Latest / The SHEA Podcast / The Promise and Pitfalls of Procalcitonin (PCT) in Antimicrobial Stewardship

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The Promise and Pitfalls of Procalcitonin (PCT) in Antimicrobial Stewardship · The SHEA Podcast

• 0:03
  SPEAKER_02: Welcome to another episode of the SHA podcast.
• 0:07
  SPEAKER_02: My name is Dr.
• 0:08
  SPEAKER_02: Jonathan Ryder, and I am an assistant professor at the University of Nebraska Medical Center Division of Infectious Diseases and Associate Medical Director for the Antimicrobial Stewardship Program and the Infection Control and Epidemiology Program in Nebraska Medicine.
• 0:22
  SPEAKER_02: As a member of the SHAY Antimicrobial Stewardship Committee, I will be serving as today's host and moderator.
• 0:29
  SPEAKER_02: And I'm pleased today to present a little bit of a unique format where we're going to do a little bit of a pro-con-friendly debate via podcast on the topic of procalcitonin, which is an often discussed and contentious topic that leads to much debate.
• 0:47
  SPEAKER_02: And on the pro side today is Dr.
• 0:49
  SPEAKER_02: Michael Mansoor, who is an associate professor of medicine at Harvard Medical School, and in the Division of Infectious Diseases at Massachusetts General Hospital.
• 0:59
  SPEAKER_02: And representing the con side today is Dr.
• 1:01
  SPEAKER_02: Sheena Kandaya, and she is a senior physician and professor of medicine at the Emory University School of Medicine, in the Department of Medicine, the Division of Infectious Diseases at Emory University Hospital, and the director of the antimicrobial stewardship program at Grady Hospital.
• 1:19
  SPEAKER_02: So welcome, Drs.
• 1:20
  SPEAKER_02: Mansoor and Kandaya, and thanks for joining us today as we will start thinking about how procalcitonin plays a role or doesn't in antimicrobial stewardship programs.
• 1:30
  SPEAKER_02: And I'm looking forward to hearing your opinions on this topic today.
• 1:34
  SPEAKER_02: So we're gonna first start off with Dr.
• 1:37
  SPEAKER_02: Mansur.
• 1:38
  SPEAKER_02: And I just want you to kind of describe uh procalcitonin and its role as a diagnostic test, including how it works.
• 1:46
  SPEAKER_00: Great.
• 1:47
  SPEAKER_00: Thank you, Jonathan.
• 1:48
  SPEAKER_00: And it's uh it's a real pleasure to um have this exciting, friendly debate about PCT, procalcitonin.
• 1:56
  SPEAKER_00: Procalcitonin, just as a as a background, just to set the stage for us, is a pro-hormone molecule.
• 2:06
  SPEAKER_00: It's the precursor to mature calcitonin, which really regulates calcium homeostasis.
• 2:12
  SPEAKER_00: Uh, what was found is that the conversion, the cleavage of this propeptide to mature calcitonin happens to be exquisitely sensitive to inflammatory markers and inflammatory mediators.
• 2:26
  SPEAKER_00: So, in this setting of infection and inflammation, you can see a rise in pro-inflammatory cytokines, which actually inhibit this conversion, this cleavage of the propeptide.
• 2:39
  SPEAKER_00: And therefore, you see resulting elevations of pro-calcitonin, which can be measured quite accurately with antibodies directed at the molecule.
• 2:49
  SPEAKER_00: So, in that setting, there's been the initial outset of you know, bacterial infections resulting in specific cytokines will inhibit this conversion, whereas viral infections do not.
• 3:04
  SPEAKER_00: And there begins the initial birth of this debate of PCT being more specific for bacterial mediated inflammation versus viral.
• 3:15
  SPEAKER_02: Dr.
• 3:16
  SPEAKER_02: Kandaya, anything to add to Dr.
• 3:18
  SPEAKER_02: Mansur's description about procalcetonin in in general?
• 3:22
  SPEAKER_01: So, firstly, thank you for having me on.
• 3:24
  SPEAKER_01: I'm I'm excited to talk about this.
• 3:26
  SPEAKER_01: I've had the opportunity to work with Dr.
• 3:28
  SPEAKER_01: Mansor in the past and just around the topic of procalcitonin.
• 3:32
  SPEAKER_01: So this is a really good is is a fun debate for me.
• 3:35
  SPEAKER_01: I obviously don't have anything to add to the physiology of um procalcitonin and how it works, but I think one of your questions was, you know, as a diagnostic test, what's the role of procalcitonin?
• 3:46
  SPEAKER_01: And really at this point, multiple organizations, including the ATS, IDSA, and surviving sepsis, suggest that there's insufficient data to recommend procalcitonin as a diagnostic test.
• 3:57
  SPEAKER_01: It certainly does.
• 3:58
  SPEAKER_01: I agree with Michael, it correlates with bacterial infection when it does rise, rise, but it still does not necessarily justify initial starting of antibiotics and stresses the importance of clinical judgment and not withholding antibiotics, meaning if it's low and a patient appears ill, then it is appropriate to initiate antibiotic therapy.
• 4:18
  SPEAKER_01: It also has not shown benefit in mortality, ICU, or hospital length of stay when procalcitonin has been used to, as a diagnostic test, to use for antibiotic initiation.
• 4:30
  SPEAKER_02: Excellent.
• 4:31
  SPEAKER_02: Let's uh let's talk a little bit more about some of the data.
• 4:34
  SPEAKER_02: So on the pro side, what does the evidence show about procalcitonin guided therapy regarding reducing antibiotic use or improving outcomes?
• 4:44
  SPEAKER_02: And for what syndromes and conditions has it best been studied?
• 4:49
  SPEAKER_00: That's a great question.
• 4:50
  SPEAKER_00: And I think what Sheena just said really highlights some key aspects of our approach to procalcytonin.
• 4:58
  SPEAKER_00: So let's let's just step back and just go back to the basic biology of PCT.
• 5:06
  SPEAKER_00: PCT rises quickly in the setting of inflammatory cytokines that seem to be specific to bacteria versus virus.
• 5:14
  SPEAKER_00: Sheen is correct that when you look at PCT and that rise in the setting of inflammation, if you apply this diagnostic in the setting of antibiotic initiation versus antibiotic cessation, there is a clear clinical experience that separates the two.
• 5:37
  SPEAKER_00: So Sheena's correct that using it to initiate antibiotics, which has been studied extensively, does not seem to provide adequate guidance, meaning that if someone appears ill, if our patients appear ill, we all agree we probably should really just initiate antimicrobial therapy.
• 5:58
  SPEAKER_00: I think where PCT shines and where the strongest data sits is on the other side, is antibiotic cessation.
• 6:07
  SPEAKER_00: So once our patients have been started on therapy, and the question is when do we stop?
• 6:13
  SPEAKER_00: When can we stop earlier?
• 6:15
  SPEAKER_00: This is where the majority of the trials starting from the beginning with the major study, the pro hosp study, which was a multi-center Swiss study that was in JAMA 2009, since then repeated many times in multiple European studies and studied at Cochrane level meta-analyses, all have shown positive impact in reducing antibiotic usage or cessation.
• 6:42
  SPEAKER_00: So that's really where PCT has landed in terms, you know, in my opinion, as a major player in the field, it's stopping antibiotics, not initiating.
• 6:54
  SPEAKER_00: So that's where the majority of the data exists for its for its usage.
• 6:58
  SPEAKER_00: And I will say in most European medical centers that do use PCT, they're using it as guidance for cessation.
• 7:07
  SPEAKER_00: Uh, and that's that's the the main the main impact PCT has had.
• 7:12
  SPEAKER_02: Great.
• 7:12
  SPEAKER_02: That's an excellent overview.
• 7:14
  SPEAKER_02: All right, Dr.
• 7:14
  SPEAKER_02: Kandya.
• 7:15
  SPEAKER_02: Do you do you find this evidence convincing or are there some limitations or maybe more neutral findings that uh that concern you?
• 7:23
  SPEAKER_01: It's tough, especially when you read these studies.
• 7:25
  SPEAKER_01: Some of these studies can be super compelling and and really kind of push you in one direction or the other.
• 7:30
  SPEAKER_01: But I think probably the those the thing that I probably one of my biggest resources is actually a Cochrane review that actually looked at procalcitonin in acute respiratory tract infections between 2017 and 2020.
• 7:45
  SPEAKER_01: And they looked at 26 trials, upwards of six over 6,000 participants in 12 different countries.
• 7:50
  SPEAKER_01: And the in and really the review showed that there was decreased mortality, decrease in antibiotic use by two and a half days.
• 7:58
  SPEAKER_01: There was no change in hospit, hospital or ICU related length of stay.
• 8:02
  SPEAKER_01: But I think the biggest limitations as as like kind of drawn from this Cochrane review were that the studies were all done very differently.
• 8:13
  SPEAKER_01: There's a fair amount of bias related to blinding or not blinding, more importantly.
• 8:18
  SPEAKER_01: So I think that you know, I think it's about how you sort of look at the data and the reliability of the data.
• 8:24
  SPEAKER_01: Um, I think the biggest thing that I sort of took from it is that the data was not necessarily generalizable to as they excluded immunocompromised patients and there was exclusion of certain organisms.
• 8:35
  SPEAKER_01: And on top of that, there are, you know, other other factors that can also lead to potential false positives.
• 8:41
  SPEAKER_01: So, you know, I don't I as as I think that the there's also very good data, I also think there's some significant limitations to the data that exists.
• 8:50
  SPEAKER_02: Yeah, absolutely.
• 8:51
  SPEAKER_02: I think it's always important to be a little bit critical of data, even even when it's uh fairly robust.
• 8:57
  SPEAKER_02: So Dr.
• 8:58
  SPEAKER_02: Mansoor, procalcitonin is often claimed to be able to differentiate between bacterial and viral infections.
• 9:05
  SPEAKER_02: Is that a is that true?
• 9:07
  SPEAKER_02: And how does the test perform in in that particular capacity?
• 9:11
  SPEAKER_00: That's a great question.
• 9:13
  SPEAKER_00: And obviously the the different classes of pathogens that we tend to deal with, or respiratory infections specifically, but also in those responsible for you know sepsis and septic shock, have uh a different stimulatory capacity.
• 9:30
  SPEAKER_00: So um I'm also an immunologist, and so when we think about our host immune response to the different decorations and epitopes, antigens on gram positives versus gram negatives versus virus, viral pathogens, they really are quite different, and the pathways being stimulated are quite different.
• 9:55
  SPEAKER_00: So, therefore, it's it's not really a surprise that you can see different elevations of PCT under the influence of the mixture and the combinations of cytokines elicited when our host immune response encounters these different types of pathogens.
• 10:15
  SPEAKER_00: So, from that perspective, there is a clinical difference in the rise of procalcitonin when you encounter different pathogens.
• 10:25
  SPEAKER_00: And that's been really borne out in several studies, where one can almost use the PCT level in a sense to predict what pathogen is being encountered by that host immune response.
• 10:41
  SPEAKER_00: So some of the more inflammatory uh bacterial pathogens include, you know, uh strep species, some of the less inflammatory ones for reasons that we can really get into when it comes down to molecular mechanisms of immune response, happen to be gram negatives like Pseudomonas.
• 11:02
  SPEAKER_00: And so there are studies that show variable different PCT levels as one encounters these different pathogens.
• 11:11
  SPEAKER_00: So there, so the the point is we're on a spectrum.
• 11:14
  SPEAKER_00: We're on a spectrum of stimulation, we're on a spectrum of PCT elevations.
• 11:20
  SPEAKER_00: Um, cutoffs have been drawn based on diagnostic performance.
• 11:25
  SPEAKER_00: That said, if you encounter one or the other, you may see differences in general.
• 11:32
  SPEAKER_00: If you are a gram-negative, gram-positive pathogen, you will definitely rise or increase PCT to a higher degree compared to a viral pathogen.
• 11:43
  SPEAKER_00: But there are exceptions that exist in both camps.
• 11:47
  SPEAKER_00: Um, one of the you know more famous ones is SARS-CoV-2.
• 11:52
  SPEAKER_00: SARS-CoV-2, when advanced in disease, will increase PCT.
• 11:59
  SPEAKER_00: Um, and so we we know COVID can do this.
• 12:02
  SPEAKER_00: There's also some evidence some of the pair influences can do this.
• 12:06
  SPEAKER_00: So there are examples on both sides where this rule, so to speak, is you know, is sort of violated.
• 12:14
  SPEAKER_00: But in general, if we take this diagnostic and we fit that into our approach to the patient, coupled with our clinical assessment, that's where you know, uh in a in a very sensible way, PCT should live in our mind.
• 12:30
  SPEAKER_00: It's not a standalone, it's not going to replace clinical assessment or judgment.
• 12:37
  SPEAKER_00: It's an adjunct.
• 12:38
  SPEAKER_00: It's another tool in our toolkit.
• 12:41
  SPEAKER_00: And we should always remember that we're couching it within the clinical assessment of the patient and all other diagnostics we have available to us.
• 12:50
  SPEAKER_02: That's a really nuanced approach, I think, to that complicated question that I think we oftentimes simplify and provides really great context.
• 12:58
  SPEAKER_02: Thank you.
• 12:59
  SPEAKER_02: So on the other side of this, uh, critics kind of point out that procalcitonin lacks some specificity, and this is because levels can rise for reasons that are unrelated to infection.
• 13:11
  SPEAKER_02: So, Dr.
• 13:12
  SPEAKER_02: Candia, what are some of these reasons for false positives and how can we carefully interpret results in in these settings?
• 13:20
  SPEAKER_01: Yeah, so this is where I find it most challenging, especially at Grady, which is my institution, which is a level one trauma center.
• 13:27
  SPEAKER_01: It's also a burn center.
• 13:29
  SPEAKER_01: I think the most relevant ones are trauma, surgery, um, and burns, and then renal insufficiency by itself.
• 13:37
  SPEAKER_01: And there is there is some evidence that it rises in cardiogenic shocks, severe heart failure.
• 13:43
  SPEAKER_01: Um, and as Michael mentioned, COVID-19, so even influenza, severe influenza, it can also rise.
• 13:51
  SPEAKER_01: Um, so there's even some data that with metabolic syndrome and obesity that people have chronically low-level elevated procalcitonins, likely related to inflammation, as Michael actually mentioned.
• 14:02
  SPEAKER_01: So, you know, it's difficult when you're educating um your clinical staff on how to use procalcitonin, where you're going to say, this is how it's used, this is how you should interpret it.
• 14:12
  SPEAKER_01: But, you know, only in these populations, you know, don't worry about your trauma population, don't worry about your burn population, just think about the ones that are, you know, that that sort of don't have conditions that could potentially um create a false positive situation.
• 14:26
  SPEAKER_01: And that makes it challenging for implementation.
• 14:30
  SPEAKER_01: But um, I don't, when you say how can we carefully interpret those results, I'm not sure how to interpret those results necessarily in that population, other than to really just utilize clinical judgment.
• 14:42
  SPEAKER_02: Yeah, totally agree.
• 14:43
  SPEAKER_02: I have the same experience uh trying to trying to better understand what to do in those circumstances can be challenging.
• 14:50
  SPEAKER_02: How do we uh how do we go about interpreting procalcitonin levels over time when we're managing our our patients, Dr.
• 14:58
  SPEAKER_02: Mansur?
• 15:00
  SPEAKER_00: I think all the points that Sheena just made are you know are so good.
• 15:04
  SPEAKER_00: And you know, Jonathan, you're reflecting on your own personal uh practice when it when it comes to use of PCT.
• 15:13
  SPEAKER_00: I think PCT is a you know it's a personalized diagnostic in a sense, and it really requires careful stewardship.
• 15:20
  SPEAKER_00: Like all new diagnostics, um pro BMP for heart failure went through this, even troponins went through this in the in the in their beginnings.
• 15:30
  SPEAKER_00: There is there is a you know like a struggle of where do I where do I put this diagnostic marker, which definitely has benefit.
• 15:42
  SPEAKER_00: It's just a matter of trying to find the correct setting, the appropriate population to apply it to.
• 15:49
  SPEAKER_00: And I think you know, I I do a lot of transplant ID and we struggle a lot with beta D glucan, galactomanin, and other fungal markers.
• 15:57
  SPEAKER_00: Uh, when ordered haphazardly, you it just causes absolute pure confusion and honestly waste, waste of money.
• 16:06
  SPEAKER_00: Uh, so PCT is not you know um free of these pressures and these sort of variables.
• 16:14
  SPEAKER_00: So, just like all other diagnostics, we have to know where to apply this diagnostic properly and into which cohort.
• 16:21
  SPEAKER_00: So, when when when you ask your very good question about how do we use it to manage our patients over time, one, let's make sure we're in the right patient population.
• 16:32
  SPEAKER_00: Um, Sheen has already highlighted some patient populations where there really hasn't been good data to apply PCT, burns and the surgeries, immune compromise patient populations, those have just not been studied well.
• 16:47
  SPEAKER_00: Of course, I think the challenge is they're PCT is being applied to all of them.
• 16:52
  SPEAKER_00: And therefore, we get confusing results and then subsequent frustration with the diagnostic because it doesn't help yield um clear management guidance.
• 17:02
  SPEAKER_00: But if we remove those patients and really stick to our, by all accounts, an incompetent patient population with community acquired pneumonia, for example, if we stick to that population, PCT measured over time when it decays, and you've and we've addressed that pathogen and that infection appropriately with treatment, you'll reduce inflammation, you'll see a decay of procalcitonin, which happens at a very predictable about every 24 hours, you'll see a halving of that PCT level.
• 17:39
  SPEAKER_00: And that will inform us that we are now approaching a point where we can stop antibiotic treatment.
• 17:46
  SPEAKER_00: And when you do it that way and you study it in that scenario, you see great benefit.
• 17:53
  SPEAKER_00: And we've recently done a randomized controlled trial looking at that in US hospitals, and we saw exactly that.
• 18:01
  SPEAKER_00: We saw a nearly two full day reduction in antibiotic duration with no ill effect from a safety perspective.
• 18:11
  SPEAKER_00: So when done properly, it really has benefit.
• 18:14
  SPEAKER_00: But I think practically, and maybe we'll talk about some of these challenges, you unleash it into a hospital system, and then it's being ordered and applied to probably inappropriate patient populations or scenarios or infections or inflammatory disorders.
• 18:31
  SPEAKER_00: And I think that's that creates a lot of confusion.
• 18:34
  SPEAKER_02: Definitely.
• 18:35
  SPEAKER_02: And I think Dr.
• 18:36
  SPEAKER_02: Kandaya is going to talk to us a little bit about what are what are some of these common pitfalls that that uh clinicians run into and where do they kind of go wrong with with trend interpretation?
• 18:48
  SPEAKER_01: Yeah, so I think one of the most important things is there's no really standardized approach or algorithm to, you know, that's that's generalizable across um the country.
• 18:57
  SPEAKER_01: As I mentioned earlier, a lot of the studies that were done use different sort of interpretive criteria.
• 19:03
  SPEAKER_01: It's very difficult to sort of um understand which is the best for the particular institution.
• 19:09
  SPEAKER_01: Secondly, clinicians need to understand the algorithm.
• 19:12
  SPEAKER_01: And I think that's where we probably, uh at least at my institution, run into a lot of problems.
• 19:17
  SPEAKER_01: As we all know, when you're educating and educating a large, you know, population of clinicians who are rotating from hospital to hospital where you know different algorithms exist in different places, that can also be a challenge.
• 19:29
  SPEAKER_01: There's also they need to be educated not just on how to use it, but how when not to use it, as Michael actually alluded to.
• 19:36
  SPEAKER_01: Um, and I think again, making sure that people know those that information can be a challenge.
• 19:42
  SPEAKER_01: And we we certainly can rely a little bit more on the EHR and some of the clinical decision support in EHRs to do that.
• 19:50
  SPEAKER_01: But as we all know, there's alert fatigue and other reasons that that creates a little bit of a barrier as well.
• 19:56
  SPEAKER_01: So the other concern is also that I have found that some of the clinicians will do the opposite, where they have a condition such as, let's say, acute renal failure, where the procalcitonin remains elevated for longer than than it would if with normal kidney function, and I get, well, the procalcitonin was still high, so I continued antibiotics.
• 20:17
  SPEAKER_01: So that can also, again, goes back to how you interpret it, how you understand it, and getting that education in effectively can be a challenge by itself.
• 20:27
  SPEAKER_02: Certainly.
• 20:28
  SPEAKER_02: So uh one of the more commonly used uh scenarios for procalcitonin is is the syndrome of sepsis.
• 20:36
  SPEAKER_02: And so, what what is the utility of of procalcitonin and sepsis and and where do we see that being useful?
• 20:46
  SPEAKER_00: So so sepsis is the the other sort of large uh syndrome that has been studied well with PCT.
• 20:55
  SPEAKER_00: Uh the first one being lower respiratory tract infections.
• 20:59
  SPEAKER_00: So these these two have been the most heavily studied, and you will encounter the largest number of studies looking at PCT in these two areas.
• 21:08
  SPEAKER_00: In sepsis, again, it's a I'll to boil it down, I I see that it's a very similar story to lower respiratory tract infections where initiation has not really been very fruitful, but antibiotic cessation again comes through as a very useful area for PCT guidance.
• 21:29
  SPEAKER_00: And so in sepsis, people will use that decay of procalcitonin as an as an indirect measure of pathogen control um and source control.
• 21:41
  SPEAKER_00: And so when that happens and you've really removed that stimulatory burden of pathogen from the patient using using antimicrobial treatment, you will then see a subsequent decline in PCT.
• 21:57
  SPEAKER_00: And so when we wonder how long The antibiotic therapy should go.
• 22:02
  SPEAKER_00: PCT guidance and multiple studies has demonstrated a safe reduction in the total duration of antibiotic therapy when we're looking at the septic patient cohort.
• 22:15
  SPEAKER_00: So that's really where it's been shown.
• 22:18
  SPEAKER_00: There's also a good set of data that suggests that initial PCT can also serve as a prognostic indicator.
• 22:33
  SPEAKER_00: The higher the PCT, the likely higher burden of pathogen, more immune stimulation, more cytokine, more PCT.
• 22:41
  SPEAKER_00: So immunologically, it makes sense why an elevated level early in the diagnosis of sepsis can also give you a sense of prognosis.
• 22:53
  SPEAKER_02: Great.
• 22:53
  SPEAKER_02: So uh Dr.
• 22:54
  SPEAKER_02: Candia, are there are there some limitations or areas where procalcitonin may be kind of misused or misinterpreted in sepsis, um, especially around antibiotic use?
• 23:08
  SPEAKER_01: Yeah, so sepsis is a very special topic to my heart.
• 23:11
  SPEAKER_01: I actually chair the sepsis committee at our institution as well.
• 23:14
  SPEAKER_01: And, you know, procalcitonin has come back, come up as a topic in the past as part of whether it's appropriate to include it as part of your initial sort of workup for sepsis.
• 23:24
  SPEAKER_01: And you know, the concern that I would have really is that in early sepsis, there's data that that it's actually negative, it may not be high early in sepsis, um, giving people sort of a false sense of security if they're using it as a diagnostic test, um, which, you know, there are other things that we use for diagnostics for sepsis, but um I'm I'm concerned, I'm concerned when people see that low procalcitonin that they decide that they want to actually, you know, stop antibiotics or or call it not sepsis, because as we all know, sepsis is a spectrum.
• 23:55
  SPEAKER_01: Um so, you know, I have concerns about it, um, at least in early sepsis.
• 24:01
  SPEAKER_01: And then on top of that, there was a paper that was published, a small paper in April of 2025, um, which showed procalcitonin levels can be elevated in both non-septic and septic critically ill patients in the setting of acute kidney injury or or SH renal disease.
• 24:17
  SPEAKER_01: So it does, it makes me uncomfortable to know that it doesn't necessarily effectively distinguish sepsis from non-sepsis critically ill.
• 24:25
  SPEAKER_01: So again, it gets to the um question of are we using it correctly?
• 24:31
  SPEAKER_01: It was a small retrospective study, but it does, I think, raise some red flags.
• 24:36
  SPEAKER_01: I think ultimately procastotonin, it demonstrates moderate discrimination for bacteria and sepsis with the sensitivity and specific specificity for sepsis that it has of about 77% and 79%, respectively.
• 24:50
  SPEAKER_01: But again, it's highly variable by pathogen, infection source, and patient acuity.
• 24:56
  SPEAKER_01: So just things to think about as we as we use it.
• 24:59
  SPEAKER_02: Awesome.
• 25:00
  SPEAKER_02: So uh Dr.
• 25:01
  SPEAKER_02: Mansoor has already talked about this a little bit with lower respiratory tract, but just more specifically, what what is our utility that we can use procalcitonin for uh pneumonia, lower respiratory tract infections, and and in what setting should we you know implement this or or will we find it useful?
• 25:20
  SPEAKER_00: Uh yeah, so as as um as we've mentioned, I I think if again applied properly um to communicate acquired pneumonia um and other lower respiratory tract infections, with the exceptions of bronchitis or COPD, where there really isn't enough invasiveness to make PCT useful in that from that point of view.
• 25:44
  SPEAKER_00: Um it's not about initiation.
• 25:46
  SPEAKER_00: And I, you know, hope my messaging is clear.
• 25:49
  SPEAKER_00: And I think I'm really saying the same thing as Sheena in many ways that initiation really has not been where this biomarker has helped.
• 25:59
  SPEAKER_00: It's really about cessation.
• 26:01
  SPEAKER_00: So, again, for sepsis and for pneumonia, um, the initial decision to start treatment should be clinical.
• 26:08
  SPEAKER_00: It should be a judgment on the severity of illness in in our patients.
• 26:15
  SPEAKER_00: But if we look at duration of antibiotic, that's where that's where we really should apply it.
• 26:20
  SPEAKER_00: And that's where I would apply it for pneumonia and for sepsis is to limit duration of antibiotics, which of course, as we all know, has you know direct benefit and um reduction of a variety of nosocomial infections, resistance, evolution, etc.
• 26:37
  SPEAKER_00: And I do want to add one more thing to sepsis.
• 26:40
  SPEAKER_00: This is um a recent study that was published in JAMA just this year called the Adapt Sepsis trial.
• 26:48
  SPEAKER_00: Um, and and here again, there was a random, it's a randomized study looking at antibiotic duration.
• 26:54
  SPEAKER_00: Again, it's duration, not initiation.
• 26:56
  SPEAKER_00: And they looked at two two biomarkers, PCT and CRP, to help with guidance.
• 27:02
  SPEAKER_00: And in the adapt sepsis trial, which was just published not too long ago, um, there was a significant reduction of antibiotic usage in the PCT guided arm that showed really complete safety.
• 27:17
  SPEAKER_00: There was no safety signal there.
• 27:19
  SPEAKER_00: But CRP, another nonspecific inflammatory marker we all know, um, was unable to provide that guidance.
• 27:27
  SPEAKER_00: So it's not just an indirect measure of inflammation.
• 27:33
  SPEAKER_00: There is a specificity to PCT that adds to an ESR or a CRP type general inflammatory marker.
• 27:43
  SPEAKER_00: There's a that specificity of cytokine production in response to these pathogens is really informing us about what our patients are undergoing from a pathophysiology perspective.
• 27:58
  SPEAKER_00: And when we apply that that characteristic of this diagnostic, we really do see benefit.
• 28:05
  SPEAKER_00: Um, and I and I see that over and over in both the pneumonia and the and the septic shock population.
• 28:12
  SPEAKER_02: Absolutely.
• 28:12
  SPEAKER_02: I think we can all use uh tools to help reduce antibiotic use.
• 28:17
  SPEAKER_02: So Dr.
• 28:18
  SPEAKER_02: Kandaya, the question about pneumonia and procalcitonin is is there still a role uh to use procalcitonin when we're already kind of shortening durations, especially for community acquired pneumonia now, as short as you know, three to five days.
• 28:36
  SPEAKER_02: Um, and and even HAP and VAP, we're seeing shorter durations of antibiotics than than traditionally given.
• 28:44
  SPEAKER_01: That's a great question.
• 28:45
  SPEAKER_01: Um and I think it depends on a couple of different factors.
• 28:47
  SPEAKER_01: One is your turnaround time in the institution.
• 28:50
  SPEAKER_01: Three to five, three to five days is short.
• 28:52
  SPEAKER_01: So, you know, so uh we have it in-house, we get it back fairly quickly, but if you're looking at turnaround times of 24 hours, that I think that could be I think that could be sort of cost prohibitive by the time you get the information you need.
• 29:05
  SPEAKER_01: They've sort of already reached the end of their potential potentially have reached the end of their therapy.
• 29:10
  SPEAKER_01: I will say that if an institution has a recommendation of three to five days and the patient is improving, um, I think it could actually help clinicians feel more better, more comfortable to adhere to the recommendation rather than extending beyond three to five days.
• 29:25
  SPEAKER_01: We know there are lots of clinicians who are are, you know, who have had been doing longer courses of therapy for a very long time and they're not comfortable with the three to five days, where I think proCetonin certainly could help kind of convince them that it's okay to stop antibiotics.
• 29:39
  SPEAKER_01: The problem comes when it's still elevated, even if a patient is improving where the opposite may be true, and antibiotics are unnecessarily extended.
• 29:48
  SPEAKER_01: So I actually do agree, despite the pro-con debate, that um with Michael, that I think that there is a role for antibiotic cessation, but again, with it it sort of has to be under very controlled conditions.
• 30:03
  SPEAKER_02: Yeah, that's great practical application.
• 30:05
  SPEAKER_02: So are there are there any particular scenarios that uh are outside of kind of sepsis and pneumonia in which procalcitonin's been shown to have a role, or that there's been strong evidence to support its use?
• 30:21
  SPEAKER_00: There are some uh studied areas such as uh meningitis, specifically in the pediatric population.
• 30:29
  SPEAKER_00: Um, is a it's been shown to have really good sensitivity and specificity in differentiating bacterial versus viral meningitis.
• 30:37
  SPEAKER_00: There's some evidence in septic arthritis that PCT can also help differentiate infectious versus non-infectious inflammatory causes, crystal versus bacterial septic arthritis.
• 30:52
  SPEAKER_00: And it's really been, you know, there's a smattering of studies where PCT has been applied in a variety of areas.
• 31:02
  SPEAKER_00: But outside of sepsis and pneumonia, I would say meningitis and arthritis are probably the two next well best well-studied areas.
• 31:13
  SPEAKER_02: Very interesting.
• 31:14
  SPEAKER_02: All right.
• 31:15
  SPEAKER_02: Well, many of our audience members are part of antimicrobial stewardship and diagnostic stewardship teams.
• 31:22
  SPEAKER_02: And so uh this is for you, Dr.
• 31:24
  SPEAKER_02: Mansur.
• 31:25
  SPEAKER_02: How can we best implement procalcitonin to ensure responsible antimicrobial and diagnostic testing use?
• 31:35
  SPEAKER_00: It's a fantastic question.
• 31:37
  SPEAKER_00: And I I think one we all struggle with, and you're hearing both my and Sheena's responses uh reflecting you know some of that struggle even within our within our own hospitals.
• 31:47
  SPEAKER_00: Um, I think I think I've always been struck by the discrepancy of incredibly positive studies in multiple European medical systems that are quite diverse.
• 32:01
  SPEAKER_00: And yet there's a there's a drumbeat of like positive impact benefit antibiotic reduction, which is safe, that comes from numerous studies um all across the European continent and other parts of the world.
• 32:18
  SPEAKER_00: And yet, when we turn to the United States, the studies we have here are really hit or miss, and mainly miss, you know, when it comes to how to use this biomarker.
• 32:32
  SPEAKER_00: And I'm I'm really I'm struck by the possibility that you know the real approach is all about stewardship and applying a new diagnostic to us in a very proper way.
• 32:48
  SPEAKER_00: And I and again, I I I see parallels with other diagnostics that suffer from the same problem where we're ordering and applying these uh tests to the incorrect population or incorrect scenario.
• 33:02
  SPEAKER_00: And I would say a key to this, a key answer to your very good question, is that we probably need to have more enforced diagnostic stewardship to really make the most out of procalcitonin.
• 33:18
  SPEAKER_00: And I think the there's been many examples where unleashing procalcitonin without any guidance has really shown uh no benefit, as as Sheena's reflecting in her own experience.
• 33:31
  SPEAKER_00: Um, so that's that's really where I think uh the main pitfall of the diagnostic, this diagnostic test exists.
• 33:40
  SPEAKER_00: And I think the answer is really going to be stewardship and guidance of some sort.
• 33:44
  SPEAKER_00: And I think that's that's the real debate I think we need to have is what is that guidance?
• 33:51
  SPEAKER_02: Agreed.
• 33:51
  SPEAKER_02: Uh very important for all of our novel tests that we're uh encountering.
• 33:56
  SPEAKER_02: So uh, Dr.
• 33:57
  SPEAKER_02: Kendaya, there is this you know known monetary cost of procalcitonin.
• 34:02
  SPEAKER_02: We've discussed the many different kinds of challenges with interpretation.
• 34:06
  SPEAKER_02: And so do you have suggestions on how we can help mitigate these things as antibiotic stewards, or should we, you know, go the route I guess some institutions have, which is to kind of just avoid the test in its entirety and not even kind of offer it, which is kind of the other sort of extreme?
• 34:24
  SPEAKER_01: That's a really hard question.
• 34:26
  SPEAKER_01: I think Michael brought up a really important point about, you know, again, making sure that there is there are protocols in existence on how to use it and how to interpret it.
• 34:36
  SPEAKER_01: Some would say that the cost benefit in stopping antibiotics, and I I would say Michael would probably say this would would be, you know, decrease in adverse effects related to antibiotics, which actually is has been shown.
• 34:47
  SPEAKER_01: Um, decreased nursing and pharmacy resources would be offset, could potentially be offset by the cost of procalcetonin, um, you know, potential decrease in length of stay with you know earlier cessation of antibiotics.
• 34:59
  SPEAKER_01: So I think there are certainly you know positives there, um, again, under very controlled conditions.
• 35:06
  SPEAKER_01: The algorithms and the protocols on how to use it are a critical piece, obviously, like any test, um, to be sure that you have clinician buy-in, um, which means that you have extensive education, which is often difficult to keep up with.
• 35:20
  SPEAKER_01: But I think that the role that I see it most useful is if there's consistent protocol adherence and antimicrobial stewardship involvement, which can be resource intensive.
• 35:29
  SPEAKER_01: So I think Michael also alluded to this about making sure that stewardship was involved, and I'm fully in support of that.
• 35:34
  SPEAKER_01: However, we still do not even really have um standardized criteria for how many pharmacists are appropriate in a in a hospital for stewardship, um, different hospitals, different resources, um, different complexities of patients that sort of are could potentially, you know, um utilize a lot of the time of our antimicrobial stewardship team.
• 35:55
  SPEAKER_01: So I think the most important sort of thing there is it could be very much resource intensive.
• 36:00
  SPEAKER_01: Um, there are guardrails for this test, which we've talked about earlier in the podcast, which really challenge effective implementation.
• 36:07
  SPEAKER_01: I think that answer to that question makes it very facility dependent.
• 36:13
  SPEAKER_02: Yeah, it seems like a common theme here is that uh stewardship guidance is absolutely essential when using this test.
• 36:22
  SPEAKER_02: Um Dr.
• 36:24
  SPEAKER_02: Mantour, can you give some examples of how stewardship programs are incorporating procalcitonin into their protocols or how they're monitoring use and kind of some success stories?
• 36:38
  SPEAKER_00: Yeah, for sure.
• 36:39
  SPEAKER_00: Um there's um I think it really relates to the um acuity of your patient population, size of your medical center.
• 36:48
  SPEAKER_00: So I can speak really from a variety of sizes of hospital systems, and say, in general, what I've seen is challenges in the larger medical center system is that as Sheena just uh touched on, there is a maybe an insufficient number of stewardship bodies and staffing to really steward all these, all these diagnostics, plus the uh additional antimicrobial oversight that needs to be that needs to be uh performed.
• 37:24
  SPEAKER_00: And so it really becomes a people power issue uh in a larger hospital system.
• 37:30
  SPEAKER_00: And so to address that, many have tried basic guidance that will come up as pop-up windows in your ordering system.
• 37:41
  SPEAKER_00: So if you go to order procalcitonin, you'll be flagged with informational guidance, you know, to maybe prompt you to think about is this the right patient?
• 37:54
  SPEAKER_00: Often with the result of the PCT value.
• 37:58
  SPEAKER_00: People have put in more guidance uh as part of that uh result to help you understand what this value actually means and how to use this value properly.
• 38:09
  SPEAKER_00: And I'd say in general, those have been insufficient guardrails, uh, to use Sheena's words.
• 38:17
  SPEAKER_00: Those really have been insufficient, and I think they're insufficient for many of our diagnostics.
• 38:22
  SPEAKER_00: I think people just they're busy and they kind of blow through these guardrails, and they're not really incredibly useful.
• 38:30
  SPEAKER_00: Where it's been the most useful is the most labor-intensive, and that's been really having uh looking at smaller hospital systems, community hospital systems, where you have either infectious disease faculty guidance or a dedicated stewardship team that is at the right ratio where you can deliver either an in-person message, an email or a or a page, or there's a more of a personal touch to that hospital, hospitalist team or that hospitalist caring for that patient, and you're specifically speaking about that patient.
• 39:09
  SPEAKER_00: And I think that's where the most impact has been had.
• 39:14
  SPEAKER_00: Now that's not really realistic in our large hospital systems, and as we all feel more and more pressures uh for delivering efficient care, I think those types of things become more difficult, even though they've they really seem to be the best.
• 39:28
  SPEAKER_00: And that's where new concepts, AI-based concepts or other electronic or web-based modalities, may maybe um could maybe fulfill these unmet needs and provide that guidance and maybe offload the work that a stewardship team would need to take on.
• 39:50
  SPEAKER_00: Um and I'm excited to see what those areas will come to show us uh in terms of solutions.
• 39:57
  SPEAKER_02: Yeah, those definitely sound like exciting opportunities.
• 40:00
  SPEAKER_02: So, Dr.
• 40:00
  SPEAKER_02: Kandia, where do you see kind of programs that are trying to implement this run into trouble and the the major barriers that they've had in implementation and tracking of procalcetonin?
• 40:12
  SPEAKER_01: Yeah, so just a couple would be limited test availability, um, protocol variability, inconsistent clinical adherence, um, and a lot of uncertainty about optimal monitoring and cutoff cutoffs.
• 40:25
  SPEAKER_01: There's a lot of heterogeneity in procalcytonin guided algorithms in clinical practice, and I think that lack of standardization makes it difficult to compare outcomes.
• 40:35
  SPEAKER_01: Um as Michael mentioned, some of the studies in the US have not been have not really been fruitful in giving us a really robust recommendation that this is great and this we should totally use this.
• 40:46
  SPEAKER_01: Um, but there has been sort of some low-level recommendations that it could be useful.
• 40:50
  SPEAKER_01: Um, so even research by itself can be can be challenging to interpret when you're trying to implement and develop a tracking system for this.
• 40:59
  SPEAKER_01: But clinical adherence, like everything in stewardship, is a whole other challenge.
• 41:03
  SPEAKER_01: Um, we struggle with clinician adherence to institutional stewardship protocols.
• 41:07
  SPEAKER_01: So coordination, education, buy-in means resources, going back to that again.
• 41:12
  SPEAKER_01: And um, where variability itself also exists on stewardship staffing, it can make it complicated.
• 41:18
  SPEAKER_01: Um, I also think that clinicians develop sort of a belief system of that's pretty black and white, either they believe in it or they don't.
• 41:25
  SPEAKER_01: And um, because the evidence is not, you know, super robust, it can make it challenging in the clinical setting where one person feels like it's great and the other person does not really like to use it.
• 41:37
  SPEAKER_01: Um, so there's just so much inconsistency that I think that until we can sort of have a consistent messaging um system, it it there will continue to be challenges.
• 41:49
  SPEAKER_02: All right.
• 41:50
  SPEAKER_02: Well, next question that we have is really about prescriber behavior.
• 41:54
  SPEAKER_02: So, Dr.
• 41:55
  SPEAKER_02: Mansour, do we do we think that procalcitonin can change prescriber behavior when it comes to antibiotic decisions?
• 42:03
  SPEAKER_00: It's a really interesting question, Jonathan.
• 42:05
  SPEAKER_00: I you know, I'll I'm reflecting a little bit on personal uh research experience.
• 42:11
  SPEAKER_00: We've recently finished a randomized uh controlled trial looking at um PCT guided usage um for antibiotic cessation in patients with pneumonia.
• 42:24
  SPEAKER_00: Uh Sheena was a site PI at Grady for this study.
• 42:30
  SPEAKER_00: Our study basically showed, as I had mentioned, a two-day reduction in antibiotic usage.
• 42:36
  SPEAKER_00: Uh, what was interesting here is that we used the same protocol trial design as PROACT, which was a negative study published in 2018 in the New England Journal of Medicine, showing in US-based hospitals there was no difference.
• 42:55
  SPEAKER_00: The key differentiator between PROACT and our study, ProSave, which will hopefully be published soon, is that we placed the PCT values in antibiotic stewardship hands, and they provided the recommendation uh to the hospitalist team.
• 43:15
  SPEAKER_00: It was interesting to see that depending on the team structure, we had different concordance rates and protocol adherence to that to that advice.
• 43:26
  SPEAKER_00: And that really began to reflect a little bit about prescriber behavior and team structure, and began to maybe shed some light on how we mentally sort of socially approach decision making in our hospital systems.
• 43:46
  SPEAKER_00: And that really seems to correlate with what kind of uh structures we build to care for our patients.
• 43:54
  SPEAKER_00: So, on a more granular level, here at Mass General, we have several team structures.
• 44:00
  SPEAKER_00: We have our very traditional hospice run services, or a hospice with one or two residents, or this kind of collective thought process where there's two attendings and five residents.
• 44:14
  SPEAKER_00: So and every decision is made as a team, as a full collective team.
• 44:19
  SPEAKER_00: And it's no one, no one's individual decision that will change that patient's management.
• 44:27
  SPEAKER_00: And when we measured the concordance and the protocol adherence amongst these three, it was the team structure which had the highest concordance.
• 44:37
  SPEAKER_00: So we're I've been thinking more about that and how to study that.
• 44:42
  SPEAKER_00: And is that a means to implement a better diagnostic approach to managing not just pneumonia but many other, many other diseases?
• 44:54
  SPEAKER_00: And is team structure something that will help us deliver more homogeneous, consistent care because there's a because there's that kind of collective thought process.
• 45:07
  SPEAKER_00: So just a little um insight into just our busy lives and how we approach patients.
• 45:15
  SPEAKER_00: And maybe you by yourself making decisions versus having colleagues to brainstorm, bounce ideas off.
• 45:24
  SPEAKER_00: Maybe all that changes, you know, really how we've make our final decisions on management.
• 45:30
  SPEAKER_00: Um and so that that's this study has maybe shed a little bit more light on team structure and sort of the uh this the social structure of medicine and how we deliver care, which has been pretty interesting.
• 45:44
  SPEAKER_02: That's absolutely uh fascinating and uh I think an area of stewardship that we're increasingly finding um to be a really important aspect of uh decision making.
• 45:55
  SPEAKER_02: So Dr.
• 45:56
  SPEAKER_02: Kandaya, do you do you think that uh from what you've seen that you know clinicians may rely more on their kind of intuition or their experience um than lab values when approaching antibiotic use and procalcitonin?
• 46:11
  SPEAKER_01: Yeah, so I think the best time to incorporate a test into clinical practice is at the trainee level, um, you know, because it sort of becomes almost muscle memory that this is the way that you're supposed to use it, this is how you're supposed to use it with trainees.
• 46:23
  SPEAKER_01: But I think with older clinicians who don't have, you know, um, who don't have experience with the test, who are sort of relying on data, um, but you know, they've had a lot more experience making decisions and they can do it without an ejective test quite confidently.
• 46:38
  SPEAKER_01: And I feel like those people will continue to do that way.
• 46:40
  SPEAKER_01: Um, I think it's very difficult to change that behavior, like, you know, as people, you know, move farther in their career.
• 46:47
  SPEAKER_01: Um, so I think that those coming out of training will probably utilize it more, whether correctly or incorrectly.
• 46:54
  SPEAKER_01: Um, so I think it is really going to depend on the clinician and the culture of the institution.
• 46:59
  SPEAKER_01: Again, uh going back again to the team structure and how involved the antimicrobial stewardship team is in using it.
• 47:06
  SPEAKER_01: Um, so I don't think there's necessarily one generalizable answer to that question, because there's many things that sort of weigh into that.
• 47:14
  SPEAKER_02: Perfect.
• 47:15
  SPEAKER_02: Absolutely.
• 47:16
  SPEAKER_02: Uh definitely there's some complicating factors in how these things uh are interacting with uh our clinicians.
• 47:23
  SPEAKER_02: So all right, to close us out, um uh Dr.
• 47:26
  SPEAKER_02: Mansur, any kind of final thoughts or advice that you would give uh when when considering the use of procalcitonin, uh in particular amongst stewardship teams that might be wanting to implement it uh in a more effective manner.
• 47:40
  SPEAKER_00: Great.
• 47:40
  SPEAKER_00: Thank you, Jonathan, for the opportunity to have this very healthy debate about this uh this biomarker.
• 47:47
  SPEAKER_00: Um I'd like to sort of conclude and say, you know, it's let's use all our diagnostics and and very specifically on today's topic, procalcitonin, in the correct cohort for the for the correct um disease management.
• 48:05
  SPEAKER_00: And I think by doing so, we can see really positive impact.
• 48:10
  SPEAKER_00: Uh, these are not small patient populations, sepsis and pneumonia account for probably a majority of the patients we admit and manage for infectious complications.
• 48:20
  SPEAKER_00: Um, and so PCT, I think, really still has a major impact in our antibiotic usage.
• 48:29
  SPEAKER_00: Uh, we're we're really targeting very large consumers of antimicrobials.
• 48:36
  SPEAKER_00: So I think there is room to move.
• 48:38
  SPEAKER_00: We just need to find the correct implementation.
• 48:41
  SPEAKER_00: And I think stewardship is the answer.
• 48:45
  SPEAKER_00: Uh, we just need to find a very more practical way to do so.
• 48:50
  SPEAKER_00: If you are in a smaller hospital, it may be a simple as simple as an email page, and maybe in your ecosystem, that's going to work to deliver interpretation of these values couched in the setting of this patient.
• 49:06
  SPEAKER_00: Uh, I think if you're in a larger hospital system, you have you have some additional challenges.
• 49:13
  SPEAKER_00: Um, and here in that in that area, you know, hopefully research in AI or team structure um or you know how we interface with stewardship and the large complexity of hospitalist teams uh is going to be really fruitful.
• 49:31
  SPEAKER_00: And I look forward to that uh that line of research uh rolling out in the future.
• 49:38
  SPEAKER_02: Excellent.
• 49:39
  SPEAKER_02: Uh and Dr.
• 49:40
  SPEAKER_02: Kandaya, what uh what kind of closing thoughts do you have and and cautions or caveats that you want to offer to similar institutions that are that are looking to implement this in different ways?
• 49:52
  SPEAKER_01: So before I answer that question, I want to just say that I'm so grateful for Dr.
• 49:56
  SPEAKER_01: Mansour, who I've had the opportunity to work with, who really made me think about think hard about procalcitonin.
• 50:02
  SPEAKER_01: Because I think when reviewing the literature, I think it's a little bit confusing to tell you the truth.
• 50:06
  SPEAKER_01: And I think he he really sort of forced me to think very hard about the role of procalcitonin um and what role it would have in my institution.
• 50:15
  SPEAKER_01: So, because of some of the clinical controversies, controversies, I think I would say there is a place for it, but the clinical scenarios must be very specific and very spelled out.
• 50:25
  SPEAKER_01: Um clinicians need to have an education, um, and to implement it would require buy-in from all areas, including the C-suite, which means justifying the cost-benefit.
• 50:35
  SPEAKER_01: Um, and finally, antimicrobial stewardship would really need to be super hands-on and making sure protocols are followed and there's good antibiotic and diagnostic stewardship.
• 50:44
  SPEAKER_01: So to conclude, I think it has its place, but I think there is a lot we need to work through and we need and and the infrastructure really needs to be present and the culture needs to buy in um to using this test.
• 50:58
  SPEAKER_01: Um, I do think that with you know evolving at uh electronic medical records with uh with you know good clinical decision support, they're becoming a lot more sophisticated.
• 51:09
  SPEAKER_01: And there may be ways to do this that can also add uh remove some of the burden from antimicrobial stewardship.
• 51:16
  SPEAKER_01: But until that happens, I'm just not sure.
• 51:18
  SPEAKER_01: I'm just not sure that it would it's it's gonna be sort of effectively implemented appropriately.
• 51:25
  SPEAKER_02: I think there's a a clear theme at the end of this podcast, which is that uh stewardship teams play an essential role in in the use of this test uh across the board.
• 51:35
  SPEAKER_02: And I think we can all agree that that's an important concept.
• 51:38
  SPEAKER_02: So I want to say thank you so much to um Dr.
• 51:41
  SPEAKER_02: Zmansur and Dr.
• 51:42
  SPEAKER_02: Kenday for sharing your perspectives and experiences today.
• 51:46
  SPEAKER_02: Um very fascinating topic, lots of nuances, um, and really brings to light some of the important aspects of antimicrobial and diagnostic stewardship uh during today's discussion and uh how we can improve patient care.
• 52:01
  SPEAKER_02: So uh want to thank you all so much.
• 52:04
  SPEAKER_01: Thank you so much for having me.
• 52:06
  SPEAKER_00: Thank you, Jonathan.
• 52:07
  SPEAKER_00: Thanks so much.
• 52:08
  SPEAKER_02: All right, that concludes this episode of the Shea Podcast, and thank you for tuning in.
• 52:12
  SPEAKER_02: We encourage you to check back for more episodes launching soon.