SPEAKER_02 0:19

Hello and welcome to Inpatient Update. I'm your host, Mason Turner, and this is your podcast for practice changing evidence for the working hospitalist. Today on the show, I'm joined by Dr. Ernest Murray, as we bring out the evidence to test two antibiotic assumptions. Do hospitalized patients with community-acquired pneumonia really need seven days or even five of antibiotics? And do we really need to tiptoe around the QTC every time we prescribe ciprofloxicin? Two common decisions, two prescribing reflexes, and two places where the evidence may push us towards a more precise approach. Let's get into it. Today on the show, I'm joined by Dr. Ernest Murray. He's a mid-career hospitalist and excellent clinician, one of the founding members and the inaugural president of our local SHM chapter, and is also just a joyful person to work around, work with, and be friends with. So thank you so much for being on the show.

SPEAKER_00 1:17

My pleasure. You're a joyful person to work around too.

SPEAKER_02 1:20

Dr. Turner. So, Dr. Murray, how often do you treat a patient for pneumonia?

SPEAKER_00 1:26

Like all the time. It's like our favorite. It's pneumonia and urinary tract infections. House of us love diagnosing those two things. If not, we're going to find it. If anyone looks weird, we're doing chest x-rays.

SPEAKER_02 1:37

So for the community acquired pneumonia, at least prior to this, did you have a hard and fast minimum duration you would give to patients?

SPEAKER_00 1:47

Yeah, I mean, uh, for the last few years, you know, basically since, you know, 2019, I think a lot of people have been going towards the five-day plan. Um, you know, I think that uh the big study that kind of supported the 2019 thing was this Spanish study that includes or I think it was initially, but mostly pushed by Lebiquin. So I was always cautious about lebequin being used as a primary agent because the half-life is so much longer. So I always write my note five to seven days, but really five days.

SPEAKER_02 2:15

Yeah, yeah, certainly. I similarly like five to seven days is what I have in my head. I'm usually, particularly if my patient's doing well, I'm happy with five days, at least until recently. So you wanna you want to tell us about the article we have here today, and then we can get more into our thoughts and how this might change our practice?

SPEAKER_00 2:32

Yeah, you know, a very interesting article that was published in the Annals of Internal Medicine that looked at using this uh target trial emulation, which is a which is a very cool retrospective kind of study that looked at community acquired pneumonia in a group of people in Michigan. And so they looked in this large uh database where they they were able to squeeze out 60 something hospitals of information over the over a course of um a few years between 2017 and 2024. And um, they were focusing on trying to figure out whether or not there was any difference between treating people for five days or treating people for three days for community acquired pneumonia. And so they looked at this kind of retrospectively using this target trial emulation, and uh their outcomes were 30-day all-cause mortality or 30-day readmission or urgent care visits, and and then specifically the antibiotic associated uh C diff. And so they they were able to squeeze out 55,000 cases uh in this uh retrospective analysis of CAP, but then they they they tailored the the the trial to look very similarly to this study, the PCT study that um uh that looked at a short course of pneumonia. So they had a very large exclusion criteria. So they were only able to get 5,000 patients or uh roughly 5,620 patients, or about 10% of that big group of population to be that the meet clinical criteria for the study. So they compared the control versus the intervention groups, where intervention groups were three to four days versus control was five plus days, and they found that ultimately that there was no significant difference between mortality, urgent visits, C diff infection, or readmissions. Some of the issues, of course, were that they could only find about um 440 patients that actually uh met the criteria for the intervention. So um, you know, we're talking about out of the 5,000 patients, you know, there's a like a basically less less than 10% uh of the patients or 7.9% of the patients were able to meet that criteria. Actually had the primary outcome. Actually had that primary they were they were actually able to to have antibiotics for three to four days um during this time. Um and so uh that kind of adds a little bit of a limitation, if you will, to this. Um and there's a lot of interesting conversations to have about this retrospective approach. Um, but uh the that's what the study shows is that that you know three to four days uh may be safe. The issue, of course, with the confidence intervals being between uh 0.1 to 2.25 may be you know a huge range there, maybe more of a factor, the fact that there only only three people died in the intervention side. And so uh that kind of perhaps blew up the um the kind of instability of the statistical analysis there, but kind of suggests something that we've seen in some earlier studies, which we can we can talk more about. But that's the result. The result is that maybe they're they're the same.

SPEAKER_02 5:41

Yeah. Yeah, I kind of see this as this is reassuring.

SPEAKER_00 5:46

Right. I agree. Like um, I think that they they saw this need, they were like looking for ways to support this idea to build the the the literature to to move towards more of a three-day thing. And I think that they they they did a fair they did a good job. They did a fair job. I mean, it's it's cool how they can just look back on this whole body of data, you know, between 2017 and 2024. Of course, the big issue, of course, is that something happened during that time, you know. Yeah, well, they excluded they excluded COVID. Yeah. They excluded a million things, obviously, or they excluded COVID, you know.

SPEAKER_02 6:21

Right. Which that was and you kind of alluded to the sort of you specifically mentioned it. But obviously, a big limitation and a big caveat of this as far as generalizability of the headline here of three days of antibiotics was just as good as longer, is like you said, only like 10% of the patients met the inclusion criteria of everyone with pneumonia in this system, only 10% didn't get excluded. And like a couple of the things they excluded for that were you know, underlying severe lung disease, immunosuppression, like pretty obvious stuff. The stuff that's but then anyone who you thought might be have a drug-resistant organism, or I guess whether they did, or if they were being treated to it. So anyone who was on, you know, Venk, cefapime, or presumably zocin, because any they said anyone who had pseudomodal coverage for two days got kicked. And so that's it's gonna cut your numbers down a lot if you're treating hospitalized patients with ammonia.

SPEAKER_00 7:19

Yeah. I mean, I I think that the interesting thing is that you know, we're trying to support that these guys were trying to support the idea that using antibiotics less is better. In 2019, these exact same guys came out with a study that showed that using antibiotics longer increased antibiotic associated side effects by five percent for every day that you do it. They these guys were gun-ho about doing that. For good for good cause, too. These are the crowns of medicine, you know. Uh, and we are afraid to hurt people, you know. They supported that with this, and I think that with the 2000 twenty-five guidelines, I think it it's opening the door for us to use antibiotics less. Looking closely at those guidelines, you know, in three days, can you really eradicate an infection in three days? And I think the answer is you're not, actually. You're not eradicating the infection, but do you need to? Right. Totally.

SPEAKER_02 8:09

Yeah. I like your point. I mean, there's in all of antibiotic treatment, we're now there's so much of a less is more push. I think before, like you say, we don't want to hurt patients, we kind of do a more is more and reflexively say, all right, everyone gets at least five days, or some people are everyone gets seven days. But this is giving us the comfort to be, okay, let's just take this patient by patient.

SPEAKER_00 8:34

Yeah, I mean, it begs the question, you know, in 2017 when they started collecting this data, who was actually doing three days for ant for CAP treatment, right? Like that was like what clinical, what clinician was doing that? And why were they doing that, right? You know, so like could you basically doing that? And that is that a you can't you can't like adjust for a clinic clinician decision making, like for that particular thing. So obviously these patients were probably a little bit more stable than your conventional patient, and or they had some other confounding thing that that made you think that that you know antibiotics wasn't too big of a deal, though they still met criteria for treatment because that was also looked at. And so, you know, when I look at that, I'm like, well, maybe these are the wrong patients. These are not my patients, you know. And I and the way how I get kind of elated that concern is that the 2025 guidelines supported, but also, you know, the first thing when you reached out to me talking about something like this, I was like, well, actually, there's data in the ICU for VAP that we can also treat for three days. So like I look at something like a change in my day-to-day management as being something that exists on more than one side, you know, like how many blind people touching the elephant to make the right decision. And so the critical care doctors are looking at VAP and saying, with the regard VAP that you can get away with doing three to five days in somebody who is, you know, hemodynamically stable, they're doing okay, they're they're not requiring pressors. But sure as I'll get out being excluded from this trial. They would have been excluded because they would have they were in the ICU and they were intubated, you know, for two days, you know. So like uh those patients sometimes are doing, those patients are doing okay from you know, with only three to five days of antibiotics. So if I'm seeing it from these higher risk patients, then maybe, maybe we don't need to eradicate it. Maybe we don't have to push that hard to treat patients with antibiotics. And then the, you know, looking at the the uh 2025 uh guidelines, you know, they comment on on the lung microbiome as well, which I I didn't know that much about. Maybe everyone's thinking everyone talked about the gut microbiome, but if you look closely, the lung has other stuff in it as well. And you know, knocking out everything may not be as That's fascinating. I missed, yeah, I missed it. There was a paper there and I was looking, I was like, oh my gosh, I never thought of it that way.

SPEAKER_02 10:49

See, in my head, I'm like, and this is how I've done with patients. I want my lungs to be sterile. Completely sterile.

SPEAKER_00 10:54

Well, I mean, if we're doing if we're doing you know, you if you but if you do a bronch and whatnot, you're gonna find, you know, that they're gonna be like usual flora or whatever. Yeah, we only we only point out the stuff that's bad, you know. And then knocking it everything out may not be the right knocking everything out completely sterile, you know, you lose a little bit of the of your body's ability to handle what's going on.

SPEAKER_02 11:14

And I like the thought of thinking about antibiotics as almost like we're we don't need to think about sterilizing things, we're just sort of trying to kick start the the destruction of the pathogenic organism, that then your body's gonna take it from there. That you don't, the course of doesn't have to be all right, what was it gonna take to totally eradicate this organism? It's what's gonna take to control this organism to the point that I'm no longer actively sick, and then my body's immune system does the rest.

SPEAKER_00 11:43

Need it to be treated again. You don't need to have readmission for that. And uh I think that's kind of an interesting way, you know, like I uh like the whole idea behind the asteroid coming towards her. You don't need to blow up the asteroid, you just need to push it a little bit out of the way. You don't have to, you just gotta move, you know, just bring out the the the small the And the outcome's the same.

SPEAKER_02 12:01

Yeah the the 30-day mortality is the planet where you blow up the asteroid or sneaking the legs. Swing by just fine.

SPEAKER_00 12:07

You don't have to blow it up, you just make sure it doesn't hit us. Um that's so I think I think this is this is a cool kind of um a cool idea that um they're they're using a uh kind of an interesting way to look at it it from a different angle too, but highlights kind of what I think is probably more of a cultural shift.

SPEAKER_02 12:24

And we should say it's talking about the guidelines, specifically they're the what have at times been the ATS IDSA joint guidelines or just ATS guidelines on pneumonia. The 2019 guidelines said a minimum of five-day duration for treatment of pneumonia, carte blanche. But then these updated 2025 guidelines, for anyone who hasn't seen that yet, had said that so basically the minimum is three days and the recommendation less than five days if they're really stable. Basically, what we're seeing in this in this study, um, and despite some of the trauma about those guidelines, the IDSA backed up uh and agreed on on that part. So I'm mostly agreed. Mostly agreed. Mostly agreed. Um yeah, but any other any other specific thoughts on those guidelines you think the that people need to know?

SPEAKER_00 13:12

This is a good question about what are the kind of patients that we're talking about here, other than having requiring hemodynamic stability, other than requiring that you're your ephibril, other than you, you know, you're off of the oxygen. The the other thing is like who are the what's the patient population? And our patient population are the multi-organ system failure, solid lung and transplant, you know, or solid organ transplant, you know, people that are on stereotypes, those are the patients that were all excluded, you know. So like people that are immune-suppressed, you know, they probably, you know, they probably bought themselves a few more days of antibiotics, even if they are clinically improving fast. But um, but a majority, you know, the the question should be asked for those relatively stable patients who are not, who are not in that kind of higher risk category.

SPEAKER_02 13:52

Agreed. Yeah. Sort of my takeaway. Taking the 2025 guidelines and like you're saying, the the data on VAP and this data. Basically, my takeaway is that my mental minimum needs to be three days, not five to seven days. But I'm treating my patient in front of me and they have to be very stable, not complex. Right. Um, for me to to be comfortable doing that that minimum, at least based on current evidence.

SPEAKER_00 14:19

Yeah, that that's my take on this as well.

SPEAKER_02 14:25

So speaking of oral antibiotics, not exactly in the lane of treating pneumonia, but in trying to transition to someone with oral antibiotics, which is something that we do in the hospital often, we're gonna jump into another study. And so, um, Dr. Murray, uh, how often do you prescribe fluoroquinolins?

SPEAKER_00 14:44

Oh man, I want to say I prescribe it often, but I can't really, because our institution has a restriction on them. So yeah, it's not as common. It's not as common as I'd like.

SPEAKER_02 14:53

Um and when I do So how often do you want to do it, but you can't for some reason?

SPEAKER_00 14:58

Oh yeah. I mean, look, uh a lot. A lot. I think I get to I know probably about I probably prescribe it, I probably actually prescribe it a couple of times a month because of gram-negative bacteria. And I think that's probably the most common thing is that now we are avoiding, you know, when I say now, it's not recent, but we stop doing IV antibiotics for uncomplicated gram-negative bacteria, and we we do kind of these, you know, fluoroquinolone is a fantastic agent to use because it has excellent treatment for bacteria.

SPEAKER_02 15:27

Oh yeah, it's sitting there crossing our fingers, hoping the gram-negative rods end up being something that's susceptible to super.

SPEAKER_00 15:35

And super, super rarely, but occasionally, the bigger dosing for pseudomonas, so if you get it, if you can get a pseudomonas that's susceptible to fluoroquinolones. Yeah. And it it's not common, but it'll happen every once in a while.

SPEAKER_02 15:45

Yeah, I mean, so I mean, great, great med for us if we can use it in that. You got an oral medicine you can treat pseudomonas with. That's fantastic and incredibly liberating. And also an oral medicine you can treat bacteremia with. Often, I mean, often we've got like UTIs that are resistant to a lot of stuff, except for Cypro. So it's a medicine that like we want to use a lot, but either our institution prohibits it or limits it, or we're worried about we're worried about complications. Yeah. Because it's certainly a medicine that, you know, it's got a black box warning on it.

SPEAKER_00 16:22

It's a pendulum, though, right? We used to prescribe it all the time. I think our current thing, our current culture is a pendulum against prescribing it and maybe swinging back a little bit.

SPEAKER_02 16:33

Yeah, certainly. It's a a powerful and useful med. So there was this recent study and part of that pendulum swing. Um, in the it's a really interesting little study. It was in the Journal of Antimicrobial Chemotherapy just recently that it was called the effect of oral cipofluxicin at conventional doses on the QT interval in a tertiary outpatient setting, which that kind of tells it all. I mean, it is, it is what it sounds like it is, that it was a retrospective study where it was patients that they had, you know, they were like us, they were wanting to prescribe CIPRO for people, and they were. Um, and they're particularly looking at that QTC prolonging concern when it comes to CIPRO and trying to see is it valid? So there was a relatively small study. This was 88 total patients at this like single tertiary referral center. But what they specifically did was they did an EKG on before they started therapy. They started CIPRO, standard doses. There was a variety of doses, but everything within what you'd typically be putting a patient on. And then two days after starting therapy, they did an EKG again. And then they did some statistical analysis to compare: was there a statistically significant difference in the QTC before CIPRO and after CIPRO? And they picked the two days because for the half-life of CIPRO, that should be steady state. Sure. And the headline takeaway was QTC was not statistically significantly different before or after CIPRO when they they did sort of the the average QTC for both groups, 415 on the buttons both times. Some people would go up, some people would go down. But the but the average across the board was but the average across the board was it didn't seem we didn't have any indication based on this data that the CIPRO itself was really making an impact on that. Two patients did end up, so I think I think only one patient they said they didn't start the CIPRO for specifically within the people they were considering because their QTC was greater than 500. Um, and then two patients were greater than 500 afterwards. And I think they had mentioned some one of them had had some diarrhea and that kind of thing. And then, yeah, the other one concurrent amiodrone and mitoprolol. And so, yeah, and one of them was on Delt. So they had they had had like other reasons that they might have changes in their cardioelectric activity and their QTC specifically, which sort of backs up that don't really see a statistically significant difference in the QTC when you start CIPRO on these people.

SPEAKER_00 19:09

Yeah, I mean I I think that like I love I love the the talking about CIPRO, you know, because uh it it reopens the conversation about bringing this back on board more regularly. Going back to why people are so focused about QTC in these patients is the fact that before I was a hospitalist many years ago, I used to be a chemist. I used to be on medication. That's right. Yes. So I that's why I like I personally am intrigued with this kind of stuff because you know, when I started off in chemistry back in the early 2000s, the FDA was pulling medications off the market because it was hitting a receptor, it was hitting the potassium rectifier, it was hitting something called the human etherogo gene receptor, right? The HERG receptor. It was hitting things, it was like they were pulling mark med medications off the market. They're pulling off like medications for your science, like the celdane, which was uh which is uh which is antihistamine, was being pulled off the market. But the active metabololite was physifenidine, it ended up becoming Allegra. So when I was making these molecules in 2002, everybody had to have medications that proved it wasn't hitting this receptor. Because this receptor was getting hit by everything. So basically, I don't know what the percentage, but a large percentage of medications out there on the market right now at a high enough dose will act as a class three anarrhythmic. You know, they will hit this. And so when when we think about this, it's like I think that they courageously looked at this patient that this patient population with doses as high as 1,500 milligrams, 750. That's the big dose. So they were really pushing hard and they were saying, you know, hey, we really only see this issue when it gets to 100 micromolars in the 100 micromole concentration when, you know, normal concentration is 10 times less than that in the blood. And and that kind of highlighted the fact that maybe we only have to worry about the people who are really kind of have these higher concentrations of, you know, people with in-stage renal disease or whether or not they have acute kidney injury or they have these other things that are kind of make increasing the the uh cardiac irritability, you know. And so a patient who is completely stable, not having anything, should you be worried about and getting an EKG in the answer? Probably not.

SPEAKER_02 21:05

What's your practice for CIPRO now? Do you make sure you have a baseline EKG? Do you tell them to follow up with a PCP to get a EKG? If you've got a E. coli bacteremia or something and it's susceptible to CIPRO and you're trying to discharge the patient on oral, what do you do with EKGs?

SPEAKER_00 21:19

Anything? I mean, if the the person who's getting E. coli bacteremia is probably not the 100% completely normal person. It's not this person who's getting outpatient, you know, treatment for bronchitis or something like that. These are the patients that probably have something else going on. They're on medications that can interfere. So you probably are. And so is that going to change what I'm doing right here? Um, you know, if they are non nothing, then I think I feel a little more, but you have to you have to kind of look at their meds.

SPEAKER_02 21:45

I'm getting a baseline EKG at least. You know, because I mean, as a hospitalist, it's like, well, why not? I mean, it it is someone has to do the work to put these leads on them. But if they've got a reassuring initial QTC, then I'm not worried about like, hey, Once I start this CIPRO, you need to follow up in two days and get an EKG from your PCP or anything like that. And this reassures from that. I mean so I think it's helpful.

SPEAKER_00 22:10

I think a lot of us too will get that one or two dose. That one or that we don't wait for the steady state too. So are we even doing a good enough job? Are we doing the correct job in figuring out whether or not it's truly gonna have effect after it reach a steady state? And I think that we're doing these half measures probably a little more than we than we'd like to admit, but I think it's okay.

SPEAKER_02 22:29

Yeah, I think it's I I agree. I think and and I think that kind of goes to your point for concern about QT in general and QT prolongation, because like obviously, like that's just the number, and we don't actually care about a random number we calculate on EKG. We care about the complication.

SPEAKER_00 22:48

Yeah, and I I I'm I'm trying to mention earlier that I've the one person that I saw was in the ICU receiving IV, uh, I think it was IV phenytoin. So it was like an antiseizion medication that sometimes is associated with it. Then if you receive an IV medication, that increases the like of it happening. They were in the ICU receiving IV phenytoin, they had a low mag, and they were also on amioderone. So they were like they had like 50, they had several things. And and and you know, what we do is always for someone who has an unstable polymorphic VT is that you like, do you give mags? Just no, no, you you shotgun first because you're in the ICU and this guy's crashing. And so that was like, you know, I think when I saw that um in in my training many years ago, I was like, you know, that helped me kind of realize that um, you know, this kind of whatever it says, 0.3 per 10 million cases per 10 million prescriptions for CIPRO. Yeah, for CIPRO alone. Is that really that that really means it's never happening? No, I mean it happens. You know, it's not documented as much as literature, but it it happens in my short career. I've seen it happen. And so um it's something that we pay attention to. You know, the FDA was right to start paying attention to it as well. Um, and uh we're gonna make a we're gonna make 10,000 decisions a day. I think you have to kind of you know make sure that you protect yourself from that idea.

SPEAKER_02 24:03

I think it's the kind of thing that when you when you like start prescribing medicines as an intern, you're a little bit probably over hyperaware. Because I mean, you're like the the intern page of an anti-emetic, you're constantly getting that. And you're like, okay, they need an EKG. And then, but to your point, the patients that we're actually seeing either could significant prolongation or a lot more importantly, actual bad outcomes from this is it's the people who are on it's multifactorial almost always. And I mean, it's gonna be significant. It's not, it's not a patient who's on no other medicines, electrolytes are okay, and you're giving some on Dancitron. Like that, you're you're not you're not doing it by generally that's that's gonna be really unlikely. So I think generally thinking about QTC as a whole, to your point, it's something to keep in mind, something to keep in mind that can cause a problem. Keep the mental list of the medicines that can contribute to it and be aware when you're giving several of those at once that you need to dial back or or need to be cautious about it. But we don't need to necessarily deprive someone of a medicine like CIPRO that can get someone out of the hospital sooner because it gives them an oral hospital option or alleviate them of an IV or a pick line when they go home or something like that.

SPEAKER_00 25:18

I I don't think that this is a I don't think this is gonna be incredibly practice-changing, but maybe kind of bring down your concern just a little bit. Is something that has is a is a study that only has 88 patients powered enough to look at an event that happens 0.3 per 10 million? Yeah, that's a good question.

SPEAKER_02 25:38

My major takeaways from our trials today are for a patient that is stable and improved after three days of treatment with antibiotics for community-acquired pneumonia. I don't need to reflexively do five to seven days. If I think the patient's better, I can stop after three days if it looks like they're stable otherwise. And the evidence we have supports that they won't do worse in the aggregate. And then when I'm prescribing CIPRO, there are the other limitations, but when it comes to QTC, the the evidence supports that there's not a massive change in the QT. And so for my practice going forward, probably getting that initial QT, the initial QTC with an EKG, checking their med list, and as long as that looks good, being comfortable starting a patient on CIPRO and not worrying too much about following up QTCs going forward. And maybe use CIPRO a little bit more to switch people to oral options.

SPEAKER_00 26:36

Thank you for uh letting me join your uh your rundown here. Uh it's it's been fun. Yeah, thank you so much.

SPEAKER_02 26:44

And for my listeners, if there's any new evidence you think hospitalists should be talking about, or if you're a clinician with insight that could help us take better pair care of hospitalized patients, reach out. Find Inpatient Update on social media or email me at podcast at inpatientupdate.com. And if you found this useful, please share it with your colleagues, trainees, or anyone involved in inpatient care. Thank you so much for listening. This has been Inpatient Update.