Episode 51
51: Febrile Digest - Across the Pond with the ID:IOTS Podcast
Gentamicin over a best-a-lactam?! Listen in as Jame & Callum from the ID:IOTS podcast extoll the virtues of aminoglycosides in empiric therapy…and teach Sara some Scottish slang
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Transcript
Hello everyone.
Sara Dong:Welcome to Febrile, a cultured podcast with all things infectious disease.
Sara Dong:I'm Sara Dong, your host and an adult and pediatric ID fellow.
Sara Dong:We are back with another Febrile Digest.
Sara Dong:I know it has been a while, but these are bonus episodes in between our cases about various topics or questions in ID.
Sara Dong:I am always on the hunt for different resources to share with people.
Sara Dong:And I found a new podcast, but it's not actually a new podcast.
Sara Dong:It's just new to me.
Sara Dong:um, so I invited some new friends from the ID:IOTS podcast, but, uh, rather than introducing you as an idiot, I would much prefer if you guys would tell everyone a little bit about yourself.
Jame McCrae:Uh, thanks, Sara.
Jame McCrae:Uh, hi everybody.
Jame McCrae:Uh, we are from the ID:IOTS podcast that stands for Infectious Disease - Insight of Two Specialists.
Jame McCrae:I'm Jame, and that's Callum, Cal, how you doing?
Callum Mutch:Good.
Callum Mutch:Uh, I was saying before we started recording that I thought it would be strange because I'm usually the editor and it's such a, such a joy actually to be thinking that I'm not gonna be listening back to myself and having to edit out all the I, well, I don't actually have to edit myself at all because everything I say is, is just straight away correct and right.
Callum Mutch:so difficult.
Sara Dong:Well, can you guys tell everyone, maybe just like a quick snippet about like, why you started the podcast and what you guys cover.
Callum Mutch:Sure.
Callum Mutch:So, um, we, Jame and I were training together in Scotland in Infectious Diseases, and we were both sitting a, um, infectious diseases exam that we have to sit for.
Callum Mutch:Well, for Jame, it was his exit exam training.
Callum Mutch:And for me it was part one of a two parter.
Callum Mutch:And we were revising for that.
Callum Mutch:And we, I guess we thought that there was a, a gap in the market for another resource to help people revise for the exam.
Callum Mutch:So that's really where it came.
Callum Mutch:Um, that's the combined infection certificate examination.
Callum Mutch:I never quite remember what it stands for.
Callum Mutch:Mm.
Callum Mutch:Uh, so Jame, at this point, well, I'll let Jame say, but I, I, I'm still in training.
Callum Mutch:I've got two more years left of infectious diseases and um, medical microbiology, uh, training before becoming a consultant or attending.
Callum Mutch:Although at the moment I'm doing a medical education fellowship.
Callum Mutch:Ah, so that's me.
Jame McCrae:Yeah, and I'm, uh, I, I finished training, so I, um, I've come down to, to England and I'm doing a, uh, post CCT clinical fellowship, uh, in infectious disease, uh, in Naedosh Royal Infirmary [South], which is the fictionalized hospital that me and Callum, uh, working, uh, and Cal remains in Naedosh Royal Infirmary [North], which we anonymized several weeks into the podcast and stated several times before we did that, we worked in Lothian.
Jame McCrae:And just to be absolutely clear, Callum has not moved since we started the podcast, but nevertheless, we have completely anonymized, um, where we work.
Jame McCrae:So Naedosh Royal Infirmary North is an undisclosed location in Scotland.
Sara Dong:I see, well, one, I wanted to introduce everyone to you guys.
Sara Dong:And then two, we get to talk about whatever we really want in these digest episodes.
Sara Dong:And we thought that talking about how gentamicin is used in different settings would be really interesting, um, which in the States is, is really just not that much, but you guys have a lot more experience with Gentamicin
Jame McCrae:Let, let me start by asking you a question.
Jame McCrae:Um, Sara how much gentamicin or any aminoglycoside do you use in your practice?
Jame McCrae:Be it pediatric or be it adult.
Sara Dong:In general.
Sara Dong:It's I mean, it's not a lot.
Sara Dong:I, I would say most of the time it comes up, it's gonna be some kind of combination therapy.
Sara Dong:You know, in the empiric setting, it might be that we're already giving some kind of cephalosporin and, you know, you're worried because of either the patient's history or they're really sick, critically ill.
Sara Dong:And so you think you might be dealing with a serious Gram negative infection.
Sara Dong:And so you give a second agent, meaning the aminoglycoside, in hopes that your bug is susceptible to at least one of them.
Sara Dong:And then we'll sort of peel it off as quickly as we can.
Sara Dong:Mm.
Sara Dong:You know, it's in, in pediatrics, it's not uncommon for neonates to get the ampicillin gentamicin combo, but some of it is often historical or just protocol based.
Sara Dong:And so I think a lot of us see perhaps OB GYN infections that are based on older guidelines that recommend combos of amp[icillin], gent[amicin], and clinda[mycin]..
Sara Dong:Typically, if we're consulted, we'll come on and say, oh, there's not really any reason we can't use an alternative and we'll transition them.
Sara Dong:There are of course cases where we might use it for directed therapy when you have a known resistant organism.
Sara Dong:But I think monotherapy in most settings in the States is relatively rare.
Sara Dong:and outside of that, it's usually synergistic settings, like for endocarditis, but really even in that setting, I feel like we're moving away from that if we have some sort of alternative that we can use.
Jame McCrae:Yeah.
Jame McCrae:I feel the same, particularly with enterococcal endocarditis.
Jame McCrae:Yeah.
Jame McCrae:People have moved away from AEG, so amoxicillin plus gentamicin and towards AC amoxicillin ceftriaxone for toxicity concerns and that's that's happening even in, in Scotland where, um, me and Callum were working and Callum still works where people are very comfortable with aminoglycoside use.
Jame McCrae:Um, because it's used as our, in our empirical, uh, therapy, and that's kind of why we wanted to, uh, to talk about it today.
Jame McCrae:So this is a bit of a, sort of an intellectual sort of like why you would want to use this more and how you could use it and why you may be moving towards using it more in the future.
Jame McCrae:As we encounter more problems with like kind of antimicrobial resistance.
Jame McCrae:Callum, do you want to kind of go through the sort of structure background bit?
Jame McCrae:Or do you want me to take that?
Callum Mutch:I, I can take something cause I feel like otherwise there's gonna be another, uh, Jame McCrae show
Jame McCrae:Jame's rants nonstop.
Callum Mutch:Also.
Callum Mutch:I feel like I might just like simplify it a little bit because, uh, Jame uh, not only trained infectious diseases, but also in clinical pharmacology.
Callum Mutch:And so I don't think there's anything that you like more in life than.
Callum Mutch:Uh, explaining the, the, the, the minutiae of, uh,
Sara Dong:He's drawing molecular structures in the wall.
Jame McCrae:this is all scurrilous accusations, which I'm not going to deny . Um, but,
Callum Mutch:um, so aminoglycosides are, uh, so most people likely know, but they're amines, that's a protein part.
Callum Mutch:And then glycosides, that's the sugar part of the molecule.
Callum Mutch:They're very polarized.
Callum Mutch:So they, they have a, a charge.
Callum Mutch:And that means that they usually stay where you, the, the space that you place them into.
Callum Mutch:So whether that's topical, so thinking about like ear drops or something,
Callum Mutch:uh, and if you're giving it intravenously or, uh, in the urinary tract, Um, they've been around for quite a long time.
Callum Mutch:So streptomycin neomycin discovered in 1943 and is for TB treatment.
Callum Mutch:Uh, although we're still getting more.
Callum Mutch:So the newer one is plazomicin 2018.
Jame McCrae:Callum.
Jame McCrae:Why do some of them, uh, end with an -my, -mycin and some end with an -mi, -micin.
Callum Mutch:Well, I'm glad you asked uh, so the ones that end with an -my are in the Streptomyces group, whereas the ones that end of -micin they're in the micromonospora group.
Jame McCrae:And they-, they're what you can isolate them from, uh, the different aminoglycosides
Callum Mutch:so generally speaking, the older ones are in the Y group, but that doesn't always bear out
Jame McCrae:yeah, yeah, yeah.
Callum Mutch:Um, and you can also structure them.
Callum Mutch:You can group them by a chemical structure as well, is the other way of doing it?
Jame McCrae:Yeah.
Jame McCrae:I think that's the better way of doing that, actually.
Callum Mutch:Yeah, it makes more sense.
Callum Mutch:Doesn't it?
Callum Mutch:So, uh, you've got your streptomycin group, so that's streptomycin or the neomycin group, which is neomycin, which is generally only used topical I believe, cuz of toxicity reasons.
Jame McCrae:Uh, yes.
Callum Mutch:Um, and, uh, paromomycin, which, um, I don't think actually recognized was an aminoglycoside until right now, but we use it for GI clearance of Giardia to, um, get rid of the cysts.
Callum Mutch:I forget the term
Jame McCrae:it's for intraluminal clearance of the Giardia
Callum Mutch:That's right, its the intraluminal clearance.
Callum Mutch:Yeah.
Callum Mutch:Um, and then finally got the kanamycin group, which has got gentamicin, tobramycin, amikacin, and plazomicin, which is, I think, you know, we use gentamicin in Scotland mostly, but other centers will use different ones usually based on local epidemiology of resistance.
Callum Mutch:Yeah, well, quite a lot of the time actually, it's due to what got the license first.
Callum Mutch:So, um, uh, gentamycin and tobramycin and in Eastern Europe, it would be streptomycin, are very commonly used.
Callum Mutch:Um, some centers would suggest that tobramycin cuz it's got better Pseudomonal cover should be the drug of choice.
Callum Mutch:And really in terms of toxicity, they're both kind of about the same.
Callum Mutch:Um, and so you've got that better Pseudomonal cover without kind of a noticeable increase in side effects and certainly EUCAST would, uh, agree, which will come onto in a sec.
Callum Mutch:If you're gonna use an aminoglycoside, Sara, would you,
Jame McCrae:Yeah.
Jame McCrae:What do you use in the US?
Sara Dong:Um, people will use gent or tobra for those sort of like, um, Uh, empiric settings and then, you know, amikacin when we're treating TB NTM type stuff.
Sara Dong:Mm.
Sara Dong:Yeah.
Sara Dong:So there's a mixture.
Sara Dong:Most places have, I feel like they'll have all of them available or maybe they'll only stock one or the other, but,
Jame McCrae:um, yeah.
Jame McCrae:And is it hospital specific?
Jame McCrae:So if you go to a different hospital, would you have a different one or is it sort of by, by, by kind of area or like would all of Boston use the same one or is it not like that?
Sara Dong:I feel like most places could have access to both, but there may be places that they like tend to use one more than the other.
Jame McCrae:Mm-hmm
Jame McCrae:. . Yeah.
Jame McCrae:So, um, I suppose the, the kanamycin group is the one that's got the antibiotics that we use for, uh, for kind of serious um, infection.
Jame McCrae:Uh, Callum how do they work?
Callum Mutch:How do they work?
Callum Mutch:So they irreversibly bind to the 30 S subunit of the rRNA complex, and that leads to misreading of RNA codons.
Callum Mutch:And that leads to impaired protein synthesis.
Callum Mutch:So they're in this sort of, if you, you know, bacteriostatic category from that,
Jame McCrae:if you care about that anyway
Callum Mutch:We don't really.
Callum Mutch:Yeah.
Callum Mutch:I feel like it's something that you learn and read in textbooks and then people talk about, oh, well, you know, you can't use that on its own.
Callum Mutch:Cause it's, bacteriostatic, but I don't know if it's ever really born out in the data to say, you know, and I think I'm sure I saw a paper recently, which was comparing bacteriostatic and bactericidal agents.
Callum Mutch:And they're just like, you know what.
Callum Mutch:Who cares.
Callum Mutch:Like the clinical importance as being important.
Callum Mutch:So why do we keep teaching it?
Jame McCrae:And if by recently, Callum
Callum Mutch:static, like why, why are we perpetuating?
Callum Mutch:Isn't it
Jame McCrae:if, uh, by recently Callum you mean three years ago in a journal club presented by me then yes.
Jame McCrae:You have recently, uh, uh, watched a paper being presented and yes, you're right.
Jame McCrae:The static versus cidal thing, I think it's actually pretty well known in the ID community now is absolute nonsense.
Jame McCrae:And the fact they there's plenty of antibiotics like linezolid is a bacteriostatic, um, uh, antibiotic and has gone head to head with fluclox for treatment of Staph aureus infection, and is the only thing that's ever been, non-inferior, to the best of my knowledge, uh, compared to anti staphylococcal penicillins, be it fluclox or cloxacillin or, or diclox.
Jame McCrae:So I mean that just kinda on its own sort of puts the whole idea of static and cidal to bed, but they do have another, a second mechanism of action, don't they Callum, a bactericidal
Callum Mutch:because it's cationic.
Callum Mutch:So we talked about having a charge.
Callum Mutch:So, uh, it's cationic, uh, charge, which means that it binds the anionic cell membrane components and the, the sort of charge effect.
Callum Mutch:It reduces the membrane integrity, which leads to cell lysis.
Callum Mutch:And that part is thought to be bactericidal
Jame McCrae:mm-hmm and that's, um, kind of hard for the cell to deal with because the gentamicin is usually actively transported into the cell.
Jame McCrae:I forget exactly the, the mechanism.
Jame McCrae:Uh, I know that streptococci don't have it, and that's why streptococci aren't covered by, uh, uh, by aminoglycosides, uh, in general.
Jame McCrae:Um, Uh, and it's something that can be lost, like pseudomonas likes to lose it.
Jame McCrae:And that's how it requires resistance.
Jame McCrae:That's the main mechanism, um, that, and aminoglycoside modifying enzymes.
Jame McCrae:When it comes to sort of spectrum of action, gent and tobra have very similar, uh, spectrums of action.
Jame McCrae:So in fact that that most of them will cover staphylococci and they'll cover Gram negative organisms.
Jame McCrae:And they'll cover Pseudomonas except streptomycin doesn't cover pseudomonas so much.
Jame McCrae:Uh, another reason that, that you might not want to use it as your kind of baseline, um, gram negative cover.
Jame McCrae:Um, but it does cover TB as does amikacin.
Jame McCrae:Tobramycin has, as we've said before, has better anti pseudomonal cover.
Jame McCrae:And so some people like the Canadians for example, would suggest that if you're covering, if you're trying to treat pseudomonal infection, you should just use tobra, um, all the time we can.
Jame McCrae:So why are we talking about this historical drug?
Jame McCrae:Everybody knows it's got terrible kidney, uh, toxicity, and it can make you go deaf and it can make you have vestibular symptoms as well.
Jame McCrae:We've got other things that cover gram negatives.
Jame McCrae:We've got pip-taz, we've got coamox.
Jame McCrae:We've got, um, you know, cephalosporins.
Jame McCrae:Why would you bother using gentamicin at all?
Jame McCrae:So
Callum Mutch:I presume this is where you tell us.
Jame McCrae:Yeah.
Jame McCrae:Well, I'm just trying to figure out what to talk about first.
Jame McCrae:Um, so about, uh, here's a quick history, uh, lesson, Sara.
Jame McCrae:Up, until about maybe 10 or 15 years ago, Scotland and the rest of the UK were using cephalosporins as their, as their, um, sort of gram negative cover for empirical treatment of infection.
Jame McCrae:And historically sort of up until the eighties, when cephalosporins became widely available, people would usually use something like amoxicillin or ampicillin plus gentamicin to cover stuff.
Jame McCrae:If they had an infection and they didn't know what they were covering.
Jame McCrae:And then because cephalosporins are, you know, cheaper, some of them are once a day.
Jame McCrae:Like ceftriaxone, uh, is once a day.
Jame McCrae:Um, and, uh, that's less nursing time.
Jame McCrae:You know, people just kind of moved over to that and cephalosporins and things like amoxicillin-clavulanate were used as the kind of basic cover.
Jame McCrae:Uh, I've mentioned before on our podcast, like when I was starting training as a, as a F1 in 2006.
Jame McCrae:So like the first year, uh, of, of being an intern, uh, the joke was that if you came in under the surgeons, you got ceftriaxone metronidazole.
Jame McCrae:And if you came in under the medics, you got coamoxclav and clarithromycin, uh, to treat chests and basically just treat everything.
Jame McCrae:And it was kind of true.
Jame McCrae:And then in 2008 or in the two years for 2007 to 2008, there was a C diff outbreak in a small hospital in Scotland called Vale of Levin.
Jame McCrae:Uh, it was in the two years of the outbreak, there were 143 cases of C difficile and uh, 34 of them died.
Jame McCrae:That is a 24% mortality.
Jame McCrae:And Sara, just for reference, this is a 92 bed hospital, so barely bigger than a community hospital or a cottage hospital in the west of Scotland, sort of, kind of west of Glasgow.
Jame McCrae:So these are absolutely massive numbers.
Jame McCrae:Like a big proportion of people were getting C diff if they went to the Vale and then, uh, some of them were dying and there was a huge inquiry, uh, and.
Jame McCrae:There was lots of reasons for failing.
Jame McCrae:The building was kind of falling to bits as some, quite a lot of hospitals in, in the UK are.
Jame McCrae:There were no wash hand basins in some wards.
Jame McCrae:There was lots of understaffing.
Jame McCrae:All the doctors were basically juniors.
Jame McCrae:There was hardly any consulting cover.
Jame McCrae:And one thing that also came out was that the prescribing was absolutely terrible.
Jame McCrae:People were basically going on ceftriaxone at the drop of a hat and people thought that that was one of the, one of the main contributors, because if you've got a drug environment where Cdiff can flourish, because everybody's on ceftriaxone or coamoxiclav, if you have an outbreak strain, because there are outbreak and non-outbreak strains of C diff, and it gets into your hospital, it's just going to spread like wildfire
Jame McCrae:and, uh, then you know, a bunch of people are gonna die and that's exactly what happened.
Jame McCrae:It was, you know, it was profoundly embarrassing for the, for the government.
Jame McCrae:And then people said that basically this is, this should never happen again.
Jame McCrae:So starting in 2008 in Glasgow and Lanakshire, and then spreading throughout the rest of the country over the next six years, we moved from
Jame McCrae:using cephalosporins and coamoxiclav and ciprofloxacin and other quinolones and what's the other four Cs?
Jame McCrae:Clindamycin.
Jame McCrae:We took them out of our empirical, uh, treatments for everything basically, except where they were absolutely essential.
Jame McCrae:Like ceftriaxone for meningitis or clindamycin for necrotizing fascitis.
Jame McCrae:And we replaced it with our current, uh, sort of regimen.
Jame McCrae:So just give people an idea of what it is.
Jame McCrae:Say, Sara, you wanted to cover somebody for kind of broad spectrum infection.
Jame McCrae:So you didn't know what you were wanting to cover and you wanted to cover Gram positives, gram negatives, maybe Pseudomonas, maybe not.
Jame McCrae:It doesn't matter.
Jame McCrae:And anaerobes, what would your choices be?
Jame McCrae:What would you use in your, in your hospital?
Sara Dong:Yeah, I mean, most of the time it's gonna be something like ceftriaxone or cefepime plus or minus anaerobic coverage if they need it plus, or minus MRSA coverage if they need it.
Jame McCrae:Mm.
Jame McCrae:And so for MRSA, what would you use?
Sara Dong:I mean, usually vanc
Jame McCrae:Vancomycin.
Jame McCrae:Yeah.
Jame McCrae:Okay.
Jame McCrae:Fine.
Sara Dong:I mean, if the, I, I would say in the adult hospital.
Sara Dong:There certainly is more clindamycin use in pediatrics, but, um, that's probably usually the combo they'll get placed on in the emergency department.
Jame McCrae:Yes.
Jame McCrae:Yes.
Jame McCrae:Um, and that's, and, and that's even true of where I work, uh, uh, at the moment down here, because this, what Scotland has done.
Jame McCrae:Um, it's not spread throughout the UK.
Jame McCrae:It hit the border and then like nothing happened.
Jame McCrae:Um, and that was kind of a bit of a shock to find out.
Jame McCrae:So say you, uh, came in and you had sepsis of unknown source and you were in Glasgow, Edinburgh and, or what have you, um, we would give you.
Jame McCrae:Amoxicillin to cover streptococci and some enterococci but mostly it's the streps that matter.
Jame McCrae:Gentamicin for some Staph aureus cover.
Jame McCrae:It's not as good as anti staphylococcal penicillin, but it'll do, and gram negatives and pseudomonas.
Jame McCrae:And metronidazole is anaerobic cover.
Jame McCrae:If we thought there was like a GI thing going on, or if there was a possibility.
Jame McCrae:And so if you think of somebody coming in with say, Chest infection.
Jame McCrae:Um, the amoxicillin is good for that.
Jame McCrae:Gentamicin what's it contributing?
Jame McCrae:Probably not all that much.
Jame McCrae:if it's skin and soft tissue, I have to say we'd probably just give them flucloxacillin and we wouldn't give them anything else.
Jame McCrae:But this is for people where they've got sepsis and you don't know where it's coming from, so you have to cover urine, chest and GI.
Jame McCrae:And then if you're thinking about urine chest and GI sources, amoxicillin, gentamicin, and metronidazole is appropriate polymicrobial cover.
Jame McCrae:It's appropriate urine cover.
Jame McCrae:Um, and.
Jame McCrae:It's uh, okay for the chest.
Jame McCrae:I mean, it's not very, uh, good.
Jame McCrae:If you were really concerned, you might want to consider adding a macrolide or changing the amoxicillin to coamoxiclav but certainly that's kind of reasonably broad cover.
Jame McCrae:And the, the reason that we started using it is that it's a low risk for C diff.
Jame McCrae:So metronidazole and gentamycin are, you know, low, not zero risk, but very low risk for C difficile.
Jame McCrae:And amoxicillin is only kind of mild to moderate, really.
Jame McCrae:Whereas just giving everybody coamoxiclav or just giving everybody ceftriaxone plus or minus metronidazole, um, is quite Cdiff-ogenic
Jame McCrae:so if you have that in your empirical guidance, you run the risk of having another outbreak.
Jame McCrae:And at the time that it was implemented in Scotland, that was just completely unacceptable.
Callum Mutch:I was gonna say that there, because I guess we talk about individual antibiotics and say, this is low risk or this is high risk
Callum Mutch:And, you know, you can find there's like a meta-analysis that's is it meta-analysis or is a systematic review where they do a forest plot of all the, an different antibiotics.
Callum Mutch:And I find that quite useful to go back and review because the qu-, the like level of evidence and the quality of the evidence to make these inferences about the C diff risk and different antibiotics, I don't think is very good.
Callum Mutch:But the clinical data for, for this is good in terms of, you know, well, you were talking about the, the history there.
Callum Mutch:2008 comes around and you can see a marked drop in C diff rates with the change to the gentamicin backbone.
Jame McCrae:Yeah.
Jame McCrae:So, so what happened, uh, then Callum, what were the effects of, uh, changing over to this, uh, this kind of low risk?
Callum Mutch:Yeah.
Callum Mutch:So, um, You know, after it's changed over, I think one, there was a lot of people that spent a lot more time prescribing as gentamicin is more complicated to prescribe.
Jame McCrae:Mm it is.
Callum Mutch:And I, something that popped in my head there was actually is, is the fact that there's a slightly higher barrier to giving antibiotics.
Callum Mutch:It's slightly more difficult.
Callum Mutch:Does that make people actually.
Callum Mutch:That balance of , you know, if, if it's slightly more difficult to do something you're less likely to do it and you don't give antibiotics just because it's easy to give, you have to like, actually think, do I really want to go and do a gentamicin chart?
Callum Mutch:I mean, that's an aside and I don't know about the answers to that, but what we do know is that there was a lot lower C diff risks.
Callum Mutch:So you can see there's like graphs, where they look at the, the rates over time and map it to the health board.
Callum Mutch:And when they change and, you know, very sizable drop in C diff rates.
Callum Mutch:Um, other thing that we noted was lower, lower MRSA rates.
Callum Mutch:Mm.
Callum Mutch:Um, there may be other reasons for that ongoing in terms of that time period, but, you know, prior to 2010, there was quite a big problem of MRSA in Scotland.
Callum Mutch:And that's really, MRSA I would say is now very rare, uh, to encounter as a clinical phenomenon, uh, unless the patients had a lot of healthcare
Callum Mutch:contact.
Jame McCrae:Yeah, that that is, um, a bit odd.
Jame McCrae:And I don't really know that I've got like a hard explanation for that, but certainly that's something that we saw when we looked at the data.
Callum Mutch:Um, and then the other things, as you see that there, the mortality rate from gram negative sepsis dropped, um, there wasn't any difference in ICU admission, length of stay or need for renal replacement therapy, which was a sort of proxy for, um, uh, nephro toxicity.
Callum Mutch:Uh, we also haven't really seen an increase in aminoglycoside resistance.
Callum Mutch:So although.
Callum Mutch:The vast, you know, 30% of hospitalized patients end up with an infection and of those in, uh, in Scotland, most of those patients will be treated of aminoglycoside.
Callum Mutch:We haven't seen a rise really in aminoglycoside resistance, and we've got really good data for this, which is really.
Callum Mutch:You know, surprising, I guess.
Callum Mutch:Uh, and the other thing we've seen is a drop in coamoxiclav, ceftriaxone resistance.
Callum Mutch:We don't really map like most labs in Scotland don't look at the mechanism of resistance or test for, so you can infer but, you know, ESBL and ampC uh, rates have of dropped as well.
Callum Mutch:So, which does mean that when you have to use those antimicrobials, then you're less stuck, you know, I guess.
Callum Mutch:In my head part of it is, is it actually because of which antibiotic we're using or is it because, and there's so many other things that have happened, but there's a real big focus on antimicrobial stewardship and saying to people thinking hard about, do you actually need to start antimicrobials?
Callum Mutch:And that is in the.
Callum Mutch:But then, you know, I guess my clinical experience is that we still use loads and loads of antibiotics, and most people end up getting some antibiotics during their admission.
Jame McCrae:So, well, yeah, we do, but I mean, the antibiotics that people are using are narrow spectrum and and sort of low risk.
Jame McCrae:And so if there's less of a need for stewardship, if they're reaching for the Amox and the gentamicin as opposed to if they're reaching for the ceftriaxone or meropenem, do you know what I mean?
Jame McCrae:Like, if you're trying, if we're trying to preserve beta-lactams cuz beta-lactams are best-a-lactams and.
Jame McCrae:They're the thing that everybody uses, then that's gonna be really difficult because, you know, resistance you're, you're gonna create a hospital environment in which third generation cephalosporin resistance and coamoxiclav resistance is like the first on the priority list of the bugs.
Jame McCrae:And if you're a hospital, uh, bug and you're trying to live in the environment like a Serratia, you're living in some of these GI tract, like your top priority will be to acquire resistance to third generation cephalosporins.
Jame McCrae:If that's the only thing that you see all the time.
Jame McCrae:Um, so yeah, I mean, there, there are other reasons for thinking that the, uh, switching to, uh, to gentamicin is a, is a good idea.
Jame McCrae:The bit that was surprising, that was, is that we've not really seen an increase in resistance.
Jame McCrae:And the only thing that I can think of as a, as a kind of a reason is.
Jame McCrae:It's hospital only.
Jame McCrae:You can't really get it in the community.
Jame McCrae:We certainly in Embra, at Lothian I mean, wherever Naedosh Royal infirmary north happens to be, um, never really used it in OPAT in an OPAT setting
Jame McCrae:um, unless we absolutely had to.
Jame McCrae:And even then some of the times you would be given amikacin for, for kind of resistance issues.
Jame McCrae:And I guess the, the fact that you can't give it, and I guess that's true of ceftriaxone too, but certainly coamoxiclav you can get in the community and it can be prescribed, you know, in a range of infection scenarios, and, and that can sort of increase your, your, uh, kind of risk of resistance developing.
Callum Mutch:So.
Callum Mutch:Why, why is, you know, we're, we're extolling the virtues of moving to, uh, aminoglycoside base backbone for your treatment.
Callum Mutch:And, you know, I think you've left the bubble, um, Jame and, and moved somewhere where they're not using it.
Callum Mutch:And I know that we've had many conversations offline.
Callum Mutch:About about this and your, your thoughts on it.
Callum Mutch:So why, you know, is, is this a failure of, of us to, to, you know, evangelize the use of aminoglycosides and go around with, you know, branding, you know, what what's happened?
Callum Mutch:That means that nobody else is doing that because you know, my experience in training is, is really just been in Scotland.
Callum Mutch:So I haven't practiced elsewhere.
Callum Mutch:And, uh, I, I can't really imagine a world where I wouldn't be using it.
Callum Mutch:I guess that's that happens a lot of the time for silo of practice.
Callum Mutch:Isn't it?
Jame McCrae:Well, imagine my shock Callum when I, uh, left, uh, Scotland for pastures new and found that everybody was getting coamoxiclav with one hand and ceftriaxone with the other.
Jame McCrae:Um, but I, I, I dunno what to tell you.
Jame McCrae:I, I mean, I certainly, I there's lots of reasons not to use aminoglycoside, um, you know, giving ceftriaxone is easier.
Jame McCrae:You know, it's, it's one dose a day and you've covered Gram pos and Gram neg in a, in a variety of different situations.
Jame McCrae:And you know, the metronidazole, you can just give orally, you don't even need to, uh, give it as an injection.
Jame McCrae:Injection unless the oral route is compromised.
Jame McCrae:Um, whereas if you're given, say amoxicillin-gentamicin-metronidazole, uh, amox-gent-met for, uh, sepsis unknown source or intrabdominal sepsis, the amox it can be IV or oral, but it's three times a day, no matter which it is say it's IV it's three times a day.
Jame McCrae:The gent is one time a day.
Jame McCrae:That's four.
Jame McCrae:And then there's the metronidazole two.
Jame McCrae:So there's more nursing time involved with administering.
Jame McCrae:Particularly if the amoxicillin is IV, but then also there's calculation time as well.
Jame McCrae:And this is the thing gentamycin has to be dosed according to the patient's weight and their renal function.
Jame McCrae:And you need to do kind of trough levels to make sure that they, um, have a sort of a gent free period in the, um, uh, that means that junior doctors have to do the.
Jame McCrae:Our pharmacists, depending on where you do it in the UK, it's junior doctors, would've to make the calculation initiate the prescription.
Jame McCrae:And that introduces the possibility for error.
Jame McCrae:Um, and, uh, the.
Jame McCrae:Scottish antimicrobial prescribing group, who are the people that draw forward with this kind of like, um, this policy realized that in advance and developed a calculator that basically every trust uses that are in one form or another to automatically do.
Jame McCrae:It's an Excel spreadsheet.
Jame McCrae:You open up, you put in the patient sort of age, height, sex,
Jame McCrae:weight and creatinine and it spits out value and it says, give this idiot and they print it out and they give it, um, and then it even tells you when to do the troughs.
Jame McCrae:It has a little chart so that you can, you can sort of look at it, um, and figure out when you're going to do the blood level.
Jame McCrae:It's goes in the patient's notes, the nurses all are trained on how to use it.
Jame McCrae:Every new junior doctor in Scotland has taught how to use it mandatorily as part of their induction training.
Jame McCrae:So it's completely uncontroversial and you need all of that in the background in order to prescribe aminoglycosides safely and.
Jame McCrae:That's, uh, certainly not the case in other parts of the UK and all of that kind of backbone,
Jame McCrae:if you don't have that, aminoglycosides become really dangerous.
Jame McCrae:Uh, all of a sudden, uh, if you're giving more than one dose, uh, of it, if you're giving just a stat, it's really hard to kind of screw up some of these kidneys.
Jame McCrae:But if you are giving three days or five days, or even god forbid seven.
Jame McCrae:Um, that really has kind of a follow on effect.
Callum Mutch:The, the toxicity is more to do with the duration of therapy and, and lack of time free from gentamicin so, you know, you it's really, I don't think you can really cause harm, generally speaking, by a one off dose of gen and sometimes, you know, you would give it empirically before you even had the renal function.
Callum Mutch:You know, you went to get antibiotic in quickly and then it comes back.
Callum Mutch:The creatinine was actually 800 and they had a massive AKI.
Callum Mutch:Whoops.
Callum Mutch:But you know, generally speaking, if they've got sepsis, then this is what I had this conversation quite a lot, if even if someone's got renal impairment, but they've got a severe infection, then the most important thing to do is to sort that infection and the renal function will
Callum Mutch:if, if it is related to the sepsis improved.
Callum Mutch:So, um, even then I'm not, I'm not too concerned, but as you say, it's the, it's the duration and the time.
Callum Mutch:So most of our policy is related to around.
Callum Mutch:Okay, well, let's start with gent and then, you know, either after two or three days, they'll be ready for an IV to oral switch and we'll use something else, um, or they're not getting better and they'll be a discussion with an infection specialist.
Callum Mutch:In which case, you know, we can review that, um, You know, sometimes that discussion is let's keep going for gent out to five days.
Callum Mutch:You know, that's the best agent at this point.
Callum Mutch:And we'll just be really careful about asking about symptoms of toxicity and measuring the renal function and levels, or sometimes it's, you know, let's switch to piperacillin-tazobactam or something.
Sara Dong:Is that usually are ID consultants involved in all?
Sara Dong:Is, is this happening in like the primary teams, like without ID input?
Sara Dong:No, this is like, there's also an ID person involved to yeah.
Sara Dong:Think through that.
Callum Mutch:Right?
Callum Mutch:Our, our setup is, is most of these calls will come.
Callum Mutch:So we've got, you know, clinical microbiology or medical microbiology however you put it, uh, which are, um, usually accessible by, by phone.
Callum Mutch:And so I'd say the vast majority of less complex infection consults happen through that channel and each, you know, microbiologist will have an input to a department with a, with a link.
Callum Mutch:Um, and so, you know, the timeframe of getting advice will be, you know, we've got really great guidelines, which people use for anything routine.
Callum Mutch:So, you know, they shouldn't call us.
Callum Mutch:And if someone called me with a question that was in the guideline, I'd be like, go and look at the guideline.
Callum Mutch:Uh, N no, if it gets to like 3 day, I mean, like I said, they'll phone micro is what it's always written the notes.
Callum Mutch:And I think we're quite lucky as a specialty in that, that there's a real.
Callum Mutch:We we've got our thumb in all the pies and everyone phones us.
Callum Mutch:And, uh, you know, you're really tuned into the hospital and you get a lot of calls.
Callum Mutch:Um, but I think that's really great because there's a sort of trust.
Callum Mutch:It means there's a slight de-skilling of everybody else.
Callum Mutch:I'd saying that I dunno how it works in, in America.
Callum Mutch:Uh, and in infectious diseases really are the people that come in and, you know, we have a lot of time and will do consult in person.
Callum Mutch:So most of the consult work for infection is done by telephone and nobody won't go and see the patient.
Callum Mutch:It's more just about like talking through.
Callum Mutch:Yeah.
Callum Mutch:Okay.
Callum Mutch:And then, then if it's more complicated, then we'll, we'll get someone to go.
Jame McCrae:Uh, I saw a tweet, uh, today, which was, uh, ID docs, uh, seven new consults on the Sunday.
Jame McCrae:This is too much.
Jame McCrae:The teams are killing us, but also ID docs.
Jame McCrae:Our study clearly proves that ID consultation, approves patient morbidity, mortality, fertility, stamina at a credit score, the weather, blah, blah, blah.
Jame McCrae:so political teams just can't win or lose.
Jame McCrae:Can they, like, we want them to call us, but we also don't want em to call us.
Jame McCrae:Cause we're too busy.
Callum Mutch:I always try and keep that frame in my head when I'm like really busy, uh, on call and someone's phoning.
Callum Mutch:And they ask me a question that in my head I'm like, oh, like, it didn't really need to phone me, but like, I'm like, well, at the end of the day, you know, I want the best outcome for that patient.
Sara Dong:And so they called you because they, they need help and thats sort of the bottom line
Callum Mutch:I really enjoy like having that, that role of someone that is there to, to help.
Callum Mutch:And you, you sometimes end up with calls and you, you get the sense you like, you're just calling me cuz you knew you wanted someone and we're very available to help.
Callum Mutch:And it might not actually be the antibiotics is the bit that you're advising on it.
Callum Mutch:Some something unrelated.
Callum Mutch:Like actually maybe you need to, you know, maybe this patient's dying or you know that that's the sort of role that you play, but that's a real privilege to get to.
Callum Mutch:I mean gone way off topic.
Jame McCrae:Sorry.
Jame McCrae:that's alright.
Jame McCrae:Well, I mean the, the 72 hour review is baked in to the empirical guidelines.
Jame McCrae:So if you're still on, you know, gent at 72 hours, you have to call and that, that even goes for something like, like necrotizing, fascitis, um, gentamicin is involved there as well in their, in the sort of local protocol.
Jame McCrae:You would still call and check.
Jame McCrae:And that, that provides a good point on which to deescalate, um, and, and do an antimicrobial switch.
Jame McCrae:And then at that point, you can, you can, you know, think about using piptaz or coamox or ceftriaxone on, or, you know, whatever, uh, is considered appropriate.
Jame McCrae:A bit about dosing side effects, cuz people might not realize this.
Jame McCrae:So the, the main two side effects are nephrotoxicity and ototoxicity.
Jame McCrae:Nephrotoxicity is dose dependent and ototoxicity is duration dependent but dose independent.
Jame McCrae:So it doesn't matter how much of it you're giving, it doesn't accumulate like that.
Jame McCrae:But what's happening is that every, you know, the, the length of time that the patient's on, uh, gent the, some of it is getting into the hair cells
Jame McCrae:in the, in the, in the vestibular apparatus and they're not getting out.
Jame McCrae:So once they're in, they can't go.
Jame McCrae:And then the hair cells get killed, uh, by the, by the local, um, increase in gentamicin levels.
Jame McCrae:And so that is usually seen if therapy extends beyond seven days.
Jame McCrae:And there are few case reports where if you're given a second ototoxic agent, like furosemide is the main, uh, or furosemide is the main, uh, culprit there.
Jame McCrae:Uh, and quite a lot of people in the UK are on furosemide it's the main loop diuretic.
Jame McCrae:Um, Uh, used in heart failure.
Jame McCrae:Um, you can get ototoxicity sooner.
Jame McCrae:That's, that's kind of a reason to maybe kinda, if you can pause the furosemide until they're finished, uh, their gentamicin of course, or use something else, obviously.
Jame McCrae:Um, and the nephrotoxicity.
Jame McCrae:There was a lot of concern when we moved over to this, that we were gonna have like this massive increase in dialysis rates and people's kidneys were gonna get completely screwed with these, these courses.
Jame McCrae:But because we've kept the courses short, when you look at the sort of before and after they're introduced by trust the rates of AKI one.
Jame McCrae:According to KDIGO, uh, categorizations, that's kind of creatinine of, um, creatinine loss of about maybe 20 to 40%.
Jame McCrae:I think, um, those rates increase, but rates of AKI, 2, 3, 4 and need for dialysis stay the same.
Jame McCrae:And if you look at people like six months down the line after they've had a course of gentamicin and when they're out of hospital, their creatinine is returned to whatever their baseline rate was.
Jame McCrae:So there's no kind of permanent loss of renal function.
Jame McCrae:So if you're just using short little tiny courses, like what we are doing, there's no problem.
Jame McCrae:Really.
Jame McCrae:You just need to watch their creatinine in.
Jame McCrae:um, in the moment.
Jame McCrae:And, and for that reason, our monitoring is pretty tight.
Jame McCrae:Like if you are on gentamicin and you have a gen level and a used knees, uh, uh, or, you know, renal function checked every day, uh, without exception there's no, uh, wait a couple of days and then give it a check and then see what's happening.
Jame McCrae:Like none of that, you have to take it and it must be plotted.
Jame McCrae:And if you don't, it.
Jame McCrae:Know, reported on as a, as a failure of care.
Jame McCrae:And the nurses all know this as well.
Jame McCrae:And so the nurses will all kinda make sure that it's done as well, kind of a belt and braces, uh, approach clinic, uh, clinical and nursing staff as well.
Jame McCrae:But this is gonna be increasingly hard to sell outside of Scotland.
Jame McCrae:Um, because of something that EUCAST have done.
Jame McCrae:So, do you know who EUCAST are?
Jame McCrae:Sara?
Sara Dong:I do.
Sara Dong:Yeah, I do.
Jame McCrae:Um, so for the loyal listener and, uh, uh, febrilologist listening,
Sara Dong:I still have not found a name.
Jame McCrae:You have not find a collective name for febrile.
Jame McCrae:Well, I'm putting febrilologist as a, as, as a possibility, um, the EUCAST are the EU version of C LSI and they set the, uh, the break points, um, for what is susceptible and what is resistant.
Jame McCrae:And, uh, C LSI have got some break points for, uh, for aminoglycosides, which I think are pretty sensible.
Jame McCrae:Um, and so they are so for Enterobacterales and Pseudomonas, there's, there's no difference.
Jame McCrae:If it's less than equal 4, susceptible.
Jame McCrae:If it's greater than 16, it's resistant.
Jame McCrae:And if it's eight, then it's in considered intermediates.
Jame McCrae:And probably, and, and I dunno how you feel about this here.
Jame McCrae:I'd probably avoid it if I possibly could.
Jame McCrae:And to try and use an alternative when intermediate.
Jame McCrae:EUCAST changed their interpretation of aminoglycosides breakpoints.
Jame McCrae:And so now for Enterobacterales, if it's less than a equal to two, so it's quite a lot lower than, um, C LSI, that's sensitive.
Jame McCrae:If greater than two is resistant.
Jame McCrae:And for Pseudomonas, those break points apply only to tobramycin.
Jame McCrae:And there are separate ones for amikacin as well.
Jame McCrae:They've got, they've got three points for that too.
Jame McCrae:Um, but not to gentamicin so we talked about how gentamicin's got, um, uh, is, is not so good for a.
Jame McCrae:Um, pseudomonas compared to a tobramycin and EUCAST certainly agree.
Jame McCrae:And that's because of research, they've done about kind of ECOFFs.
Jame McCrae:And at this point I will hand over to Callum, who is normally the microbiologist of the two of us in the ID:IOTS podcast to remind me what the hell an ECOFF is and and why it applies, uh, here.
Jame McCrae:Callum.
Callum Mutch:Yeah.
Callum Mutch:I don't know if this has been talked about before, but.
Callum Mutch:in febrile, but, um, so I think CSLI call it, uh, ECV and EUCAST they call ECOFF, but it's epidemiological cutoff values and
Sara Dong:ECOFF sounds a bit fun.
Sara Dong:More fun, huh?
Callum Mutch:Yeah.
Callum Mutch:Yeah.
Callum Mutch:E ECOFFs quite cool.
Callum Mutch:Sounding nice.
Callum Mutch:ECV is quite hard to
Jame McCrae:say.
Jame McCrae:Yeah.
Jame McCrae:Sounds like a brand of espresso, but I mean, that's very European.
Jame McCrae:Like your
Callum Mutch:now to go to coffee shop, just get.
Callum Mutch:Email coffee um, it's measures of the drugs MI C distribution that separate the bacterial populations into that is, which are fought to be the wild population without any new resistance mechanisms and those with an acquired or mutational resistance.
Callum Mutch:And so.
Callum Mutch:You're basically looking at the whole range of what isolates are found, and they do this by gathering samples from all over Europe and then testing them essentially.
Callum Mutch:And the idea is that the ECOFF gives you a rougher idea of, of where you should set your break because you know, breakpoints are, are, are made up.
Callum Mutch:And really you're just balancing the risk of calling something sensitive when it's resistant or calling something resistant when it's sensitive.
Callum Mutch:And there's a huge field, which I don't know a huge amount about, but of, you know, setting those values.
Callum Mutch:And that is hugely important to get it right, because if you get it wrong, then you, you might, you know, Uh, mistreat someone.
Callum Mutch:Uh, so it's a really hard question, but I think, I don't know, in this situation, um, it's quite hard to say.
Callum Mutch:What do you put your faith in?
Callum Mutch:Do you put it in ECOFFs?
Callum Mutch:Do you put it in, uh, in, uh, vitro data and the lab side?
Callum Mutch:Although it makes sense scientifically, but then, you know, clinically we have this wealth of experience and it's being used very well.
Callum Mutch:And obviously it's not like you can just say, well, we want you gentamicin and no problem, you know, there's huge risks to getting rid of that as a treatment.
Callum Mutch:So I, I think in this situation, it's not, not been the right decision.
Jame McCrae:Yeah.
Jame McCrae:I mean, yeah.
Jame McCrae:In resistant to these definitely.
Jame McCrae:So like what the ECOFF for tobramycin is two,
Jame McCrae:and so that corresponds with sensitivity and the ECOFF for gent is eight.
Jame McCrae:Is that right?
Callum Mutch:Yeah.
Callum Mutch:So the ECOFF for, uh, for Pseudomonas, yeah.
Callum Mutch:Uh, for gent is eight, uh, compared to two for tobra or 16 for amikacin.
Callum Mutch:Okay.
Callum Mutch:Uh, which, you know, we, we, we knew that already.
Callum Mutch:We, it kinda makes sense.
Callum Mutch:Less resistant, but now they're saying can use gent for Pseudomonas at all.
Jame McCrae:Yeah.
Jame McCrae:And I mean, I, I, I, I certainly know in my local hospital, uh, Naedosh south, we still report gentamycin.
Jame McCrae:Um, we report all three, so we report gentamycin, tobramycin, amikacin.
Jame McCrae:Um, but we use gentamycin or amikacin, basically.
Jame McCrae:We don't really use tobra.
Jame McCrae:Um, uh, and.
Jame McCrae:Um, but yeah, like for, for, you know, kind of in the wake of this.
Jame McCrae:Because this, that, that position statement, the ECUAST, um, gave that came out in 2019, 5 years after the last trust, which was Lothian by the way, adopted these kind of narrow spectrum guidances.
Jame McCrae:And we'd been using gentamicin, you know, um, in, uh, Scotland as the gram negative backbone, including pseudomonas cover for five years, by that point, the whole country and bits of the country from 2008 to, to 2014.
Jame McCrae:And.
Jame McCrae:We'd basically not had a problem, uh, with, uh, with outcomes, uh, dropping with pseudomonas and we, then the Scottish antimicrobial prescribing then had to kind of think, well, what are we going to do?
Jame McCrae:Like, are we going to, uh, Move everything over to tobramycin.
Jame McCrae:Are we going to do, you know, something else that was felt to be logistically quite difficult.
Jame McCrae:And, um, so they put out a position paper, um, which we can link to, uh, in the show notes, that's freely available online, basically saying we note what EUCAST have said.
Jame McCrae:Um, and we're going to ignore it because we've got a nation of 5 million people, uh, being covered with, uh, aminoglycosides for, you know, five to.
Jame McCrae:10 years, uh, at this point.
Jame McCrae:And we've had no problem, uh, with it, as long as you use the dosages that are commonly used these days.
Jame McCrae:And that brings me to something that I want to point out.
Jame McCrae:So EUCAST have did a pretty big literature review of, um, gentamicin before they decided to kinda recommend against it.
Jame McCrae:And if you look at that literature and you look at the dosages that are used, they're all really titchy doses given multiple times a day.
Sara Dong:What is titchy mean?
Callum Mutch:I, I knew you were gonna ask that.
Sara Dong:Not first thing I, I Google it look at, but no, I want you, I think it'll be better if you tell me
Sara Dong:what
Jame McCrae:no problem, Sara titchy means wee
Callum Mutch:what does wee mean, Jame
Jame McCrae:oh, we means toaty
Callum Mutch:what does toaty mean?
Jame McCrae:toaty means titchy.
Jame McCrae:Oh, no.
Jame McCrae:Um, so if you look, so if you look at the doses that are being used, they're all little, um, and they're, we they're, you know, some of them, maybe some of them add up to five milligrams per kilogram per day, but they'll be given three over, over three doses.
Jame McCrae:So it'll be 1.6, six milligrams per kilogram, per dose.
Jame McCrae:And quite a lot of them are even less than that.
Jame McCrae:And this is kinda all relating back to how aminoglycosides were given before the Hartford nomogram.
Jame McCrae:So the Hartford hospital, which is in, Hmm, Connecticut, I think I want to say they at, at some point in the nineties, they were like, well, gentamycin is
Jame McCrae:expresses concentration dependent, killing what really matters is how high above the MIC you get.
Jame McCrae:So why are we giving it three times a day?
Jame McCrae:Why not give it once a day?
Jame McCrae:They've got this concentration dependent killing, which is good.
Jame McCrae:They've got a post antibiotic effect which means even when you drift below the MICC, the bugs are too stunned to start growing again.
Jame McCrae:And so you will still have kind of a beneficial effect even though, uh, the level is, is, is below the, I see in the blood and, you'll get less nephro toxicity because the kidneys to have a gentamicin free period.
Jame McCrae:It's gentamicin accumulating renal tissue.
Jame McCrae:And it also accumulates in the urine, obviously, which is why it's so good for UTIs and pyelonephritis.
Jame McCrae:But if your kidneys have a period of the day, even if it's just like two or three hours where the gent level is quite low, you get less nephrotoxicity compared to giving it three times a day.
Jame McCrae:Even if it's the same total daily dosage.
Jame McCrae:And so the Hartford nomogram came out, it become fairly quickly adopted in the US and then that spread over to the UK and the EU.
Jame McCrae:And so that's now what we give.
Jame McCrae:So we now give gentamicin in this kind of optimized way, but when EUCAST were looking at how good it was and what the outcomes were, they were looking at all the old data from the sixties, seventies, and eighties, when we weren't giving it optimally.
Jame McCrae:And so they looked at all that and they said, uh, this is, um, You know, this is not very good.
Jame McCrae:And we don't think that you're gonna get good levels.
Jame McCrae:Uh, and even if you did, um, uh, even if you did, we, we, uh, think that that ECOFF is too high for pseudomonas.
Jame McCrae:And so we're not gonna recommend, uh, using it.
Jame McCrae:And that ignores all of the real world hard outcome data that, uh, could have been, uh, obtained from Scotland at the time.
Jame McCrae:And I know that that's not like a double blind multicenter, pragmatic, randomized control trial.
Jame McCrae:It's not the Recovery trial we're talking about here, but quantity has a quality all of its own as Diane Carlin would say.
Jame McCrae:And if you've got a nation of 5 million people relying on gentamycin for their empirical Pseudomonas cover.
Jame McCrae:And you see no increase in mortality that is worth taking notice of.
Sara Dong:So do
Sara Dong:you have a t-shirt that has gentamycin rules on it?
Sara Dong:you guys need merch for idiots?
Callum Mutch:All gentamicin.
Callum Mutch:This
Jame McCrae:I did.
Jame McCrae:We did have a, I was thinking at what point would Callum suggest that we get merch
Sara Dong:well, now, you know what your first item
Callum Mutch:will.
Callum Mutch:If whoever makes gentamicin is listening, then, you know, get in touch.
Callum Mutch:. Well,
Jame McCrae:I suppose the last thing I'll, uh, I'll point out is that if you are going to use, um, there, there, there's another reason to consider moving over to, to gentamicin as your gram negative backboard that's for stewardship considerations.
Jame McCrae:And in you, your audience will probably have heard of the Access Watch and Reserve, the WHO classification of antibiotics.
Jame McCrae:And, they, that was kind of brought out, and I think 2016, the idea is that most of the antibiotics used should be Access antibiotics.
Jame McCrae:And then the Watch ones are for kind of moderately resistant disease to kind of get you rid of a bind and Reserve is kinda last resort stuff.
Jame McCrae:And that's kind of what you think about like carbapenems and kind of aztreonam on one end and amoxicillin and, and trimethoprim on the other.
Jame McCrae:And NHS England took Access Watch and Reserve classifications moved a few bits around to kind of like support UK practice and then, uh, put it out and said, trusts have to have 60% of their antibiotics be access by, you know, this such and such a date.
Jame McCrae:And they keep on sort of shifting the goalposts as kind of people keep on hitting target.
Jame McCrae:So it was 55 and then it's kinda moved up and.
Jame McCrae:You know, the we've, we've got our show notes, like a, a slide that I picked of the, uh, of the Access Watch & Reserve.
Jame McCrae:So I'm not gonna read them all out, but if you look at the Access ones, um, Sara and Callum, um, you have a look at those.
Jame McCrae:And the, the, the listeners should know that the access thing are things like penicillins, um, co-trim, doxy, oral fosfomycin but not IV, um, gentamicin, metronidazole uh, and look and try and concoct an empirical antibiotic regimen that was only Access.
Jame McCrae:So you're not allowed to use cephalosporins.
Jame McCrae:You're not allowed to use chloramphenicol.
Jame McCrae:You can't use Quinones and you can't use coamoxiclav or piptaz.
Jame McCrae:What would you give if you wanted to try and sort of cover everything?
Jame McCrae:So like, to my mind, there's only really two options you can use cotrim plus metronidazole, or you can give amox-gent-met.
Jame McCrae:Those are the only kinda options that I can see that we give you decent grams to cover good gram negative cover, and, you know, for add cover, it's really just, just metronidazole
Jame McCrae:isn't it.
Jame McCrae:Everything else is sort of like, I would use it for urine tract infection, you know, or say penicillin.
Jame McCrae:I would use it for if I knew it was targeting streptococci, only streptococci I'd use doxy for a chest infection, but basically everything else is, is too narrow spectrum.
Jame McCrae:So if you are creating.
Jame McCrae:List of sorry, creating an empirical antibiotic treatment list.
Jame McCrae:And you want to try and use as much access antibiotics as you can, because you're trying to hit this, this target.
Jame McCrae:That's really the only game in town or you put everyone in cotrim-met, which cause is perfectly a reasonable take home conclusion from this, uh, this as well.
Sara Dong:Co-trim is
Sara Dong:trimethoprim-sulfa?
Jame McCrae:Trim-sulfa yes, that's right.
Jame McCrae:Sorry, Bactrim um, uh, sometimes known as, or, uh, Septra yeah.
Jame McCrae:Exception in the UK.
Jame McCrae:I think
Callum Mutch:that's a across the pond.
Sara Dong:Well, I, I slowly am like picking up which ones things are, but
Callum Mutch:I, you yes on otherwise just be saying it in your term.
Callum Mutch:Cause it's your podcast.
Callum Mutch:So we should, should be telling us what words are
Jame McCrae:meant to be using.
Jame McCrae:Do you know what that's absolutely true, actually.
Jame McCrae:Yeah.
Jame McCrae:So, um, you
Callum Mutch:can splice, you could edit like over every time you can like record a snippet of us saying.
Callum Mutch:augmentin and then everything it says just goes augmentin no, I mean, I think
Sara Dong:it's good for people to know the different names for things.
Sara Dong:I hope everyone enjoyed your pitch for gentamicin and maybe they can, on Twitter where they can find idiots podcast and, and me, and they can let us know what they're using and what they think.
Sara Dong:But I would love to have, you know, one last plug about where people can find you guys and find ID:IOTS podcast.
Sara Dong:Um, and of course, any other closing thoughts you.
Jame McCrae:Yeah, so they can find us at @IDIOTS_pod on Twitter, uh, idiotspodcasting@gmail.com and, uh, IT:IOTS that's ID colon.
Jame McCrae:I OTs because I didn't realize how much that would screw up the search algorithm.
Jame McCrae:Um, if you plug that into your podcast, pair of twice in our faces will pop up and you can subscribe it to your leisure.
Jame McCrae:Yeah, thanks very much for having us on Sara this is like, yeah.
Jame McCrae:Thanks for, thanks for having us.
Jame McCrae:And, uh, this is like podcasting with ID podcast royalty here.
Jame McCrae:I feel like I'm having tea with a queen.
Sara Dong:I don't know about . Well, we're hoping that.
Sara Dong:I, I really want you guys to come back and for us to keep talking about, we can make it a series and call it like across the pond or something, but just like talking about in daily practice, the things that we're doing similarly or, or
Callum Mutch:differently.
Jame McCrae:Yeah.
Jame McCrae:Yeah.
Jame McCrae:The differences.
Jame McCrae:Yeah.
Jame McCrae:I mean, this was a weird one, cuz it's different practice in different bits of the UK, let alone across in the us.
Jame McCrae:But then, um, you know, the way that we do things, uh, differently in the UK, us, that's definitely rich ground.
Jame McCrae:Um, we'll have plenty more.
Jame McCrae:Yeah.
Jame McCrae:So yeah.
Jame McCrae:Uh, thanks for having us
Callum Mutch:on.
Callum Mutch:Thanks.
Sara Dong:All right.
Sara Dong:Thanks to Jame and Callum for joining Febrile today.
Sara Dong:Everyone, please check out the ID:IOTS podcast for more and send us topics that we can chat about in future combo episodes.
Sara Dong:Don't forget to check out the website, febrilepodcast.com to find the Consult Notes, our library of ID infographics, and a link to our merch store.
Sara Dong:Thanks for listening.
