Hello, everyone. Welcome to Febrile a cultured podcast about all things infectious disease. My name is Sara Dong. I'm your host and a Med Peds ID fellow. We are back for another Febrile Digest and I have a new friend with me here today, Michael. Can you introduce yourself and say hello?
Thanks so much for having me here. My name is Michael Cosimini. I am a pediatrician. I am at OSHU right now, and I am a real enthusiast of medical education and this podcast in particular.
That's very nice. You're an honorary ID person because of all your love for antibiotics.
I'm, uh, I am a ID Twitter lurker. Absolutely.
Well, I was going to say if people don't know you, um, run the Empiric game account, which has a lot of jokes, often at the expense of cefdinir, which is fair. Um, so we were going to talk a little bit today about pneumonia in kids, and then hopefully a little bit just about some serious gaming.
Yeah, absolutely. There's been some really good pediatric pneumonia studies that have come out in the last year and I'm glad to have had a chance to review them for this.
Yeah. We in ID often get this very skewed perspective of pneumonia, and I think it's because we generally are seeing kids that are in the hospital, that have been admitted or have some sort of complication. And so this was a really good exercise for me as well, to think about some of the newer literature that had come out for treating young children with community acquired pneumonia, or I'm going to say CAP because it is easier to say.
So we're going to start first by just doing a quick refresher on the microbiology or the etiologies that we see with CAP. What do you think, Michael?
I think community acquired pneumonia or CAP is a tough diagnosis, and I think that there is a lot of variability of what people are calling this and how it's diagnosed. And I think that's really important when we think about these studies. There was an excellent presentation at PAS last week actually, where they were showing huge variability in rates of diagnosis of CAP in patients hospitalized with lower respiratory tract infections. And that feels totally right to me.
Um, and there's also like not great inter-rater reliability of some of the findings that we use to diagnose CAP in an outpatient, like auscultation for crackles or for reduced breath sounds. You put two different docs in the room and they're going to say different things. So this is a hard diagnosis. It's not like got a great research definition and it's hard to diagnose clinically. So I think that's like an important first step to think about when we think about these studies.
The second half of this, which bugs are we dealing with? And that's also not perfectly known in kids. And I'm sort of excited to be talking to an adult about this. Cause like, I think like pediatric pneumonia is not the same thing as adult pneumonia. And so, and we don't know exactly what's happening, right?
What we know is like kids that are admitted to the hospital with pneumonia often have positive viral tests really, really frequently, but like if I go viral test the kids in the grocery store, a lot of them will also have positive viral testing. Pre pneumococcal vaccine, a huge percentage of kids, you could demonstrate pneumococcal infections in. Post pneumococcal vaccine, that's not the case anymore, right?
Like one of the best like that, 2015 Jain, et al. epi study where they tried to figure out why hospitalized kids had pneumonia. They prove like 5% of them have pneumococcus. And so what are we dealing with, right? Like what is pneumonia? I'm not totally sure, but Strep pneumo is still the most important, like quote unquote, typical pathogen. After that, it's the gram-positives that every pediatrician needs to love Strep, um, Staph aureus, and Group A Strep.
And after those three, it really is rare to have specific individual bugs other Strep Viridans, Chlamydia pneumoniae, H flu, and maybe other gram negatives. But, you know, it's only the really sick kids where you prove what it was. And what's actually going on in the alveoli of those other kids. I don't know.
Yeah. Yeah. And I feel like, I always want to think about Mycoplasma, but it's pretty uncommon in younger kids. So I have this tendency to want to throw it on my list. When in reality, I don't think it's actually that common, especially for the really much, much younger children.
Yes. It very quickly becomes the most common single identified bacteria in kids as you get older. Like if you NP PCR all these kids, old kids are gonna have Mycoplasma pneumonia. But we're not exactly sure. We don't typically cover for it. We're not sure if coverage helps. It's a tough, tough position to be in.
Yeah. Well, so we don't always know exactly what we're treating and then the other big question that we're going to focus on today is how long do we treat children for CAP? And so there's some WHO recommendations of three to five days, which is specifically targeted towards low and middle income countries. And I'd say historically for high-income countries, we use somewhere around five to 10 days. And so the first question people always ask is, are there guidelines?
Yes, but they're a bit dated now. So there's a 2011 archived, uh, PIDS, so Pediatric ID Society, and IDSA, ID society of America guidance. Um, that at that point had said, yep, 10 days is the best studied, but we probably can do shorter durations for mild cases. And they make a point of having that little caveat of antibiotics probably aren't needed for preschool aged children because they probably have a virus.
And separate from that, there's a British Thoracic Society guideline also from 2011 that essentially says the same thing. This is kind of our baseline, somewhere in this like ambiguous five to 10 days. And then since honestly, just in these past couple of years, I feel like several of these papers that we're going to talk about, uh, came out.
And so, although there's been several randomized trials for, uh, children with non hospitalized pneumonia and low and middle income, we're not really going to talk about those quite as much today, or we're going to focus on what's available to us for uncomplicated pneumonia. And if you look at high-income countries, that's only actually a handful of a couple named trials that I think everyone has probably heard over the past year or two.
And so we're going to focus on those, the one suggesting somewhere between like three and five days. Um, so I guess I will start with the first one. The one that I have to start off with is the SAFER trial. S A F E R, um, by Pernica and others in JAMA Pediatrics from last year. So this one was a randomized trial at two Canadian centers that looked at children six months to 10 years old with CAP. So they had fever.
They may have had some respiratory symptoms like tachypnea or like a primary diagnosis of CAP from the emergency room. And so they looked at five versus 10 days of high-dose of amoxicillin. So that meant our control arm was amoxicillin at 90 mg/kg/d split three times a day. And then the intervention arm is the amoxicillin at that same dose, but just for five days followed by five days of the placebo. And so the clinical cure for these essentially the same about an 89, 90%.
Um, and so that, that's where I'm going to get us started. I'll throw it over to Michael.
Yeah. And I love this trial. I feel like these are Canadian ED docs, diagnosing pneumonia. It's probably similar to the kids I'm going to say have pneumonia in my clinic, if not a little bit sicker. So they slightly sicker kids are doing okay on 5 days. Love it. The two threads I'd pull on on this one is they talk a little bit in one of the appendices about caregiver absenteeism, and they find in the younger group that the kids on the longer course of antibiotics, the adults miss more work.
And as an adult with my own like little humans at home, I think that's like a super important outcome. There's like a, uh, longer median time missing work for the adults in that, in that group. And this is like TID dosing too, which I know is probably optimal for Strep pneumo, but contemporary Strep pneumo is probably less likely to be resistant than it was back in the day. And maybe BID dosing would help a little bit with that caregiver absenteeism.
Yeah. I don't know, but a couple of threads I wanted to pull out on that one, but I love this study. Okay. I've got one for you.
I'm ready.
This is SCOUT-CAP. A lot of, a lot of good acronyms today. This one is a study where they enroll about 380 kids. These are kids that have previously been diagnosed, whether it's in primary care primarily or urgent care, or the emergency room with community acquired pneumonia. It's like now it's day three, four or five of antibiotics. If they're getting better or they're not having persistent fever, they're not still very sick with that.
They get randomized to complete a 10 day course with their original beta lactam, amox mostly, but also some with amox-clav or cefdinir. Ooh,
your favorite antibiotic
Um yeah, so they, they randomize either to complete the course with the originally prescribed beta lactam for 10 days, or to switch to a placebo at day five and look at their outcomes. The outcomes in this one is a little bit tricky cause they, they have the sort of ranked score sort of thing. It would take a while to explain it. I'm not going to bother, but basically the antibiotic side effects were the same in the two groups. The clinical outcomes were the same in the two groups.
Um, no one got hospitalized and they have less total days of antibiotics in the group that got shorter courses of antibiotics, somewhat unsurprisingly.
Yeah, and I feel like I'm learning a lot about the way that they did the primary outcome for the, I'll put a link for everyone to read about, uh, that outcome ranking. But I, I summarize it to myself as they have the same clinical response with probably the same adverse effects and the one that has a shorter duration wins, which I think is a very practical way to look at antibiotics and what we do in ID.
Yeah, and they do one other interesting thing, which is they, they, they go back at these kids and look at their rates of antibiotic resistant genes and they do show a little bit less, a little bit less of antibiotic resistant genes in the kids that got the shorter course of antibiotics, which is not super clinically applicable for me. Like for the next kid that I see in my outpatient clinic. But it's something to think about.
Yeah. All right. And then the third kind of major one that we wanted to make sure we talked about is the, I've been saying CAP-IT trial. I hope that's what everyone else has been saying.
Can you "cap it off" for us, Sara?
So this is from, Bielicki and others from JAMA also this past year. Um, and this is what has really been suggesting the push towards three days of amoxicillin. So they had a little under 600 children that were at least six months old. The median age was about two and a half years. Um, and they looked at children discharged from the ED with CAP and treated with amoxicillin at either a lower or standard dose of 35 to 50 mg/kg versus the high dose, so 75 to 90, it was dosed twice a day.
And then they did either three or seven days. So these, all these patients, I guess I didn't mention where in the UK and Ireland, and so they didn't need x-rays or specific labs to be included. And they showed that the rate of antibiotic retreatment within 28 days was similar for the two groups about 12%. And so this suggested like maybe we can use three days and maybe we can use standard dose amoxicillin.
I think that there are some challenges to generalizing it and you know, how do we think about this if we're using other antibiotics or perhaps older children, but I think. I don't know that this was surprising to too many people and it just encouraging that we can start hopefully shifting towards shorter courses.
Yeah. All the, all of these studies really focus on that, that younger age group, like, right. Like I think the, the, the median in mine was three and two and a half year old. And. This one, I have a little trouble with, cause some of these kids, they also got a little bit of antibiotics in the ED or the inpatient setting before they got randomized. I don't know. I'm not ready to jump to low dose three day.
Yeah. Um, and the only other thing I was going to mention, cause I, I made Febrile Digest. So we could talk about things that are current. There actually was a, uh, article from Pediatric ID Journal, sorry. All the acronyms are very similar just from this last week that looked at some cases. Uh, it's a multi-national double-blind trial that was in Australia and New Zealand and Malaysia. And, um, looked at children that had uncomplicated, but radiographic confirmed CAP.
Uh, it's kind of interesting. They did like one to three days of IV, then they had a couple of days of oral amox-clavulanate then they got either randomized to 13 to 14 days or a standard five to six days. And there's about 300 children with similar clinical cure rates. It found no clinical benefit to doing the extended two week course, but I think at this point people have really bought in.
And I don't know that many people are using that duration for an uncomplicated pneumonia, but just another, you know, another one to add to the, to the list. So I, I think one thing that we haven't really talked about for all these papers is, how much of these children actually just have a virus? Um, yeah. Would they have done well, regardless of whether or not we gave them antibiotics? I don't know how you frame that and fit that into your interpretation of all these trials.
I think it's so hard because there probably is a large slice of kids in all of these studies that needed zero antibiotics and knowing which kids those are, is really hard to say. I think I feel very comfortable after reviewing these doing a five day course of, you know, amoxicillin, uh, for kid I diagnosed with community-acquired pneumonia, who's got a little bit of work of breathing or a little bit of sat that's lower than I expected.
Now for that kid, that's got, you know, URI symptoms and I hear focal crackles, but everything else seems fine. I think that's the kid that I feel maybe a little more comfortable saying, Hey, I don't need to give this kind of antibiotics because most pneumonia is viral. I'm not like 110% sure this kid's got pneumonia in the first place. This gives us from ground to stand on for a five day course.
And I think we always knew we had a little bit of wiggle room for treatment at all in those kids that have pneumonia that are not severe in this youngest age group. There was a really great study this year, too, that I had to bring up as well about viral testing because Hey, we know a lot of these kids have viruses, but virus and bacteria co-infection is pretty common. And, um, what to do with viral information is a little bit uncertain.
This was a single center RCT of 900 kids over the age of one with flu like illness, which they defined almost a fever, 37.8 plus cough, congestion, sore throat or rhinorrhea. They do a nasal pharyngeal respiratory panel on all the kids, but only give the results to half the docs and they look and say, Hey, does this reduce antimicrobial prescribing? And the answer was a very firm no. It didn't help. And I think people will tell you they'll use that information, but this really goes against.
Yeah,
I really love, I thought this paper was fascinating. I was really glad that you wanted to talk about it because, um, I think we see a mixture of that where sometimes we think that someone feels confident enough, but there are plenty of cases where we get that answer and they still go out with the smidge of antibiotics.
Yeah. So now that would be Rao, et al. in Pediatrics in 2021.
Yeah. And I, I mean, I feel like my sort of takeaways were similar to what you were saying is that I think most people agree that pediatric patients who come to clinic that have uncomplicated CAP at most should get five days. And there's, you know, this question of what to do with these kids that are younger than may have a virus, but. It's it's hard because I, I definitely don't see enough kids that I would be deciding if they would get three or five days.
Um, so I have to learn from folks like you and tell me, tell me what really happens in clinic.
Well, the question I would ask you, and we actually had in that very first study, is those kids that you take care of in the hospital? Are they coming in on day six of amoxicillin, day seven of amoxicillin, or are those kids getting sick right away. And in that very first study that it was SAFER I believe they said that they had seven hospitalizations in that one and six of them were hospitalized in the first five days of therapy anyways. So I thought that was like a nice little fact.
Yeah. I wish I knew what, what I've actually seen. I do feel like that seems to be more common, you know, when I've seen patients who come early on rather than later, but, um, it would be nice to have a sense of what that number actually is.
Yeah.
Great. Well, so, I mean, I don't know that we totally solved it, but hopefully everyone feels more up-to-date and more comfortable. And at a minimum knows the new acronyms for CAP
We are in agreement five days for community acquired pneumonia. We feel pretty good about that. I wanted to get a chance to talk a little bit about medical education here with you, since you're doing such an interesting project and talk a little bit about games for med ed, because I think it's, uh, ID is just a beautiful place to use those. There's so many interesting bugs and drugs and things. Um, so if I could borrow a little bit of your time for that, I would love it.
Yes, of course, this is my secret motive was to get you on the show and tell everyone about how you've been using games to teach about our beloved bugs and drugs. And I mentioned this earlier, but just to remind everyone, Mike is the creator of the Empiric Game, which helps each antibiotics, but that's just one of several games. And we're going to talk a little bit about the perfectly named, Guess Poo
We are going to try a little bit of an experiment and we're going to play a game on the podcast. So everyone please imagine in your head, you're holding a handful of 18 cards. These 18 cards have a name of a pathogen that causes infectious diarrhea and little icons and words that describe the exposure, host factors and symptoms that would make you think that that is the type of diarrhea that you're dealing with.
This is, uh, this is just a little game exercise that's designed to teach semantic qualifiers, which is those sort of binary things we, we think about as doctors, when we're trying to figure something out. Febrile vs not, bloody vs watery, acute vs chronic.. Those kinds of things that you know, are, are helping us in our little decision trees as we're seeing patients. And so we're gonna do an experiment where we're going to play this game. Sara, do you have your cards ready?
I'm ready.
Okay, so let's have you let's have you be the, um, the one with the diarrhea first. So pick out one of those cards that is like a patient you can remember recently, or just one that you want to think about a little bit.
Okay. I'm ready.
And I am going to ask yes, no questions and try to figure out what you're dealing with right here. Okay. So is your diarrhea bloody?
No.
So it's not a bug that is typically associated with bloody diarrhea.
Nope.
Okay. So I'm getting rid of Shigella and Vibrio, like non-cholera Vibrio. I'm getting rid of non typhoidal salmonella.
I wish everyone could see how cool these cards look.
Not Yersinia, probably. Not Campy probably. All right. How about this? Is this diarrhea typically associated with travel? Like if I'm, if I live North America, is this associated me traveling somewhere and coming back with it?
Not necessarily. Um, no.
All right. So I'm thinking probably like less likely cholera, um, or Cyclospora. Okay. Is this diarrhea associated with recreational water or fresh water?
Yes.
Ooh, we've narrowed it down quite a bit. Okay. So I think this is cryptosporidium that we're dealing with.
Uh,
No! Giardia
It is Giardia! Actually I realized like now, based on the questions you said it could have been Crypto. I had Giardia though, my hand.
Nice.
Oh, this is awesome. And the nice thing is that you may, you know, you don't have to have a baseline knowledge of all of these. What's nice about these is you have something in your hands and you're reviewing it in a way that's fun. I think that's, what's been nice about seeing some of these MedEd games is especially thinking about using it for people who are not used to, or not as familiar with either the infection or the antibiotics, which is what most of the ID related ones are.
And I think that's really nice because I, I swear the most common question I get when people hear that I like ID and medical education is how do we teach antibiotics?
Yeah.
As if there's like one single, like good answer, there's not, but the more tools like this that we would have to think about teaching, uh, ID or infections or drugs is amazing.
Yeah. I think that you're bringing up a couple of important points about games, like it's active learning. Right. Which is a really good way to learn, to use active strategies. And it's like a little bit of a more low stakes environment. It's okay to be wrong. Like I just demonstrated, um, but very publicly. When you're playing a game, right. It's, it's easier to be wrong, playing a game than it is when someone asks you a question on rounds. Right.
I think that's, that's the goal is to make people feel like they can explore and they can experiment and they can practice and get it right over time in a safe way. Right. And I think games are good for that.
Yeah. Okay. Now you have to tell everyone how they can find all these games, because I want everyone to know that I printed these out today, which you could do too.
Yeah. Oh, and here's our double-sided! Yours are better than mine.
I'm double-sided and color. They look magnificent.
They're beautiful. I so all of my games that I make are free to print. It's a bit.ly/printempiric take you there. Or if you just go to empiric game.com, all one word, that's like, you can find all my stuff there. Um, my big one is empiric, which is, uh, an antibiotic card games.
Kind of like, you know, learn your antibiotics the way you learn your Pokemon with a little bit of, you know, antibiotics with iconography that helped you learn the important bugs your, your, um, your MRSAs and such a. And color-coding that helps you kind of encode those spectrum of activity from back when we had to memorize that with your beta lactams being blue and, you know, a rainbow kind of teaching you the, uh, the spectrum of activity.
You know, Febrile needed more Pokemon references. So I really appreciate your Pokemon.
I don't know if that I've heard one yet.
I know that's what I'm saying. It's been a lack of Pokemon or Pikachu references. Well, this is so awesome. So I'll make sure that for everyone who listens, I'll put a link to this, obviously on our Twitter as well, and on the website, because I hope that people can use these and, and spread the word.
I really appreciate you letting me join this community here and be on the show. Thank you so much, Sara.
Yeah. Thanks for joining. Well, I hope it was quite obvious that I had a lot of fun with this episode. Thank you so much to Michael for joining Febrile today. And I hope you'll all check out Empiric game and Guess Poo. Uh, maybe consider using it to kick off your consult rounds one day with new learners.
I will mention that after we recorded this, there actually was a new manuscript in CID on antibiotic treatment duration for CAP in outpatient children and high-income countries, a systematic review and meta analysis from Dr. Kuitunen et al. in mid May.
And that came to a similar conclusion that we've been talking about on the show that short treatment for three to five days was seen as equally effective and safe, compared to longer recommendations for seven to 10 days for children over six months of age with CAP. So we'll try to do our best to still have some literature updates here on Febrile Digest episodes, but you can also check out Puscast which is back with Daniel Griffin and myself.
We provide a review of the ID literature for the last two weeks that we found interesting or entertaining. So you can find that online at microbe.tv/puscast or in whatever podcast directory. In some other news there now is also Febrile merchandise available on our online store in case you want to get some swag, like a shirt, mug or lanyard to you show your support for Febrile.
You can check out the website, febrilepodcast.com to find the link to the store as well as links to the papers mentioned today in our Consult Notes, the written complements of the show, and lastly, the link to our new and upgraded infographic library, which is now much easier to sort and is searchable! Please reach out if you have any suggestions for future shows or want to be more involved with Febrile. Thanks for listening. Stay safe and I'll see you next time.