144. Choosing an antimicrobial part 2: Microbe, host & drug factors

How do you decide which antimicrobial to use? This is a follow on from episode 69, 'Choosing an antimicrobial'. We did an overview of spectrum and syndromes... But now let's dive into the details!

We consider the details of how to choose an antibiotic in simple, complicated and complex situations. 

We also talk about the Cynefin Framework for decision making in various circumstances; Don't worry if you don't know what that is; neither did Jame before this episode was recorded! 

Notes for this episode here: https://idiots.notion.site/144-Choosing-an-Antimicrobial-Host-Microbe-Drug-Factors-2d76a1ea09d8814787ccfc26fe779b3a 

Transcript

Jame 0:18

Callum. I have a curious clinical conundrum that I believe only you can help me with.

Callum 0:23

Oh, I'm flattered.

Jame 0:25

I've got a patient with a clinical condition and I need help choosing an antimicrobial. If only somebody had recently summated how he chooses an antimicrobial on another podcast,

Callum 0:36

Yes, I've been off without Jane in the wide world.

Jame 0:42

shitty on me. But you do that all the time with Alyssa on the fungal episode. So you know, I've got used to it now.

Callum 0:46

Yeah you're not jealous. Cohost are you?

Jame 0:49

No. So who have you been cheating on me with Callum.

Callum 0:52

this great podcast called Primary Care Knowledge Boost, which is targeted at primary care and best general practitioners, run by a lovely, Sarah and Lisa, who are based on in Manchester, England. And, it was a strange connection of people that led to us all getting together in Edinburgh and recording two episodes about infection. So the first one we'd recorded was all about antimicrobials and the second one was all about samples. And they asked me a lot of questions, some of which were quite difficult, about, firstly how you choose antimicrobial, and secondly, what happens to your samples in the lab now. we thought maybe we could speak about that again here, I listen back to the episodes and sometimes you listen back to yourself and you think you're rambling a bit and the more you talk about something.

Jame 1:47

So you don't think you're rambling

Callum 1:48

Yeah, that's true. I feel like the more you talk about something, the more honed you get at it. 'cause you think about it more and more. I have to say the number of times I've given a penicillin allergy to labeling talk now.

Jame 1:59

I know.

Callum 1:59

I don't know how many times, but it is definitely getting better each time I do it.

Jame 2:04

you have it down to fine art? Yeah, I'm the same. As well, I've got my little pet topics that I educate the f ones on one at a

Callum 2:11

Strep talk today in the wardrobe was like on point yeah.

Jame 2:14

So the last episode that we did was a couple of years ago now, and that was on choosing an antimicrobial according to the spectrum that you want to cover. So we gave pneumonia as an example. So now we're gonna be talking about the other factors that are at play.

Callum 2:28

Yeah, I think that was taking it from like an empirical antimicrobial choice. Looking at the microorganisms, the bacteria really that cause an infection, a clinical sin. Drum and then

Jame 2:40

It was a bug's eye view and it was empirical,

Callum 2:42

Eye view.

Jame 2:42

it

Callum 2:42

That's a nice way of putting it. Why didn't we call it a Bugs Eye view?

Jame 2:45

Oh, we should have, well we can go back and change it, but I also feel that's kind of cheating. If

Callum 2:50

Well, we'll do a future episode called A Bugs Eye View on Me.

Jame 2:52

fine.

Callum 2:53

There's actually a really great book by Conman which is called A Bug Story or something like that. It's a really, it's quite an old book, and it's written, it's all about bacteria. It's written from the perspective of the bacteria. I found it a bit too I found it quite hard to get into. It was straddling between serious and silly, I think too much for me,

Jame 3:10

Yeah.

Callum 3:11

this podcast.

Jame 3:11

Well, we wouldn't know anything about that, would

Callum 3:14

No. So, yeah, I think when we talked about that before, that was part of it. But I've still struggled with this question that one of the the nurses asked me on the ward. One day, which was, how would you learn about antibiotics? I still haven't quite figured that out. How do you learn antibiotics? I've still not got an easy answer to that question.

Jame 3:33

Well, well, let's break it down according to this fancy diagram, like what we are looking at right now. So, you've

Callum 3:39

Well, what was your clinical conundrum?

Jame 3:40

sorry.

Callum 3:41

You said you had a clinical conundrum.

Jame 3:42

Yeah, it was made up for the

Callum 3:43

You said that

Jame 3:44

I don't

Callum 3:44

you got me.

Jame 3:44

I don't need your

Callum 3:45

You said it was just for me. You made me feel special, Jim.

Jame 3:49

Right. Fine. I will make something up and then I will make you feel special. I have a patient who has a infection in a bone and or joint

Callum 3:58

Bone

Jame 3:59

as

Callum 3:59

and, oh no, doctor. I have a bone and joint infection.

Jame 4:04

Yes. It's a, it is a that thing. Okay, so let's talk about how you would actually choose, whatever you're

Callum 4:09

Okay. Can we define which bone it is? Maybe we'll come onto that. Actually, I'll ask you some questions as we go through. stuff.

Jame 4:14

An anatomist Callam. Okay. I don't know the names of all of the bones.

Callum 4:18

So I don't know where this diagram came from. I stored it in my folder, I dunno, maybe 10 years ago of useful stuff that I have. There's basically a target diagram that someone has made called Choosing an Antimicrobial, and it's trying to give you a little aid memoir that you could potentially print out that has all the things you need to think about when you choose an antibiotic. And I think part of the problem is that this decision, whilst often is very simple. It can be very complicated or even complex, and I've used those words specifically, which I'll come back to in a second.

Jame 4:59

Okay. Oh, this is that

Callum 5:00

This is that thing.

Jame 5:01

Fine. We will talk about that in a moment. So the concentric circles around the outside are, first there's microbe factors, then there's host factors, and then there's drug factors. Last. So let's talk about the micro factor first. You sort of covered this in that in our

Callum 5:17

Yeah, I think

Jame 5:18

episode a

Callum 5:19

that's what we've retrospectively decided what we did there In that first episode, we covered the microbe factors, and I guess there, the first thing you're thinking is one is actually an infection. Patient's got a fever and you said it was born in joint, so they've got maybe a red hot, swollen, and joint, let's say, as their knee. Right. Is it actually an infection? Have they got HESIs? Is it trauma? Yeah, exactly.

Jame 5:43

Get

Callum 5:43

Yes. Peu, gout.

Jame 5:45

for lots of reasons.

Callum 5:46

So that's the first microbe factor and okay, we think there's an infection. Is it bacterial or is it viral or fungal or parasitic?

Jame 5:57

Yeah.

Callum 5:58

when I think about infections and informative differential, I often write out just to think, but through it clearly I write out bacteria, viruses, fungi, parasites, and then I think what can I put in each one? And I think that's useful. Now,

Jame 6:13

Yeah., Let's give another example. Let's talk about chest, for example. So like you've got your typical organisms, your strep pneumos, your blah, blah, blah. You've got your atypicals, you've also got. Certain patient populations, your PCPs, your cryptococcus, gati eyes, your this is

Callum 6:30

Yes. Phone

Jame 6:31

and

Callum 6:31

patterns. Yeah.

Jame 6:33

And then I suppose in other parts of the world, or if you visited other parts of the world, you have to think about Coco mycosis and blast mycosis and histoplasma all the. Fungal di morphs and all that sort of business. So you've got your kind of your sort of people talk about the

Callum 6:48

Viruses as well.

Jame 6:49

and surgical sieves. talking about your microbial

Callum 6:54

Yeah.

Jame 6:54

you're dividing into the

Callum 6:55

Yeah I, and that's basically every time I'm like, puzzling through a complex case, that's what I do. I when I'm thinking about these micro factors choosing an antimicrobial, I just briefly write down what they are the things I'm worried about in viruses as well. And it's important because we're talking about choosing an antimicrobial, not an antibiotic. So we could be talking about antifungals here or antivirals. But. Most viral infections you're not gonna treat. So obviously if you think it's most likely to be a fungus, then you're not going to treat it with an antibiotic. Are you antibacterial?

Jame 7:26

Although quite a lot of the time they are treated with an antibiotic first, and when it doesn't work, the alarm goes off in the

Callum 7:30

Yeah.

Jame 7:32

Suppose the last episode was coming at it from the view of empirical therapy too. So like you have a pneumonia, you want to, cover the common

Callum 7:40

Yeah.

Jame 7:40

but there's also the situation where you actually know because you've cultured the organism. And if you're lucky, you've got an antibiogram showing what is susceptible or sensitive or resistant or delete as applicable.

Callum 7:54

Persist oid, is that your new term

Jame 7:56

Yeah.

Callum 7:56

Fraction.

Jame 7:57

I'm trying to roll Alternative

Callum 7:58

for increased exposure. I quite, it's a bit like so yeah, so I guess we're thinking there, is it a known organism or are you treating empirically? And that's important when you're choosing an anti, an antimicrobial 'cause it's empirical. Just follow the guidelines and this is a reason not to. And if it's a known organism, then follow a sensitivity report unless there's a reason not to and go narrow. And that's another thing to think about in the micro factor. So we said known organism versus empirical. If it is a known organism, think about the resistance and the antibiogram of that organism, but also think about the epidemiology in that area. So. If you've moved parts of the country check out your local epidemiological data and that should be birthed into your antimicrobial guidance data. But, some parts of the country, you might have a much higher rate of resistance in strep Pneumo cyclone, in which case you probably don't want to use that.

Jame 8:49

Yeah. I've just really recently moved from a part of England where there was evolving trimeth prim resistance, and so it couldn't be used first line in our UTI guidance anymore. Because of overuse, we think in the community. And so that's a a real risk. And so that's, that partially explains the variance from place to place when you move as a resident daughter that and the whims of the local microbiology antimicrobial management team, obviously.

Callum 9:16

Then the last thing in the micro factor is site of infection, which I think you could debate whether that's actually a drug factor, a host factor, or a micro factor.

Jame 9:25

I suppose penetrance is there somewhere, isn't it? Tissue penetration. So it does matter where the bug is. But let's just leave that at that. Is there anything else to say for micro

Callum 9:33

No, I think that's the main thing is, and also like sending the samples so when we're choosing antimicrobial, it's quite useful to think what do I think the cause is and therefore, what samples am I going to send? Because choosing antimicrobial isn't a single decision that's ended. So it's often something that's reviewed. So if you're in a hospital, the patients say you're gonna give a five day course of MCL for community acquired pneumonia. You're gonna review that with results if things come back. So, it's not done it's an ongoing review in decision making. So host factors so some just rapid fire. Just rapid fire. Go through these. I think they're pretty self-explanatory.

Jame 10:10

Yeah. Okay, fine. Let's go Anticlockwise.

Callum 10:12

okay.

Jame 10:12

Sorry. For our American listeners, let's go counterclockwise.

Callum 10:16

So first of all, false factors. Their immune status of the patient. Patient, so Immunocompetent versus immunocompromised. And obviously there's a spectrum between those two. Extremes. And that's important because if you're choosing an antimicrobial, you may choose something, broader spectrum. The pathogens that you're worried about are going to change.

Jame 10:35

Severity of infection. Do they have the sniffles or they're about to go into intensive care with life-threatening, a RDS or gram-negative sepsis with profound hypotension, et cetera, et

Callum 10:45

So next is allergies. I feel like this is, people talk about hearty patients. I feel like people have multiple drug allergies and that the limitations you have in your choosing antimicrobial. That's why I really struggle.

Jame 10:58

Next one is renal function. So important for I think a couple of reasons. One is that most antibiotics are excreted in the urinary tract. Some are not. but most of them actually are excreted urinary. And then that also has the effect that. At extremes of renal function, you get decreased penetrance of certain antibiotics into, the urinary tract and therefore you can no longer use them for treating ugi. Think about virto and and drugs like that.

Callum 11:29

A liver function. So I guess we did this pharmacokinetic. I say we, James did this pharmacokinetic series the end of last year, and we talked a lot there about how different drugs, some live leave for the kidneys and some live the body for the liver. So liver function can be really important for drugs that either undergo hepatic metabolism or biliary excretion.

Jame 11:51

Yeah. And some are pro drugs

Callum 11:52

yeah. Yeah.

Jame 11:53

So I think PIV

Callum 11:53

Also, the other thing to think about is that some drugs are hepatotoxic, so if someone's got the range liver function, you may not want to use a drug that's hepatotoxic because that might worsen the situation. Probably.

Jame 12:03

Although thinking back to your statement about sepsis there, if they're super septic and it is the drug that's most likely

Callum 12:09

Yes.

Jame 12:10

you can give it and then you can

Callum 12:11

Yeah, exactly. It depends on the reason why. If it's a drug induced hepatotoxicity, that's different from, say someone who's got a septic shock and they've just got a shock liver.

Jame 12:19

Yeah. Can they swallow or rather is the oral root compromised? So if the patient is unconscious because they're, too sick, or if they're old and they've lost their swallow because they're a frail elderly patient, or if they've got short gut syndrome or malabsorption because of some other issue that's currently ongoing, then you. Are less likely to use oral medication and more likely to use IV or parental antibiotics. Medical history, Callum

Callum 12:49

So there are past medical history, things that might limit your antimicrobial choices so that the classic one being myasthenia gravis because certain drugs like having glycosides, quinolones, can lead to a worsening of that disease.

Jame 13:03

And I suppose there's porphyria as well.

Callum 13:05

I always want to know the full past medical history because it will affect drug choices in some situations. And I think often referrers don't know what will affect your choice of drug.

Jame 13:17

Recent antimicrobial exposure, I think there's two things to say there. One is, risk of ciff seal, and that's more. That's more of a risk with broader spectrum antimicrobials and antimicrobials of certain categories. But also a very significant factor is cumulative exposure to selected antimicrobials. And I suppose that would also dovetail into, resistance organism colonization. So repeated exposure to beta latam might lead to colonization with ESBL or reducing organisms.

Callum 13:53

The next one is com compliance, or I guess what we would call concordance now, so.

Jame 13:58

call it

Callum 13:59

Adherence.

Jame 14:00

concordance the

Callum 14:01

Yeah. Well, okay, well, you can choose your word, but so yeah, the ability of the patient to adhere with the treatment plan. So, if that's something they're gonna struggle with, then maybe a four time times a day, oral th oxacillin isn't an ideal treatment for them. Because they might forget for example.

Jame 14:19

Yeah. And adherence is not just the patient, being naughty and not taking the pill because they're an injecting drug user with a chaotic lifestyle, blah, blah, blah. They may have dementia, they may be old, they may. Work long hours and not be able to take pills in the middle of the day. For example, they may not be able to take their medication to work. There's lots of reasons why you wouldn't be able to necessarily adhere to a a regimen that you give the

Callum 14:42

Yeah,

Jame 14:43

And lastly, does the patient have another smaller patient within that patient that you need to protect? Are they pregnant? And in fact we've had a podcast episode on this about the use of antimicrobials in pregnancy and lactation that we did with Task the Dosio quite some time ago Now.

Callum 15:00

Yeah, it was a good episode and I think the impact of, that's probably over called it's abundance of caution, but it's maybe misplaced caution because then people get, everything's got risks, isn't it? So, listen to that episodes, we'll talk about it a lot. So that's the host factors. Finally, the drug factors, the domain of the jam.

Jame 15:18

This is the bit I've been looking forward to actually. We, you did cover this a little bit though in the the previous episode, but you've thought about the bug that you want to treat, you've thought about the modifiers in the host factors that might influence your drug choice, and you've thought about the spectrum of drug, you have to have things like the risk of side effects, like c diff seal are you going to, as a general role, we want to use as narrower spectrum as we can possibly get away with. Sometimes that's not possible. But particularly in Scotland, we have this drive towards not using the four C drugs, cos ceftriaxone, clindamycin, and Ciprofloxacin because we want to minimize the CIFF risk when we are using menin either

Callum 15:58

Yeah,

Jame 15:58

or

Callum 15:59

I think c diff risk is really important. I think the data has changed a bit recently and probably our understanding of what is and isn't high risk c diff and how that's categorized, whilst that's very difficult to do in a certain scientifically robust way, is probably changed. So we used to think about just Keli SPOs in general, but actually first generation Keli SPOs are fine and it's probably the effects of the drug on the microbiome and the broadness in general, but also specifically whether or not it is active against C of a seal is probably important. So I think that is quite a complicated thing to think about, but I think a general principle, we all know broad spectrum antimicrobials. Or higher risk. So just try and stick narrow if you can. So I think that's how we would take the drug factors. If you can use something narrow and you can use one agent, then that's probably better.

Jame 16:50

Next

Callum 16:51

Duration. So this is something that's studied a lot. Shorter is better. Three versus five versus seven versus 10 versus 14 days. For pneumonia, for example. Not completely answered in a lot of syndromes. So yeah, I think that's a thing. You think about the drug factor and it changes drug to drug as well sometimes.

Jame 17:10

well, yeah and also the duration there, there may be justification for longer, durations like un, un drained abscess and very specific infections, particularly bone and joint, where we tend to use durations, although less long than they used to be. So there is a shortening even there. Then there's previous therapy that they have received. I feel this is kind of like previous antimicrobial exposure. But I suppose it's also have they had source control? Have they had an operation? Are they unfit for said operation? Did they have an operation but it failed? Is there a post-op complication You need to think about.

Callum 17:41

Yeah. Dosing. So that's something you think about a lot and we're speaking to pharmacists and it will tie in if the things like the renal, functional liver function, the route that you're using, et cetera or route the next one. Oh, I still.

Jame 17:54

Oh is the next one. You've stolen it, so you

Callum 17:56

Yeah. So they kind of go hand in hand, aren't they? So the doses dependent on the root goes without saying. And I think a lot of the time you see that it's just that continual problem about massive ranges in dosing recommendations. And I think this makes it really hard for 'em to choose antimicrobial. And you go to the BNF and it says Kein. Yeah, just give anywhere between 250 milligrams to a gram, anywhere between twice a day to four times a day,

Jame 18:22

well actually the maximum dose of Keflex is in the BNF is 1.5

Callum 18:26

Oh

Jame 18:26

four

Callum 18:27

yeah,

Jame 18:28

and you cannot absorb more than a gram at any one sitting. you're. You're guaranteed not to be absorbing. It's going out in your poo, that last 500 milligrams of CareFlex and it's a complete waste of time and money. I mean, I guess the BNF would say it's not our job to. To specify that we are just saying

Callum 18:48

is what's possible.

Jame 18:49

use it for and these are

Callum 18:49

Yeah. I think people use the BNF as, I want to give drug X. How do I, what dose should I give?

Jame 18:55

I think that works well for a lot of other drug classes, but it does not work well for

Callum 18:59

yeah.

Jame 19:00

because they refuse to set doses for para

Callum 19:03

Like most

Jame 19:03

way

Callum 19:04

say like you're starting antidepressant, you're just gonna start a low dose and then follow a guidance and titrate up to effect antibiotics. You just want to kill the bacteria. Like you're not gonna be on it for months. It's gonna be quite a short course, hopefully. So, I think people err on the side of two lower dose people that you see on three oxacillin,

Jame 19:24

500

Callum 19:25

Yeah.

Jame 19:25

Oh, it hasn't worked.

Callum 19:26

Or two 50. Yeah. So, and there's reasons to do that, it's probably better tolerated than the higher doses, but it is, I think dosing is something that we dwell on quite a lot. And the root as well. We've talked to death before in the podcast about IV versus oral roots and the evidence around that. Brad Spellberg site's very useful, so don't think we need to go into that in too much more detail. Obviously, it just depends on what route is available to you as well.

Jame 19:50

no. And we do have a podcast episode on IV all switching

Callum 19:53

Yeah.

Jame 19:54

But next we have tissue penetrance,

Callum 19:56

is really interesting.

Jame 19:58

It's super interesting. I We're gonna have to do a mini CDs on it,

Callum 20:01

I've been demanding it for years from,

Jame 20:03

I know. I know. It's on my to-do list. I

Callum 20:04

you said you did PK and do you know what goes hand in hand at PK

Jame 20:08

Yeah.

Callum 20:09

PD? So we want to do that. I think it's a big topic to cover, but you know, by that we mean

Jame 20:15

I mean, if anybody wants to help, if anybody wants to volunteer, I'd be really happy to get somebody on board to do all the heavy lifting. And then I could take all the credit a bit like Callum does at the moment with me doing the Yeah, I'd like to, I'd like to push that down. One, one tier

Callum 20:26

yeah, that's about, yeah.

Jame 20:28

But yeah, penetrance to, CNS for example, we talked about this briefly on the meningitis masterclass with Fiona. what. Is gonna get into the CNS, and where, and that, basically she was saying that she was confined to using IV antimicrobials that she knew worked in that instance if you're in an abscess, well that's an acidic environment. Most antimicrobials aren't going to work there. With a couple of small exceptions, what penetrates into pleura, for example, and what penetrates into the bone and joint,

Callum 20:59

And we go to the data, but actually a lot of these times, you know, to get actual true human data, someone needs to have taken a tissue sample and done drug levels on it. And that's very rare. So I think

Jame 21:10

Yeah.

Callum 21:10

we can theorize and extrapolate, but actually. Getting hard data and also how you interpret that so that the papers that I read about this, for bone and joint is very muddy because it's lots different papers and sometimes they come up with slightly different conclusions. So, one hand I think it's important to think about. On the other hand, I think you kind of have to just rely on clinical trial data and not get too bent up with this unless it's really complicated.

Jame 21:38

Or dare I say it, Cal we do it already and we know it works. Data.

Callum 21:43

Yes. I think that's key because when you get too much into the nitty gritty of theory and, you know, is it actually just a nice theory but doesn't really tie in. We're extrapolating a lot of in vitro data trying to apply that in vivo,

Jame 21:57

yeah.

Callum 21:57

But I think sometimes when you're stuck, it is useful to go with tissue penance. Like prostatic infections, for example, is a good one, I think, where, there's probably is a bit more data about what gets into the prostate. And that's tied into the guidelines.

Jame 22:10

So P four 50 induction is so Cyclone P four 50 system is the one that's useful for used by the liver for metabolizing most antibiotics. And as luck would have it there's three P four 50 ISO enzymes that metabolize the lion's share of all drugs. In fact CYP 3, 4 2 C nine, and two C 19. And so if you get things that induce those ISO enzymes, particularly three A four, and if you think about your mnemonic for P four 50 enzyme inhibitors, most of them are three a four inhibitors. Think omeprazole, think your allopurinol and the macrolides and things like that. They're. three A four. And that's leading to accumulation. Well take Clarithromycin for example, will lead to the accumulation of simvastatin, because it's not being metabolized by three A four. So you have to, I suppose that's kind of like a drug history, isn't it? It's like what the patient's already on, which will either mess with the antimicrobial Lima, wanting to start or. If I start an antimicrobial that's a P four 50 inhibitor or inducer, I think for fsin, will that mess with the They're already

Callum 23:23

Yeah.

Jame 23:23

That kind of

Callum 23:24

And I think that's a big like a big part of interactions, I guess interactions in separately. I feel like P four 15 induction

Jame 23:31

I think

Callum 23:32

it's a subset of interactions because there are interactions that aren't dependent on that. So I think there's some like classic ones that, that come to mind. So, is it Fluconazole and fentanyl, is a really, I think, is that a P four 15 direction, I think.

Jame 23:46

Well, fluconazole is a P four 50

Callum 23:48

Yeah, so, and it leads to accumulation of fentanyl. So it's a pretty like esoteric fact to know until you've seen someone have it and go to overdose because people don't know about it. So,

Jame 23:58

or say Fluconazole as a qt, prolong

Callum 24:01

yeah.

Jame 24:02

amiodarone,

Callum 24:02

So we talked about c diff, which I think should be in with side effects. So we're gonna change the order.

Jame 24:07

Oh God. We are gonna have to change this quite a lot

Callum 24:10

But I mean, you're gonna see it on the show notes and it's gonna be, so good. So side effects. I think that's one of the key things of with the drug factors. So, you know, we've talked about all these other things and actually you then go to the patient because. It's not us as the medical professional that's choosing antimicrobial. You're advising an antimicrobial, you're coming to that shared decision. And side effects is really important. So say, you've got the bone and joint infection that we've loosely tied a case to that not really done very well at it. And we've gone through all the different microbe factors and drug factors and host factors, and we've come down to it and we're like, well actually they're ready for roll switch. We can either give them Cipro or we get doxycycline for this. Infection that they've got in their knees, a strep or something maybe not strep, but we could either give them Cipro. Yeah, staph. We could either give them Cipro or Esli. That's a better example. So then we go have that side effect conversation. I think we list side effects, but actually when you're choosing antimicrobial, it's really thinking about like, how are you having that conversation with the patient about counseling them, about antibiotics and. I think that's really key because we need to do that from a consent perspective. And certain things have, specific things we're told to tell patients. So Cipro Fox and Quinolones have the MHRA warning about tendonitis and about a large vessel.

Jame 25:28

stuff and large vessel

Callum 25:29

Yeah. Yeah what's it called? Aneurysms. So, I guess it is about when you have this conversation a lot, you end up having a script almost that you follow in your head and you talk about the common side effects and the rare important ones. So side effects are a key drug factor, and that might, change everything else.

Jame 25:45

Really, it's the main thing that you should be presenting to the patient because it's you need

Callum 25:49

But you're not gonna talk to the patient about all these other factors, are you?

Jame 25:52

thing.

Callum 25:52

You know, that's not really the what they care about is you have to go to them and say, these are the things that we know will work. Or we think that will work. And here's the side effects. And often people like, well, I really don't want Lali because you mentioned as a risk of optic neuritis and I've only got one eye that works. Or.

Jame 26:08

Or their, Corum, Orli which both cause myelosuppression may not be the best thing to start in somebody who it would be unwilling to accept a blood transfusion if they

Callum 26:18

Yeah, that's a good, that's a good

Jame 26:19

example.

Callum 26:20

Yeah. So I think side effects are good. I just pointing people towards a resource I found used. So Public Health Wales, who do a lot of good work, they've got like a antimicrobial counseling sheets. They're really useful and I, if I had more time and energy, I would love to sit down and make some, patient information leaflets for all the antibiotics. I'd be using it locally and then like just have the counseling done because I think that this is something that, you know, particularly when, remote, I'm not involved in seeing the patient. And I like over the phone, tell the person who's gonna prescribe it, make sure to tell them about this, and this and this and this and this and this. And then they're like, whoa, I'm sorry. I dunno if they're taking that in. I always document that I've said that, but, I'm not having the conversation with patients. I don't think it's done that well. A lot of the time. That consent conversation.

Jame 27:05

I, but something that could be easily

Callum 27:07

Exactly. So,

Jame 27:08

pills. In fact, I'm surprised that the Scottish antimicrobial prescribing group hasn't already done

Callum 27:13

if they're listening then maybe that can be a suggestion, Jim.

Jame 27:15

I don't think they're, okay, so that's all the drug factors. Oh, except for one more about tio cyto versus bed tios static. Now it's very important to remind the loyal listener that doesn't

Callum 27:26

Yeah.

Jame 27:27

So that's all the factors in choosing an antimicrobial column. Is there anything else to

Callum 27:30

Yeah. So I think at the very beginning I said when we're talking about, oh, two more things to say. So one thing, going back to side effects, something I found really helpful when having that consent conversation is this brand framework. So that's.

Jame 27:43

Oh

Callum 27:44

And

Jame 27:44

risk alternatives,

Callum 27:45

exactly. So I just I try to always have that in my head when I'm doing consent because I think, it's, there's loads of different frameworks, loads of different ways to do it, but I always feel like you always have to, make sure the patient gets their brand because it's very easy to forget things like alternatives and nothing. So that's how we done. So, yeah, I just to go right back to the very beginning of this whole thing, because. I worry that we've made choosing antimicrobial sound very complicated and I think it is in some ways, like there is always to think about in these situations.

Jame 28:18

spent almost 40

Callum 28:19

Yeah,

Jame 28:20

about this. I dunno how much you're gonna cut

Callum 28:22

dunno.

Jame 28:22

yeah.

Callum 28:22

But you know, I think there is a lot to think about sometimes. But actually most of the time you're prescribing antimicrobial, you think, what's the guideline say? Is there any reason why I can't just follow the guideline and then you just do that?

Jame 28:35

Are they allergic? And usually there's an Option and then And then if that doesn't work, you phone someone

Callum 28:40

yeah. And then we think about all these things. But that's, I think that's how you choose an antimicrobial. But if you walk it back a step and you say, when do I need to think about all this? So something I found really helpful, which is a leadership and management framework called the framework, which is again a Welsh guy who did this in a like decision making, like how you process and make decisions in a management position and essentially categorizes. You can find an image of it online. It's spelled C-Y-N-E-F-I-N.

Jame 29:13

It sounds very

Callum 29:14

Yes. And categorizes problems into essentially a simple problem or complicated or complex or chaos. And then for each one, he kinda lays out how to how to respond to that situation.

Jame 29:31

Let's give an example. So let's step away from our bone and joint infection patient. Sadly, he died whilst we were discussing all the different parameters about how to choose an antimicrobial and go to our next patient who has a UTI. Let's talk about a simple version of that.

Callum 29:45

yeah, so I think a simple one is someone who's, a young woman who's got an uncomplicated UTI first episode, no previous drugs. So in that situation it's a clear situation is the other way of terming it rather than simple. And essentially you sense what situation as categorize it. So we've just categorized it into so sensing is getting the information that you need to decide what is going, categorize it as an uncomplicated UTI in a young woman who's not pregnant, and in respond you, there's a best practice. The best practice is gonna be wherever the first line antimicrobial is. So there's not really any movement around that. It's a sort of, there's a constraint.

Jame 30:24

Yeah, There's No, modifiers and there's no,

Callum 30:27

it's best practice there is like

Jame 30:29

to go

Callum 30:29

if X then do Y,

Jame 30:31

and do it.

Callum 30:31

You sense, categorize, and respond. So that's your best practice.

Jame 30:34

It's very Okay, so it's an, if this, then that

Callum 30:36

Yeah.

Jame 30:36

of thing. It could be categorized

Callum 30:38

Yeah,

Jame 30:39

easily,

Callum 30:39

that's, I mean, you

Jame 30:40

flow

Callum 30:40

to go into the whole thing about choosing antimicrobial if you've got a simple problem, because you just do the thing and then you move on to the next problem, and that's simple.

Jame 30:48

Well, let's move on to the next problem. What's

Callum 30:50

well, this is complicated.

Jame 30:52

Complicated.

Callum 30:54

So this is essentially maybe someone who's had a couple of UTIs and got some urine contra results back and they've got some sensitivities and maybe they've got an allergy or two. So it's not like a straightforward sense, you don't categorize 'em so easily. So basically you have to sense, get the information, take the history, do the examination, look at all the results. That's the sensing, analyze it. So you have to like, take in information and then come up with some sort of response. And in these situations, there's good practices, but there's not necessarily best practice. So you might have principles about, say well, it's good practice not to use a quinolone. If you can avoid it, for example, that might be a part of good practice. So, yeah, I guess complicated are situations where there's a clear cause and effect relationship. But they essentially need a bit more analysis or expertise or expert knowledge. So they might be ones where you like, go off to a specialist guideline or speak to a specialist because there's not necessarily a right way to do things. There's not like a clear answer, like there isn't a simple problem.

Jame 31:57

But what if you are the

Callum 31:58

Well then you are, you're gonna try and you'll know of the information. So it's a question that might come to you or me and we know what to do. Third one is complex. So this is situations where you don't really know what the cause and effect are going to be because you're in a situation that's really not known. So these these are like this patients that you have where you, like you are on the fifth line therapy Where you know they've got multiple allergies and myasthenia gravis and you get into this evidence free zone. And they're,

Jame 32:28

so this is the evidence free zone. Okay, I know what you're

Callum 32:31

yeah,

Jame 32:31

now.

Callum 32:31

you don't know

Jame 32:32

you're

Callum 32:33

what the cause and effect are because nobody's ever studied it before in this specific patient with this combination of factors.

Jame 32:39

Yeah, there's no trial that you refer to. You have to in fair data from multiple different trials and sources and stuff like, and then say, how does all of that apply to this

Callum 32:48

Yeah.

Jame 32:49

Yeah. Okay.

Callum 32:51

and in that one they talk about probing. So testing the watch, sensing and then responding.

Jame 32:56

What Like trialing and antibiotic or?

Callum 32:59

Yeah, the more you look into the system isn't really applied completely right. To medicine because, it's applying management thinking to patient problems. There's two other sort of. Blast BA basically complex problems are like there's emergent practice, I guess is the way to put it. So it's not really. So maybe like COVID was a good example of a complex problem initially where we didn't have, we didn't have any trial data initially. So people in other parts of the world in particular were just trying lots and lots of therapies. People were just experimenting to see what would work. Well, the last bit is chaotic where it's basically there's no cause and effect relationship and systems out of control. I think that is me, not really so much in infection medicine. I'm gonna blast past that. And then in between all four of those quadrant, there's what people call like the sword or confused. And basically that's where you don't know which of the four quadrants you're in and you just needed to figure out which domain you're in and how I find this helpful. Is not getting to the nitty gritty of sense, analyze, respond, all that nonsense. All I just really think about is is this a simple, complicated, or complex problem? if it's a simple problem and I'm trying to make it complicated and I'm overthinking it, that's not efficient using my time.

Jame 34:12

Yes.

Callum 34:12

and if I think something is complex, as an evidence free zone. Just because I haven't read the paper or I'm not aware of the data, that's a problem as well. If you're doing something and you think, oh there's no right answer here, so I'll just pick something up and it is actually a guideline or data that's a problem 'cause you're not doing good practice. So if you end up in the wrong category, when you're thinking about choosing antimicrobial it can get you in a bit of trouble. And I, but it also can be very helpful to think this is a complex problem. There's no clear right answer. So I'll just do what I think is best and that can be, I think, quite freeing for making decisions.

Jame 34:52

Yeah. This is what like an MDT is for You go to an dt, you present the problem and everybody says, well, I don't know what to do. And then you say, well, I quite like to do this, and you're like right to me, and then you're free to try. But I think this is something that I'm only now comfortable with. I've been a consultant for a few years, and I doubt that before you finished training, you would've been comfortable just throwing something at the wall to see what sticks. Whereas now I think you've not finished training, but you've finished official, registrar hood and whatnot, and, you've got, you've kind of met this minimum

Callum 35:28

Yeah.

Jame 35:29

that you've now got the. License to, with the backing of your peers, work in that complex world or chaotic end of things.

Callum 35:38

Yeah, I think just bringing it back to the topic, so choosing an antimicrobial as I say, most of the time it'll be a simple problem and you just do what the guideline says. I, you don't need to think about it too much. And we are more thinking about that those sort of drug the bug factors, the host factors and the drug factors in these more complex situations.

Jame 36:00

Okay. Anything else to say, Carl? I'm glad that we've been able to make what was initially a simple decision of choosing an antimicrobial and end up with it sounding as chaotic as possible

Callum 36:11

think I.

Jame 36:12

of 50

Callum 36:12

Yeah we should probably throw in there from the stewardship angle and the drug factors, the aware classification, because I think that's another useful thing, like if you,

Jame 36:20

Oh, dammit, that's not in

Callum 36:21

yeah.

Jame 36:22

Thing will predate the aware classification,

Callum 36:24

So I think we'll add that in because that's another useful thing to think. If you've got you pose between two drugs and you're like, I could either use Lali or Amoxicillin here. Both would be fine from all the factors. Use amoxicillin. It's Anxi drug. Don't use Lali as reserved. Like I think that's certainly

Jame 36:40

Oh, that's an

Callum 36:41

my.

Jame 36:41

point. And this, so that will tie it in with this

Callum 36:45

Yeah,

Jame 36:45

with this, what I've now decided

Callum 36:46

mini series. And the third part, I think I'm really excited to have another jam table special, which maybe little tease or you're not gonna spoil.

Jame 36:55

I will be trailing that for fine. We're going to do a big spectral palooza, so get ready for that. Everyone.

Callum 37:01

Think, think about the one anti one, the PK trade to rule them all but for antibiotics and their spectrum of action. And James has been working hard on that, so

Jame 37:12

I better get back to work at it and make it

Callum 37:14

yeah.