ID:IOTS - Infectious Disease Insight Of Two Specialists

128. Antibiotic tier list

• ID:IOTS Podcast • Season 1 • Episode 128

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Yo ho ho, for our listeners dearest

We present an antibiotics tier list 

Ranking drugs from S to D

In a manner oh so Christmassy

So sit back relax and have a drink 

As we discourse in cladist think

And if you rank a different way

We'll forgive you this Christmas day. 


Proper episodes next year. See you in 2026! 

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Jame:

Ho, ho. Merry Christmas, Callum. How are you doing?

Callum:

I'm doing well, Jane. I've had a fantastic day with my extended family and highlight of Christmas every year is granny's trifle, which is a sort of tiered dessert,

Jame:

Uhhuh ha.

Callum:

which is a coincidence because what are we talking about today?

Jame:

We are doing an antibiotics tear list. A silly episode, Callum, for a silly season.

Callum:

A silly day.

Jame:

Yeah. So I'm sure the loyal listener will have seen the, these lists they are divided into SAB, C, and DS is the top d well, sometimes it goes down to E and f as well. But we've decided just to have the five categories and you rank things from best, worse. And this on this episode, we are going to be doing our favorite antibiotics. Some rules, Callum. We have got one example from each class. Usually I've picked the most prominent or significant member of that class rather than the one that's actually the most useful. And we will have to agree on the tiering. In order to proceed to the next antimicrobial. We have 22 in total, so let's get right to it. Jim coming in on the edit here, uh, after I said 22 callum made me add two more antibiotics in, so that's why, it will be 24 from this point on in the episode. As for which or the extra two, I'll never tell.

Callum:

I do love that this has got absolutely nothing to do with Christmas. I was just thinking about why don't we do like the 12 days of like take a Christmas Carol, 12 days of Christmas.

Jame:

that is way too much work. Creating 12 separate carols to release

Callum:

This is simpler. This is simpler, And low

Jame:

simpler one.

Callum:

effort episode.

Jame:

Fine. Well, I mean, I'm nothing if not low effort Callum,

Callum:

I have to disagree, Jamie, a huge amount of effort into some of the episode perhaps

Jame:

but not this one.

Callum:

but not this one. No.

Jame:

So we've got our list here in front of us Callam, and it wouldn't be an idiot's podcast episode without Jam and Callam alternately reading out a list of things. Would you like to go first?

Callum:

Penicillin.

Jame:

Amoxicillin,

Callum:

Flucloxacillin.

Jame:

Keflex, and cefazolin,

Callum:

Ferro.

Jame:

ceftriaxone,

Callum:

Cine.

Jame:

meropenum,

Callum:

Astri.

Jame:

vancomycin,

Callum:

Ciprofloxin.

Jame:

cotrimoxazole,

Callum:

Clarithromycin.

Jame:

clindamycin,

Callum:

Linezolid.

Jame:

chloramphenicol, gentamicin,

Callum:

Daptomycin

Jame:

rifampin,

Callum:

Calderon.

Jame:

phosphomycin,

Callum:

Nitrofuran, toin.

Jame:

and Andaz. And that's the list. Let's start Callum with amoxicillin over to you.

Callum:

eight here.

Jame:

here. Eight here. Okay. your reasoning.

Callum:

It's relatively narrow spectrum so I can safely put it into narrow spectrum camp, but actually quite often we cover. A lot of different gram positives and gram-negatives and a little bit of antiope cover. It's got a reasonable oral bioavailability. So it is an oral option for some infections, and you have a huge use, like it's got probably one of the widest ranges of things that can be used for. So it's your go-to choice for invasive streptococcal disease. You can use it in CNS disease if you give high enough doses, infective, endocarditis, pneumonia, it's a huge workhorse. It's probably, I don't know if this is true, but it is probably one of the most common, if not the most commonly prescribed antimicrobial in an inpatient basis in secondary care in Scotland, I would say.

Jame:

And I think in primary care it might be close as well. If not if not, number one. I think worldwide, it's definitely number

Callum:

Yeah, it's also an access antibiotic, which I think gives antibiotic bonus points. I'm just trying to think why I'm not putting an S here.

Jame:

I think you're not putting an S here because if you mix it with its friend clave acid, all of a sudden you've got like a big diarrhea, genetic antibiotic. I don't think it's the goat. I think the ST is to be reserved for the higher ups.

Callum:

Okay. We can always reserve,

Jame:

with you eight here as tri, I'm going to say. B Tier. So I think up until recently as Tree and AM has been really uncommonly used, like what I heard about it basically until I became an ID trainee was, it was a weird antibiotic for ICU patients and I

Callum:

you're gonna say for weird people there.

Jame:

No, ICU patients and then I, I didn't know all that much more about it. And since then, because of the way that we use amoxicillin, gentamycin, and Metronidazole to cover like sepsis empirically in Scotland, after a few days, we don't want to use gen basics of the nephrotoxicity. We would swap it out usually for Astri or Temin. And we've now started shying away from that because we want to preserve Astri to be used avibactam for the treatment of difficult treat, gram negative. particularly the Beales Carbapenemases. So I think it's got its use for that, it doesn't have any gram-positive cover. It doesn't have any NAL cover. People don't really trust all that much of pseudomonas, even though it is an anti pseudomona Beyl lactam. It's IV only, and it's not without c diff risk, although I don't think it's particularly high. So I think bt.

Callum:

I, I actually saw a paper recently from, and I think it was maybe Imperial. I can't remember exactly where it was because recently some, somebody I was working with said we were gonna use Astri now'cause they're high risk to c diff. And I was like,'cause at fizz last year there was a presentation and they were looking for the new data available on c diff rates. And the problem of TRO isn't often come up in these prevalence. We use it so rarely. And this paper, which I think I'll, I'll dig out and we can put in the show notes, put mono backin right at the top of carbapenem in terms of c diff risk.

Jame:

Oh yeah.

Callum:

With the theory being that they have fairly broad gut organism killing without actually being active against c difficile, which is fought to be an important thing. So, it's not just about how broad it is, it's whether it kills a c diff as well, or doesn't kill the C.

Jame:

Yeah.

Callum:

I think it's probably, from what I've read around it, there's not that much data, but it probably is actually quite high risk c diff in my opinion. And I

Jame:

is being modified by the fact that most people that are getting Astri probably

Callum:

It's such a huge it's really difficult to say.

Jame:

first.

Callum:

We spent so much time talking about it in microbiology in particular, I think like c diff, c diff risk. It's really hard to actually quantify what the risk is for different antimicrobials. And there's I've, there's, I've got, a folder of studies saved at work and all of them are slightly different. I'm gonna say that I don't think this belongs in B here and I'm gonna, I'm gonna propose it goes down to C or even D My reasons being right that,

Jame:

I'll meet you at CTO,

Callum:

yeah it's sort of just really gram negative as you say. It's not great against pseudomonas. It's not great on its own because we're talking about Astri and I, not Astri, and I'm aaba. Not great on its own against resistant gram tus. It's not stable against AmpC. It's not stable against ESBL. And I guess pseudo bonus has AmpC in it. So potentially one of the reasons why people are worried about it. I just don't really find it that useful. So it's not that broadly usable. It's very expensive, at least in the uk, Compared to other things. And the dosing isn't even that great if you're really worried about, a difficult to treat infection using it six hourly. So you have to use it frequently. It's expensive. It's not that broad.

Jame:

n it's chum of a back time to, to do

Callum:

Yeah,

Jame:

against

Callum:

I still think DTR you can put it in CTR, which would be the compromise, I limit

Jame:

bit of compromise, Callum. So c here

Callum:

limited uses for it.

Jame:

I think DT is for the absolute drink,

Callum:

Okay.

Jame:

me, the absolute drink is coming.

Callum:

Okay.

Jame:

Okay. Zolin.

Callum:

Well, it's funny.

Jame:

by the way, these are paired up together, unlike every other drug in this list, Kexin is like the oral version of Zolin. Do you know what I mean?

Callum:

Yeah, I think these are the hot kids on the block at the moment. That's not a phrase. I'm not gonna say that. Take that out. These are the cool kids on the block at the moment.

Jame:

this episode, Cal. That is Sting

Callum:

No,

Jame:

why is

Callum:

it sounds weird.

Jame:

on the block,

Callum:

I don't wanna talk about hot kids. So yeah, I think, snap trial Zolin is the new, sta re treatment of choice and.

Jame:

they get around to publishing their bloody studies.

Callum:

But we don't have really readily we can access it locally, but it's very hard to, and it's very limited supply in the uk. So it's gonna have a sea change, it's less to than Oxacillin. It's great against Staus. It'll cover your strep as well. It's gonna become our go-to treatment in the near future for skin soft tissue infections. I imagine. Staph voice, bacteremia, all things sort of staph and str and flu coil's gonna be out.

Jame:

it was our default treatment in Australasia. We weren't using flu CLOs in this way. We were sort of using it as oral step down from ke Zolin, but we were using ke zolin and it's expensive in the uk. It's pennies everywhere else. It's a

Callum:

yeah. This, yeah. So I think for me, I would put it in. At least a maybe s here. And I think Oral Kexin is something that, I was always taught at the beginning of my training, it's only for uncomplicated UTI kexin, but the more I read about it, I think if you're using high enough doses frequently enough, you can be using Oral Keflex as a suitable oral therapy for a lot of other infections. And I guess that use with Probenecid that some centers are using is exciting. So maybe eventually we'll have that locally and can sort of broaden our use and, you know, oral Keflex and with rabid for treatment of things like BATIA is established practice in some areas. I'm not sure it quite makes into S tier because it's not it's not broad enough, but I dunno.

Jame:

s tiers for the goats and dts for the absolute direct. So I think a tier, I agree everything that you said and more fer, ine dier. I cannot think of a single indication for keine, which I wouldn't want the more gram cover of Ceftriaxone or the higher oral bioavailability of Keflex.. When you move from the first to the second generation, the first gens already have prot c Coline, klei of the p gram negative organisms. You only then acquire the Hemophilus Intact Ceia and Scia the Hess. Organisms and none of those I would really particularly want to cover with Kine, particularly Edia. I would always want to cover that with ceftriaxone. The gold standard 40% bioavailability, compared to Keflex in's, 90% bioavailability. There's lots of other options that you could use. I know it's used sometimes for surgical prophylaxis. I know even that's dying out because Zolin is taking its place. So I can think of few, if any situations where I would want to use kerosine. In fact, I can't think the last time I recommended it. Dtr. Absolute crap.

Callum:

Wow. I'm glad you took Roane and I definitely learned something there with those mnemonics, so thanks. I agree. You know, we use it a lot for surgical prophylaxis, but as you say, if we could get more czo, why we just use that. It covers the organisms and we want to cover and it is less broad. In doing this to your list, I'm trying to decide if something being broad or narrow spectra makes it better or worse. And it seems to be different between different antibiotics. It's bad'cause it's broad.

Jame:

in

Callum:

It's bad because it's narrow.

Jame:

Yeah, I know. I know. But it's a silly episode. We are allowed to be silly

Callum:

Yes.

Jame:

kef track's on call.

Callum:

Oh, so useful. Something has to be in beat here, doesn't it?

Jame:

I think this is a good candidate for Pete here.

Callum:

Yeah, I, it is a workhorse of our outpatient antibiotic team oped. It's once a day, it is really great for that point of view in terms of giving it to people with all manners of infection. You walk in the door and if, you're ambulatory and you're not too unwell, we are gonna try and get you to oat. You could argue that we could probably use more oral therapies, but at the moment, that's what the practice is. And there's a lot of c track being prescribed for things like skin, soft tissue infections, but also a whole host of other infections. And so use a lot, but, the pharmacokinetics aren't that great for once a day dosing, like the half-life is quite short from memory. Is it something like six to eight hours? Yeah.

Jame:

for a beta lactam, that's surprisingly long. I think it's maybe 68, actually. I think I'm getting confused with ertapenem,

Callum:

6, 2 8. Yeah. Yeah. It's it's not that great. And so if you're wanting to cover things like staphylococci or, severe infection, giving four grams a day, I have to say that not infrequently. People, won't tolerate that with, their liver function or blood counts and so on.

Jame:

Or you get treatment failure because the breakpoint podcast did a brilliant tear down. They do these mini, they've got the series that they've got ongoing called dosing consult, where they take one antibiotic and just like deep dive into the pharmacokinetics. Done one on K recommended, and one of the things they point out is that Kft traxon two grams BD gives you more time over MIC than four grams once a

Callum:

Oh yeah.

Jame:

and so the part of the reason for the treatment failure is they think is that you're just not getting enough time over m for your target organism.

Callum:

I think that makes sense. So it just, we're trying to use stuff once a day, but I think, as I mentioned earlier on, with Zolin, if we can find some way for that to work with Ben. Well, I think other people have found it, but if that can become established practice, it's narrower spectrum and you can, it is basically the only thing redeeming kept traction for me is once a day

Jame:

Why I don't want to move it up to eight here. it's the lazy choice. You've got an affection, you don't know what going on. Ah, calf trione will cover it. It'll do gram positives, it'll do gram negatives. If you about intrado abdominal stuff, you can just add a little bit of metro

Callum:

yeah.

Jame:

sort of stop worrying about the problem and stop thinking about what's actually going on. That's why it's not a o for me.

Callum:

And c diff obviously.

Jame:

And the c diff too.

Callum:

I do, I have to say it is probably the main time I use it. It's either OPA or someone's come back from abroad and they're sick, and I'm worried about typhoid

Jame:

I think for opa it's good, but I think it's, you should be kinda limited to opa. I know that'll sound insane to people in some parts of the world. But anyway, Keine bt again.

Callum:

Yeah.

Jame:

Kpi. We don't use it an awful lot in the UK as an antimicrobial. I think that might change as we have to deal with more and more. Ess We don't necessarily want to be using carbapenems every time we do.'Cause it's CE stable. I've not used it much as an anti pseudomonal. in other parts, in, in the world, like in America, it's used much more commonly as a workhorse. A bit like keft as I suppose B Here

Callum:

I, I think I'm fine with that. I guess it is when those, it comes back to that question later on. Is being broad, good or bad? It def depends on the situation, but it is, pretty broad. Yeah.

Jame:

broad. I mean, it's Ceftriaxone Plus it's similar to Kef, sdi, I suppose, except it's more ly stable.

Callum:

Yeah.

Jame:

Chloramphenicol.

Callum:

I don't know. I think it's pretty good. It's very broad. You can give it orally. I can't remember what the bioavailability is off the top of my head. Yeah.

Jame:

It's good actually. It's about 80

Callum:

i, don't have that much experience of chloramphenicol, but I think it's obviously been harmed significantly by the rare, but an irreversible aplastic anemia side effect, which obviously very serious. But a lot of the other anti we use have similarly high rates of very severe side effects, and we're happy to use them. So I think we've shied away from Chloramphenicol maybe a bit too much.

Jame:

The issue is it's a bit like, risk factors for, having a stroke, maybe it's one in 20,000 or something for if you smoke so many cigarettes a day, but if it happens to you, it

Callum:

I.

Jame:

to you 100%. And so if it's got one in 20 to one in 40,000 chance of you needing an entirely new bone marrow, and if you use it more in a widespread way, that's going to be a problem to the NHS on a, both on a, we then have to bone marrow transplant somebody. If we could even do it as all. And then, there's litigation at stake as, as well, it's fallen outta favor in other parts of the world as well for the same reason really, but it's pretty good for targeting. Nice. I don't think it's err D here, but it's certainly not any higher than C. So C here.

Callum:

I think it would be good to do a deeper dive in Chloramphenicol at some point because it's not something I know I hear too much.

Jame:

That's something that you're requesting.

Callum:

Yeah. And what the actual risks, what the data around it is and a bit more about the side effect because the very occasionally it's proposed when we're kinda stuck with people, but yeah, I think it's certainly not something you're reaching to. No. It's been discussed a lot and then we've decided to go over something that we have more experience with.

Jame:

I told the story before about how I tried to do that once for somebody who's had a severe penicillin

Callum:

Yeah. Yeah.

Jame:

a needed treatment for meningitis. And then the hurdles to actually get it issued and prescribed and given to a person where almost but not quite insurmountable. Ciprofloxacin, C minus tier.

Callum:

Is that because it begins of a C?

Jame:

Well, I wish I could say that. I want to put this in de here. Alright. I don't like Quin loans. I don't look at me like that. Don't look at me like that.

Callum:

We don't like them. It's like, I don't think, I don't think we should say we don't like this or we do.

Jame:

no. I don't like Cipro fluxes in. Okay. You hear me? Alright, Cipro, if you're listening in, I don't like you. Okay. Now you know that I'm a flawed individual Callum, nobody knows it more than you. In point of fact, the loyal listeners probably have a guess. one of my flaws is that I do not like this drug. Okay? And I don't like it because it's so good. It's highly bioavailable. It treats pseudomonas in difficult to treat gram negative. If you use equivalent, by all means, use equivalent. And it doesn't play by any of the rules that. Pharmacokinetically you would inspect. So normally you've got stuff that's really hydrophilic and that stuff stays in the plasma and deals with plasma borne infections, stuff like penicillins and vancomycins and stuff. And so if you're a vascularly enriched tissue, you're fine. But if you're not, then that's maybe not the drug for you. And then you've got stuff that's really lipid soluble. So like a azithromycin and the other macrolides or the tetracyclines, for example. And they don't stay in the plasmas very much, but if you are with intracellular pathogens or you've got good tissue penetrance, like say into the lung, like for the macrolides, then you're absolutely fine. Okay. And the quinolones don't ab obey either of those rules. They're quite lipid soluble and they've got quite long half-life, but they get good plasma levels somehow and get good levels into the tissue somehow, and also get into the cells somehow. And they just seemed to do everything. And they're highly bi. They should be my favorite antibiotic in the world. The problem is that they also get into the tendons and stop matrix Metalloproteinase is working or working too hard, I forget which way round it is, so that your Achilles tendon explodes and if that doesn't explode, your aorta will. they've got neuropsychiatric side effects and this side effect and that side effect. And they're too difficult to list to the point where people their PhDs writing articles about how many side effects the equivalents have. They're a massive source of litigation in the US and that they still seem to throw Levo fluxes into everything that so much has produces a cough reflex. And I just think they're the lazy man's choice, particularly for respiratory when they're dealing with infections and they want to cover pseudomonas just because they always want to cover pseudomonas a little bit. Everybody, even people that are not cfs, even people that aren't bronch attacks, people that just have like COPD. Why don't we just give a bit of Levo or Cipro in any case, and I know now I sound like an absolute madman ranting, so I'm just going to say CT R because I know that they don't deserve DT R even though just spent the last two minutes going off on you about them.

Callum:

Wow. Yeah, I, I don't know if I would say that I like or don't like antibiotics. I think you just have to weigh it up for this individual. But we're talking about this on a whole thing rather than individual basis. I think

Jame:

takeaway from what I just said.

Callum:

I probably would've put it in B, but I feel like you feel much more strongly about this than me, so I'm happy to go with c.

Jame:

Okay, fine. Well, this podcast is about nothing more than consensus clarithromycin. You're American, just replace Claro. With Azithromycin.

Callum:

Yeah. Yeah. I dunno why we don't just use a zif for more, but anyway

Jame:

too. Me too.

Callum:

yeah, so, macrolides in general great for intracellular organisms, great for that atypical pneumonia. Pretty reasonable for the rest of pneumonia covering things as well, just as good as quinolones for legionella.

Jame:

Yeah.

Callum:

so it's quite niche though,

Jame:

what do you mean by that?

Callum:

as in like, it's not something that you're ever gonna use for someone that's sick or for a, broad spectrum cover.

Jame:

it

Callum:

It's just as you said,

Jame:

to Quinones for legionella. I think that's just our plasma born infection, racism shining through. Do you

Callum:

think,

Jame:

Because Is good for that sort of stuff. It's just that we think of it as like a weak antibiotic.

Callum:

It's not good for plasma borne infections. Yeah, potentially. Although sick people quite often are battery mix, so I,

Jame:

true. Not clarithromycin fault. Callum.

Callum:

it's not, but the, that's what it is. So I'm probably put in seed here

Jame:

Yeah. I think it's a beat here.

Callum:

really.

Jame:

I think if you've got any typical pneumonia, it's the one for you.

Callum:

I know, but like overall as a total antibiotic, like we did desert eyelet antibiotics before.

Jame:

in C and I got my way. So you can put Claro and C and get your way. Okay. And then we're all happy. Bunnies, clinda, bison. High c diff Risk is an option for sta aureus batia, as per the saboteur trial. Highly by available dosing is a total nightmare. Good for toxin control in neck fash beat here.

Callum:

Really?

Jame:

Can't put everything in CTO.

Callum:

I know I just put

Jame:

too

Callum:

c you Yeah, I'd probably put Clinda and C and move Cipro up,

Jame:

fine. Well, I'll put clinda and C but I'm not moving. Spro

Callum:

Okay.

Jame:

cot.

Callum:

Well I get to do this one. I want to put this in a here. James indicating up, well, I'll make my case for a, so it's a workhorse. It's good. Oral by availability. It's one of our few oral gram negative covers. It works against some fungi like PCP, And other parasitic infections as well. So it's got a pretty broad coverage. Covers some strep, quite often covers staff. Doesn't cover Anna ropes, but you know, you can't have everything.

Jame:

Ah, well, Callum Cotrimoxazole does have a little bit

Callum:

oh yeah, actually we were talking about this. Yeah, a

Jame:

Yeah.

Callum:

little bit. Banner rope cover.

Jame:

Head of the BIA or president of the BIA Kate Jeffrey told me this when I was working at Nado Royal Infirmary South. So it doesn't have a break point, but if you actually look at the PKPD papers, you'll see that there is a little bit of annual rope cover with Cotran Amoxil. So which might explain why if you're using it for like polymicrobial liver abscesses and stuff, you can sort of drop the metro after a couple of weeks probably.'cause you've killed all the annual ropes that need killing, because Corum has a little bit of any cover going So, sorry, interrupted.

Callum:

Yeah I guess the reason why I wouldn't put it SD is that it isn't the best tolerated drug. Of all the drugs that I'm prescribing orally, I think that's probably the one that we see the most problems with, with hyperkalemia or a KI more than ver percent rise in creatinine or myelosuppression or even like more severe end of the spectrum, severe drug reactions. And I think generally when particularly older patients or co comorbid patients, when I'm prescribing code treat, I'm recommending it in the back of my head. I'm like, Hmm, I wouldn't be surprised if they run some problem. I have to switch. And I'm also thinking like, what's my next plan gonna be? Cipro, probably. So yeah, I think it's just too poorly tolerated, too many side effects. If you're gonna put Cipro down to C for, the side effects, then I think corum can't really go higher than a.

Jame:

Okay, I'm going to make the case for rest here. Here, and I'm going to say it for a couple of reasons. Firstly, I describe Cotrimoxazole to people as ceftriaxone without the c diff risk. Because its spectrum is very similar to Ceftriaxone. Lots of gram-positives, lots of gram-negatives. Does staph, does strep, doesn't do enterococcus. And then the gram-negative cover is pretty, pretty tight. And then it's got that little bit of aero cover that you've got. It's highly bioavailable. It's 90% bioavailable, there's no reason to give it IV unless the oral route is compromised somehow. it also covers ESPL and it also covers axi, and it will also cover carbapenemase producing organism too. No pseudomonas cover, but you know, just about everything. Every other ints, unless it has a defined resistance mechanism to anti folates, it'll work against it. I think that the side effects that you mentioned, you're talking about it with an OPAT hat on. You're now the king of Opat in your local area, and so you are giving corum for long periods of time. You're also tainted a little bit, I think, by giving Cori for PCP, where the dosing is sky high and therefore the side effects are really high too. So that hyperkalemia and the KI, and the severe cutaneous reactions, that's much more common with the higher doses that we give for PCP and sometimes stenotrophomonas in the nine 60 BD dosing. These are much less common and less the patient's on an ACE inhibitor, in which case if you can pause it, just pause it, and then you're much less likely to run into that hyperkalemia. but I think that, compared to some other antimicrobials, it's much better tolerated as long as it's for short courses or you know what you're doing with drug interactions and and stuff like that. I convinced you,

Callum:

No.

Jame:

No. Fine. Eight here it is fine.

Callum:

You have to do coon now.

Jame:

Dier.

Callum:

Yeah. Okay. Yeah. Not gonna argue that

Jame:

you think aminoglycosides are nephrotoxic. You just wait until you see Colistin.

Callum:

also.

Jame:

to treat a VA with Cosin? Good luck with that,

Callum:

Yeah, it just,

Jame:

et

Callum:

every trial is like, it doesn't really work very well, but

Jame:

Yes,

Callum:

enough. If that's all you've got, like you have to use it, but it's not what anybody wants to have Fender covered, does it?

Jame:

And like it truly is an antibiotic blast resort because it's crap. Daptomycin kill.

Callum:

Oh oh, I'm gonna say B here.

Jame:

Yep.

Callum:

Do you agree?

Jame:

Yes, I do.

Callum:

Yes. It's sort of just gram-positive. There's not really any gram-negative cover. It doesn't work in the lungs, which is the annoying sometimes where your patient with a skin soft tissue infection develops some pneumonia and you're like, oh you always have to warn people about it. It's not that well tolerated. Like it's not that uncommon that you see myositis.

Jame:

But you do, when you're using it for like endocarditis dosing,

Callum:

yeah, I think the higher dosing, yeah. Yeah.

Jame:

mgs per K to 12 mgs per k. Also, I don't like that. We've got the staff dosing eight to 10, and then the enterococcus dosing at 10 to 12. Just use 10 for everything. Like what? What are you doing? Why are you just making this more difficult than it has to be? Do you know what I mean?

Callum:

It is very complicated to prescribe. Yeah, we've got a local very useful page that I just say, go look at this page, because our antimicrobial management team put together a link of all, you know, all the side effects, all the monitoring, everything just makes my life so much easier. Just go, go read this website. Goodbye.

Jame:

That's the other thing. People aren't familiar with it, so

Callum:

Yeah.

Jame:

tell'em to go and prescribe it, they're like, oh, I need a bit of guidance on this. So it's more time intensive for you as the infection specialist

Callum:

Familiarity of teams is so important. Like you think about that, like the patient who's got ascites from their alcoholic liver disease and they come in for a drain and they get managed in the GI ward.

Jame:

Yeah.

Callum:

It goes smoothly. Try and do that in any other ward disaster because people aren't familiar with the process. And it's the same with antimicrobials. Like the number of phone calls you get are queries about people that are on unfamiliar antimicrobials or like, people miss the pitfalls. So you always have to say to'em like, if they have pneumonia, daptomycin doesn't cover it. Although, to be honest, they're probably gonna phone you anyway. Anyway, we, why are we talking about this so much? We agree. Beat here. Done.

Jame:

Fine. Doxycycline s here. Yes.

Callum:

Yes.

Jame:

Yep. The absolute goat treats just about everything you can shake a stick at. Really good for tropical disease, good for helmuth ocs, et cetera, et cetera. Like, I don't think this requires any explanation. Well, we just move on Kyle.

Callum:

I think it, it's also just very well tolerated and I guess it's not like for really sick people, like it's got some down, down points, but

Jame:

And yet no one dies without doxy. If you have even so much looked as a picture of a tropical island in a book you're getting doxycycline on the off chats that you've contracted infectious disease whilst out there.

Callum:

malaria prophylaxis,

Jame:

malaria prophylaxis. This list is of antibacterials. We're not even really listing on the anti parasitic and anti helman thick properties, but if we were, doxy would win. Hands down.

Callum:

it is not perfect, I would say, but I think nothing here is perfect and every drug has got side effects. So you just have to.

Jame:

perfect to be asked here.

Callum:

But the side effects of it, I think are pretty manageable. Like, just don't go in the sun, wear some long sleeves, the, even the GI side effects are pretty manageable, so,

Jame:

Totally.

Callum:

yeah.

Jame:

Flu oxacillin, Callum

Callum:

Oh, here.

Jame:

D. Okay. State your case.

Callum:

If you'd asked me this a year ago, I would've probably said B.

Jame:

I thought you were gonna say B.

Callum:

Maybe C is better. I, it's just, I'd much rather use Keflex and Zolin now.

Jame:

Me too.

Callum:

It does everything oxacillin does with a lower risk of a KI and just as good outcomes. So,

Jame:

highly bioavailable

Callum:

and better by availability than oxacillin. Yeah.

Jame:

Version. Yeah. And the dosing of Keone three times a day with flu clocks, it's four times a day.

Callum:

I just can't find any reason to, I

Jame:

it's cost, right? The reason is it's cheaper, but if they were the same cost, I don't think I would be touching flu clocks anymore.

Callum:

And the number of patients that have horrible vaso toxicity with it. Like, you put a cannula in one dose later is burning and painful, like, I think it's about 10%. So it's not insignificant. And when you see those patients.

Jame:

we are using usually the eight grams a day dosing, and so that probably makes a

Callum:

Potentially, but I think even then it's not many doses and the poor, resident doctor has to keep going back and put more and more lines in the patient's sitting there being like, there must be something else. Yeah, I think that patient experience part of it always struck me giving people IL and yet still do it because I don't have zolin yet. But yeah, I, I'm bit, bit of a D here. Like, it's useful. You do use it a lot but there's something better available.

Jame:

something that we use all the time in D here think that, I think it's probably c, let me put it this way, Kam, have you removed it from every single guideline in your local guidance?

Callum:

I wish I could, I also don't have any power over the guidelines, so it wouldn't be up to me.

Jame:

Let's call C.

Callum:

Okay. Yeah.

Jame:

Okay, fine. Oh, phosphomycin, C here

Callum:

is, I guess you're talking about oral, aren't you?

Jame:

I'm talking about both. So I think Oral Phosphomycin, it's got its role, although there has been it certainly didn't beat nitrogen and to, in a uti I head-to-head trial, so I think, nitrogen and tone is gonna end up above it. The is poor, but as long as it's going straight into the urine, no problem. Who cares? I know there's been some publications using it as step down after three days of IV treatment for pyelonephritis. So as tail therapy for that phosphomycin until we got the new beta lattin, beta-lactamase inhibitor combinations in CCF called the Trojan Horse. It was one of the things that we used for difficult to treat gram-negative infection and staph, but it was really difficult to administer. It was eight grams IV three times a day, if I remember rightly, and really high rates of treatment failure. It's got low barrier to resistance. It's not dt. It's still useful sometimes, like think of your old lady that you want, just want to give one sache to

Callum:

it

Jame:

it's

Callum:

is so, it's so niche though. It's like basically the break point's only for e coline now. And like I know you can test it against other things, but it's a bit of a faf and

Jame:

able to test against pseudomonas, but they removed that because the EEC cough was so high

Callum:

yeah, and it's such a high rate of FSE in pseudomonas. I think we talked about that in our antibodies. I think it's still something that I've, on a very rare occasion. Have tried for patients with pseudomonas in the urine And it has worked with a couple people, but I don't think,

Jame:

weren't just gonna get better?

Callum:

yeah, it's far from,

Jame:

right?

Callum:

it's far from a first line treatment option for that. So I think CCI, I would al almost tempted to put it into dt. It's not like unhelpful though. I guess DT is like, why did they exist?

Jame:

completely useless. Is not completely useless.

Callum:

yeah.

Jame:

like limited use. Fine,

Callum:

Oh, I guess du Gentamycin ha

Jame:

do, oh, you lucky pup.

Callum:

beat here.

Jame:

How dare you justify this erroneous opinion.

Callum:

Well, we use it a lot, but I think there is genuine concern about his pharmacokinetics in terms of its treatment effectiveness against gram-negatives in particular Pseudomonas. And also the toxicities. You can't use it for more than. 3, 5, 7 days generally without starting to increase quite significantly your risk of nephro or auto toxicity. It's not something, I think it's useful from a stewardship perspective because it is quite narrow spectrum. And I also think the difficulty of administering it drug levels for patients, for teams, changing the dose, calculating all that, it's not something that's very easy.

Jame:

those ADRs and the fact that you have to do dosing monitoring to justify this B tiering, are you.

Callum:

Yeah. And also I just don't think it's gonna ever be, I know we use it for gram to cover, but like we don't really have the data to back that up. So we'd need clinical trials really to go out and say it works. Like it's got a couple of cool bits and the post-treatment effect, et cetera, from a theoretical point of view could be better. But I think until we really can prove that. It is as good as we think it is. I'm not sure I would put I and b.

Jame:

Okay. I would've put it an a, I wouldn't have steered it. And I understand that there was concerns about, PKPD of Gentamicin and I take on onboard the dosing and the nephrotoxicity and the ototoxicity as well. I disagree with the fact that it's narrow spectrum. It's not narrow spectrum covers staph, it covers intact ales, and it covers pseudomonas in the urine. And if you want an anti pseudomonal oxide, you've got tobramycin and Amikacin just sitting right there. But me ask you this, Cal, you're dealing with uncomplicated gram-negative infection. What dosing duration are you going to use? For bacteremia. Sorry. Uncomplicated

Callum:

or seven days.

Jame:

seven days balanced trial. What duration was non-inferior to 14?

Callum:

7.

Jame:

You see where I'm going with this, right? You don't want to use for Gentamycin for longer than seven days. I say there's almost no infection where after you've got source control, you need to use it for more than seven days. And actually after, if you only want to use it for 48 or 72 hours and then switch to an oral therapy, it's perfect as a drug. The people that are clutching their apparels at the fact that we're using gen in the cover, empirical sepsis infection. They're all using ceftriaxone and keine. They're all using IV therapies instead. They're not all using cotrimoxazole. So

Callum:

Yeah,

Jame:

saving the cannula, you're not saving any IV time. Fine. You don't have to do levels for ceftriaxone and stuff like that. Bt, or did you say

Callum:

it is sort of B plus I, I think.

Jame:

B plus?

Callum:

Yeah, I think it is really useful. It's just hard to sometimes find it hard to be as evangelical about it without really being able to point people towards the clinical data to back it up. I,

Jame:

Yeah. All you've got is the evidence that for the past 20 years that gram-negative mortality rates in Scotland have not changed at all, despite the fact that we're using genta to cover gram-negative sepsis in almost all empirical cases.

Callum:

I think someone needs to do a really high quality publication on that. Jim

Jame:

Fine. Sli. Beat here.

Callum:

B here?

Jame:

Yeah, beat here. It's good for staph Reus. It's good for, grandpas of battery emia. It's highly bioavailable. Actually I'm changing my mind. Eight here.

Callum:

Yes.

Jame:

Yeah, fine. It's got that long-term myelosuppression and some

Callum:

neurotoxicity

Jame:

as well. But

Callum:

and also serotonin syndrome?

Jame:

I think that's a pile of crap.

Callum:

I think there is clinical data to say that it does increase the risk, but

Jame:

A very minor amount. Certainly not as much as we thought.

Callum:

No

Jame:

to justify all the,

Callum:

I the pull out about it. Yeah.

Jame:

that was happening before a few years ago.

Callum:

Yeah. No, I think it was a bit overblown I guess we're gonna see more and more esli resistance emerging because people are using it too much. It's so good for Gram positive. It's like, basically. Give it orally and forget.'cause you don't have to worry about resistance other than the monitoring. But the problem is,

Jame:

where I'm currently working, we have an MDT where we look at all the complex infections and we spend the rest of the week telling everybody, don't use SLI unless we tell you to go battalion to the F1 that prescribes sli. And then in our MDT we're like, let's put everybody onli and just forget about the whole thing. See you in the PAC Clinic Buster.

Callum:

yeah it's great. It's a really useful antibiotic, but it's a reserve. Antibiotics. We shouldn't be finding it out. There's something else you can use. You should do something else.

Jame:

Yeah. Agree. Should be tear then?

Callum:

no. Do you like it though?

Jame:

Meropenum

Callum:

Has to go an 80 year, doesn't it? This is this me choosing.

Jame:

yeah. It is you choosing. But I

Callum:

Yeah,

Jame:

I agree. I don't think it's asked here, but I think that, as your get outta jail slash sbl treatment slash I don't know what's going on, but I want something hard and fast. I think it's hard to beat.

Callum:

it's hard to be like, obviously resistance, ciff risk, microbiome toxicity, it's got a lot of negatives. But if you have something in your pocket for res, really sick, that's probably what you're gonna reach to obviously, unless you're

Jame:

you want to be

Callum:

Yeah,

Jame:

you're in the intensive care unit you want to be on

Callum:

yeah. Unless you're in a high CPE. But this is a UK thing and we don't have that much cps frankly. So,

Jame:

well if they haven't figured out they were a UK podcast by now and a Scottish podcast in particular, then I dunno what they're still doing. Hanging about.

Callum:

yeah, they probably need to do a different tier list of like, difficult to treat gram negatives tier list. Well, but I guess that'd be quite easy.

Jame:

that. Oh, that's for next year, Callum. Oh, I'm looking forward to that. Metro Metronidazole,

Callum:

This is you.

Jame:

it's A or B. What do you think?

Callum:

I would check it in b.

Jame:

Okay. I think what I like about Metro highly bioavailable, you might as well give it orally if you can. It's really, there's nothing better for an robe infection, if you want to cover an robes, like it's the thing to go to. It's also got its uses and other conditions, bacterial vaginosis and all that sort of stuff. We did use to use it for CD if we don't really anymore, very limited in its. Activity and spectrum, but then that's what you want it's also got it's broken down to an active metabolite. So actually if people don't tolerate three times a day dosing, or if you know that you're going to be giving it for a long time, like for a liver abscess or something, and you're gonna be giving it for a month because the neurotoxicity is cumulative, you can cut the dosage to BD dosing and that should be just as effective.'cause it's got a long half-life and it's got that and metabolite that it's broken down And that also simplifies the dosing if you're giving it with something like Oxil, which is twice daily anyway. So, yeah. But I think because of its limitations, as in it's not, active against a bunch of different stuff. Beat here

Callum:

yeah. I was gonna say beat here admittedly, because of how much effective has on the microbiome. And also just.

Jame:

might think.

Callum:

I also feel like it's just way overused. Like, going into the evidence behind why we people give it for an aspiration pneumonia or hepatobiliary infections, like these sort of minor infections where people have this idea like, oh, this infection means there must be ROEs, therefore we must give metronidazole because they have to treat opees rather than thinking like one opees aren't often that important. Things like aspiration, pneumonia or, and non-severe hepatobiliary infections and a couple of other ones and abdominal infections, for example. And two, you're probably gonna cover opees sufficiently with the other antimicrobial you're giving. So put it down a tier because I think we reach for it too often almost. And it's like, just like this held up as like anaerobic equals me. Or rather than saying are there actually anaerobic and do you actually need mein?

Jame:

yeah. Or are those Annie rubs going to survive very long in the most oxygen rich environment in your entire body, but a conversation for another time, Callum, at night,

Callum:

Yeah.

Jame:

and to.

Callum:

C here you can treat a UTI and that's about it. And it's got some really horrible side effects if you use it for long periods of time. So it's just a very niche antibiotic. It use

Jame:

But if you have a UTI, it's probably going to sort it out.

Callum:

Yeah. It's great for UTIs. It's great. It's really good.

Jame:

but just for cystitis. And

Callum:

Yep.

Jame:

dosing is a bit icky as well, four times a day, unless you've got the MR formulation available to you. But that's something like five times the cost in the UK to get the MR dosing to make it bd. So that's sort of limited. Its adoption, but if you're in some place where it is BD dosing, have at it Penicillin. S here. It's the one that started all Callum. So, when, Alexander Fleming Scott discovered penicillin in Britain, which makes it by the way not only a British drug, but also a Scottish drug. He opened up a whole world of antimicrobials to us, that rabbit hole that we've been falling down ever since. And if antimicrobial apocalypse comes to fruition we will shortly get to the end of, but it all started with penicillin. I don't care if it's useless for pretty much anything these days. That's like saying that Muhammad Ali wasn't a good boxer because he's currently dead. Penicillin the absolute champion of antimicrobials.

Callum:

It sounds like you're giving a talk in a speech in the musical, the mold that changed the world.

Jame:

I dunno what the mold. Oh I've never seen it.

Callum:

I've seen it twice different productions at the fringe and it's great. Recommend it if you can get a chance to see it. So, yeah, all that being said, okay. Some detractors from penicillin and

Jame:

You can see your piece Ka,

Callum:

basically,

Jame:

you to know I'm not changing

Callum:

okay, fine. It gets into the body for fatigue quickly. Scar is out the kidneys, it's, so much so that initially they collected from patient's urine in order to minister it because there's so little of it. So you know, it's straight outta the body, so you have to dose it like crazy. Every four hours giving a person infusion if you really want to give them high time of MIC. That's quite onerous.

Jame:

Yeah. Yeah,

Callum:

onerous, pretty terrible. Orbi availability, I can't remember what it is, 40%, something like, okay.

Jame:

the thing is benzo, penicillin has no oral bioavailability you don't absorb it. That's why they had to act the phenoxy

Callum:

Yeah.

Jame:

it to make phenoxy methyl penicillin. So that happened later. That happened in like the fifties or

Callum:

But

Jame:

that?

Callum:

with the orals, you still have the problem with the rapid excretion. So,

Jame:

is still true. The PK is very

Callum:

stuff about giving pen, ben fall or pen G, which gonna call it for Pen V for strep throat. Like why just give amoxicillin? Like the EBV thing the rashes, a is a myth. So, yeah, I think it's got a lot of problems and it's obviously, it's very narrow, which is maybe good, maybe bad depending on how we've been discussing it today.

Jame:

Well actually Brad s Spellberg has a a Twitter thread or X thread where he goes through actually how broad spectrum penicillin it. now. actually when it first came out, it killed everything. It killed gram-negatives. It killed strep. It killed staph aureus. Before it acquired the penicillinase. It killed enterococcus. It just, they tried it against everything and it worked against everything. It was a true wonder drug. It was only later that resistance started to emerge.

Callum:

Okay, but we're in 2025, so,

Jame:

I know, but we wouldn't be here without it.

Callum:

I know it's 2025 to your list.

Jame:

column.

Callum:

Okay. I know you said you were gonna change it. I would probably put it on eight here, but I'm happy to leave it on s here for posterity's sake and wistful old Jane here. The ghost of antibiotic Christmas past has intervened.

Jame:

Fine. Amp, Maybe be tier seat here.

Callum:

it's got loads of interactions. It's a pain to prescribe with other drugs. It's, it's very low barrier to resistance. Like obviously for tb it's fantastic, but we're not talking about TB really. We're talking about antimicrobials in general.

Jame:

TB is a bacteria, so

Callum:

Well, yeah. Okay.

Jame:

but you're right, it's in P four 50 enzyme inducer, which means it interacts with everything. If you're on warfarin, say goodbye to your INR stability, the barrier to resistance, which actually is an issue with the quinones as well, that I forgot to mention before. One single snip and all of a sudden all of the quinones are rolled out. Pathetic. Pull yourself together, Ciprofloxin. They're so bad that you've to pa pair it up with rifampicin. In order to properly penetrate biofilm and protect each other against resistance development in staph aureus. yeah, you're right, it can

Callum:

We religious dropped out.

Jame:

with Cipro.

Callum:

I think if it was just a TB thing, then yeah, it would be OPS here probably is amazing for tb or even with all the problems. But in general, and I think, in general, antimicrobial infection, we're using it in sort of biofilm, prosthetic joint infections. Like there is some evidence for Cipro and rif, but I think the degree to which it is, universally accepted, rifampin is anti biofilm and it has this. Effect. I kind of remain a bit skeptical, the arrest trial, which poured a bit of cold water on that viewpoint from a staph pho perspective. But it's a nice theory, but we know as for, tidal, ver bacterio, static, theories don't often hold or sometimes don't hold up in clinical practice. And it's not like anybody's ever really definitively said that you must give revamp. So I feel like it's somewhat over eggs. Like, don't get me wrong, you should use it.'cause that's what's all the guidelines and that's what we think is the best thing to do at the moment. But and it's just not got that greater data set.

Jame:

too. But that I hate that phrase. You have to do it because it's what in the guidelines? Because it's implying that the guidelines are, I know you don't do this, they are in violet or inviolable and that. Thinking leads to us doing stuff just because it's in the guideline and the guideline might be wrong, as evidenced by the fact that guidelines change over time as the evidence becomes more

Callum:

change over time. Often.

Jame:

Very slowly.

Callum:

Yeah. Yeah.

Jame:

Yeah. I, yeah, I also think that we currently have a shortage in in the uk of Rifampin at the moment. And so that's led us to reconsider what we are doing for its use, particularly in bone and joint infection, where it's used with Cipro rif, but it's also used with other agents as well, for which the evidence is vanishingly small, if any. So actually the big bone and joint infection center that I formerly. Was associated with, I know that they have limited their Rifampin only being with Quinones and for anything else. They're either using fu acidic acid or nothing at all for their combination therapy. if you're on, a Beal latam, you're not getting Rifampin with it. And we're

Callum:

Okay.

Jame:

replicate that locally as well.

Callum:

Yeah, I think that makes sense.

Jame:

is perfect for Rifampin, Callum,

Callum:

Okay, so you've got the last antibiotic last day. It's Christmas day now on number 24.

Jame:

I know. And we finish as we sometimes do in real life with Vancomycin b.

Callum:

Yeah, that's fine.

Jame:

Many people have a problem with vancomycin Callum, and don't like it as an antimicrobial, and that's fair enough because it's crap. It's got nephrotoxicity. Maybe not as bad as Gentamicin, but it's still, it's up there and you need to monitor the dosing. Trough levels and it's IV only, and usually two or three times a day to administer. It's that all of that is a real pain, but you're dealing with serious staph aureus infection, you can usually give it. Enterococcus for that matter, safe in the knowledge that it'll probably work. Vancomycin resistant Staph aureus is really not very much of an issue in the UK and elsewhere at all. Despite earlier fears, the MROA was going to evolve into VRSA, a Vancomycin resistance, doesn't seem to be all that stable in Staphylococci, as opposed to Enterococci where it's a real problem.

Callum:

Yeah, I think it's a bit of a pain. It's got toxicity. You need monitoring. Often the levels aren't achieved in younger patients with good kidney function. But nothing has really ever been definitively proven to be better than it. I think I saw Brad s Spellberg tweet about that one time, which kind of was surprising to me when I was more junior because I felt like there was a lot of Vancomycin bashing going on.

Jame:

Huh? Yeah.

Callum:

You know, people, oh, you know, quick get them onto daptomycin or, but we, we were often switching people all vancomycin when they weren't doing well. But actually, yeah, don't necessarily know that anything's superior to Vancomycin other than Beta Tums, to my understanding.

Jame:

Yeah. I agree. I mean, I've never seen any evidence to see that anything except the Beal lactams, anti Cocal Bee lactams in particular, Esli have beaten

Callum:

Oh yeah, I know that.

Jame:

in a

Callum:

Sorry. Yeah.

Jame:

in a head to head. Like everything else, I think is sort of on the level of, vancomycin

Callum:

Yeah.

Jame:

And, particularly for serious Staph Aureus infection, if I'm not for some reason able to use beta latam or esli, that's my next go-to for initial treatment of infection.

Callum:

Yep. Okay, so should we just quickly run through the tiers before we finish?

Jame:

Yeah,

Callum:

Let's start with D and work our way up.

Jame:

Fine.

Callum:

D here we've got Coxy and Colistin

Jame:

In Cir, we have Astri, chloramphenicol, ciprofloxacin, clarithromycin, clindamycin, Flufloxacillin, phosphomycin, 90 Ferone, and Orin.

Callum:

In B here we've got Ceftriaxone, Keine, daptomycin, gentamicin, me, Niaz, vancomycin,

Jame:

In a tier we have Amoxicillin, Keflex, and Cefazolin, cotrimoxazole, Lin, lid, and Meropenem.

Callum:

and in S. Here together. Now we've got Doxycycline penicillin.

Jame:

That's gonna be an absolute nightmare to sync up.

Callum:

There you go. Well, you better remember this because it's probably gonna come up in your exams. Maybe we can put this out as a survey on Christmas Day and ask people to fill it in themselves and then we can at some point in the future, follow up and tell you what the, how wrong we were.

Jame:

Yes. Although if you do actually put out something that's different to us are not going to accept that, and you will have to unsubscribe from the show, but you may be thinking about doing that. Anyway, after this absolute drop kick of an episode,

Callum:

Oh, well, have a Merry Christmas and a Happy New Year.

Jame:

Merry Christmas.

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