardiac silhouette. Rheumatoid blood gas is 752, 28, and 57. Over the course of the next two hours, he requires mechanical ventilation. Which of the following diagnoses is most consistent with this man's clinical and laboratory presentation? Is this tularemia, Q fever, plague, anthrax, or murine typhus? The impetus for this question was a really important thing that I learned from Dr. Brad Svelberg, who's the chief medical officer at the LA County USC Medical Center in Los Angeles. Brad is a brilliant thinker and made a comment recently in an ID board review about community-acquired pneumonia syndromes that might require doxycycline. So essentially he was referring to those things that are not just classic bacterial infections like pneumococcus legionella, or maybe even the classic aerobic gram-negative rods. This patient's history includes all the epidemiology for each of those. He came across a dead rabbit, so was it tularemia? Was close to a dairy farm, is that Q fever? In an area where he was maybe exposed to some kind of vectors, is it plague? Does he, because he lives in an encampment in Los Angeles, get exposed to rickettsia typhi? And is this murine typhus? Or in his governmental working, is this exposure to spores? And could this be anthrax? I put this table together to cover those entities. We're not gonna go through everything on the table. It's for your review, but let me give you a couple of highlight points. If you take a look at tularemia, we understand it as being tick-borne, but there are reports when people are mowing their grass and run over a rabbit in hell. So it's both vector and inhalation. With plague, it's gonna end up being inhalation of infectious droplets, but we understand that in patients who were bitten and developed bubonic or septicemic plague, they can then develop now the pneumonia, which is in its early stages pre-inflammatory, but it leads to a very severe pro-inflammatory response. With anthrax, that governmental worker story that we talked about in the case where there may be the inhalation of anthrax spores. And then finally, the outbreaks recently in some of the encampments in LA of murine typhus, which is really gonna be fleas from rats and can present with an acute illness. The takeaway point is that in people who come in with life-threatening forms of community-acquired pneumonia, it may not always be pneumococcus, legionella, mycoplasma, or just regular organisms. It may be some of these unusual pathogens. If you look at the right-hand column, there is a role for doxycycline in each of these, sometimes in combination therapy, but keep in mind the concept that a classic regimen like vancomycin, piperacil, and tazobactam probably wouldn't work in these. And you can imagine, therefore, why these five infections might be reasonable for your consideration is pneumonic syndromes that are life-threatening that may show up on an exam. If we go to a more typical form of pneumonia, I would propose to you that we think about hospital-acquired pneumonia. These are the 2017 European guidelines for HAP and VAP. And I like these guidelines a lot because what they give us permission to do is to think about heterogeneity and the way we treat pneumonia. So, for example, if you go all the way to the left and you look at what they're calling low-risk for multidrug-resistant pathogens, and that's less than a 15% chance of dying, they talk about the opportunity to give drugs, and all of those drugs, ertepenum, ceftriaxone, et cetera, do not have activity against Pseudomonas aeruginosa. If you move to the other category where there is high risk of multidrug resistance, they talk about severity of illness, which I consider to be one of the most important markers for stratification, with no septic shock, maybe a single agent, but with septic shock, dual pseudomonal agents. And so, as you think about the conceptualization of HAP, do you have to cover Pseudomonas or not? And there's some situations, like, for example, non-ventilated HAP on the floor where the mortality rate is less than 15% in papers after this one was written, versus people who come in with HAP that don't have septic shock, versus that classic person that you encounter who's on a ventilator and has ventilated HAP who may now need two gram-negative agents. There are some life-threatening viral pulmonary infections. For years, we thought about Hantavirus as being the Southwest United States, associated with maybe the deer mouse or perhaps even some rats, and presenting as the classic form of respiratory failure. There are reports more recently about droughts followed by floods. We see that in Louisiana, where there's the ability of the rat vector to lead to Hantavirus infection. It may present in two forms. There's a renal failure with bleeding form that can mimic leptospirosis. And then there's this respiratory failure due to inflammatory pulmonary edema. The classic feature on the peripheral blood smear will be an immunoblast. In the world of influenza H1N1, people talked about that entity of single organ failure, the desquamation and necrosis that you can get into trouble with. I don't think you will see SARS-CoV-2, although a highly inflammatory pneumonia, where we understand that things like prone ventilation and steroids or high-flow oxygen may be the things most traditionally shown to have some efficacy. A 56-year-old woman with a 20-year history of rheumatoid arthritis who was started on TNF-alpha inhibitor therapy three months ago, presents acutely ill with fever and shortness of breath. Her vital signs are temperature 38.8, pulse 133, blood pressure 88 over 46, and respiratory rate of 32. Other than diffuse crackles in ronchi in both lungs and marked splenomegaly, her exam is unrevealing. Laboratory data are noteworthy for a white count of 1,180 with an absolute neutrophil count of 430. Her chest X-ray is shown. On the basis of the available information, the most likely pathogen causing this woman's clinical presentation is Staph aureus, Mycobacterium tuberculosis, Histoplasma capsulatum, and Acardia asteroides. This question lends itself very nicely to the concept of anchoring, that is grabbing onto the first thing and holding onto it, and she's on a TNF antagonist that we know about granulomatous infections, and so one could easily jump on TB or histo. Except if you look at her chest X-ray and you see those cavitary lesions, those are very consistent with the nematocytes associated with Staph aureus bacteremia. And when you look at this lady's long-standing rheumatoid arthritis and her splenomegaly and her neutropenia, she has Felty's syndrome with a predisposition based on her granulocyte deficiency to Staph aureus bacteremia, which is what she had. In the world of rheumatology and its predisposition to infectious diseases, the way that I've thought about it is, is it the disease itself or is it the therapy for the disease? And the therapy of the disease we will look at a little bit later. But if we look at the disease itself, Felty's syndrome is that triad of long-standing RA where the antigenic stimulation and the ability to try and clear that can result in splenomegaly and the splenomegaly can result in sequestration of white cells and neutropenia. With class IV lupus nephritis, patients often are at risk of the nephrotic syndrome. And with nephrotic syndrome, there is hypercatabolism of immunoglobulin, not loss in the urine like we see with clotting factors and the risk then of pneumococcal sepsis. In bad psoriatic arthritis, the risk of cellulitis, but that doesn't usually lead to life-threatening problems. In that group of patients, and with Sjogren's syndrome, problems with either bacterial keratitis or periodontal infection. But the world of rheumatology often takes us to the world of immunology. And as we begin to see the explosion of new drugs, we're challenged to think of a way to approach them. And I would propose that we think about them as the immunosuppressive drugs versus the immunoboosting drugs. In the immunosuppressive category, the monoclonal antibodies make us think about TNF-alpha antagonism, where TB and histoplasmosis have really become very important. In the small molecular inhibitors, the NIBs, things like imatinib, but not usually so much in association with an infectious disease. In the immunoboosting category, interleukins, but the interleukins are usually associated more with adverse effects. In contrast, if we look at the checkpoint inhibitors, we see the classic organ systems of involvement being the GI tract, the endocrine system, the skin and the liver, often presenting with elevated temperature, the ability to make us think that this is gonna be infection, when maybe it's really gonna be the adverse effects due to checkpoint blocking agents. So this table brings in both non-infectious as well as infectious causes of elevated temperature with hyperthermia being a possibility. The story about steroids and infectious diseases is not one that has been resolved. This table initially started out as a report in the last reference by McGee et al from the Archives of Internal Medicine in 2008. I've expanded it based on new information that we've gotten. So for example, in the new guidelines that look at tuberculosis, it is now stated that tuberculous pericarditis may not always need steroid therapy, although steroid therapy is continuing to be recognized in all people with tuberculous meningitis. Our information about SARS-CoV-2 and the role of steroid therapy has now been recently reported in the reference that cited. And as we think about situations where the treatment may be effective and improve symptoms, but maybe not improve survival, the entity of herpes zoster. And it's important to note that even though steroids may play a role in herpes zoster, it does not decrease the risk of post-traumatic neuralgia. The immune reconstitution inflammatory syndrome is essentially our giving the immune system back to people who are HIV infected and then watch what they do with it. And so you can imagine as their immune system begins to take back over, we can see flares of disease. And clinically that's gonna be most manifested in the eye with CMV retinitis and in the brain with cryptococcal meningitis because of the visual problems and the headache that can occur. But we see it in all kinds of other situations. Death has been reported in about 5% of patients with any type of iris. And we understand that the risk of iris is gonna be associated with lower CD4 counts that rapidly go up. We talked about duration of therapy in the presentation about bacterial, fungal and viral infections. But I'd like to look at essentially when you start therapy based on the entity of immune reconstitution. In a study that looked at HIV infected people with cryptococcal meningitis, it was shown that deferring antiretroviral therapy for five weeks after diagnosis and the initiation of ART was gonna be important. In contrast to people with tuberculosis, the ability to start ART with their antiviraculous therapy was something that was reasonable to consider. One of the important things in the world of gastroenterology is the pathogenesis of disease. And the pathogenesis of disease can be considered in a couple of ways. First, what the symptom is gonna be. Is it vomiting or is it gonna be diarrhea? Vomiting usually occurs within about six hours of the ingestion. And the implication is it is the ingestion of preformed toxin. Staph aureus, the short acting form of Bacillus cereus. And keep in mind that Clostridium botulinum is really a foodborne illness. The ingestion of a food with the spores and then the production of a GI illness followed by the descending paralysis. In contrast, if we look at diarrhea, it usually means that the organism has to get down to the lower GI tract, where it's either the organism itself invading or it's the organism producing toxin. Toxin production we think about in terms of Bacillus cereus, the long acting form, Clostridium botulinum, but very importantly, the Shiga toxins. More than just E. coli 0157H7, but a whole host of gram negative organisms. The literature shows that drugs that halt peristalsis of the GI tract predispose the Shiga toxin diarrheas to HUS and TTP. That association has not been definitively established for antibiotics, although some studies showed a trend toward that. With tissue invasion, organisms like Campylobacter, Salmonella, Shigella, invasive E. coli. And as we talked earlier about Yersinia enterocolitica, the possibility of transfusing either the organism or the toxin with a blood transfusion and hence both bug and toxin. A 43 year old woman with acute myelogenous leukemia, status post-anthracycline-based chemotherapy three weeks ago, has been neutropenic for the past 12 days. The tunnel catheter through which she received her chemotherapy was placed one month ago. Three days ago, the patient began having a nonproductive cough. This morning, she begins having hemoptysis. Workup reveals that she's hypoxemic. What's the most likely pathogen to be causing such a clinical process? Is it Staph aureus, Pseudomonas aeruginosa, Canada albicans, or Aspergillus fumigatus? In the approach to patients who have neutropenia, it's probably important to think about how long the neutropenia has existed. In the first four to seven days, we worry about normal flora. Staph, strep on the skin, aerobic gram-negative rods in the gut, and those are what are normally defended against by their polys. Once the duration of the neutropenia goes longer than about a week, particularly if they've been on antibiotics, we shift to fungal pathogens, and the classic fungal pathogens are Canada and Aspergillus. Keep in mind that the guidelines state that Canada albicans pneumonia is exceedingly rare, and in fact, to make the diagnosis of it, you need histology showing invasion of the Canada into lung tissue. I finished my ID fellowship in 1983, and in the 38 years that I've been doing infectious diseases, I have never diagnosed a case of Canada albicans pneumonia with the invasion of Canada into the lung. I probably missed some cases because we didn't do the lung biopsy, but by definition, we didn't see it. And so this is a patient who has Aspergillus based on that property of angioinvasiveness in neutropenic patients. As you think about seriously ill people, I ask you to ask the question initially, is the patient a normal host or they not normal? And if you think about the not normal group, is it a problem with their defense barriers? Is their skin broken down like with a burn? Do they have mucosal insult like chemotherapy and they don't have that barrier? Or do they have stones in their gallbladder or kidney or just a big prostate? There are groups of patients who are really not classically immunocompromised. They are immunodysregulated. Alcoholics have risk of pneumococcus, diabetics of Staph aureus, cystic fibrosis patients of Pseudomonas, cirrhotics of a host of organism, including Listeria. But the classic limbs of host defense are neutrophils, humoral immunity and cell-mediated immunity. Polymorphonuclear leukocytes are supposed to protect us from our normal flora. And so what we see in neutropenic patients who get infected are infections usually with our normal flora. The gram-positives listed on the slide in the enterobacterials, previously known as the enterobacteriaceae, the enteric gram-negative rods. Pseudomonas is not part of our normal flora, but it gets acquired in the hospital. And so because it gets acquired in the hospital, it essentially takes over and acts like our normal flora would do. And so the risk of Pseudomonal bacteremia. When we begin to look at late infections, usually after four days of fever and antibiotics, we shift from the bacteria to the fungi and the approach to yeast versus moles. So let's look at the acute presentation that may lead to mortality. It may be in a patient who comes with these Bullous Hemorrhagic Skin Lesions. These are the lesions of Ecthyma gangrenosum. And in neutropenic patients, Ecthyma gangrenosum is considered to be Pseudomonas unless you prove it definitively to be something else. The histology is gonna be the invasion of Pseudomonas into the dermal veins and these lesions. In the mid-1980s, the group at MD Anderson and Jerry Bode published a report that taught us why Pseudomonas is so necessary to treat in empiric therapy. In neutropenic patients who had Pseudomonal Bacteremia, who did not get appropriate therapy in the first 24 hours, their mortality was 27%. When they looked at 48 hours of non-appropriate therapy, the mortality went up to about 70%. The bottom line is that Pseudomonas aeruginosa is always the pathogen covered in febrile neutropenic patients. If we shift from neutrophil function to humeral immunity, the story of Asplenia comes in. This review in CHEST in 2016 looks at the pathogens involved. The most classic pathogen making over 80% of the cases is Streptococcus pneumoniae. But when you think about pathogenetic mechanisms, Haemophilus influenzae, Kapnosidophagia, Babesia, Plasmodium, and Bordetella are pathogens that have been clearly implicated without spleens. And then finally, in the people where it's possibly involved, Neisseria meningitidis, E. coli, and Staph aureus can occur, but not as classic as that middle group. And then finally, the report said that in patients with life-threatening illness and Asplenia, it may be not just infection. There's an increased risk of thrombosis, and so is this the presentation of something like pulmonary embolism? Or is their acute manifestation really just gonna be a further exacerbation of underlying pulmonary hypertension that has also been reported in increasing incidents in Asplenic people? In learning theory, there's this concept called vertical learning that says we learn better if we compare similar things. So if we were gonna vertically learn about the Asplenic and some common bugs, I would say the three organisms to consider are Pneumococcus, Capnocytophagia canamorsis, and Meningococcus. Because if we look, they're different. Pneumococcus is normal flora, Capnocytophagia is usually through a dog bite, and Meningococcus is aerosolization that colonizes the posterior pharynx. Splenectomy is a risk factor for Pneumococcus, Capnocytophagia as we saw in the preceding slide, but it's more deficiencies than the late complement components with Neisseria. And as we think about organ systems, the lung in Pneumococcus leading to bloodstream, with Capnocytophagia, it's gonna initially be a wound infection leading to bacteremia, and with Meningococcus, a real predilection for the meninges that go to the adrenal glands. In the approach to patients with defects in cell-mediated immunity, it's not the usual bugs. The bacteria all share in common an intracellular location, and these are the seven that are the most likely. The fungi are based on epidemiologic exposure. Most of the viruses on this list are DNA viruses, but there are some RNA viruses. There's a list of the parasites in protozoa, and then there's Treponema pallidum in this other category. As you think about patients on the exam, look at the host defense problem, and if it's cell-mediated immunity, realize these categories, and it's not your usual staph, strep, pseudomonas. So what about some of the classic presentations in that group? A classic one is gonna be Necardia, because of the triad of disease that it causes. It's essentially lung infection, often with a single cavitary lesion, with pustular skin lesions, and it's free of neurologic involvement. Rhodococcus equi, which is epidemiologically linked to horse exposure, does exactly what Necardia does, and there's no way that you can distinguish the two of them apart based on just clinical grounds. For Sulfa, the treatment is gonna, with Necardia, the treatment is going to be Sulfa. In contrast for Rhodococcus, vancomycin. And a very important principle is because these organisms are both intracellularly located with the macrophages, the predominant phagocyte in cell-mediated immunity, they require prolonged duration of neutropenia. For Necardia, literally months of therapy because of the inability of those macrophages, even though they've ingested the organism, to effectively kill them. The list of cell-mediated immunity pathogens showed us a group of viruses, and I think the important virus to know is gonna be cytomegalovirus. The presentation is gonna be different based on the host. In HIV-infected people, the chorioretinitis that shows up is hemorrhages and exudates. The adrenal insufficiency that classically occurs with CD4 counts less than 50 are probably the two most classic. And the hematopoietic cell transplant patient, the bone marrow transplant patient, the risk of pneumonia. But we fortunately don't see that as much. In the pre-preemptive therapy for CMV days, the CMV pneumonias killed 90% of patients. What we now find is with preemptive therapy with a CMV drug like ganciclovir, that mortality goes down to about 5%. And so we don't see as much CMV pneumonia. But we have come to understand that CMV can be an indirect cause of graft versus host disease. And so the issue of it, does there need to be prophylaxis against CMV to prevent things like graft versus host? The solid organ transplant patients get a host of medications that knock out their cell-mediated immunity. And these people often present with a viral syndrome because the pathogens are intracellular as all viruses or leukopenia can occur. The ability to infect the liver to give us sometimes a seronegative hepatitis occurs. The risk of ulcers in the GI tract presenting as bleeding or just pain. And then rejection is an indirect cause of CMV. Our therapies are usually thought of as definitive whenever we talk about organisms, but preemptive therapy becomes important because preemptive therapy says we're gonna begin to treat when we can detect by markers organisms in the blood but before they actually cause disease. This is why bone marrow transplant patients has been so positively impacted. And then finally, the New England Journal report in 2017 about laterimivir is perhaps being prophylaxis against CMV. A 38-year-old diabetic man who recently waded through water for several days rescuing people from a flash flood presents acutely ill with confusion, jaundice, and renal failure. His illness began three weeks ago with symptoms of fever, malaise, myalgias, and red eye that resolved over about five days. He now has a temperature of 103, a pulse of 132, and a blood pressure of 114 over 88. Other than confusion, scleral icterus, the exam is unrevealing. Laboratory data are notable for a creatinine of 3.8, a total bilirubin of 4.3, transaminitis five times normal, white blood cell count of 8,900. Your analysis is positive for both protein and blood. The most likely pathogen causing this presentation is group B strep, Pseudomonas aeruginosa, Hepatitis A virus, or Leptospira interrigans. The epidemiology fits every answer. He's diabetic. Remember the increased risk of group B strep infections in diabetics. The association of Pseudomonas is a water bug. The fact that Hepatitis A is enterically transmitted, so did he get Hepatitis A from the water that he may have swallowed walking through? But what this patient has is Leptospirosis. Picked up the spirochete walking through the water and develops that triad of liver, kidney, brain dysfunction. So I'd like to look with you at the kidney as a result of infectious diseases. The way that I broke this down were into three kidney processes, acute kidney injury, chronic kidney disease, and end-stage renal disease. Notice that there are three processes that lead to acute kidney injury, sepsis. And if you invoke now the 2016 definition where it's end organ, and we know that the kidneys and the brain are the classic end organs, and any person who shows up with an acute kidney injury, one should at least ask if they're seriously ill, might this be sepsis? Leptospirosis classically is one of those liver-kidney interaction processes. And so in acutely ill people with profound liver kidney, think about Leptospirosis. But also think about Hepatitis B because Hepatitis B is highly immunogenic. And even though we think about it as a liver process, when antibodies are formed against the Hepatitis B virus, they deposit in the kidney and they can develop an acute glomerulonephritis. Post-infectious glomerulonephritis, classically by things like group A strep, but more commonly now associated with staph aureus infections can lead to chronic kidney disease. But chronic kidney disease has the ability to lead to things like nephrotic syndrome, where there's hypercatabolism of immunoglobulin, and so the risk of pneumococcal infections. It can lead to be on the basis of vasculitis or other immunologic injuries like antiglomerular-based membrane disease, for which the therapies can lead to a risk for infection. And with end-stage renal disease, transplant patients are on drugs that knock out cell-mediated immunity. We've looked at those bugs. And they have foreign bodies, either in their blood vessels or their peritoneal space, which can be now the mechanical device for which infection can occur. Coagulates negative staph, important in those regards. Dermatologic lesions may be very helpful in the ICU in terms of helping us think about what the disease state is. And you can think about the derm bleeding into the skin lesions as being petechiae, purpura, or ecchymoses. The sizes are the general sizes reported in the literature. They are more to guide you. They are not absolutes. But remember that petechial lesions occur on the basis of platelet problems. Classically, we think about Rocky Mountain spotted fever with petechiae around the ankles, the wrist, on the palms and the soles, because the rickettsia invade the endothelium, and they allow now the platelets to leak out and give you those petechial lesions. In patients with pneumococcal sepsis, they really develop purpura on the basis of coagulopathy. And the coagulopathy occludes dermal veins. The pressure backs up, and it gets into now the capillaries. The capillaries leak, and you get this bleeding into the skin, the lesions of purpura fulminans. I will tell you, I can't really distinguish purpura from ecchymoses. Look at the size difference, nine versus 10 millimeters. But it's more the concept. And ecchymoses are due now not to blood vessels with clot, but they're really due to clotting factor deficiencies, as we see in people who have overwhelming meningococcemia. It would be very fair to ask on an exam for people who use a lot of antibiotics, the classic mechanisms of antibiotic resistance. At the first level in this slide are the ways that resistance can happen. You can alter the bonding site. You can change the permeability of the cell wall so drug can't get in. You can turn on a pump that extrudes the drug once it gets through the outer wall, or you can make enzymes that destroy it. The two classic pathogens that have altered penicillin-binding proteins is their mechanistic resistance, or MRSA, and penicillin-resistant pneumococci, which means that giving a beta-lactamase inhibitor for either one of these drugs would make no sense. Within permeability, we know that in the cell wall there are pore channels that were initially designed to let nutrients in and extirpatory products out. Closure of those channels leads to Pseudomonas aeruginosa resistance to carbapenems. And then finally, when you see resistance to multiple classes of drugs, everything on the report, that's probably efflux because there's no other way it could happen. But it's gonna be enzymatic destruction that will be important both in your clinical practice and on the exam. The most classic organism that you will encounter that will be carbapenem-resistant will be Pseudomonas aeruginosa. And that will not occur because of a carbapenemase. It will occur because you've got a beta-lactamase in that Ambler C category, but not a carbapenemase, in association with either porin channels that are closed or efflux pumps that are turned on. That's in contrast to what you're hearing about now in terms of actual carbapenemase production. In the Ambler system, the A's and the D's are serine-based. The B is gonna be metallobase. And it's the B that's gonna be the most difficult. The drugs that you have on the market to treat the Ambler A's are ceftazidime, ab-bactam, mirapenem, vabrabactam, and imipenem relabactam. The most difficult, as I mentioned, are gonna be the Ambler B's, those like the New Delhi metallos. But this paper would lend itself beautifully to a question because it asks, can you give piperacillin-tazobactam and treat an ESBL-producing bacteria in the blood and have a result as good as mirapenem? It was an international trial in nine countries. And what they looked at was they looked at mortality at 30 days post-randomization. And what they found was that the mortality was 12.3 in the piperacillin-tazobactam treated patients versus 3.7% of the mirapenem treated patients. So that if they were to give you an exam question of somebody with a urinary tract infection or an intra-abdominal infection who showed up with life-threatening illness, the thought process would be they were at risk of E. coli and Klebsiella. Those are the two most likely organisms to make an extended-spectrum beta-lactamase. And even though the lab may say it's susceptible to piperacillin-tazobactam, the correct answer on the exam would be mirapenem. That would apply to practice as well as the exam. This is a list for your review. It looks at vector-borne infections presenting as critical illness. I wanna make a comment only about one on the list. It's under tick-borne and tick paralysis. The tick paralysis syndromes are a neurotoxin infused by the tick into the human, and literally by removing the tick, the paralysis can be alleviated. So keep in mind, in terms of life-threatening illness, tick paralysis. The other ones that may show up may be with nervous system involvement. We've spoken already about Rocky Mountain spotted fever being nervous system and about West Nile being nervous system. But again, a list of vector-borne diseases. The critical care boards have a propensity to look at things like infection prevention since that is so big in the ICU. There would be two organisms, I believe, that lend themselves most easily to be asked about infection prevention. One is Acinetobacter. And like Pseudomonas aeruginosa, it's classically a non-fermenter. Acinetobacter is resistant to a lot of things, but notice that Sobactam, a beta-lactamase inhibitor, has some intrinsic activity against Acinetobacter. In fact, it is the only bacteria you need to remember for which the beta-lactamase inhibitor itself may work. And a task force recently said that anytime you see a patient colonized with Acinetobacter, you should assume that there's a potential for transmission to other patients and think about infection prevention. Candida auris is said to be the fungal counterpart to carbapenem-resistant gram-negative bacteria. We see it a lot in ICUs. Again, the need to isolate patients if this occurs. In terms of infection prevention, this is a slide for your review. We don't need to go over it, but if you were gonna look at A1 recommendations in critical care, these are the A1 recommendations. Again, there are many other things, but if they were gonna ask for a single best answer, they would have to go with A1, and this was the list that I put together of A1 recommendations. And then a final comment. When you see patients in the intensive care setting who have an elevated temperature, I ask you to think first about naming it as just elevated temperature because that elevated temperature may be only hyperthermia, that is, not resetting the hypothalamic thermoregulatory center, in which case you would think about things like the serotonin syndrome and the malignant neuroleptic syndrome and malignant hyperthermia, which can happen as late as 24 hours after anesthesia. If, on the other hand, you call everything with elevated temperature fever, you walk away from hyperthermia. And then finally, remember that many of the true fevers are not infectious in origin. Thank you very much for your time.

infectious diseases

intensive care setting

endocrine emergencies

adrenal insufficiency

valve replacement

hospital-acquired pneumonia

streptococci

pulmonary infections