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Biomerieux: This podcast is sponsored by bioMérieux. In cases of acute community-acquired pneumonia, patients are frequently treated with empiric broad-spectrum antimicrobial therapy while awaiting diagnostic results. This can lead to overuse of antimicrobials. Diagnostic solutions from bioMérieux provide fast pathogen identification and support effective antimicrobial therapy management through innovative biomarker detection. Learn more about these solutions from the leader in infectious disease diagnostics at biomerieux.com.

Dr Pam Peeke (Host): Hello and welcome to the Society of Critical Care Medicine Podcast. I'm your host, Dr. Pam Peeke. Today, we're going to be talking about identifying bacterial co-infections in patients with lower respiratory infections. I'm joined by Dr. George Sakoulas, who is Chief of Infectious Disease of the Sharp Rees-Stealy Medical Group, and addition is Professor of Pediatrics, University of California, San Diego School of Medicine. Welcome, Dr. Sakoulas.

Dr George Sakoulas: Thank you for having me.

Dr Pam Peeke (Host): Very good. Before we start, do you have any disclosures to report?

Dr George Sakoulas: Oh, I'm a speaker and consultant for bioMérieux.

Dr Pam Peeke (Host): Thank you very much. Now, what I'd like to do is go over the learning objectives and why this podcast is so needed. The learning objective is to educate ICU physicians and hospitalists on identifying hospitalized patients with moderate to severe respiratory infections where antibiotics are not necessary.

Why is this podcast needed? It's because ICU physicians and hospitalists need to be more confident in not prescribing antibiotics in cases of hospitalized patients with moderate to severe viral respiratory infection, what are the knowledge gaps that this podcast will address? The first is lessons learned from the COVID-19 pandemic. Despite only a very small number of patients hospitalized with COVID-19 having a secondary bacterial pneumonia on presentation, a very large percentage were unnecessarily treated with antibiotics. And in addition, utilization of biomarkers in antimicrobial stewardship will have different impacts in academic teaching hospitals versus non-teaching hospitals. Dr. Sakoulas, why is this podcast so important at this juncture, as we are coming out of two years of hospitalizations with COVID-19?

Dr George Sakoulas: Yeah. So, the last two and a half years have put a lot of pressure on our ICU physicians, nurses, everybody who takes care of patients that are critically ill and even on the floors. And as you mentioned before, we saw a lot of patients just because of their severity of illness at presentation, physicians having very low threshold to initiate antibiotic therapy in patients who were very sick with a viral infection and its immune reaction is triggered by the viral infection. In other words, you know, only 2% or less of patients who presented with severe COVID-19 were found to have bacterial infection, yet the majority of those received antibiotics. And the consequences on that were that many hospital's anti-microbial resistance, antibiograms worsened. We saw a rise in increased resistant pathogens in our ICU nosocomial pathogens that were more drug-resistant, because of this heavy burden. So, I think physicians still need to do a better job when facing these critically ill patients, and feel more confident in not prescribing antibiotics when they're not really needed. Of course, that's easier said than done because when you're faced with admitting multiple patients and you're in disaster triage mode, and you have people in the hallways and you're overwhelmed, the attitude is to shoot first and ask questions later. Unfortunately, that does make you feel better to move more confidently, move on to the next patient. But having that style of practice over a long period of time, like a couple of years, it does have consequence on driving antibiotic resistance.

Dr Pam Peeke (Host): Thank you. So, what factors go into deciding empiric antibiotics in patients with community-acquired pathogens?

Dr George Sakoulas: We have the traditional clinical markers, right? The patient has a fever, tachycardia, the signs of sepsis, if you will. There are some laboratory markers that we use, like white blood cell count, C-reactive proteins, lactate, all of these they're very simple tests that we can order. But their specificity is quite low. Patients with fevers and elevated white blood cell counts may not necessarily have an infection. We see patients with pulmonary emboli or massive bleeding that will present with tachycardia, low-grade temps and elevated white blood cell counts simply by the stress of the reaction.

So clinicians will use these sort of traditional tests, physical exam and x-rays and these other laboratory tests. But there's room for improvement. Then, we have started incorporating procalcitonin now that is a much more specific test for deciding whether a patient has a bacterial infection requiring antibiotics. Unfortunately, like I said, sometimes if you're in a mindset when you're very busy, it's also very challenging to rely on a simple blood test when you have a very sick patient in front of you. So, those are the general tests that we use. Unfortunately, unlike cardiologists who have a troponin and EKG and a CPK, they can pretty reliably tell you if someone's having a heart attack. In infection, the markers are a bit less specific.

Dr Pam Peeke (Host): Excellent. And would you tell us about the procalcitonin testing, and really how it supports prescribing decisions and reducing antimicrobial use safely in patients with respiratory tract infections?

Dr George Sakoulas: Yeah. So, procalcitonin is a prohormone of calcitonin. it's normally present in very, very low concentrations in the blood. It's produced by some thyroid cells and some neuroendocrine cells in the lung under normal conditions. So, your levels are almost undetectable unless of course you have a tumor in those rare cell lines that produce it.

But under conditions of bacterial infection, the procalcitonin is stimulated to be produced by all of cells of the body. Remember all the cells have the gene, but the gene is repressed except in those few cells I mentioned earlier. But then, if you have a systemic infection, there's immune stimulation to turn on expression of this protein, procalcitonin, and it can be detected in the blood. And the concentrations actually are in a dose-dependent fashion, slightly increased in local infection, even more so in systemic infection, and even more so in severe sepsis and even highest in septic shock. So you have not only a dose response based on the severity and spread of the infection, but it can be used as a prognostic marker. So if you have someone who you're starting on treatment and some patients respond real quickly to therapy and you can see a procalcitonin drop quickly. You have other patients for a variety of reasons who don't respond as rapidly and have worse outcomes. You can also detect that serial change in the procalcitonin failing to decline in a rapid fashion. So, it's a test that can be reliably used to detect bacterial infection and then also monitor the adequacy of what you're doing to the patient in the course of their hospitalization.

Dr Pam Peeke (Host): How well integrated into the hospital system nationwide is the of procalcitonin testing?

Dr George Sakoulas: I believe it's pretty well uptaken, certainly in academic centers and in larger hospitals. There may be smaller community hospitals that may not have it available. I mean, everybody can order it. It's just a matter of can you get it promptly through an in-house test. And when we first were using it, we were sending it out and it took three days to come back, and that of course isn't very helpful in most cases. But now, a lot of the larger hospitals, a lot of the teaching hospitals. And even private hospitals like the one I'm at, that takes care of highly complicated patients like transplant patients, ICU patients, things like that, we have it in-house and get a result back in a couple of hours and can make clinical decisions based on the results that we have. It's taken a while. I mean, it's been available for close to 10 years, I believe, but it's only been in the last few years that the uptake has been greater.

Dr Pam Peeke (Host): Excellent. And how important is ongoing comprehensive education within your team to be able to stay up with PCT testing appropriately and its integration into the overall standard operating procedures?

Dr George Sakoulas: Yeah, education. I think, continuing education is very important for all providers, nurses, physicians to keep up to date on literature, not just on procalcitonin, but new antibiotics. It's a little harder now to get novel education to clinicians now because of this widening gap between the medical system and pharmaceutical companies, for example, in the name of disclosure and purity. It's just harder to get in front of physicians now and give them education on what new tests are available and what peer review publications have shown them to improve practice and not just with diagnostics, but also with therapeutics.

It's amazing to me how many times I'll see an antibiotic that's been on the market for three or four years, and you'll talk to clinicians in the hospital and they've never heard of it, which is challenging. I think you want your doctors to know what's available out there. Whether they prescribe it or not is up to their own discretion and their education and their comfort level. But I think getting physicians that are making decisions on taking care of patients, they should know everything that's available. I mean, whether it's a diagnostic test like procalcitonin and other diagnostic tests or even therapeutic agents, because you want your doctor to know everything, because there may be cases where the newer therapy may offer some benefit that your doctor may not even know about.

Dr Pam Peeke (Host): That's excellent. And I think it's really important that this podcast get this message out there, and that there are resources for critical care peers. And those healthcare providers who really need to understand that there are other options to be able to make these diagnostic calls. Speaking of which, if we look at methicillin-resistant Staphylococcus aureus, would you consider this to be a community-acquired pneumonia pathogen?

Dr George Sakoulas: You know, I'm actually very glad you asked that question, particularly with what is anticipated in the coming months. Typically not. Under most circumstances, baseline conditions MRSA is a very small percentage of community-acquired pneumonia. in fact, if you look at the ATS, American Thoracic Society and IDSA Guide, it's not generally considered in most empiric therapy. However, there are blips that can last for a few months and that they're geographic blips and also temporal time blips. And I mentioned that, because when MRSA can become a more significant pathogen is when you're under a lot of respiratory virus stress in the community, whether it's influenza, COVID, other viruses, and we know what's heading this way. In fact, I think some east coast states are starting to deal with it already. When you start dealing with respiratory virus, it's very well described that pneumococci, Staph aureus, both MSSA and MRSA. There's an upsurge in methicillin-resistant in community-acquired pneumonia cases.

So, given that this bacteria is quite virulent, you kind of want to make sure you have it covered earlier rather than later, because there's nothing worse than having a really sick patient admitted with a community-acquired pneumonia and they get it prescribed the usual ceftriaxone and a macrolide or quinolone, and then MRSA grows in the blood and the sputum, and then you wind up having to add back linezolid or vancomycin two days into it. That's not a good feeling to be in as a provider, and certainly even less so being the patient.

So, I think, given what's at least what's projected to be coming and what we're seeing signals already with RSV, influenza and even COVID now, we have to have our radars up in young patients with pneumonia, particularly after a viral or influenza-like illness that we're admitting to the hospital.

Dr Pam Peeke (Host): Thank you so much. So, let's get more specific. In a patient admitted with severe community pneumonia, what cases would you be confident not prescribing antibacterials?

Dr George Sakoulas: That's a very good question that we had a lot of practice in over the last couple of years. We've had patients who'd get admitted to our ICU or the floor with bilateral infiltrates. Most of those wind up having COVID. A lot of them will have an elevated white count and, you know, they're quite hypoxic and quite sick, their x-ray looks terrible. But then, if you get a procalcitonin test on these patients and it's 0.1, 0.2 and in very low numbers, you can feel pretty sure, particularly during a middle of pandemic, and in a heavily burdened respiratory season in the middle of winter, you can feel pretty confident that that patient doesn't have a bacterial super infection.

I think it's important that if the patient is sick, to check that test regularly, you know, daily and see for any increase in case a super infection does creep up. But we've had many patients with low PCTs, that we would stop antibiotics on, even though they were very sick with a lower respiratory tract infection. I think a PCT can be very good.

Now, if a procalcitonin is elevated, it doesn't necessarily mean they have a bacterial infection. We've had many really sick COVID patients who also wind up having concomitant elevated procalcitonins, but they didn't have a bacterial infection, just of the nature of the illness being very severe. Sometimes COVID causes low-grade gut ischemia, that causes sort of a low-grade gut translocation, that will elevate your procalcitonin without necessarily causing a direct bacterial infection. But the negative predictive value of a PCT in such settings is very, very good. And you can feel confident that if someone has a very low procalcitonin level, that they don't have a bacterial infection.

Dr Pam Peeke (Host): So, is there a benefit in looking at C-reactive protein and PCT concordance versus discordance?

Dr George Sakoulas: Sometimes we'll see patients with a high CRP and low PCT that'll go along with a viral infection. Actually, pre-COVID, we would see cases of vaping lung injury that would also show a similar phenomenon. They would come in and it would have a precalcitonin that was very low, but they would have severe infiltrates in the lung, fever, elevated CRP, but then you'd get a history from the patient that they were heavy vaping. And so, you get this vaping lung that was well described prior to the pandemic. So in addition to viral infection, there's that situation that the one also needs to be under consideration. So, that's also a good signal that someone might need, for example, immunomodulatory therapy, like steroids, like in COVID and in vaping, as opposed to antibiotics, where you would have both tests elevated.

Dr Pam Peeke (Host): All right. So, this really feeds into this whole issue that we brought up earlier of antibiotic stewardship. So, taking all of this into consideration, and you've done a masterful job of summarizing the high points here, what would you consider to be the real milestones in your mind as a diagnostician making this decision when someone comes in with a respiratory infection. Antibiotic stewardship, what's the optimal antibiotic stewardship?

Dr George Sakoulas: Yeah. I think antibiotic stewardship has various components, right? I mean, it's minimizing antibiotic use, using narrow spectrum antibiotic, reducing the cost of antibiotic care. And fortunately, that seems to be the pillar that is the easiest to target and keeping budgets down is sort of taken up as a big component because it's a much easier target to go after.

But for me, the low-hanging fruit for antimicrobial stewardship is, one, not prescribing antibiotics if we don't need them. There are plenty of patients out there who receive unnecessary antibiotics. The data is about 50% of antibiotics that are given to patients with respiratory infections are unnecessary. It's a lot. I mean, given that respiratory infections themselves are such a large component of types of infections that we see. So, not giving antibiotics to patients who don't need them to begin with.

And second of all, discontinuing them earlier. Duration of therapy, in the old days when I was in training, was 14 days for everything. And I remember asking my mentors, you know, "Why 14 days for pneumonia, skin?" And it really comes down to the first case is from the 1940s. Many of you may have seen that Mayo Clinic Proceedings article from the early '40s where a young girl had a severe streptococcal infection and was given 14 days of penicillin. And it was cases and experiences like this, these single anecdotes from 1940s, that really drove 14 days for everybody for decades.

And we now know that for respiratory infections, you don't need 14 days. You don't even need seven days for most infections unless the patient-- you know, what goes into longer therapy? For me, I would say an immunocompromised patient, difficult to eradicate organism like MRSA and Pseudomonas legionella. Those are kind of a different category. You might have to treat those longer. But for the vast majority of patients, you're looking at seven days or less. And your procalcitonin test can even be used to make that decision if you check them serially and you have an 80% reduction in PCT from baseline from when they first came in. That's been established as a pretty good marker to when you stop. But even if you don't do a procalcitonin and you don't have it available, and for most patients, they feel well, fever resolves, white count resolves, 48 hours later, you can likely stop antibiotics in most of those settings.

Dr Pam Peeke (Host): And finally, if a hospital does not now routinely use PCT, what's entailed in actually getting this established in the hospital as an in-hospital to be able to receive optimal and expeditious results?

Dr George Sakoulas: It essentially would require a decision from the laboratory personnel to bring in the platform, the Vidas BRAHMS platform that's FDA approved. There are other procalcitonin assays that are done, but I think they have an official FDA approval, but it would be a decision by the laboratory. A lot of those decisions are really driven by medical need requests from clinicians. Clinicians go to conferences or speak to colleagues at other hospitals that have used the tests and describe their experiences. They can go to the laboratory to see if they can bring this platform in-house and run the assay in-house.

How beneficial is it going to be? It's going to depend a lot on the type of environment. I think if you're in an academic setting, you have physicians, they're rounding, you have an intern, a resident, a fellow, attending at each step of the way, challenging does the patient need antibiotics? Does the patient need antibiotics? There's more of a drive to stop antibiotics or, in that setting, bringing in a procalcitonin test. It may not necessarily make as much of an impact as opposed to a private hospital where a physician has to round on 20 patients and, at each moment, he or she rounds from patient to patient. The status quo of continuing antibiotics and onto the next patient. If you have a procalcitonin test, it tells you can stop, it might be a little more helpful in that setting. So if you decide to bring it in, it can make a different impact depending on what setting you're in.

Dr Pam Peeke (Host): Excellent. Dr. Sakoulas, we thank you so much for being our expert on this topic today. And everyone, this concludes another addition of the Society of Critical Care Medicine podcast. For the Society of Critical Care Medicine podcast, I'm Dr. Pam Peeke.

Biomerieux: This podcast is sponsored by bioMérieux. In cases of acute community-acquired pneumonia, patients are frequently treated with empiric broad-spectrum antimicrobial therapy while awaiting diagnostic results. This can lead to overuse of antimicrobials. Diagnostic solutions from bioMérieux provide fast pathogen identification and support effective antimicrobial therapy management through innovative biomarker detection. Learn more about these solutions from the leader in infectious disease diagnostics at biomerieux.com

Dr Pam Peeke Bio: Pamela M. Peeke, MD, MPH, FACP, FACSM is a nationally renowned physician scientist, expert, and thought leader in the field of medicine. Dr. Peeke is a Pew Foundation scholar in nutrition and metabolism, and Assistant Professor of Medicine at the University of Maryland. She holds dual master's degrees in Public Health and Policy, and is a fellow of both the American College of Physicians and American College of Sports Medicine.

Dr. Peeke has been named one of America's top physicians by the Consumers Research Council of America. She is a regular in-studio medical commentator for the National Networks and an acclaimed TEDx presenter and national keynote speaker. Dr. Peeke is a three-time New York Times bestselling author and is a science and health advisor for Apple.

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