Thank you. Thank you very much. I think the previous speakers already nicely showed how complex it can be to come to a diagnosis. And I'm afraid in infections and sepsis, this is no different. These are my disclosures, none of them in fact relevant for this presentation. I don't think I have to convince this audience that sepsis is important. And, well, if we want to treat sepsis properly, then an infection diagnosis is actually very important. And I'll explain you why. Well, the first and simple reason is that by diagnosing infection and diagnosing it early, well, you avoid progression from an infection without any organ complications to sepsis and eventually septic shock. So trying to break this vicious cycle early is quite easy and straightforward if you get your infection diagnosis early and correct. Organ dysfunction, of course, may have multiple causes and is definitely one of the confounders. And in our approach to sepsis, we need to understand there's two important elements. There is, on the one hand side, the organ dysfunction that is quantified in the sepsis tree definitions. And we have the tools. We use the SOFA score. But the infection is often taken for granted. There's no guidance in the sepsis tree guidelines about how you diagnose an infection. There's even barely mention of that. And I'll come back to that in a minute. Very importantly, better infection diagnosis leads to better sepsis treatment. And there's two important reasons why I think this is the case. Not every patient with sepsis will get the same antibiotics. If a patient is suspected of suffering from meningitis or an abdominal infection, well, you will be administering different antimicrobials. And more importantly, and this is a topic dear to my heart, source control. You need to have an infection diagnosis, an anatomical diagnosis, in order to be able to control the source of infection when necessary, of course. And only if those two things are right, then you can start thinking of treating sepsis with any new sepsis-specific drug you are interested in. In the end, also, better sepsis diagnosis, better infection diagnosis, will lead to better sepsis research. Because let's be honest, a lot of those patients in sepsis studies, they come down with what we call a culture-negative infection. We assume an infection is there, but actually we cannot document it. I'm not saying that those patients will never have an infection, but I'd rather see a microorganism identified when I treat a patient with sepsis or septic shock. So this search for a reliable sepsis infection diagnosis has been going on for quite some time, but we made very little progress, I think. This is coming from a Dutch study. The Netherlands, as you know, this is a country where the threshold for giving empirical antimicrobials is quite high. But they looked in this study, patients admitted to the ICU through the ER, and they checked three days down the road whether the initial diagnosis of infection was correct. And you can see that this, in this figure, that one out of six patients, it was very clear there was no infection at all. On the other side of the spectrum, one out of three patients, it was very clear. And the rest was, well, somewhere in between. It could be infection, but it could be something else. So we need to be aware that we are not very good at diagnosing infection. We're good at diagnosing sepsis, at least the organ dysfunction associated with sepsis. But the infection part itself, it's much more challenging. And the reason why, well, there's so many diagnoses that look like sepsis. And I'm sure you can add many more to this list. And often also, once we get a diagnosis of, make a diagnosis of sepsis, we are often happy. We are in a busy ICU. Once we have this diagnosis, we just switch off our brain. We move on to the next patients. And we do not consider, we do not revisit this diagnosis. There's a lot of confounders already mentioned symptom overlap. But we have to admit that patients may be admitted with pulmonary embolism, which mimics in many ways an infection. Patient comorbidities make it more difficult. And especially this ultra sensitive and probably overused imaging. We scan everybody. We echo everybody. And then we come up with, well, things that maybe are totally irrelevant. But we try to use it in our construct of an infection. And finally, information coming back from the lab. It's increasingly sensitive. Tests are being used. It gives us more information. And it tells us that a pathogen is there. But you don't just need a pathogen to have an infection. It should be an invasion by a pathogen, multiplication and causing disease. This is what constitutes infection and not the mere presence of a pathogen. And especially distinguishing colonization, because you can culture your patients and you always will get a number of pathogens back from the lab. But that necessarily doesn't mean that an infection is present. So two important distinctions need to be made. Of course, we need to diagnose sepsis. But the focus there is on host response and the quantification of organ dysfunction. But when it comes to diagnosing infection, we need to take a different approach. We need to look for signs and symptoms of this infection. Because if you have a skin infection, well, then you will have signs and symptoms of that infection. And always use a contextual approach. If a patient is admitted three or four days after elective abdominal surgery with abdominal pain and signs of sepsis, well, it's not that likely that this patient will have meningitis, if you see what I mean. SERS. There's been a lot of SERS bashing, of course, in the past years. And we all feel a bit awkward when we still would even mention it. But let it be clear, also in the sepsis three guidance, it was explicitly mentioned that, of course, we don't use SERS criteria for the sepsis diagnosis, but nonspecific criteria like SERS will continue to aid in the general diagnosis of infection. And this is something that we need to remember. These are tools that help us to diagnose infection. But above all, I think we need to look at our patients. We need to use the tools. So that means our brain, our eyes, our hands, our ears. And go and look at patients. This is very important. Look at a patient's history. Often there are clues hidden there. Clinical evaluation. Very simple, very simple things, but all too often forgotten. Why? Because we often skip and we go for echo. We want to scan and we just, well, we'll see what comes up from the scan. And it's not about just one of these items. It's about integrating all this information and revisiting when necessary, of course, that brings you to a diagnosis. This is one of the big problems in this context. We forgot about physical examination. We like all the other stuff, the biomarkers, very exciting changes in biomarkers and the ultrasounds. But physically examining your patients actually will help a lot, I think. And I often see residents these days, you know, they're behind their computer ordering the tests. But actually, did you look at the patient? I will do it. I will do it in five minutes. But they are not using that to actually inform the tests. I'm not saying it easy. It is very complex in ICU patients. And I think we've discussed a number of the reasons why. But that should not chase us away, I think. I like to use a simple practical approach. It doesn't need a lot of time. Again, your hands, your eyes, your ears. Just focus on the most plausible sources of infection. You know, the most plausible sources of infection is pulmonary, first of all, okay, two-thirds of our patients. And then abdominal, urinary tract, catheters, neuro, not very often. If it's a surgical test, you look for the skin and wounds. And actually, this, in 60 seconds or less, you can already have a good idea where the problem is located and what it can be. And maybe you will be stuck indeed with undetermined infections or bacteremia or candidemia indeed. But often, again, this can really help you. Of course, we all like the new fancy biomarkers and the new diagnostic tools, often hoping that it will bring more information. As far as I'm concerned, often this is information overload. We get more microorganisms reported from the lab. We get more detailed biomarkers. But actually, quite often, they are not contributing in a relevant way. So, in conclusion, I hope I've convinced you that diagnosing an infection is very important for treating patients with sepsis. Again, quite difficult and challenging in the ICU. But clinical examination with contextual thinking can actually already bring you quite far. But using this integrated approach, all this information, going at the bed of the patient. And I do realize we need better tools. We need better strategies, better biomarkers. But I'm not sure if they are around the corner. And with this, I would like to end. Thank you for your information, and I'm happy to take questions.

infection diagnosis

sepsis

diagnostic tools

clinical examination

biomarkers