56. Antibiotics, Breastfeeding and Infant Health

We were delighted to be joined by Dr Anastasia "Tash" Theodosiou to talk about breastfeeding, antibiotics and the risks of antibiotic harm to mum and baby. Tash is an infectious diseases/medical microbiology trainee, host of the HelloMicro blog and has volunteered as a Breastfeeding Peer Supporter.

*Note the NICE guidelines have been updated and do not recommend trimethoprim in any stage of pregnancy

Transcript

Callum: 0:00

Hi, everyone. Welcome to the idiots podcast. That's Infectious Disease Insights of Two Specialists. I'm Callum. That's Tash. And we're going to tell you everything you need to know about infectious disease.

Jame: 0:13

Soon may the ID team come to discontinue to Ta-zo-cin. One day, when the CRPs done we'll take our leave and go

Callum: 0:23

Tash. How are you?

Tash: 0:24

I'm great, Dennis. Hello?

Callum: 0:25

I've got the pleasure of being joined today by Tash, who is a fellow infectious diseases, medical microbiology specialty trainee in the UK who is also undertaking a PhD in early life microbiome. And also as a certified breastfeeding superior support. Tash, thanks very much for for joining us.

Tash: 0:47

Yeah. Thanks for having me. It's really really nice to be here.

Callum: 0:50

We've had many conversations in person and by email about your PhD, which is very interesting. And I think this is certainly a topic, because what are we here to talk about? Maybe you'll put it better than me.

Tash: 1:02

I was hoping to talk a little bit about the role of breastfeeding in establishing a healthy infant microbiome and really how that's relevant to us as infectioning doctors, as prescribers and as microbiology specialists. And I think sometimes that can get a little bit overlooked or maybe tangled up with prescribing in pregnancy so that we could untangle it and give some top tips for clinicians, specifically infection specialists dealing with lactating patients. I feel

Callum: 1:32

that you said you said you had an analogy about this.

Tash: 1:35

I do. So I think I've been tasked with making the the pun, the awful pun of the episode. So I have an analogy that I'm going to be milking throughout the episode, and so I'm gonna get right started with that. So I have an analogy for trying to explain the microbiome. And the way I do this is it's like decorating a house. A baby is literally just a series of rooms with bare plaster walls because babies are basically sterile when they're about to be born. And then As the baby's born and it passes through the rhino and becomes covered with moms perineal flora, that the chimer that gets applied to every single wall in the house inside and out. And that chimer is what we call the Pioneer Microbiome them. So in the first sort of twenty four hours of life, the baby's just covered with all this undifferentiated microbiome from the mom. But even though every room in the house gets exactly the same primer, you then have to go around and paint every room in the house with a different color. And that is where the baby gets all the microbes from prolonged contact with the mom's milk, with her skin, with her mucosal surfaces, And so that's where you go from this really undifferentiated ioneer microbiome to having a niche differentiate microbiome. So that's where every bit of the baby has its own unique microbial profile and that starts to become evident from as early as about forty eight hours after birth. You know, so you start to see the differences between all the different anatomical profiles in the baby. And that's based on the the contact of mom's milk, month's skin and a mucosa. But what's important is that without the right primer, the right microbes might not stick. So that's the real problem is that unless you have that primer that perineal flower during during the vaginal birth, you might not get the right microbes sticking. And we know that because baby is delivered by a C section, have a very different microbiomes and babies born vaginally, and those differences can be apparent for months or even years later. And if you don't use that optimum primer right at the very beginning, the quality of the paint that you use becomes even more important. So that's why we know that, for example, breastfeeding, which is, you know, one of these paints that we talk about, these these form, the the sources and microbes, and even more important in situations like c sectioning. So, breastfeeding in in that disrupted microbiome can actually offset some of that microbiome perturbation. So so that's my I've merely milked my analogy as far as it can go, so that pioneer microbiome being the primer, that that perennial flora, and then all those different paints are are sort of late to microbiome. But then antibiotics, as you can probably get, is paint stripper. It is it is just indiscriminate paint stripper sprayed in a room that you are trying to decorate. For the very first time. And it's true that antibiotics can have a really profound and prolonged effect on the microbiome with even a single dose of antibiotics given to a pregnant woman being able to have a measurable impact on the baby's microbiome after it's born. And that's really important to us as infection doctors because we know that twenty five to fifty percent of pregnant women in pine come trees and seeds, antarctic and up to eighty percent of baby by the age of two have received a course of antibiotics. So, you know, this isn't a a minor or small scale issue. So that's that's the analogy. That's to lose how the microbiome develops. But why why does this matter so much? And it's because this spine and painting and establishment of the microbiome is predictable and it coincides with normal immunological development. But when you deviate from this normal, predictable microbiome and immunological development, so for example, with c section or antibiotics or formula feeding, there are associated changes in these microbiome and immunological profiles that correlate with adverse health outcomes. So that's why this is so important because babies that have had that have been born by C infection, who received antibiotics in pregnancy or or after birth. Or who have received formula are more likely to have GI and respiratory infections in childhood, they're more likely to have allergies, asthma, and they're more likely to have obesity and diabetes even well in the later life. And so this is really relevant to us as IV and MicroTracking. Because antibiotic stewardship in this population isn't just about, you know, antimicrobial resistance and all the usual jazz, it's about protecting a baby's immune development. And potentially preventing adverse health outcomes for decades to come. So yeah, Kevin, I

Callum: 6:24

guess, someone who hasn't I've not really sat down and fought about this that that much. But it just makes complete sense. I really like the analogy of the of the paint and the and the paint stripper in in terms of the primer and so on. Thank you. One question that I had in my head and this might be a a stupid question. But, hey, the name of the show is it yet, so I can ask Jippe questions. So you were saying that the sort of perineal floor is the the primer? So as anybody looked at --

Tash: 6:51

Mhmm.

Callum: 6:52

-- if we have a baby that's delivered by c section and they miss out on that primer stage, could you collect some, you know, fluid and and then up apply it in a way? Is that something that's looked at? Or you'd be looked at?

Tash: 7:08

Yeah. So that's going on at the moment. So the earliest trials are in progress at the moment. So if you take a step back, so We said that that that the gional and perineal flora is mainly sort of priming. So it's not like the baby's skin is gonna look like a perineum or like a vagina for a week to months to come. It's just that it lays the groundwork so that the incoming microbes and stick in the right places and establish properly. With a c section baby, that in your microbiome looks more like skin and environment, which I guess is what you'd expect because that's the first thing it comes in contact with. And then there are some trials at the moment. Where with elective c sections, they incubate their all gauze in the vagina and then after delivery, apply the gauze to the baby's skin and faith. Those are in really early stages. I think it's a fast making concept and the early signals are that they couldn't push the microbiome more towards So from the C section baby, push it more towards what you'd expect to be a vaginally delivered baby. I mean, I think the the jury's still out on, you know, clinical utility, safety, I think being able you know, assuming that that applying a gauze is exactly the same as as the journal delivery. I think it's something that's gonna need to be borne out by the data. So definitely don't think it's something that should be being done, you know, in a outside of clinical trials just yet, but it is a really, really interesting concept.

Callum: 8:35

Thanks for walking through it. So we've we've heard about the microbiome aspect and some of the sort of the issues that I can lead to.

Jame: 8:44

What's next?

Tash: 8:45

So I was gonna talk a little bit about some of the specific functional and physiological aspects of of breath milk itself. I think typically we think of or maybe we're taught of breast milk as being nutrition and hydration. But I primarily to be honest, I think a bit more as immunological training, and I think the evidence is growing rapidly over the last two to fifteen years or so that that is the case. I think we've mentioned some of the microbes already. I think what you the actual live bacteria in rest milk is really interesting. So we've said, you know, that it's It's not the primer, but it's the paint. And what it is that it's coating the the infant gut and the respiratory tract with. Lots of different things. The key players are things like bifida bacteria, lactobacilli, staphylococcal and briny bacteria. But what's interesting is that you get very divergent profiles in the gut microbiome and the inflammatory profile of a breastfed baby compared with a formula baby. So the breastfed baby is the gut is rich in these anti inflammatory actinobacteria, like bifida bacteria. And you also get a skewed key helper cell polarization towards t h one, which we know is important in cellular immune responses to pathogens. Whereas in formula fed infants, there is more of a trend towards pro inflammatory proteobacteria like enterobacteries, and more of a Th2 polarization, which we know is associated with overactivity in things like asthma and allergies. Now obviously, it's not completely binary. It's not like, you know, breast fat infants are going to have, you know, never have allergies and formula fat infants are always going to have infections and allergies. But but those are the data profiles that emerge at a sort of microbiome and immunological level. Then one of the key components of of breast milk apart from the actual microbes is human milk oligosaccharides, which are quite possibly my my favorite thing in microbiology that's not actually a microbe. So they are sugars that make up about fifteen percent of the milk, but babies can't actually digest them. And I mean, if you think about that at at an evolutionary level. That's that's mind boggling. We've evolved fifteen percent of the breast milk that we make Isn't feeding our babies? It's feeding bifida bacteria. It's it's it's farming bifida bacteria in the baby's guts because the baby can't digest it. But the but the favorable anti inflammatory Keystone commensal that we mentioned and digest it. So that's why we're providing it for them. And what's also fascinating is that a lot of enteric pathogens can't digest it either, so they try to digest if they become immobilized on it, and then it gets excreted in the infants pool. So really, really fascinating. So that's that's the microbes themselves, the human milk, thesaccharides. There's also a lot of really interesting research at the moment into extracellular reficles. It the science here is quite new, but it looks like these extracellular vesicles from mum contain maternal MIRNAs can actually change the infant's gene expression, and it can also contain dead bacterial DNA from moms. So basically, it's providing androgenic exposure in the infant gut so that you can stimulate an adaptive immune response without having to see the microbe itself. I mean, that's really cool. And then lastly, I wanted to give a shout out to the Cree CreeIGA, which I think people always think about it as being just kind of passive immunity. But you need to remember that it's passive immunity that changing continuously based on what the mom is being exposed to, both in her gut and in her respiratory tract. So it is possibility, but it's it's changing with what what bugs the baby is gonna be exposed to. And there's even evidence now that the secretory IgA in the breast milk might respond in part to the microbes that are in the baby's mouth. So really, really quite an interesting relationship.

Callum: 12:41

The more I learn about medicine than the human body and the microbiome, the more complicated it becomes. And the immunology of it is really fascinating. So banks for giving such a, like, overview of of what I imagine is a lot of different science and hard work to to to uncover that. So so I guess you know, thinking from from the perspective of of infections and so on, I guess, to summarize that you're you're you're saying that there's two things I guess. One is that breastfeeding and and milk has lots of benefits and we're learning more and more about that. And to the antibiotics have a big negative impact on the microbiome. So I guess our aim should be to try and maximize or minimize interruptions to breastfeeding so that they get those benefits and minimize antimicrobial use. In general, but also when we're using antimicrobials, think about those effects that they're gonna have on the microbiome as part of our risk assessment about whether we should give antibodies or not. Because I feel like the default position often is we're so worried about sepsis that and and we we don't really place those opposing risks high enough to think --

Tash: 13:58

Exactly.

Callum: 13:59

-- do do we really need, you know, sepsis as a label applied very loosely, sometimes doesn't it?

Jame: 14:04

Jame has entered the chat. Yes. Absolutely. And particularly when there's a mom and baby, I think that there's a real strong preponderance to hit hard with antibiotics and think later because you've got two lives that's taken, you know, and you got a mom and you got a kid. And most moms are, you know, by definition young. And therefore more able to kind of tolerate a harder hit for the broad spectrum anti microbial, which is true. I'm not arguing with that. But it then means that there's not much of an incentive to be stewards about it. You know, you can just give them all cobalt to collaborate and and then just kinda go home and assume that the job has done. And that leads to quite a lot of broad spectrum antimicrobial use and not a lot of thinking behind it.

Callum: 14:58

Yeah. I guess, how how we weigh risk is based on the things that we that we consider as the problems. And all you need is one pregnant woman to die from an infection or, you know, I guess, with group a strap being such a concern recently. We're so worried about, you know, the adverse outcomes of an under managed infection. And or over treating, or recalling infection is is and I guess that had to be equipment stewardship in every setting, isn't it? But seems like rather than here being the area where we can relax because patients are young and quite robust and maybe reframing that and saying this is the area where we should worry about stewardship the most. Would that be fair to say? Maybe it has the biggest you're saying -- Yeah. -- biggest impacts, biggest evidence based behind it.

Tash: 15:43

I think the biggest evidence based for for the potential adverse effects of antibiotics and the by standard effects of antibiotics. I think it is very fair to say that the most robust evidence is an early life. Completely need to, you know, obviously emphasize that that undertreating infection is not in any way what we're suggesting. But it's as you guys are both very rightly said, it's about recognizing that there's there is a risk to over treating that it's not sort of that this idea of just to be on the safe side assumes incorrectly that there isn't a downside to over treating antibiotics. And I think that's all that it is. It's about making that more aware. And also, I think Bear in mind the you know, as as you both said, it's it's not just the baby or just the woman, it's the mother and the baby together. And you know, I've I've been a best breastfeeding mother. Breastfeeding is is difficult. It's exhausting. And at moms, we are very, very good at creating guilt for ourselves. So last thing we need is for clinicians to add to that by judging any of our choices. So this isn't at all about shaming any individual choice about how you feed your baby, how you birth your baby, or what medications you give your baby. It's about upskilling clinicians to be a constructive player in those choices. That's all that it is. Yeah.

Callum: 17:02

I guess, all we can do is look at the evidence and the data and and the facts. And use that as best we can.

Jame: 17:09

Tash, can you tell us a bit about how drugs from plasma across the placenta? To the fetus and into milk and how they differ.

Tash: 17:20

Yeah. So, yes, I think they often get lumping together, don't they? We often talk about sort of pregnancy and breastfeeding. But actually, if you break it down from a drug transfer point of view, it's completely different situations. So the one you've got direct blood flow from the mother to the fetus. And actually, in pregnancy, you've got a significantly increased relative blood supply to the uterus. So in some cases, the blood's the drug concentration in the trans placental blood will exceed that in the systemic maternal circulation. You've also got the fact that moms' systemic circulation has increased in both volume and cardiac output. So that all these additional things to think about, you know, increased renal blood flow and associated increased eGFR. Changes in in metabolic enzymes in the liver. So all of this means that depending on your drug, you might end up with higher concentration than you would otherwise have if she wasn't pregnant. You might end up with a lower concentration of the drug than if she wasn't pregnant. And because of this enhanced blood supply to the uterus, you could have an even higher relative concentration in the in the transplant center blood. If you contrast that with blood needing to get into milk because rather than sort of mom's blood intrapating directly with the baby's blood, it has to go via the breast milk. And so when you think about it sort of logically, the drugs that are going to be at highest risk are going to be those that are – have very low plasma protein binding in the mom because then more of the drug is free to cross into the breast milk or drugs that are very lipid soluble so they can dissolve in the milk. That would be things like your lithium and amiodron or drugs that have very high inherent toxicity would usually be contraindicated even if the concentration in milk is very low. So that would be like you should have, you know, chemotherapy cytotoxic. And we've we've just had an off air conversation where we couldn't think of a an antibacterial that was an absolute contraindication in in breastfeeding. But yeah, so those are the those are kind of two considerations there. The other one that's more of a relative thing to think about is where there is either a risk harm from animal models, but not in clinical models, and that's where you then have to weigh that up. Or if there is just a lack of safety data directly from breastfeeding women. And that's where it comes a little bit harder harder to do. Yeah. You know what to do?

Jame: 19:53

So, I guess, the new drugs you know, particularly some something comes onto the market. It will almost definitely not have been tested in pregnant women for us unless it specifically for for use in in pregnant people.

Callum: 20:09

Wasn't that the EMA were saying that you had to have the data for children. Mhmm.

Jame: 20:13

But yeah. But, you know, in terms of trials of pregnant women, I don't know there's any mandatory.

Callum: 20:18

It's really difficult to do to do that trial. Like, I don't know how could feel about it. But I think, you know, I think people are happy to to participate in research in situations where, like, there may be a benefit to themselves or is a lack of harm. But if you say to someone like, we want to give you the Santa Monica and we're not sure it might cause a problem if you're unborn child or your child that you're breastfeeding with. It's it's quite a hard sell, I think.

Tash: 20:43

So we actually delve into this quite a lot my PHD, it involved an interventional study in pregnant women. And so I kind of dug down into the historical context of this. And it's really fascinating because for exactly those reasons because of concerns about harming pregnant women and their babies and because of a couple of very high profile disasters, thalidomide, and also the DS. There was a widespread international moratorium on including pregnant women in research at all for many years, so write through from sort of nineteen seventies, through the nineteen nineties. The pocket where they were actually carved is a vulnerable population, which is quite interesting considering that they were, you know, by and large, consenting competent adults. And that did actually get reversed in the nineteen nineties in has been growing calls to involve more pregnant women in research because, on the one hand, you could say, you know, we're trying to protect women. And their babies. But on the other hand, you're saying, well, actually, we're going to not test these medications in a potential target audience. And we're then going to either have to give them a second line choice that has more evidence or give them a first line choice without evidence to back it up. So, you know, especially as things have moved away from kind of quite paternalistic medicine towards more you know, the patient, a more patient centered approach. I think there have been some more calls to to involve pregnant women with more in interventional research. They're still by no means sort of huge uptake, but it but the kind of rhetoric around that is starting to change a little bit.

Callum: 22:20

Yeah.

Tash: 22:21

But as you say, by and large evidence that we have of drug safety in pregnant women and in lactating women comes mainly from from post marketing surveillance. And so there's a few different ways that neither reports of drugs that have been used or those pregnancy registries, those national and international, or inadvertent and that's usually the first trimester where women take a drug before finding out that they're pregnant. And so that's usually where this information would come from rather than from a Phase one and Phase two or you get a Phase three trial.

Jame: 22:54

Yeah. Or the drug has just been used historically before we even thought about tardataGenicity. So their data has come from the fifties and sixty and then because it was really only after thalidomide caused birth defects that we felt that drugs might cause birth defects at all. And before that, we were just basically giving everything that we had to women regardless of, you know, whether or not they were pregnant. And then that led to a grandfathering in of a bunch of antibiotics, which we know, know, or safe. But most of the info, you know, when you look up, you know, a certain drug on on the UK territory information service, you would be you probably wouldn't be that surprised, Tasha, about how many times it says that so accidental use in hundreds of women has not resulted in tobacco gene editing, but it's never been compared in

Callum: 23:55

the clinical trials. So it's just accident that's resulted in a load of safety data. It's not because of any brilliance on the part of researchers. So I I find this is quite you know, certainly when when I get asked for advice on patients with infection, you know, there's certain calls when people say stuff I find, I'm like, oh, no. So when someone says I think this is maybe not right. I don't know if you're gonna admit this, but if someone's pregnant or breast breast feeding, then I do do sort of internally grow in a little bit because I'm like, this is gonna be complicated. And it's not something that I'm like doing enough all the time to have memorized all the advice. So, you know, it it is difficult, which I guess is why we're talking about it. And how would we classify, Jane, the risk for different drugs, I guess, in in use in these situations?

Jame: 24:53

Well, classification of risk is really difficult in these situations. Because so here here's how they they used to be classified, and this is no longer in effect, but the CDC had a good goal at classifying drugs by risk and pregnancy. And they had a sort of a to d scale that people were using. And a would be perfectly safe. And then it went to d, which would be absolutely contraindicated in pregnancy and or breastfeeding. So a class D drug would be thalidomide, for example. You're not meant to use that at any stage. And then an example of a Class A drug would be, say, penicillin, you know, penicillin is reasonably safe. They've stopped that now. And the reason that they have done is kind of twofold. The first is that almost every drug was either Class B or Class C. And so that communicated kind of very little information about it. So a Class B drug could be something which as far as we know, was as safe as a Class A drug. It's just that it never been confirmed in clinical studies. And a class C drug. The kind of the barrier between a class B and a class C drug was was kinda reasonably fuzzy. So but then the other the other big issue was that the risk varies by trimester and if the patient is breastfeeding or not. So tax is already touched on this that the the risk from breastfeeding in the drug transparency is very different if whether the drug is crossing the placenta, which is actively throwing stuff for the baby to try and get to grow or if it's going into breast milk. And but the the other issue is that the the risk of it is by Trimester and that wasn't really reflected in this A to D classification. So for example, Trimethrom is Class C. And that means that you've got to worry about it. There's, you know, lots of danger, etcetera, etcetera. You definitely don't want to give it to somebody in the first trimester. But after the first trimester, and as a reminder to throw a mobile listener, in the first trimester, the thing is going from a fertilized cell to the end of embryonic development sort is written about the end of the first trimester. And from then on, it's just getting bigger. All the tissues and organs are going to be developed, being developed, they just need to get larger and mature. And so trimester's two and three, it's just growing. So the drugs that you need to worry about, the ones that stop it growing. Trimester one, you can interfere with a neural tube, you can cause real problems. And Trimethram does that in Trimester one, but it doesn't do it in Trimester two and three. So it's perfectly safe. After that point, but that wasn't really reflected in the CDC guidance. So the CDC had a look at this, and they thought we're just gonna get rid of this completely. And instead what we're going to do is we're going to just dump all the information somewhere and it's on the CDC website And in Europe, what they've done is they've set up territory information services in lots of different countries. The new case got its own one. And they essentially have all the information. It's freely available. And in fact, the UK technology information service, you can access it. You have to register with it, but an NHS email is all that you need, and you'll get full access to all of their information. And they've done this so that you could then take this information and turn around and inform the mother so that they can make it informed showing some of this classification has kind of gone away because people didn't really there there were lots of flaws in it and rather than trying fix it and have, like, a classification for the first trimester, a classification for trimester two and three and another one for lactation. They just scrapped it entirely. And I think that's probably for the best, to be honest.

Callum: 29:17

So UK, the UK tests website. It could be one source of information attached. What what what's your sort of approach when you're looking for information on on what is safe and and what's not as other resources that you would go to?

Tash: 29:34

Yes. As you said, the in pregnancy, up absolutely the territory territory information service is the the number one protocol. If it is a lactating woman who's already given than I think there are a couple of other options. So nice guidelines recommend both LactMed, which is an American resource that is really useful, regularly updated -- Mhmm.

Callum: 30:00

--

Tash: 30:00

by the by the US NIH. So that's where I would go to look something up. For more nuanced advice, there's also UK dialers from the the UK's specialty pharma specialist pharmacy service.

Jame: 30:16

What does that That's fine.

Tash: 30:17

A couple of your users.

Jame: 30:18

What does that stand for again? UK.

Tash: 30:21

As UK drugs and mutation and vice service.

Jame: 30:25

Yeah.

Tash: 30:27

And that can be a really great useful resource for two reasons. One is that it's got a a risk assessment to to sort of get you thinking about the types of conversations you need to have with the with the the mother and what information needs to gather. And for more nuanced questions where you can't find the answer on BlackMed, They have a phone in or email in service where you can come up with a comprehensive plan for that particular patient. So those would probably be the to better recommended most widely and certainly by the nice guidelines. And then, obviously, during pregnancy UKTIS.

Jame: 31:03

Yeah. And the the, like I say, UK dialysis, it's on the SPS, the Specialist Pharmacy Service. They also have a sort of similar sanction for pregnancy as well. Which people might want to go look at. There's a they've also got subsex infections and pregnancy, and they've got sort of it's not very comprehensive. They've just basically got advice for UTI and treatment of thrush and vaginal candidate. It looks a bit like a work in progress. I think when they if they turn their attention to it and produce much effort into us, they've done with with lactation that it'll be really really useful.

Callum: 31:48

And you mentioned did you mention they're attached that you could contact? Contact them.

Tash: 31:54

Yes. You can contact them for a bespoke advice.

Callum: 31:56

And and when you have you contacted them before? And and how how know, how easy is it to get through, sort of, is it because I've never contacted them. I don't even know that.

Tash: 32:05

So I've Yeah. I haven't needed to contact them previously. I have contacted the breastfeeding network, which also so that's a registered charity that has drug fact sheets and advice, but it tends to draw from other resources rather than being sort of licensed pharmacists or clinicians themselves. Both, you know, it's another really, really useful resource. But I think in terms of, you know, what the, certainly, the nice recommended ones would be would be lapped med and uk dialysis first. But the best breastfeeding network is fantastic for a more holistic approach that also takes into account particular breastfeeding problems that the that the woman might be having. Yeah.

Callum: 32:53

Because I think you've mentioned before because we've we've obviously talked about the effects of positive effects of breastfeeding, but I I guess one of the things that you you'd mentioned before the show was, you know, the the negative effects of interrupting breastfeeding and how how important that is and and and part of this. So, you know, making sure that although we're we're thinking about lots there's so many different things to think about, but that that's something that, I guess. We could, you know, or just stop breastfeeding for a few days, you know, and maybe I certainly I think before we've had this conversation, maybe undervalued the the potential negative impacts of that in my head?

Tash: 33:34

So I've come across that a surprising amount. So clinicians calling for microbiology advice, and it usually goes along the lines of I've looked it up in the BNS the BNF says don't use this drug in lactation. So should I not use this drug or should I just tell her not to breastfeed? And it's interesting that those are the two things, those are the two options that the clinicians calling me about. And often, it haven't involved looking beyond the NF. Using eucidialis and MacMed like we mentioned. Mhmm. And it's sort of for them, it's a toss-up between not using the drug or using the drug and interrupting breastfeeding. And I think for a lot of the reasons we've already said, both of those can be quite problematic. So, you know, we've already said that So if I kind of split those up, so going straight to the BNS and stopping at the BNS is actually not what the nice guidelines recommend that you do. So in both pregnancy and breastfeeding, the nice guidelines acknowledge that the BNF's advice is not comprehensive enough for those particular situations. And the reason for that is the information is often based on the summary of product characteristics, which is sort of based on the drug trials themselves and the drug licensing. So it's got a really, really high threshold to achieve recommendation by sort of at a licensing level, which means just because the B and F says there's not enough information to recommend it. It doesn't mean that it's not safe, and that's why it's important to go to those other resources that we talked about. So that's the one side of the coin. The other side is what would happen if you interrupted breastfeeding. And again, this this depends a lot on the woman. It depends a lot on how long she's been breast speeding, but just that you have someone coming in the first few weeks where they've tried to establish feeding, two things are going on at that point. So the mum supply so her actual milk supply is becoming established. And in those early days, every single feed contributes to establishing a consistent and successful supply. And there's also that they latch. And so while, yes, absolutely, some babies may switch seamlessly between a breath and a bottle. There is absolutely no guarantee that if you take a baby away from the breast, for a few days or a week or however long the prescription is, that they will transition seamlessly back to the breast. So both supply and bladder can be affected. And Even more so, I mean, we're infection doctors. There is a statistically significant increase in the risk of mastitis. When you interrupt breastfeeding because even if you were to pump and throw away the milk during that time, you can't always match pumping and and and breastfeeding exactly. And so there is an increased risk of mastitis and engorgement if you interrupt breastfeeding. I guess my worry is that right now, there's probably clinicians up and down the country who, without realizing it, their advice or their conversation with another clinician or or with a patient. It may have been the thing that actually stopped that woman's breastfeeding journey. And I think most of those clinicians will have no idea that they were involved in and they'd probably be horrified if they found out. So again, it's not at all about pointing fingers or or causing shame or blame. It's just about making sure that we're thinking about this and thinking about the impact that some of these, you know, individual conversations that we might have with women at this crucial time might have.

Callum: 36:56

I guess, there's two there's two things that, you know, if you're getting a phone call for advice, like, you you attach specifically, there's there's gonna be plenty of interactions that people have, but they just don't phone for advice. And so, you know, what's happening there? But also, I'm sure there's interaction that people do phone for advice and people are quote unquote and risk adverse. With antibiotics and pregnancy and so advise, you know, potentially stopping breastfeeding. So it goes both ways. So I guess, you know, that's a message to everybody that's involved in giving advice are are are interacting with these patients. I guess that's where we can get the guidance from. And I think I've I've certainly used LatAm quite a lot, but the the others are sort of new to me. So I'll need to go off and use them in more detail.

Jame: 37:46

Yeah. We can include a few resources in the in the show notes. So LACMed and UK relapse from the SPS are good resources. UKTIS is really it's it's not really patient facing. It's for medical professionals to go look in detail. And then there's a paper that I will include that I thought was a pretty good summary as well. And there's also a nice little summary in GP notebook of the stuff that's -- Yeah.

Callum: 38:18

--

Jame: 38:19

generally good to scribe for GPs that I use that as my jumping off point when I was making my big what's safe and what's non document, which will base the show notes on as well.

Tash: 38:30

And also the GP infant feeding network. They're all kind of sort of connected to each other. And I sort of have different reasons for going to different ones, but but the GPU and the competing network is also really useful. And I think, you know, you mentioned about UK TIS, not being patient facing. They've got all so bumps, which is related to UK TIS, which is all patient facing leaflets. And then breastfeeding network has lots of patient facing stuff. And I think those are really important because, I guess, you know, when doing the risk assessment, Kellogg and I were shutting back this beforehand. But I think because women are very engaged in healthcare, in the sort of pregnancy, and postpartum period, and there's a heightened sensitive awareness about their health decisions and potentially walking concern and more fear around about their health interventions. We always need to remember that just because we've prescribed something doesn't mean that that's where the story ends. So that woman might be concerned and might not actually taking the drug because she's worried about the impact on her pregnancy or on breastfeeding. And I think so those patients, they think resources are fantastic. Let's just sort of closing the loop in the risk assessment and prescribing for infections in pregnancy and breastfeeding.

Jame: 39:44

Yeah, true enough. That's a really good point.

Callum: 39:47

So we've done a lot there about, you know, where to get information. Jane, you you mentioned you you've hinted or or teased, I guess, this resource that you'd come up with. So maybe can we just talk a little bit briefly about, you know, more specifics in terms of antimicrobials and you know, what things are just some general points. I think, hopefully, you've got the message from this is that anytime that you're prescribing antibiotics in situations, you need to go and look at these resources yourself and and and get an authoritative answer. But what's the sort of general thoughts on which Chandler Macroebills are safe to use? So there's with the what what the show notes will be based on is a document that I drew up for Nidosh Water and Facility South. Microguide. And what I've wanted to do was It was part of a

Jame: 40:44

a bunch of documents that I was drawing up as a sort of like advice for f ones. Kind of thing. So like, what's what do you need to adjust in, you know, renal failure, liver failure, obesity, and pregnancy? And breastfeeding as well.

Callum: 41:01

Can I get a copy of those?

Jame: 41:04

Yeah. You can. And so what I wanted was it for it to be you know, easily present with the information that they might need kind of upfront. So to to kind of gloss over it, and then we'll talk about it in a bit more detail. The stuff that is generally considered to be safe in pregnancy and breastfeeding are sell wall agents, so beta lactams and your glycopantides, although they're evidence for the long acting like hepatitis lacking your dauper vancans and your oral vancans. Some, protein synthesis agent, so you're gensamycin, macrolides, and clindamycin. Metronidazole, trimethopram after the first trimester, all your standard TB drugs, so you're fast and nice and frozen by nifabutil. And topical agents, no problem. So uprolesin and pussidid, if you need to give that. But as you may be aware of comments, not if if you actually go and look at the UPTAS guidance and the SPS, as in Yuki dial lasts and their their stuff from pregnancy as well. It's it gets a little bit more a little bit more fuzzy. So let's start with the beta latams because the beta latams are beta latams. Generally, they're considered safe at all parts of pregnancy, but recently there's been a signal where combos a class of all things. They have a recommendation to avoid it with premature rupture of membranes because of an increased risk of neck in the baby after it's born. And then the other third trimester, warning agent as the cataractants can cause keratitis in the knee and knee. And I think that's pretty well known in the PDF tricks that KFRAXdom is opposed to kFRAXIM can cause jaundice, neonatal jaundice. And for that reason, KF taxane is prepared generally, particularly in the first two weeks. But even after that, you see that an intense KF taxane is usually given KFraxone is excreted partially into bile, which can explain why it has it can have that effect on occasion because it's called stasis. But then in terms of safety and breastfeeding, there appears to be no dangerous signal whatsoever with the with the beta lactams. Would you agree with that hash?

Tash: 43:42

Yeah. I think so.

Jame: 43:44

And then I

Tash: 43:45

mean, apart from the the sort of microbiome things that we said, but no specific drug.

Jame: 43:49

Specific. Yeah. And then for the glycopetides, for van den Tycho, they are generally considered safe throughout all trimasters, and the new agents, there's just a lack of data. It's not that we know that they're dangerous. It's just that we don't know that they're safe. And that's where the BNF will say something like No known safety data manufacturer recommends VoIP. Of course, the manufacturer would recommend VoIP. That doesn't let you know anything really. That's just them covering their own back sides and the B and F unfortunately has taken the position of basing the recommendations mostly, not exclusively, but mostly on the on the SPS data and that's kind of results in this kind of cautious approach.

Callum: 44:40

I found that interesting and Ashley, you were saying that that your experience of people just look at the B and F and stop. So I do wonder if there's a missed opportunity there for the B and F section to say, like, This is our recommendation of the data. This is where you can go for more information and just signposting that and making it really easy for people. And I I wonder why that isn't.

Jame: 45:01

Well, I don't I don't know why they don't. The B and F tends not to refer out to other organizations because it is a reference document. It is sort of, you know, got this history of meaning to be printed, which means that links are not really Absolutely. Yeah. Well, I mean, slowly that is being changed and so that you now see that in the sort of summaries that they've got. They're they're sort of linking it to the NICE CKS. It's basically been integrated slowly into into NICE. But it's still run by the Royal Pharmaceutical Society. It's not run by NICE. Yeah. It's just that they've got a very tight relationship to each other. And then in terms of the other sort of protein synthesis agents, so for amyloid like signs, they're generally considered safe, but because of an extensive pattern of use, gentle lysine is the preferred agent. There have been reports of fetal heating loss with strength to lysine. And for that, they've recommended avoiding that. But I think in certainly in Western Europe and U. S. That will be an issue to optimize and it's not really very commonly used for other reasons, resistance, rapidly evolving.

Callum: 46:17

Do you do you think that that's to do with what you said earlier on about concentration of drug into the treated placenta. You know, if is that something that would affect immunoglycosides? Because we know that the you know, the hearing loss thing is of accumulation of drug and the effect on the hair cells, isn't it? So Could

Jame: 46:36

that be Well, it is, but I think it might be a drug effect as in streptomycin is more likely to cause the hearing loss. Just even a normal non pregnant people up here to gent mice. Yeah. And then let's turn to the macro lights because they've they're a bit funny. So there are different recommendations on different sides of the pond. So if you are in the UK, we will advise you to use arithromycin because there's a large body of evidence that it's safe to to use and failing that to use Azithro and failing that to use clarithromycin as last resort. There is a unproven minor association in the first trimester with unspecified birth defects. This is all from the UKTIS. And so they say use alternative if possible, but a few if you can then. They're with some licenses, one for you. In America, they will advise you to use azithromycin first, and to use a rithromycin last. Because they they have a body of evidence because they use it as a formicin a lot more than we do. And so they would generally consider it to be safe, and they think that using neuroscience and pregnant women is akin to torture, because there's no GI side effects and and what have you. Yes. So to clindamycin is generally consider safe air pregnancy. When it comes to breastfeeding, there's a rare association with antibiotic associated colitis. When I say rare, I mean, there is one reported case. But for this, the UK TIS have kinda seen fit put a warning there. And I guess that makes it worth discussing with with breastfeeding patients. But generally throughout pregnancy, clindamycin is used as I'm sure we're aware with reckless abandon. And then the other proteins that this agent to mention is is Korlym Fenical. So Korlym Fenical is basically contraindicated throughout pregnancy because of this phenomenon called grey baby syndrome.

Tash: 49:02

It's one of the classic ones where pregnancy is a far, far higher risk than breastfeeding because you do that's one of the dose related side effects of of cornpinnacle. So therefore breastfeeding would be high risk than pregnancy would be high risk than breastfeeding. It's an interesting one. Because it brings up some of the non dose related side effects. So things like, you know, the classic being chloroquine and venetal associated with dyskinesia, which is, you know, it is in bracket not related to the dose. So theoretically, you could get that by breastfeeding. Although as far as I'm aware, there haven't been any recorded cases of chlorothenical induced atlastic anemia in breastfeeding. But it is an interesting one that, you know, it is worth thinking, what we said about breastfeeding and because the doses are much lower thinking that it's lower risk, obviously, that wouldn't apply to side effects that are not dose related.

Callum: 49:57

Mhmm.

Jame: 49:58

Yeah.

Callum: 50:01

So James James entered the chat. And James has left the chat. Just as suddenly, unintroduced as he entered. So and I guess, in terms of the other protein synthesis agents that we might think about, So, I guess, you want to talk about tetracyclines and the nesalid?

Tash: 50:20

Yeah. So I think There's historically, there's been a big thing about people to discoloration with tetracyclines. And so for that reason, generally speaking, the guidance is to to sort of avoid. And that's more in the second and third trimesters. There is some guidance that you can use it with caution in the first trimester in terms of more to do what the teeth are actually developing. And then with breastfeeding, again, it's one of these kind of like amber type things. So the theoretical risk of discoloration because of the tetracycline getting into the milk buy the mom, you know, then getting into milk. But in practice, those those resources that we recommended would say that you can use it safely, but that you should avoid long courses.

Jame: 51:07

That makes sense.

Callum: 51:09

And then Lonezolid, I guess. There's a sort of blanket, I guess, orange. Look at that. And I I I'm not sure if that's just because there's not enough evidence. Use of risk outweighs benefits. I guess just from a sort of the pharmacokinetic perspective that that that was discussed are they on, to my mind, La Nizlet is one of those drugs that would fit that, you know, low protein binding, high lipid solubility, high orally bioavailable drug. And it does have quite a lot of toxicity concerns, particularly if used longer. I don't know how you feel about that. I think I would have to look it up to know I'm certain if he could use it or not. Not something that I've had to use before.

Tash: 51:53

Okay. So LacMed says the baby would receive about six to nine percent of a standard dose. Yeah. And that resulting infant serum levels are trivial.

Callum: 52:05

Trivial as interesting.

Tash: 52:07

So if lenazilib is required by the mother, it is not a reason to discontinue breastfeeding.

Callum: 52:14

Great. Well, that is a a work example. So if you don't have a Jane and then you can you can see there that this despite Jane, departing and abandoning us in our time of need. We were able to talk about tetracyclines and Lynnezzolid What about DNA agents?

Jame: 52:33

Okay. So the DNA Oh,

Callum: 52:35

James back. Oh my god.

Jame: 52:37

James has reentered the chat again. Yeah. So and let let's start with Trimethrum. Will we So Trimethrum, you you know the story. It's it's Nancy Foley. It's similar to methotrexate. Only it's working in Prokaryotes rather than new carriers except it also works in new carriers a little bit. And that particularly important early on when the neural tube is being formed. And so if you give somebody an anti folate agent, then you can get issues with neural tube closure. Now the first trimester is when that's most important because that's when the neural tube is is is kind of form and and closing. And you, you know, if it doesn't close the top end, you get in and carefully if it doesn't close the bottom end, you get spina bifida. You can give tremorium if you absolutely need to. I can't imagine a situation where you would want to. But if your back was against a wall, that was the only thing you could give, you could supplement the mother with five milligrams of bifolic acid. So that's high dose spolic acid as opposed to the normal dose, which I forget for that is task, do you know? Do you remember?

Tash: 53:51

Let's say, four hundred micrograms, but it's double test.

Jame: 53:54

Yeah. So if you need to, you can give it. You just give also forecast. A bit like if you were gonna have some of your methotrexate, you give them forecast on every day except the day that they take the methotrexate. And it's safe in the rest of the trimastrooms. With coterminal,

Callum: 54:12

the same is true of

Jame: 54:16

the first trimester, the same advice that is. The second trimester, again, is safe. Third trimester there's a recommendation to avoid after thirty two weeks, and that is not because of anything to do with the tremorpiprole. But because of a signal seen with sulfonylites antibiotics. So the sulfur talks as always the issue there. And they can interfere with neonatal bio conjugation, which leads to hemolysis and and jaundice. And this is particularly of risk in G6 PD deficient patients. And so once you move from the third trimester into breastfeeding, that warning signal remains. And they say that if you're going to give cosomoxazole to either the mother or an infant. And there are reasons where you would need to use it in an infant. To check for Jesus PD deficiency in advance. And don't use it if they're joined us and try and limit the use below the age of six weeks. So that's kinda interesting. And then the other DNA agent I think of are the other quinolones and Here, there's a recommendation to avoid throughout pregnancy because of a theoretical risk of meaning to arthropathy.

Tash: 55:40

That's all based on animal studies.

Jame: 55:42

It's all animal studies. Yeah. But there are safety signals because we have sometimes have to give zipper flopses in for meningococcal prophylaxis and people have then done kinda monitoring studies in pregnant patients. And that single dose is safe. And there's enough data in the first trimester that the UK TIS has said, if you need to give it for, you know, say, a pilot of Practice, for example, a five to seventy course of Cipro is safe. So I'm just gonna finish off with a quick sort of Roan Robin of of random antibicrobial antibiotics that can be used in pregnancy. So for daptomycin, for example. The manufacturer stated use of risk outweighs benefit. Basically, is code four. We don't think that there's any tardive genetic state, but we are too scared to say so. And so we see this instead. And then it's also got a kind of conditional use for breastfeeding too. Again, I think that's just a lack of safety data. Fosfomycin. It says generally considered safe use of risk outweighs benefits, which is a code for. We are very sure that this is safe, but we also don't have the coagones to say so. And then the breastfeeding gain is sort of conditional use. Miftrols, as I said, is considered to be safe. The manufacturers does see to avoid high dose regimens. In the first trimester, and that's because of some animal data, but the the high dose regimen would be eight hundred milligrams three times d, and I I'm not sure I can think of an indication that isn't a parasite that you would do that. And then lastly, Nefuron Torn is safety using the first and second trimasters. In the third trimester, there is theoretical risk. Of hemeleast anemia in G6PD deficient babies. So they recommend to avoid independent person and also to avoid invasive PD deficient infants once breastfeeding because, of course, once the baby is out, you can do genetic testing for GCPD Deficiency. Yep. And that's that's all I had to say.

Callum: 58:12

And I love the tables you've made, Jim, as they've been the show notes. And there's a lot of stuff on antifungals, antivirals, and other things as well.

Jame: 58:20

So Oh, wait. Wait. Calum, I'm not gonna include that. We're just gonna talk about anti bacterial today.

Callum: 58:25

Oh, so we're not doing that in the show notes.

Jame: 58:27

I don't think so.

Callum: 58:28

Why not?

Jame: 58:28

Where? No. Wait. Do you think I should?

Callum: 58:30

Yeah. However, to the people, get them the information. Loyal listeners would be very loyal and they deserve a little treat.

Jame: 58:37

Alright. Fine. I'll tell you what. Fine. You've persuaded me I will

Callum: 58:41

celebrate fifty thousand windows. There's a bonus content of anti bundles and antivirus and COVID-nineteen treatments. And entrepreneurial.

Jame: 58:51

I mean, bear in mind the COVID stuff might go out of date. But how will it go out of date is the stuff that's recommended to avoid will will become green. So just bear that in mind. Yeah. But yeah. Okay. Fine. We'll include all that stuff too.

Callum: 59:07

That's the drug section, drug section done. Well, I think that covers all the things that we wanted to talk about and So maybe Tasha is a is a guest who has the sort of specialist knowledge knowledge in the areas or sort of like a take home message or like a closing thoughts that you you would want to leave the the liar listener with.

Tash: 59:28

I think just this idea that women who are pregnant and in the sort of early postpartum period period, are incredibly primed to receive information, to date with how for themselves, for their babies. And I think for that reason, it's not only a great privilege to care for these patients, but it's also a really powerful time where we can make a really big difference. So I think if there's nothing else, then I think from today, take away that you do have a role in interfacing with these patients and that role extends beyond just providing antimicrobial advice because we can actually influence behavior change, we can educate in a way that maybe patients aren't always as receptive towards So I think use these resources, go out and really sort of enjoy the privilege of caring for these patients and try to help them on what is a really exciting journey.

Callum: 1:00:27

Well well, a huge thank you for for coming on and and certainly I think I've learned a lot and I'm I'm sure those listening have I've got some new information to take from that. Yeah. Thanks, hopefully, we can have you on as a as a guest at some point in the future. I know you've got a lot a lot to to share intel. And a small plug as Tasha's got. A blog and video tutorials, which you can find online, which is called Hello Micro.

Jame: 1:00:53

Yeah. Well, include a link of the show notes as well.

Callum: 1:00:55

Or include a link in the show notes.

Jame: 1:00:56

Be the first link. It will have pride of place in all the links.

Callum: 1:00:59

Sign up for a mailing list so I get regular email when when there's a new else coming out, sir. Oh, I recommend having a a little read.

Tash: 1:01:06

Cool. Thanks so much for having me.

Jame: 1:01:08

Questions, comments, suggestions, why don't you send them into idiots podcasting at gmail dot com have a five star review in your pocket. Calvin, I would love to have it please drop it in your podcast player of choice. We tweet at ADS underscore pod. And if you want to donate to support the show, there's a link to do so in the show notes. But until next time, I'm Jane. I'm Colin.

Tash: 1:01:28

I'll touch.

Jame: 1:01:29

See you there.

Callum: 1:01:30

Bye.

Jame: 1:08:25

Now that the episode's done, we hope you learned and had lots of fun. Go forth and treat people with some of what you now know