The Incubator

#192 - 🦠 Probiotics Mini Series - Prebiotics, Probiotics, and antibiotic stewardship (Ft. Dr David Kaufman)

March 10, 2024 Ben Courchia & Daphna Yasova Barbeau Season 3 Episode 19
#192 - 🦠 Probiotics Mini Series - Prebiotics, Probiotics, and antibiotic stewardship (Ft. Dr David Kaufman)
The Incubator
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The Incubator
#192 - 🦠 Probiotics Mini Series - Prebiotics, Probiotics, and antibiotic stewardship (Ft. Dr David Kaufman)
Mar 10, 2024 Season 3 Episode 19
Ben Courchia & Daphna Yasova Barbeau

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In this episode, Dr. David Kaufman discusses his interest in pediatrics and infectious disease, particularly in the prevention and treatment of neonatal infections. He highlights the challenges of antibiotic use in the NICU and the interplay between probiotics, prebiotics, antibiotics, and infections. Dr. Kaufman emphasizes the need for better quality control and standardization of probiotics, as well as the importance of consent and shared decision-making in their use. He also discusses the potential benefits of lactoferrin in reducing necrotizing enterocolitis (NEC) and the future directions in infection management. The episode concludes with a discussion of the Neonatal Antibiotic Stewardship web app.


As always, feel free to send us questions, comments, or suggestions to our email: nicupodcast@gmail.com. You can also contact the show through Instagram or Twitter, @nicupodcast. Or contact Ben and Daphna directly via their Twitter profiles: @drnicu and @doctordaphnamd. The papers discussed in today's episode are listed and timestamped on the webpage linked below.

Enjoy!

Show Notes Transcript

Send us a Text Message.

In this episode, Dr. David Kaufman discusses his interest in pediatrics and infectious disease, particularly in the prevention and treatment of neonatal infections. He highlights the challenges of antibiotic use in the NICU and the interplay between probiotics, prebiotics, antibiotics, and infections. Dr. Kaufman emphasizes the need for better quality control and standardization of probiotics, as well as the importance of consent and shared decision-making in their use. He also discusses the potential benefits of lactoferrin in reducing necrotizing enterocolitis (NEC) and the future directions in infection management. The episode concludes with a discussion of the Neonatal Antibiotic Stewardship web app.


As always, feel free to send us questions, comments, or suggestions to our email: nicupodcast@gmail.com. You can also contact the show through Instagram or Twitter, @nicupodcast. Or contact Ben and Daphna directly via their Twitter profiles: @drnicu and @doctordaphnamd. The papers discussed in today's episode are listed and timestamped on the webpage linked below.

Enjoy!

Ben Courchia MD (00:00.854)

Hello, everybody. Welcome back to the incubator podcast. We are back for another episode of our mini series. And today we are joined by Dr. David Kaufman. David, good morning and thank you for being on the show with us today.

 

David Kaufman (00:13.457)

No, thanks a lot for having me, Ben.

 

Ben Courchia MD (00:15.97)

For people who are not familiar with who you are and your work, you're a professor of pediatrics at the University of Virginia School of Medicine in the Division of Neonatology. You did your pediatrics training at Albert Einstein Medical Center in Philly and your fellowship at the Children's Hospital of Philadelphia. Your research focuses on the prevention and treatment of neural infection. You've done incredible work on fluconazole prophylaxis. I think it's one of these things where many people have read your papers. They have not connected the name.

 

yet because we don't pay that much attention sometimes to the authors in these articles. But incredible work that you've done on that. And you've chaired the Neonatal Sepsis Club at the annual Pediatric Academic Society's meeting since 2003. And you're currently a member of the Committee of the Fetus and Newborn, the coffin of the American Academy of Pediatrics. Impressive bio, David. Thank you. Thank you so much for making the time to chat with us this morning.

 

David Kaufman (01:13.084)

No, thanks. Thanks for that introduction, Ben.

 

Ben Courchia MD (01:15.602)

No worries. I'm curious to ask you about not only your interest in pediatrics, but your interest in infectious disease, right? And trying to the prevention of infections and the management of infectious disease and neonates, where did that interest come from? Because it seems like this is a passion of yours based on the amount of papers you've published on the subject. Was that something that happened in training or afterwards? Can you tell us a little bit more about that?

 

David Kaufman (01:43.76)

Yeah, I don't know if it's just intrinsic obviously to pediatrics to want to like prevent infections with obviously growing up, you know with Vaccines finally becoming available when I was a kid to prevent a lot of diseases Having like a real strong pediatrician who? um who emphasized all those things and then um I I’ve heard you speak of this too, but like having these mentors that really empathize with you and direct you in that in that area

 

Ben Courchia MD (01:53.902)

Mm-hmm.

 

David Kaufman (02:13.844)

But for whatever reasons, I always found infections challenging and hopefully preventable as an area to try to study and bring to the NICU.

 

Ben Courchia MD (02:25.786)

That's very interesting. And so what's sometimes a bit frustrating is the fact that antibiotics are one of the few things that we do have as agents to address a specific pathology in the NICU. And obviously, there's been a lot of swinging of the pendulum back and forth between overuse and now we're in the era of antibiotic stewardship. And so I'm just curious if that's

 

If this interest came from the standpoint of trying to address the rampant infections that we see sometimes in the NICU or more from the standpoint of maybe we're using too much antibiotics and maybe we need to slow down. Where were you at when that began?

 

David Kaufman (03:11.36)

I think I was more at just seeing these infections that unfortunately for very preterm infants and extremely low birth weight infants, just having such high mortality, even in term infants, seeing G group B strep, you know, take the lives of some of these kids just in like 6 or 12 hours. It's like you'd have the symptoms. You'd try to get ahead with antibiotics and you still...

 

couldn't be successful. So I think like Carol Baker's work with IAP and everyone else who contributed in that area made it powerful that maybe we can use antimicrobials in a way of prevention in a targeted manner. Obviously with IAP, we give it every four hours with patients who we identify as high risk mainly by culture methods. And it just,

 

lent that ability. And then I really had a great mentor here, Dr. Lee Grossman, who was like, antifungal prophylaxis works in bone marrow transplant patients. They're similar to our extreme preemies. They don't have a lot of neutrophils. For our preemies, our neutrophils don't work. They're exposed to antibiotics and cephalosporins and things that put them at high risk, but just for a short time period.

 

learning from her and doing like those first fluconazole prophylaxis studies, targeting high risk patients just when they're high risk, like when they have the central line, when they're on antibiotics, you know, when they're getting TPN, just was like a nice powerful way to try to hone in when to use antimicrobials in a preventative way.

 

Ben Courchia MD (05:04.846)

Mm-hmm. And what's interesting about the management of infections and how we use antibiotics is that we're discussing, this is a mini-series on probiotics, and I think the interplay between probiotics, prebiotics, antibiotics, infections, is something that is a balance we have yet, I think, to achieve as a field in general. Can you tell us a little bit about what we've learned over the years about...

 

the delicate balance of the baby's microbiome and our use of antibiotics, all that compounded with the risk that they are at for the general infections.

 

David Kaufman (05:47.828)

I think in the last 30 years, I guess there were like two movements. First there was like these antibiotics can hurt kids and hurt the kidneys. So nobody wanted to use like gentamicin anymore. But then we learned by treating kids right away with cephalosporins for early onset sepsis, presumed rule out. There was a higher mortality in very low birth weight patients.

 

I think we were trying to do something good, but then we had to learn. Then fortunately, a lot of work on donor milk took a pause in the 1980s as we were dealing with HIV and having a safe blood supply and then realizing, okay, we could have a safe donor milk supply. So getting moms to pump and provide breast milk and having donor milk available, starting about 20 years ago, really ramped up.

 

like our ability to somewhat boost these babies' immune systems. Like naturally, they don't have good immune systems, so they don't reject their mom in utero. But obviously, once they're born premature, we sort of want to boost however we can. It's been really hard in various studies to prevent infections by giving IVIG. I think because they're

 

their white cells, their complements, the other parts of the immune system are still immature. So, whether it's through human milk, getting a more diverse microbiome, having that available, having donor milk available so we're not causing gut injury with different bovine proteins, I think that made a big difference between 2000 and 2010 and keeps improving as there's more donor milk available and there's more ways to support.

 

you know, having mom's milk. Like there's a study at Rush right now looking at, you know, financially helping moms to, you know, make it more feasible to have milk and pump longer to benefit their infants.

 

Ben Courchia MD (07:56.654)

Mm-hmm.

 

Ben Courchia MD (08:01.603)

And so I think that's interesting now to discuss this in the context of the probiotic sagas, I think as we can call it, where there's been evidence published all around the world about how the use of probiotics, quote unquote, in general, has led to a reduction in the incidence of necrotizing enterocolitis. And

 

And while it's been very exciting to see these results and to see the potential benefits of probiotics, we've also been struggling with the standardization of how to deliver this. And with your role on the committee of the fetus and the newborn, you were one of the authors of the recommendations of the AP on the use of probiotics. And I wanted to maybe get your thoughts on the difficulty as

 

as an expert panel to try to come up with recommendation in this specific scenario where there isn't like a single molecule that you can say, oh caffeine, which is this molecule has these properties and dealing with this really this plethora of evidence, but all coming from different places with different strains and different kinds of right. How did you guys navigate all this data as you were trying to

 

to wrap your head around it and come up with actual recommendations.

 

David Kaufman (09:30.164)

Well, I think the evidence of some of the bigger, later studies that had more babies that were less than a thousand grams had more control for knowing what the babies got. One of the problems with a lot of probiotic studies was the baby getting human milk, donor milk, formula. What else was affecting the microbiome you bring up?

 

David Kaufman (09:59.732)

you know, probiotic, prebiotic to select for a diverse and healthy microbiome. And it seemed like the later studies were able to capture that, like the initial studies don't even mention some of that important information. So I think that helped guide us and also, you know, not seeing a benefit in the kids' less than a thousand grams, where those are the kids that we were more often seeing, you know, dying from NAC.

 

you know, having more severe neck and having all those challenges. So I think as far as talking about like less than a thousand grams, I think it was somewhat easy to pinpoint the data from those studies. And you know, more data keeps accumulating that maybe favoring getting mom's milk. There was a nice QI project from Calgary that was just published in Pediatrics November

 

this quality improvement project, trying to really improve having mom's milk and the introduction of donor milk. And that alone decreased it significantly for those kids less than a thousand grams in that study. So I think all these studies helped forge the thing. And I think the real goal of that statement was just to say, you know, we're going to

 

we need a better product that's got good quality control. Like even one of the things I'm trying to study is lactoferrin and it's also an enteral supplement. It's also like a powder. It also has this risk of being contaminated and things like that. So having good quality control that you know there's no bio burden in the product that you have a test to test potency. Like those things.

 

entering the realm of probiotics just weren't there. Even just asking probiotics to have like grass status, generally regarded as safe, like just getting those things to happen, I think was really the main goal and to continue to study it better, knowing what formulas things that kids are getting or human milk that they're.

 

David Kaufman (12:23.412)

getting. And there is right now an RCT with an IND being done in the US. So for better or worse, it's just on a single agent, not a multi-strain product. But maybe that will bring, keep moving this evidence further to how we can, like you're saying, engineer that microbiome with human milk, with donor milk, with other things that can give us a safer

 

diverse environment for a preemie so pathogens don't emerge.

 

Ben Courchia MD (12:55.454)

Yeah, yeah. And the quality improvement project that you mentioned was published in Pediatrics. And I think, as you said, it's coming from the University of Calgary, and it's called the Quality Improvement Initiative to Reduce Necrotizing Enterocolitis in Very-Pretty-Term Infants. And it is a very interesting, it's a very, it's a breath of fresh air, I guess, as you mentioned, because it is showing us that there are interventions that taken together can reduce necrotizing enterocolitis quite significantly. I think their rates went down from like 6% to 2%.

 

And that's super reassuring. I wanted to track back one step because you did mention the concept that I think not everybody may be familiar with. You mentioned prebiotics versus probiotics. And I think for many people, they're like, well, is that the same thing? Can you tell us what is the difference between a probiotic and a prebiotic?

 

David Kaufman (13:44.808)

Yeah, so the prebiotics are usually these simple sugars. They often have these names, FOS, GOS, these oligosaccharides that are the nutrition for the bacteria we want to select for to grow and also to have a diverse microbiome. So there hasn't been a lot of studies, but there's one or two just showing certain oligosaccharides can get you a healthier gut.

 

microbiome in these preemies. And I know in the previous podcast people mentioned combining obviously probiotics with prebiotics. So then the probiotics are the actual bacteria. And that also brings up a quality thing. We don't always know are all the bacteria alive and what's the active dose. And like I was saying before, if there was some potency test or knowing, okay, this...

 

probiotic gives this microbiome signature, I think then we'd be able to better know which ones to choose in addition to having safety data around them.

 

Ben Courchia MD (15:01.646)

I think it goes back to a discussion that was obviously mentioned in the AP report, which is, well, is probiotic a drug or is it a supplement? I mean, I think for the general population, probiotics are supplements. They buy probiotics off the shelf at Walmart and whatever place they shop. But we're talking about it in the sense of really an agent to help with a signal pathology.

 

Ben Courchia MD (15:30.722)

to tease apart whether, like what exactly, because we're taking probiotic in a direction that is different from what the general thought has been about what a probiotic is. Can you tell us a little bit about like drug versus supplement? Like how do you think about that? And where are we now in neonatology when it comes to probiotics?

 

David Kaufman (15:50.268)

Yeah, and this might be something that's a little unique to the to the United States because the FDA is somewhat the driver of the definition of a drug and you know right now through the FDA while they're trying to diversify and being able to better study biologics, they still only have this IND, you know for drugs like

 

Ben Courchia MD (16:07.54)

Mm-hmm.

 

David Kaufman (16:20.124)

they don't have an IMB for like a biologic or an INS, you know, for a nutritional supplement or something like that. Where like in some other countries, like they'll have a, they'll have like INDs, but they'll also have like clinical trials that can look at other outcomes, you know, growth or, you know, infection with biologics and still get like some of the safety.

 

Ben Courchia MD (16:20.365)

Right.

 

Ben Courchia MD (16:27.911)

Ha!

 

David Kaufman (16:48.364)

mechanisms. But what we really lack in the US is that it's not drug companies right now making these probiotics. It's like you're saying, it's nutraceuticals, it's these nutritional companies. So when you go to the FDA, they want a big document and dossier on how it's made and how it's prepared and all these other things. And I know there's different quality for foods.

 

We use infant formula all the time. We feel that's a safe product, but that's not something that has an IND. So we somewhat need like that level playing field, the same way we use formula, like you're saying as like this nutritional supplement, this nutritional source, have those same standards and quality control for biologics or nutritional supplements that we want to benefit our kids, whether it's to prevent infections or improve brain growth.

 

anemia, you know, all these other things that they potentially can do.

 

Ben Courchia MD (17:48.916)

Yeah.

 

Ben Courchia MD (17:52.394)

It's interesting, I think in the AAP paper, you guys mentioned this at some point, that there was a study showing testing of 16 commercially available probiotics and looking to see if what was in the product was listed on the label. And that's basically only one out of the 16 products containing the biphidobacterium matched the label exactly. And that's for one of the products tested that contained none of the species listed.

 

So it's true, it is a serious concern that if we take a label at face value, but we're not sure that our patients are going to get what we intend them to receive, it could create a lot of problems. Yeah, please.

 

David Kaufman (18:38.132)

Yeah, I would echo that point, because we want to know what to choose and know the patient's getting it and then critically evaluate that outcome.

 

Ben Courchia MD (18:47.334)

Mm-hmm. And I think there was a very nice editorial recently published by Jen Canvasser about the whole probiotic saga from the perspective of her as a mother. And I think she was commending the work of the committee of the fetus and the newborn, because in that report, I think you guys highlight very well what's known, what is not known, and what is ongoing. But you also offer...

 

recommendations for people who are interested in continuing to use this potential therapy for babies while the current FDA memo really seems like it's going to halt everything until more products are available. What do you think about where we are right now? Do you think that there's still a path for people to...

 

continue using probiotics until some of these products and some of these studies are finalized, where like in the clinical report, you mentioned getting consent, having shared decision making with the families. Is that still an option, you think?

 

David Kaufman (19:55.904)

I mean, we hope, like in the NICU, that everything we're providing is to benefit the baby and balances the harm versus safety. So I'm not really a proponent of having to get consent because I think it will just really slow the progress of everything that we're trying to do in the NICU to improve survival and long-term outcomes.

 

Ben Courchia MD (20:16.019)

Mm-hmm.

 

David Kaufman (20:26.384)

I think what we hope that will come up with this dialogue with the FDA is, I guess, nudging to have a better way to study these products and to somewhat approve them. Like the IND, you know, treating probiotics like a drug, the bar is just too high and almost impossible.

 

David Kaufman (20:55.508)

has a little trouble to like when something's intravenous versus enteral. Like there's different quality control and safety measures there. So I don't know, hopefully this will all lead to a better discussion that maybe an IMB or something, like something to really study biologics and to have those same quality control things like the formula we give, we want to know it's got X amount of protein and carbohydrates and fat

 

the other things that we want in that. And the same as you mentioned with the probiotics, we want to know, you know, this product is, you know, it is the right identity, it is the right concentration, what's live, what's not live, and does that product have like the potency we want it to have to be able to, you know, work in the microbiome of the infants that we take care of.

 

Ben Courchia MD (21:53.002)

Yeah, we were talking about that with some colleagues that the FDA and regulatory bodies in general, not just the FDA, but others are going to have to shift because we are entering the era of biologics. And I think our understanding of the microbiome and all this dysbiosis, as we've talked about, is something that will lead to more potential interventions. So I think, like you said, there's going to have to be a mechanism in place to try to provide some

 

quality control for these products so that they become available to help our patients. Yeah, I think that's very interesting. I wanted to pick your brain a little bit about probiotics, but not for NEC and talk to you as an expert on infection, because I think that what we had seen before this whole FDA brouhaha happened is that there was an increased use of probiotics in older patients that were being treated for...

 

general infections who were on antibiotics for five, seven days, sometimes even the babies who were receiving antibiotics for 21 days in the case of meningitis and thinking, oh, maybe we can do a little bit like our older, our pediatric colleagues and our adult colleagues are doing and trying to not completely destroy the gut microbiome. What are your thoughts on that? Is that something that you think is just a trickle down from other specialties or do you think there's...

 

there's evidence to support potentially the use of probiotics in that sense, in older patients in an ICU setting who are being treated for other infections.

 

David Kaufman (23:26.536)

No, yeah, I think this could be a great way and it sounds so simple and Ben you outlined it great. Like this is like a perfect study. And I think what's needed is to like critically think, alright if you're, you know, unfortunately have a baby with like E. coli meningitis and they're on, you know, cephalosporin or you know, some other really broad spectrum antibiotic for 21 days, alright, what probiotic could you give them to keep their...

 

um their microbiome balance that won't get killed by the cefepime like that's where the missing data is like all right which one should we choose plus unfortunately what's available is so scarce so sometimes we only have one choice in our hospital or a NICU but like that's I think where a lot of the fruit um is um I know Mike Sherman who did a lot of work in um like preventing

 

neck, he did a study of lactoferrin and he was looking at the microbiome and he saw when kids were getting antibiotics, like there was really no effect of like the lactoferrin on the diversity, but you know when they were off antibiotics then it could really work. So I think it's trying to figure out, you know, do we need it during or right after or which probiotics won't get killed by the antimicrobial we're giving at that time. So then we can

 

you know, start it right away or, you know, two days before we're coming off so we can sort of balance it working. I think we all believe if we can figure out the right one, it will help rebalance and diversify the microbiome. But the timing and dose and having a good product, I think we all believe will work. We just have to like figure out how to study it or get to that point.

 

Ben Courchia MD (25:23.122)

Yeah. And so let's, I mean, we're coming close to the end of our half hour together. And I wanted to talk a little bit more about lactoferrin, because it seems like it's quite unique in this discussion to talk about lactoferrin, which is basically a protein, right? And it's interesting to see that this has the potential to decrease the occurrence of NEC. And I think there was a, there's many papers that have been published on this, but

 

Can you tell us a little bit about what do we know thus far about lactoferrin and its potential benefits in reducing the rates of NEC? How effective is it? And then we'll talk about future after that. I'm going to let you answer that first.

 

David Kaufman (26:06.652)

Yeah, so I know the initial studies were done like a multi-centered trial in Italy by Paolo Manzoni and he showed like a 66% decrease in bloodstream infections and in very low birth weight infants and it was for like gram positive, gram negatives, as well as like fungal infections, as well as a decrease in NAC.

 

And he studied it like in three groups. He had like one that got lactoferrin and one that got lactoferrin with a probiotic And then there was a placebo group. What's interesting about that lactoferrin We talked about these prebiotics is that it did have a prebiotic in it So certainly similar to probiotics some of the products might not be the same But like that really invigorated a lot of people to study it and he used like somewhat of a standard dose

 

Ben Courchia MD (26:45.589)

Mm-hmm.

 

David Kaufman (26:59.664)

of around like 150 milligrams per kilo. When larger studies were done, I know with different products, we didn't see the same benefit. At the same time, a few studies that used higher doses of like 200 and 300 milligrams per kilo showed that for the kids less than a thousand grams, it can be effective at preventing

 

David Kaufman (27:29.988)

and or neck for these kids. It somewhat works. It's a real strong iron scavenger, so it sort of competes with gram negatives and other bacteria for iron in the gut. And then it also has an effect on maturing the gut, like enterocyte stimulation and proliferation. And then the other thing we love when we're trying to prevent neck is it has like this anti-inflammatory.

 

properties. So those three components make it exciting. So I know my interpretation of the literature is like we've done a lot of good work, but maybe we didn't do those smaller studies to get the dose right before jumping to a real large multi-centered trial and studying higher doses of like around 300 milligrams per kilo, which is what is somewhat in colostrum when we look at lactoferrin.

 

proteins concentration. So my theory is that, you know, for preterm baby, they probably need that colostrum dose, you know, through whatever, 34 weeks or, you know, until they're closer to term, just to help mature their gut and to give that, you know, backup immune protection until their own immunity matures.

 

Ben Courchia MD (28:51.65)

There was a very interesting paper in JAMAPEDES published not too long ago, I think, with the first author was Yu-Ting Wang that looked at what's called probiotics, prebiotics, lactoferrin, and combination of products for the prevention of mortality and morbidity in preterm infants. And as you said, I think...

 

I mean, I pulled up the article because I read it a while back, and I don't remember all the details, but I do remember that they were testing things in combination. They were testing like, oh, let's look at single strain with some lactoferrin or multiple strain and so on. And I don't have it in front of me, but I'm not going to go through my highlights right now. But do you think that then this is the next step in terms of trial, maybe saying, well, accessing probiotics is a little bit more difficult at this time. Should we start looking at lactoferrin alone with a robust human milk?

 

program where babies are getting like mother's milk and see if that is that you think the next step coming up for that specific area?

 

David Kaufman (29:53.028)

I agree with you Ben, I think having this combination makes more sense because human milk isn't just one thing. It's got lactoferrin, it's got lysozyme, it's got white cells, it's got myoglobin, it's got this combination and unfortunately in medicine sometimes we want to simplify things too much and just study one thing. But one thing your previous podcast brought up, if we just do one thing at a time, we

 

Ben Courchia MD (30:08.735)

Mm-hmm.

 

David Kaufman (30:20.384)

It's going to take us 50 years to figure out what five things to put together. So I don't know, we need to do studies better where we're using, we might need four or six groups but one group's getting the combination of three things or another's getting four things because I think it is that combination that's going to make a difference. And doing smaller, more rapid pilot studies to get the dosing right, I think can help

 

Ben Courchia MD (30:23.264)

That's right.

 

Ben Courchia MD (30:45.663)

Yeah.

 

David Kaufman (30:49.78)

get to these endpoints quicker to benefit our patients as soon as we can.

 

Ben Courchia MD (30:58.235)

Mm-hmm. In terms of any other aspects of the management of mortality, infections, NEC in the unit that you think holds promise, especially it could be anything specific. It could be something like an individual agent, or it could be maybe an approach where we're going to look at bundled approach where we're going to put a bunch of different interventions together.

 

a little bit like the QI project that we were discussing earlier in this podcast. What do you think is going to be, what gets you excited for, what are you excited to maybe start your own project in the coming months or years?

 

David Kaufman (31:43.392)

I guess on the prevention platform, I think whatever it is, trying to focus more research on preventing gram-negative infections is really key because they continue to evade our preventative strategies and just have the highest mortality and sometimes the quickest and most devastating effects on these small preemies not surviving to go home.

 

Plus if we could have something, hopefully we'd be doing less sepsis evaluations, you know, make this a smoother course for kids. So I think trying to advocate, I don't know, industry and other partners to think how we can better, you know, study ways of protecting kids. I mean, obviously with antifungal prevention. I know we are...

 

like fortunate, like we have fluconazole, and we haven't seen resistance, but we always worry about that emerging. So we hope these biologics will, you know, will, you know, replace the antimicrobial prevention, you know, both with even GBS for moms to prevent early onset GBS. But I think also in treating infections, I think we can do a better job.

 

There's other studies in adults whether giving a small fluid bolus with the antibiotics, like simple things like that, I think can make a big impact. We have a lot of studies saying there's a lot of AKI, which maybe points to not having good fluid status at the early part of infections.

 

Ben Courchia MD (33:34.278)

Yeah, I think that's very true. And I think when we're talking, so then I was sort of asking you this question because I wanted to maybe end this episode and highlight a little bit the, I guess the website, the web app that I think you've created that's called the Neonatal Antibiotic Stewardship. We'll put the link. It's nicu-frontend.hirokuapp.com.

 

Ben Courchia MD (34:02.478)

And it's quite, I love it because it's very simple to use where you basically would enter a baby's age and weight. You would enter whether you have a specific site of infection, whether it is, whether you have CSF and so on. And then, and then you would get, you would get information and advice on antibiotics stewardship. What, what was the driving force behind this project? And what can you tell us about that?

 

David Kaufman (34:28.544)

I think the driving force was that we have tons of textbooks and tons of papers with nice algorithms, but neonatologists, and maybe all humans, love having an app. They can put in five or six things and it tells them, points them in the direction. Obviously, it can be in their hand. Nobody grabs a textbook anymore. We can't even find them. So I was just like, all right, this is working that way. Can I get something to...

 

Ben Courchia MD (34:39.211)

Yeah.

 

Ben Courchia MD (34:48.222)

No. Ha! This-

 

David Kaufman (34:57.064)

you know, put something together that sort of, you know, nudges us to stop antibiotics when we don't have an infection. You know, also there's a lot of time to positivity work, so maybe for early onset sepsis, we only need to give, you know, like 18 hours of, you know, actual antibiotics to cover, you know, 24 plus hour period. For late onset sepsis, maybe just 36 hours of dosing. Just cutting those doses.

 

there as well as when you do have a gram-negative pathogen, adding a cephalosporin until you know you don't have meningitis, just some of those other things that there's so much we have to know in neonatology. It's good to have something quick and easy to use that can guide people through the night when nobody else is around until they can have a more fruitful discussion on rounds the next day.

 

Ben Courchia MD (35:51.542)

Yeah, where we don't want to wake up your ID attending. I think as fellows specifically, it's always nice to not to wake up someone because you never know how that's going to go. No, but congratulations. It's very simple to use. I really like it. And then again, like I said, we'll put the link on the episode show notes. David, this was super interesting conversation. I think you've given us a lot to think about.

 

David Kaufman (35:54.281)

Hehehehe

 

Ben Courchia MD (36:19.062)

I really enjoyed our discussion on lactoferrin and we'll put all the papers that we mentioned in the episode show notes and we'll put your contact info if people are interested in finding out more about the work that you do. Thank you so much for making the time to be with us today. It was a pleasure.

 

David Kaufman (36:33.896)

No, thanks, Ben. It was great being here.

 

Ben Courchia MD (36:36.15)

Thank you.