98. Meningitis

Jame and Callum are joined by Dr Fiona McGill, lead author of the 2016 Joint Specialist Societies Meningitis Guidelines.

Listen to hear an overview of the epidemiology, presentation, diagnosis and management of both bacterial and viral meningitis in the UK.

Show notes for this episode here

Transcript

Jame: 0:23

Callum, we've got a real special guest today, a titan in her field. You could say that this episode is going to be men and giantess. And what a coincidence that is, Callum, because who's our guest today?

Callum: 0:42

We're delighted and honored to be joined by Dr. Fiona McGill. Fiona McGill is a consultant in infectious diseases and medical microbiology at Leeds Teaching Hospitals NHS Trust. She has spent several years working alongside Liverpool Brain Infectious Group. Researching the epidemiology and diagnostics of meningitis in the UK. She was the lead offer of the Specialist Societies Meningitis Guidelines 2016. And her current areas of research interests are TB meningitis and viral meningitis.

Jame: 1:15

Fiona, welcome to the show.

Fiona: 1:17

Thank you very much. Great to be here. thank you for inviting me.

Jame: 1:21

Yes, well, we've been wanting to do a meningitis episode for a long time, and we eventually decided that maybe we should just get somebody on who actually knows what they're talking about. So thank you for accepting our invitation.

Fiona: 1:34

No problem.

Jame: 1:35

So Fiona, why is Meningice important to you? Why have you, Dedicate a part of your life to researching this.

Fiona: 1:42

Interesting. So, to be 100 percent honest, that's where I got my, research post and I got a research post with the brain infections group and I was asked to look at viral meningitis in particular, actually. and I think in terms of why it still interests me, we. It's something we don't actually see that often. You see a lot of people come through the front door with suspected meningitis. But actually not that many of them have meningitis, and it is less and less frequent. It's certainly bacterial meningitis, and I think it's really difficult for everybody to keep up to date, know what to do, know what the right thing to do is, and that's why we wrote the guidelines, really, isn't it? When you've got something that's becoming rare, you need an expert group of people to give some guidelines on, on, on what we should be doing. So I think in some ways it interests me because I've spent a long time doing it. And so that's why it now interests me. and I think, Viral meningitis, patients sometimes get a little bit overlooked, and I've got a bit of sympathy for that because it does actually affect them for a significant amount of time afterwards. And then with bacterial meningitis, it is not always that common. And so we just, to try and do the right thing is not always that easy.

Jame: 2:51

Yeah, I, Agree, like particularly when I'm doing general medicine and people are coming in on the take. Meningitis is very often in the differential, but not very often the final diagnosis. In fact, I'm not sure I've made a single diagnosis of. Uh, of meningitis, viral or bacterial. most of the time they go home with a diagnosis of you have a headache.

Fiona: 3:10

yes,

Jame: 3:10

And the other sort of thing that I think makes meningitis interesting is that dichotomy between viral meningitis, which not a lot of people die of, frankly. and may have some long term sequelae, which you can inform me about later on. But, really there's not a huge amount to do. And bacterial meningitis, which carries, High enough mortality that you should worry about it in all your sepsis cases and, prompt administration of antibiotics is essential. And that dichotomy, I think, leads to a lot of antibiotic over administration. I'm stopping a lot of Keftraxone in people that come into my take.

Fiona: 3:46

I

Jame: 3:46

But you mentioned the epidemiology, you mentioned that the prevalence is falling, so do you want to take us a little bit through the epidemiology

Fiona: 3:53

yeah, I guess probably most people are aware, certainly with bacterial meningitis, we, over the last 20, probably longer than that, 25 years, we've had significant vaccines for some of the major causes of meningitis, so in particular Haemophilus. Haemophilus influenzae type B used to be a massive issue. That we hardly In this country, we just don't see it. It's just not there. We do see Haemophilus influenzae. I will caveat that, but it's not type B. But we do see Haemophilus meningitis. It's very rare, but we do see it. And then also, obviously, meningococcal vaccines. And, Pneumococcal vaccines have come in, they've had varying effects, so Meningo, we had Mensee vaccine, which came in around 2000, I reckon I'm a bit older than you two, and I was at university in the late 1990s, and that was around the time when, if you were 18, 19, 20, most people knew somebody who'd had meningitis around that time, I had somebody in my year at medical school who died of meningitis. and that was pre the MEN C vaccine. MEN C vaccine came in, I think, in 2099, somewhere around about there, and that led to a massive drop. So, those have been the biggest effects, I think, on the epidemiology. It's the HIP vaccine and the MEN C vaccine. Um, we obviously now have MenB.

Jame: 5:14

actually, because I went to uni. I'm now revealing that I am in fact also much older than Callum. So, but I started uni in 2000 and I remember the MenC vaccine coming in and sort of us being told about this new vaccine that's going to stop you getting meningitis. And I too had somebody, In my year that got meningitis but lived.

Fiona: 5:38

and then more recently, obviously, we've had pneumococcal vaccines, which interestingly, I'm not a vaccine expert. But again, from looking at the data, my understanding is actually what's happened with the pneumococcal vaccine. You get serotype replacement, and although it has influenced respiratory infection, and I think it has reduced meningitis in children, but it hasn't actually done much to reduce meningitis in adults. And that might be to do with the Serotypes that cause meningitis.

Jame: 6:02

Yeah, they've just got backups that they can use. Okay, that's interesting.

Callum: 6:06

What I'll do is I'll find a nice chart showing that. and just sticking with vaccines, so, Haemophilus influenzae type B, MEN C, and then we've talked about pneumococcal vaccines, what about the sort of other meningococcal serotype vaccines, so ACWY and MEN B? Because I guess globally, we know that MEN W is a, main cause of COVID 19. Bacterial meningitis across Africa and leads to these sort of, epidemics. I guess my point is that, that there, it depends on what the local context is, what vaccination program is important to do. But ultimately, a lot of this is vaccine pre preventable or was, but maybe now we're in a realm where, as you're saying of the, replacements, serotype for pneumococcus. How much more is vaccine preventable or is this just something that we're gonna, we're gonna see low numbers of going forward and there's not much we can do about it.

Fiona: 6:58

I think people are working on that, so I think, one of the things that people are working on is having a pan pneumococcal vaccine, that isn't serotype dependent, and that would obviously, I think, help. And again, I'll show my ignorance here, but the MenB vaccine works in a very different way to ACWY, so it's targeting a different part of, the pathogen, and that's why it. It has a different sort of immunogenicity, and I think some of that technology, might be able to be used for pneumococcal vaccines. and the MenB vaccine, that was aimed at childhood meningitis,

Jame: 7:28

yeah, interesting,

Callum: 7:29

Yeah, interesting.

Fiona: 7:31

The other thing, sorry, just to say about epidemiology is it does change. And a few years ago, five, six, seven years ago, there was a massive spike of men W in the UK in sort of teenagers. And so at that point they then introduced the ACWY, it was previously given for travelers. But they then introduced that for teenagers, and we've seen a huge drop off in that as well since then.

Callum: 7:51

so I guess it just highlights the importance of, good public health. Well, it's both a notifiable disease, bacterial meningitis, I believe, but also the organisms, so Meningococcus and Pneumococcus invasively, are notifiable to public health. And because we've got that robust public health system in the UK, and then we have the typing and the reference lab data. that all informs, you know, a good example of where public health really informed practice and was able to have a positive impact.

Fiona: 8:16

Yeah, certainly in the case of meningococcal, absolutely.

Callum: 8:19

So I guess we've talked about why it's important. How do we, I guess before we go any further, something that I certainly see people struggle with sometimes is actually what we're talking about when we're talking about meningitis and how we define it. And this sort of dovetails into the clinical presentation, the sign and symptoms. But if we just to nail down like. How would we define things like meningitis, what's encephalitis, what's meningoencephalitis does exist, and what is like meningism because, I think that, that can be a bit of a struggle sometimes to just be clear what we're talking about.

Fiona: 8:51

Um, so most of these are pathological diagnoses, and that's part of the difficulty. We're not going to take a biopsy of the meninges to see if somebody's got meningitis, but meningitis is, as it says, an inflammation of the meninges. That's great. Encephalitis is inflammation of the encephalon, so the brain parenchyma. meningoencephalitis, I Have to say I hate the term,

Jame: 9:12

'cause there was a trend recently, uh, recently, I'm talking about like in, in the course of my medical career, that we were going to stop using encephalitis and meningitis and talk about meningoencephalitis and like brain predominant meningo, encephalitis for encephalitis and then per meninges, predominant meningo encephalitis for. So has that gone back? And can we now separate these two? clinical phenomena.

Fiona: 9:38

Yeah, I mean, I think, I think it's difficult. I think it is important to separate them the causes are hugely different. the predominant cause of encephalitis is HSV in this country and you need antivirals. The predominant cause of serious, as you say, meningitis in this country is bacterial and you need antibacterial. So it is important to know what you're talking about. I think one of the issues is, I think when people say meningoencephalitis, to me, I think what they mean is meningitis with somebody who's confused. So it's meningitis with an encephalopathy.

Jame: 10:05

And people get confused for all sorts of reasons. And people also get confused because they've got meningitis and that doesn't necessarily mean that they're about to fit or drop their GCS and all the other stuff that encephalitis does. Yeah.

Fiona: 10:17

indeed. So yeah, I think that maybe TB, listeria, those kind of things might cause a bit of an overlap, but most things, when we're talking about pneumococci or meningococci, meningitis. And so I think Callum, you asked about presentation and how that links.

Callum: 10:31

Well, well, yeah, cause I guess, those are the pathological diagnosis and we talk about meningism or being meningitic. so how would you, cause I've got a definition in my head, but I'm kind of interested about how you would. Say that,

Jame: 10:44

Oh, wait, Callum, what was your definition? And then we can talk about that. what is the definition?

Callum: 10:51

So I guess to me, if I said that someone was meningitic or they had meningism, that to me would suggest that the degree of inflammation in the meninges is sufficient that I can detect that clinically. So they've got neck stiffness or, they've got the rare, positive clinical sign.

Fiona: 11:08

which only neurologists do.

Jame: 11:10

Yeah.

Callum: 11:11

I don't do that clinically and we'll come on to why, That or photophobia, if I said to my colleague that they're meningitic, that's what I would mean.

Jame: 11:19

So I thought you were about to say the triad headache, neck stiffness and photophobia.

Callum: 11:24

I think that's probably more useful, which we'll come on to. but I guess we're, for the rest of the pod, we're going to say if someone's menergistic or not and how useful that is, hence maybe not always that useful, but yeah. what would you say Fiona? Is that about how, what you would say as

Fiona: 11:39

I think meningism or meningitis. Being meningitic, as you say, is about the symptoms, so it generally refers to somebody's got neck stiffness or photophobia, and like you say, has got, a positive sign of some sort, Koenig's or wherever, not sure how useful they are, we can talk about that, but I think probably the important thing to say here is just because somebody's meningitic or got meningism does not mean they've got meningitis, so there are lots of things that can cause meningism, and good going photophobia, neck stiffness, that aren't meningitis. I had a patient recently, just a couple of weeks ago, she had pneumonia, but she was absolutely meningitic. I would have sworn that she would have had pneumococcal meningitis, but she doesn't hurt. CSF was plumb normal.

Jame: 12:20

Do you have A sort of a list of meningism, the differential? Meningitis is on there,

Fiona: 12:25

Yeah. So if

Jame: 12:27

I put migraine there too.

Fiona: 12:29

not to, Not to promote my own work, but if you look back at the paper we wrote in 2018, which I think, I can't quite remember what it's called now, Incidents and Etiology of Meningitis in the UK, or something like that, it's in the Lancet ID. So that was a huge study looking at patients who came in throughout the UK, With suspected meningitis. So we looked at everybody who had suspected meningitis and had a lumbar puncture, so, you're slightly skewing, but, and then the top causes of people who didn't have meningitis, and we can. Talk about how we defined meningitis, but top causes were urinary tract infections. So, pilonephritis.

Jame: 13:08

Okay. God,

Fiona: 13:10

So, I always think of that.

Jame: 13:12

that's pretty far away from the brain, I'll be honest with you.

Fiona: 13:15

yeah. But it gives, I don't know, it just, it must do something to tickle your meninges,

Jame: 13:23

Okay, so UTI. Okay. and what else? What else?

Fiona: 13:27

so yeah, as you say, headache, migraine, general sort of neurological problems. And then you get other infections like respiratory infections, like upper respiratory, again, like tonsillitis, things like that often cause, a meningitic type picture.

Jame: 13:43

interesting. Perfect. Alright. Let's leave that there. Other signs and symptoms, yeah. And so of the big three, So splitting them down, headache has a very, probably the widest differential. what about photophobia? So my impression of the photophobia with meningitis is that person cannot be in a room that has a light on, and that it's extremely, pathognomic, almost. but doesn't, isn't really all that good at telling between viral and bacterial. Whereas light sensitivity that you get with something like a migraine. They don't looking at the light, but I can shine a light in their eyes and they can keep their eyes open in a normally lit room. Is that the right impression, or do you have more information on that?

Fiona: 14:25

Yeah, I mean, I think, I think you're right, obviously, photophobia is a sign of meningism. It's not very specific, it's not very, pathognomonic. I don't think neck stiffness is much more of a useful, symptom, as long as you know what you're looking for. a lot of people, again, confuse neck pain with neck stiffness. So, you are talking about being able to lift a patient's head off the bed, with their shoulders attached, as it were. I think significant photophobia, you'll be aware of, that they can't bear light, the room will be dark, they'll have their eyes shut, they'll have a flannel over their eyes, that kind

Jame: 14:57

All that, yeah.

Fiona: 14:58

think what

Jame: 15:00

and then for neck stiffness, we do sometimes talk about these signs, Koenig's sign and Brudzinski's sign. I do always get them mixed up when I try and describe them to medical students and I usually end by saying, and I don't do them anymore because their likelihood ratios are appalling

Callum: 15:15

there's a couple of papers referenced in the, joint specialist society guidelines. So, in there, summary statement, there's an advice just to say not to use it because it's not that useful. And the summary statement is they've been reported to have high Specificity up to 95%. So I guess if they have the sign, then it might be helpful, but the sensitivity be can be as low as 5%. For likelihood rate, there was a meta-analysis in children with suspected bacterial meningitis. It showed, sensitivity of 51% for neck stiffness. 53 percent for Koenigs and 66 percent for Brzezinskis. So, out of 100 people having meningitis, about half of them had a Koenigs, and about 6 out of 10 had Brzezinskis. And the likelihood ratios, they said the positive likelihood ratio is 3. 5 for Koenigs, and 2. 5 for Brzezinskis. And the negative likelihood ratio was, 0. 5 for Koenigs and 0. 4 for Brzezinskis. Now, I guess putting that into practice, so, if one of those is positive, it does make it more likely you've got meningitis. Although, I guess 3 and 2 is not a huge likelihood ratio

Fiona: 16:30

I always say about these things, I don't know if you can find a picture of Brzezinski's and Koenig, you'll see that they were good old Victorian gentlemen, and When they were around, you were talking about TB meningitis, you were talking probably about pneumococcal meningitis, things that have a really thick CSF as being your common cause is much more common. Whereas now, as we said, viral meningitis is much more common. You don't really get a big thick perillent CSF. So they're just in terms of their negative Or positive predictive value, probably not as helpful as they were in the early 1900s.

Callum: 17:06

Yeah, so I guess I don't tend to use them clinically. I've not seen anybody use one. I actually don't think I could do it now, because I've I would need to look it up. So, it sometimes shocks me when we teach medical students things and, sitting there asking and they go ahead and they're doing a new exam and they do that. And you're like, who's taught you this? So everything that we do is a cost. Isn't it? Even just the time that you spend examining your patient.

Fiona: 17:31

Yeah, but it's a little bit like, call it a diagnostic investigation if you like. is it going to make a difference? Is whether they're Koenig's positive or negative going to make a difference as to whether you're going to treat this

Jame: 17:41

Yeah, that's always my argument. If you have neck stiffness, am I going to, headache, neck stiffness, and photophobia, and you can't look at the light, blah, blah, blah. Am I going to do a Koenig's or Brudzinski's, and then if they're positive or negative, that's going to change whether or not you get an LP or CT scanning? Definitely not.

Callum: 17:58

So, we've talked a lot about, different signs and symptoms that are and aren't useful. So just to nail that down. So say I'm in the acute receiving unit and I've got someone that I think may or may not have meningitis. What would be your approach Fiona, or how would you recommend people approach that situation in terms of looking for signs and symptoms? We'll come on to the diagnostics. And I know James, it changed to talk about that, but, we've, I think we've said a lot of things that maybe aren't useful and, but what was the sort of, how would you take it all together and what would the approach be?

Jame: 18:32

our

Fiona: 18:32

So, the evidence base, to talk about that first, is, we talk about the triad, we talk about the classic triad of, Neck stiffness, fever and altered consciousness. Now there's been a few papers looking at that and actually, that is present as a triad in its entirety in less than 50 percent of people with meningitis. And again, we've looked at that in the UK population and in terms of all meningitis, it's less than about 2%. However, Van de Beek in the Netherlands, who's done a lot of research on meningitis, his group, they added in a fourth symptom, so they added in headache. And basically, between headache, next stiffness, fever, and altered consciousness, if you've got two of those, then you are much more likely to, have meningitis. The problem with that is, you then come back to me and you say, so, should we be doing a lumbar puncture on everybody who's got a headache and a fever? And my, argument is you need to think about it. So I think if you've got two of headache, fever, neck stiffness, altered consciousness, you need to consider that this person might have meningitis. not saying you have to do a lumbar puncture, but you have to think about it. And if you think that's a possibility, then you should go on and do a lumbar puncture. And I would say the ones that get missed are the fever and altered consciousness. So often gets put down to Pneumonia, because they've got a co existent pneumonia on their x ray. UTI, Eurosepsis, whatever. you need to consider that they might have meningitis, if there's no other reason for their altered consciousness.

Callum: 19:58

That's hugely helpful. And I think one thing that I always struggled with when I was doing more acute medicine was, that there's just no way clinically to say with any degree of confidence this person doesn't have meningitis. And it's one of those things that we can rule it in with the clinical science and we can start thinking about it. But there's no way Clinically to say they don't have meningitis without doing

Fiona: 20:23

A lumbar puncture.

Callum: 20:24

the lumbar puncture. Yeah. So Jane, you were itching to move on to diagnostics. It's almost like you're the microbiologist.

Jame: 20:32

so that's the, uh, signs and symptoms. Let's talk about the diagnostics now. So if, somebody comes in with suspected meningitis, what should our approach be in terms of what test order and in what order?

Fiona: 20:45

Good question. So, ultimately, we want a lumbar puncture, so we'd probably do a blood culture first. You're gonna take some blood tests, so you take a blood culture at the same time. If you can do a lumbar puncture, straight away, you do your blood test, then you go in and do your lumbar puncture. Okay. That would be the ideal situation to do it in. Lumbar puncture before antibiotics. I am very aware that in our current NHS that does not happen. Probably in less than 1 percent of cases. Does happen around the world, so it's not impossible. But it probably is nearing impossible in the way that our current NHS works. But yes, blood cultures, routine blood tests, which we can talk about, you would obviously do those. And a lumbar puncture are the key. Lumbar puncture is the key test.

Jame: 21:34

We will talk about lumbar puncture. In a future episode, Callum's going to take us through the nuts and bolts of how to get it done. But I think the, to follow up on what you said, the big problem in, The UK is at the front door, everyone is too busy, and they're just trying to get the emergency department and doing an LP in the emergency department, in most departments that I've worked in, is completely functionally impossible. And then when they get to the medical unit, they've had their antibiotics, and so the LP will be an on antibiotics LP. And then a big problem is, Finding somebody that's got the skills to be able to do it, that's at the front door and that's no longer guaranteed, as, time goes on

Fiona: 22:17

exactly. And I guess, sorry, the other thing I probably should have said in terms of what investigations you do because of that, one of the key blood tests you want to do is also a meningococcal, pneumococcal PCR in your blood, Which I think will also help. And for those who don't know, probably over 50% of invasive meningococcal disease in the UK is diagnosed by PCR alone. So you won't get a positive culture. So really, really important to get a PCR test.

Jame: 22:44

So what the front door test that you would recommend, your sort of routine bloods in somebody that's coming in infected. a, blood form Ningokokul PCR, a blood culture, and then an LP as rapidly as you can. When would you want to do a CT scan first? Because in the 2016 guide you had a brilliant sort of little box with these are the four reasons to do a CT scan before the LP. I have to say where we were working it wasn't really followed all that closely and a lot of people were getting a CT scan who didn't meet that criteria. I don't know if you've got the same problem where you are, but what were they again?

Fiona: 23:18

so they've slightly changed in the most recent NICE guidelines. But largely it is, focal neurology. so obviously if somebody's got a focal neurological sign, um, uncontrolled seizures, low GCS, and presence of papilledema should be noted, not the inability to find a fundoscope.

Jame: 23:38

What's the thing that has changed now from the 2016 one and why did it change?

Fiona: 23:43

So in the 2016, they've changed the GCS, actually. So I, like you, I think in the 2016 guideline, we had a GCS of less than 13, so 12 or less, should indicate a, CT scan or some kind of neurological imaging before lump function. There isn't a huge evidence base on what that value should be. Okay. And it's different if you look at, I think the European guidance say 10. And the thing with the new NICE guidelines is what they've done, as you may or may not know, is prior to this year, there were NICE guidelines for under 16s and meningitis, but there were no NICE guidelines for adults. So what they've done is put adults into the NICE guidelines. and the pediatric previous NICE guidelines had a GCS of less than nine. Yes, GCS of nine or less, or a progressive and sustained or rapid fall in level of consciousness. That's what the new NICE guidelines say,

Jame: 24:32

Okay, okay.

Fiona: 24:35

and I have to say I don't, I think it probably changed because there isn't a huge evidence base about what number. You choose, when you want to do a new, the reason that in the, 2016 guidelines we went for 13 was because, as Callum so eloquently said at the beginning, these were a joint specialist societies guideline, not the BIA guidelines. And it was our acute medics colleagues who said there was absolutely no way, somebody is going to do a lumbar puncture on somebody with a GCS of 12 without doing a CT scan first. so it was a pragmatic approach.

Callum: 25:05

One thing that I, you know, as James said, I am a bit of a big nerd about LPs anyway. so I think rather than bore you all solely with that, we'll do a separate episode and people can listen in to that or not. Is, my understanding is, and correct me if I'm wrong, so the reason why We think about doing your imaging before we do an LP is because if the person has raised into cranial pressure, you do a lumbar puncture, you take CSF out of the spine, the pressure there drops. So the brain can herniate, and this is based off quite historical data of patients who had a cerebral herniation. Doing a lumbar puncture, but, and the big but is, one, as you mentioned earlier on, how people present with meningitis is very different. People are presenting much earlier. We're not seeing that sort of severe end of the spectrum with as much TB and advanced pneumococcal disease. And two, if you read back on the patients where that is reported, I think that the main question I have is, wouldn't those patients have coned anyway? actually the link between LP and coning and cerebral herniation is to me pretty, scanty now. I'm not saying don't follow guidance cause I'm going to follow the guidance, but I guess it's just worth understanding why those recommendations are in there. What are your thoughts on that?

Fiona: 26:25

Yeah, I think that is. Yeah, I think that is. It's the key. People are worried about somebody coning, basically, herniation of the brain. As you say, that is actually a natural consequence of bacterial meningitis, okay? So, people with bacterial meningitis, if we don't give them treatment, and I've seen it happen, will herniate, or we give them treatment too late. Regardless of whether they have a lumbar puncture or not. And the actual, link between that has not, in terms of the, attributable mortality of a lumbar puncture to somebody coning has not been shown. Again, there was a paper that tried to show it not that long ago from Vanderbeek and colleagues, but again, they only looked at people who had a lumbar puncture. So they didn't look at the people who didn't have a lumbar puncture. So how we ascertain the attributable risk of that. is difficult. So what we say, and it's not just about raised intracranial pressure, so obviously we do an opening pressure and you know that people with, cryptococcal meningitis have got pressures off the scale. It doesn't stop us doing a lumbar puncture. it's about people who are the most likely to have a herniation, and those are the people who've got some kind of midline shift in their brain or some kind of, so much edema. And that is what those symptoms are really looking for. that's why we're saying, things that, might give you focal neurology that might indicate there's a space occupying lesion or something that doesn't give you the room to take off some CSF without having a brain herniation.

Jame: 27:48

Yeah, I suppose the other point of view is that the CT, if you have the presence of those features, the CT is more likely to give you the end diagnosis if it's not meningitis. So it's not just a clearance for LP, it's a, is there blood, is there a lesion, etc.

Fiona: 28:07

Yeah.

Callum: 28:08

And two other thoughts. So one thing in the 2016 guidelines, That they made very clear, which I liked, was the comment about immune suppression. So I think that's becoming less, but you still see people saying, Oh, well, they're immune suppressed, so I have to do imaging before I'll be. And, very clearly saying we shouldn't do that because even if you're immune suppressed, if you've got raised into cranial pressure, we should see the clinical evidence of that. If

Fiona: 28:33

of this came from a paper, I think, in the early 2000s, or late 1990s, a study done by Rodrigo Hasbun in the US. And if you look at that paper, which if anybody's ever heard me talk, they will hear me quote ad nauseum, it's a single center study in Baltimore with a 20 percent HIV positivity rate. Which doesn't equate to the population that I see, and that's one of the reasons I think why immunosuppression as a risk factor in itself got in there. but as you say, yes, if you're immunosuppressed, you might be more likely to have toxo, something like that, but you should see that with a focal neurology or seizures or something like that. Yeah,

Callum: 29:17

coming out, so maybe Santa 2025, it would be if possible, and I don't think it is possible, if we could get some way of determining if there is or not a link between LP and this risk, because imagine a world, in the future, where, and this comes onto the reason why this is important, but if we knew the LPs didn't cause us harm, then we could get rid of all this nonsense, because I guess the reason we're talking about this is that the main issue is if you delay LP, you don't get the diagnostics, if you don't get the diagnostics, you can't make the diagnosis and impact treatment, and there was a study in, now you'll be able to correct me if you don't know where exactly it was, somewhere in Scandinavia where they were looking at, basically able to show that the delay in LP led to harm. And, if we just said, actually the LP has never caused the harm, then you could just do the LP without ever needing your imaging. And we can just eliminate there's a problem and all that complexity. I just don't think we're ever going to get the data to say that LPs are always safe to do. I being realistic. So that's why we have to, take this approach. But I guess the main takeaway I always give to people is, it's really critical to get the LP as soon as possible and when it's safe to do so within the pressures you're on. So it's not something that we should just be sitting around being like, Oh, it can wait. we need to get that quickly because it does have an impact on patient outcomes.

Fiona: 30:40

absolutely. And I think diagnostic, as you say, I think, again, you often get a phone call, don't you? Somebody says, Oh, they've been on antibiotics for 24 hours. Now, do I need to do a lumbar puncture? and, it's about seeing some of those other criteria in the CSF, trying to work out if this is bacterial or viral. Antimicrobial stewardship comes into it. Epidemiology and public health comes into it. Because obviously, we need to know, What strain of meningo this is, as we talked about at the beginning. so there's a lot of reasons for doing the lumbar puncture other than just for the individual patient.

Jame: 31:10

Yeah, and usually by that point you are going by the cell count in the split and trying to get the PCR, viral PCR done on the, if you've got that in your shop. Speaking of which, What are the, common organisms that cause, let's start with viral and then we'll do bacterial and then other, meningitis?

Fiona: 31:31

Okay, so in the UK, and this is largely in adults, and I have to say I'm not an expert in pediatric pediatrics, but we can talk about that, but in adults the commonest Virus, and therefore the commonest cause of meningitis is enterovirus, which is a sort of group of viruses as we know. but that's the commonest cause. Generally affects youngish adults, maybe in their thirties and forties. They normally have small kids who've normally had some kind of respiratory illness or diarrheal illness beforehand. And that's where the virus has come from. Second to that, is herpes viruses, so generally for meningitis it's HSV2, so herpes simplex virus type 2, not 1, and varicella zoster, differing studies say in terms of differing, ratios as to the, frequency of those in the UK, in our study it tended to be HSV was more common than VZV, other parts of the world have suggested VZV is more common than HSV. and those are the main viruses, bacteria. Pneumococcal, by far the most common, and that's the one that people forget about. People think about meningo and they think about a rash, etc. But it generally is adults in their 50s and 60s with pneumococcal meningitis is the, probably the commonest. Then, meningococcal is the second commonest bacterial still. Although, significantly less than pneumococcal, and then after that you've got smattering of things. In our study, Haemophilus non type B was actually the third commonest, but again, other places would probably, Listeria would be in there. we've seen a rise in gram negative meningitis in older people. we also see group B strep, which we, again, traditionally associate with neonates, but we have seen that in adults as well. So there's a smattering of other things as well.

Jame: 33:10

And when you say gram negatives, do you mean enterobacterialis or do you mean

Fiona: 33:13

Yes. Yeah. No, entry back to that.

Jame: 33:16

And then, I think fungal meningitis will deserve its own episode later on,

Callum: 33:21

Yeah. We're going to do a lot of episodes on fungal stuff. and I guess again, it's the epidemiology. So you usually think about that in the immunocompromised hope. So, know, I guess crypto being our main one that we'd be worrying about. And then there's lots of weird and wonderful ones.

Jame: 33:35

Um, do you want to say something about TBE?

Fiona: 33:37

again, in the rarer end of the spectrum, but not to be forgotten about, and certainly not unheard of in the UK, would be TB meningitis, and obviously then you're looking at patients who have specific, usually epidemiological risk factors, either due to where they've lived or due to immunocompromising, agents such as, anti TNF alpha, I've seen that, So yeah, you do need to think about that, but that again is at the rarer end of the spectrum, I think.

Jame: 34:03

so, let's talk about the sort of typical CSF that you would find in somebody who had viral and then bacterial meningitis. Medical students will have memorized that little table that seems to be in every book as to what a viral CSF looks like in a bacterial. How true is that and how does TP break all the rules?

Fiona: 34:24

so what I always say is it gives you an indication. so again, I think we have a version of that table in the guidelines. and we are always told that bacterial meningitis, you largely have high white cells and they usually are higher than viral. So, if you've got somebody with over a thousand white cells, it's almost always going to be bacterial. Not always, but almost always, and certainly if the predominance is neutrophils, again likely to be bacterial, but some of that depends on how quickly you do your LP and how many antibiotics you've got. So you can obviously, classic, I think membership question, partially treated bacterial meningitis. So if you have either some antibiotics in A& E or you might have had some antibiotics in a GP before you came in, you can get a lymphocyte Predominance what I have noticed, this might be a bit anecdotal, that in those cases, it's not a case where you've got 95 percent lymphocytes or 100 percent lymphocytes, which is what you see in viral meningitis. It's more you might have 70 percent lymphocytes and 30 percent neutrophils. So when you get that picture and it feels like bacterial and they've had some antibiotics. That is often slightly more partially treated. There's a good paper from 2017 that I always refer to by, Ula Khatib, in the Journal of Infection on the diagnostic accuracy of various different CSF parameters, And that's, it talks about CSF leukocyte count, neutrophil percentage, etc.

Jame: 35:52

Brilliant.

Fiona: 35:52

The one thing I would say, if you can get that in some way, that it's important, depending on where you work, to ask for a CSF PCR. So some labs will do it automatically. They'll automatically pass it on to their PCR colleagues. Especially if you don't have PCR in house, they might not do that automatically, and so you do need to ask for it.

Callum: 36:11

Yeah, in terms of where to look for information on this, so there is a UK SMI on meningoencephalitis. I say that word of dread now. I think it's something that's quite short compared to some of the syndromic one. There's also specific SMIs on, investigation of CSF, etc. It's from 2014, so it's a bit old now, but they do have one of those lovely flow charts where they talk about, what all patients should have. So as Fiona was saying, it looks at the viral causes, CSF or viral PCR, and that's just a panel, blood, you're doing your PCR, for bacteria as well. and you can do the PCR on CSF, and it's important not to forget to do an HIV test. for all these patients, because it's an indicator condition and then other things, obviously we've got blood cultures, ESF cultures, but not forgetting about things like, specific agar, looking for more unusual organisms. And then other things are like syphilis screen, Might be useful, toxoplasma if they're immunocompromised. it's got some additional stuff in the SMI that's not on the show notes about things to think about immunocompromised cause your epidemiology is going to guide that.

Jame: 37:13

Yeah, no, that, that's really good.

Callum: 37:15

And then another thing, so we talked about like the delay in lumbar puncture and if you know, you said that, a lot of the time in the UK, we're not getting that lumbar puncture until after they've had antibiotics. there's a paper, from Journal of Infection, Distinguishing Community Acquired Bacterial and Viral Meningitis, from a couple of years ago. And they had a really useful graphic, which I put in the show notes, and they just lay out the microbiological and biomarkers that were used to differentiate viral bacterial meningitis. And they have a little arrow in the middle, outlining what is more or less affected by antibiotic pretreatment. so things like the CSF white cell count that we talked about before are less affected. And then obviously things that are culture based are more affected. And PCR is less affected. Now, one thing on that list. So we think about our CSF, protein and glucose paired with blood, which are, very useful and they're in that table about the different causes. But one thing that was in the BIA guidance, and I remember being very new to me when I first read it, the CSF lactate. Yeah. And I wonder if we might just talk about that.

Fiona: 38:19

Yeah, so CSF lactate, again, there was a paper a few years ago, and again, in the Journal of Infection, I think, which looks at the usefulness of CSF lactate, and essentially, if it's done before you give antibiotics, it's a really helpful, guide to whether this might be bacterial or viral meningitis. Unfortunately, I think when it's done after antibiotics, it becomes about 50 50, and I would say you might As well, toss a coin. and again, so that's part of the issue. The other thing I would say about these things, and again, some people talk about procalcitonin. I don't know if, you've read about that. So some people have looked at blood procalcitonin and meningitis and CSF procalcitonin. And again, that does come in the guidelines as a suggestion. but they are all Just suggestions, and it's all to be taken as part of the whole. so you look at your lactate, you look at your precalcitonin, you look at your white cell count, you look at your patient, and it hopefully just helps. If everything else looks like this is probably viral, but meningitis, and you've got a negative precalcitonin, then, that might be helpful. but yeah, I think they are helpful as part of the whole picture. But not in and of themselves as a single diagnostic test.

Callum: 39:24

Yeah. I put a table on the, in the show notes again, podcast medium. So sometimes it's hard to fit across all the level of knowledge that there is out there. And there's a lot of papers on this. I think for my papers in Danish, there's two I've linked to in the show notes, one critical care and the other from, infectious diseases and they have a table where they looked at the different tests, the biomarkers, and the negative predictive value of CSF lactate was about 98%. So if you had a normal CSF lactate pre antibiotic treatment, and I think that's the difficult thing, clinicians. And so myself, you see a patient, you think this is probably viral, but it's very hard to say. It's definitely not bacterial. So if you can hold your nerve, not give antibiotics, do lumbar puncture, send a c cephalitis, it's normal. To me, that's very reassuring. If your pre test probability was low that you're yes, this is

Jame: 40:14

But yeah, Callum, that's if you're able to hold your nerve, if you're willing to, risk being sued, and if every doctor who has seen the patient before you was also willing to hold their nerve and not give

Callum: 40:26

But yeah, I think that's a difficult thing because if your clinical judgment is saying this is viral meningitis. it's a, it's about supporting, obviously if you're not sure and you can, yes, you're going to have to treat, aren't you? But if you're confident that you're dealing with someone with varringitis, everything else is supporting like Fiona was saying, that whole clinical picture. I think sometimes people start antibiotics because they feel they should rather than because they actually think there's bacteria meningitis.

Fiona: 40:50

Although I guess we might want to caveat that with there is actually very little objective evidence of what tells the difference between viral and bacterial meningitis. I think subjectively, I agree with you 100%. You look at the patient at the end of the bed and you say, Okay. They've probably got viral meningitis. but objectively, it's actually very difficult, which is why in most guidelines, basically if you think someone's got meningitis, you treat them for bacterial meningitis until proven otherwise.

Callum: 41:16

Yeah. Not easy.

Jame: 41:17

Speaking of which, we, come on to, my favorite section in the whole wide world, killing the bugs. And Let's talk about the empirical treatment, then we'll do a little dive down into, organism specific treatment and what to do when you can't use the first line antimicrobial. So let's start with empirical, shall we?

Fiona: 41:37

So, empirical treatment, third generation kephalosporin, so, the new NICE guidelines we've talked about, came out this year, and one of the changes they made, is that previously, we said kephotaxime or kephotriaxone, but they have come down on kephotriaxone. I'm not sure if there is actually an overriding benefit or it's just to make it slightly simpler and it fits with PEDSA,

Jame: 41:57

I think it's, that the pediatricians have moved away from Kefataxime because they're less worried about this, neonatal bilirubinemia, jaundice, et cetera, et cetera. So now they're using Kefataxime a lot more readily. So I think in the interest of simplicity, to harmonize between adults and kids.

Fiona: 42:15

So, it covers the vast majority of, your main causes of bacterial meningitis. where you need to consider other things empirically. might be if you think you've got risk factors for listeria. and that's when we would go in with amoxicillin. and again, a lot of people, just think of the older age group or the younger age groups with listeria. So they think, oh, we give it to the over 60s and we give it to the young children. But actually, the bigger risk factors or the bigger group of people that we probably see are those with, diabetes or those with, Alcohol excess, or those with immunocompromised. And they should also all be given an additional cover for listeria. And if you're not penicillin allergic, that would be amoxicillin. Again, it's. Sometimes it's more about, as you say, simplicity, and if we start trying to delve into which diabetics should get it, I mean, we're bad enough at giving it as it is. Again, if you look at, the NICAR paper we did a few years ago looking at a UK audit, I think it was 20 percent of people who should have got amoxicillin or should have got listeria treatment did. So, yeah, so I think it's easier to make it slightly more simplistic.

Jame: 43:23

Fair enough. Okay then, so those are your two sort of upfronts. If, say, you do get an organism back, what, if any, change to treatment would you make? Or does it just change the duration of treatment?

Fiona: 43:40

so obviously if you have gone in with your ceftriaxone and your amoxicillin and you get a Pneumo or a Meningo, you can get rid of the amoxicillin straight away. So you obviously don't need the listeria cover. in terms of whether we deescalate the Ceftriaxone. So Ben Pen in. a very good antimicrobial stewardship purist way. people would recommend, if you've got sensitivities, to switch to benzoyl penicillin. However, that needs to be, counteracted with, is the patient well, might they go on OPAT, might you want to give Ketrelaxin via OPAT, if you don't have a 24 hour infusion of BenPen. So, there are risks and benefits of both approaches, but you might want to de escalate to benzoyl penicillin, if you've got a sensitive bug, which most of them are.

Callum: 44:23

Yeah, when I've suggested that locally, I've had a bit of pushback from colleagues and as always, there's this discussion about, brain penetrance and PKPD and, I'll maybe ask you a bit more about this in a second, but, I guess we're weighing up the benefits, which is a narrow spectrum of activity, potentially less side effects, but the downside being giving it more frequently, but to me it seems like, in every other situation we try and narrow down. So the patient's going to stay in. I would, I'd sort of advocate to switch to benzopenicillin if the organism is sensitive and obviously on EUCAST breakpoints and meningitis, it's a bit complicated. Would you tend to switch or would you tend to just leave them on Keftraxone? Just in terms of your personal practice.

Fiona: 45:07

We do tend to switch, and probably partly due to, as you say, that is just what we are doing more and more now to go narrow spectrum. But I think there are arguments like accessing a cannula six times a day, or four times a day, it has its own risks.

Jame: 45:21

which would you do? Would you do six times a day, BenPen 1. 8 or 2. 4?

Fiona: 45:26

so 2. 4, so you want high doses, I think, to get into the CSF, so

Jame: 45:30

Yeah.

Fiona: 45:30

we'd probably get 2. 4. Yeah,

Jame: 45:34

Yeah, I think that's the major counter argument is that you will piss off the nurses if you have to do that. There's a cannula cost associated with it. The patient has to be woken up in the middle of the night.

Fiona: 45:46

exactly. So I think you have to weigh these up,

Jame: 45:49

So Fiona, let's say that we've got, it's fully sensitive strep pneumo, but for whatever reason, we don't want to use Keftraxone. You know, what are the alternatives? And are there any oral alternatives that you would ever consider?

Fiona: 46:04

Interesting. So in the guidelines, the alternatives for, say, penicillin allergy, anaphylaxis, again, obviously, as good infection doctors, we would always stress, make sure you look at what the allergy is and make sure this is a real allergy. but if it is, then we actually recommend chloramphenicol

Jame: 46:21

and are you still recommending that. in the NICE guidance?

Fiona: 46:24

I think, yep, it is. It's still there. and part of the rationale for that on the original guidelines, so we were questioned over this, there's a letter you'll find as well in response to the original guidelines saying, Why on earth have you recommended this? Is because that's where the evidence base is. Okay? The evidence base may be in the 1970s. Or the 1980s, or whenever it was done. But that is when the randomized control trial was done, okay, and that's where the evidence base is. And we don't use Cloramphenicol that much, but in the, as we said at the beginning, meningitis is rare. You know, you want to get it right. On the odd occasion that you have to use it, go for it.

Jame: 46:59

Well, I had a story about that actually. So I was on call for microbiology in Nadosh Royal Infirmary at North. Okay. A few years ago and somebody came in with a very likely meningitis and they had anaphylaxis, full blown anaphylaxis to penicillin a couple of years ago. And not even I was brave enough to suggest delabelling them on the fly in the middle of the department at 2am so that we could give them Keftraxone. Although now I realise that actually allergy to penicillin doesn't necessarily imply allergy to Keftraxone but I didn't know that at the time. So then I, it was a what to do and I looked up the 2016 guidance and then there was chloramphenicol four times a day. So I said give chloramphenicol four times a day and the response was, oh, can we not just give him meropenem? And I said, yeah, no, this, I'm going off the guidance here. Meropenem is an option, but, And so they were like, okay, we'll call the on call pharmacist and we'll get them to schlep in from whatever they were sleeping and unlock the cupboard and give us some chloramphenicol at the back of the cupboard. And then I told the consultants in the morning about this and their response was, Oh, could you not have just given them meropenem? So I didn't know what to do, but I was like, I just pointed to the guidance and said, that, and that provided me with the protection, but I bet a lot of departments actually would have access to chloramphenicol out ours, but will have access to a carbapenem. so it's interesting to know that you are that saying that the justification is that the evidence base is that, which is of course when before carbapenems became commercially available. Would you accept a department saying, we don't have Chloramphenicol, but the vial of Meropenem is right here?

Fiona: 48:37

No, I mean, absolutely. I think you need to go. I mean, strictly speaking, certainly in my hospital, we have chloramphenicol available. again, it might depend on where you work, but, if you have it available, then I think it's good. Because again, we want to be looking for carbapenem sparing agents for other reasons, don't we? so that's good. But equally, if you get a phone call as a microbiologist in the middle of the night going, it's going to take me three hours to get chloramphenicol, what can I give instead? Absolutely, meropenem is the answer. And but remember the high dose, two grams.

Jame: 49:07

Yes.

Callum: 49:08

I think it's worth us coming back. We've done Idiot's Guide to Carbapenems. I don't really have any experience of chloramphenicol. There is a lot of concern, as you say Fiona, people are worried about the Aplastic anemia.

Jame: 49:19

Yeah, irreversible. But it's a 1 in 20, 000 or something like that. It's low risk, but it's high

Callum: 49:25

Bye. Yeah. And yeah, I have to say locally, I, I've never seen anybody give chloramphenicol but I think it's center, dependent, isn't it? And I did a bit of a deep dive and I went through all the references recently in your guidelines about the rationale for chloramphenicol and so on, in preparation for some teaching. One thing that, that struck me was the sort of statement about, PK data. one of the things that is in the guidance is to add in vancomycin if we're worried about pen resistance pneumococci, We're lucky to not have that much in the UK, but, our American listeners will be well used to dealing with that. yeah. So, yeah, and how much data is there around the treatment of that and, with, with the availability now of of generic clonazolid and the, potentially more favorable PK parameters, Jayme and I will need to do a bit of a deep dive into brain penetrance of different antibiotics, do you think that we're going to see a change in how Those patients are treated with the sort of more penicillin resistant strep pneumo strains, because vancomycin, to me, always felt like a drug that, is a bit tricky to dose correctly and the CNS penetrance parameters might not be as good as we would like. Linesolid, is oral, lipophilic, gets into brain pretty well. how are things, I guess my question overall is how are things going to evolve over the next couple of years?

Fiona: 50:48

I'm not sure over the next couple of years there will be that much involvement, to be honest. Linesolid, I mean, Jane probably knows a lot more about this than I do, but I think there's always the bacterial cytolytic, critics. A lot of people don't really like using Linesolid, I think, for neurological infections, or certainly not. First off, maybe as a sort of mop up thing. One alternative, which has been suggested, would be moxifloxacin or quinolone, which actually would probably be a better option, I think, if you've got sensitivity data.

Jame: 51:21

Yeah,

Fiona: 51:21

maybe, that's probably, again, probably not based on anything rather than feeling a bit more comfortable. giving that

Jame: 51:26

well I mean they're both highly bioavailable and they both have, reasonable lipophilicity but that doesn't necessarily equal CNS penetrance, I'm aware. But the, yeah, the, I know what you're saying about Calum, but I about vancomycin. Penetrance in CNS is, poor, but we're not talking about an infection in the CNS. We're talking about an infection in the meninges and in inflamed meninges, lots of stuff gets through that normally wouldn't. And so I think that, for vancomycin as the standard of care for penicillin resistant, I don't think, pneumococci, I'm not sure a lot's going to that over the next few years. Although I I do have the idea that. Things like Laneslet and Restrep targeting Quinlones like Levo and Moxie probably would be, fine. Which I think brings us on to oral options for the treatment of meningitis. I'm sure up front, nothing much is going to displace Keftriaxone over the next, few years. But what oral options have you been using and for what organisms?

Fiona: 52:32

so I don't use orals at all for meningitis. Um that's not to say that there isn't a role. As far as I know, I don't think anybody has looked at that. I know that recently there has been a study in Denmark looking at brain abscesses and orals. I don't know if that's been published yet, but. I always say it's not about how the antibiotic gets in, it's about how much antibiotic gets to the site of infection. So it's irrelevant how you take the antibiotic, what is relevant is how much gets to the site of

Jame: 53:01

Yeah, and it just, but it just happens that with meningitis, all of the evidence based is with IV only medications.

Fiona: 53:08

yeah,

Jame: 53:08

Well, what then if, let me rephrase this. What oral antibiotics do you think would be worth a shot? Should you, the patient is allergic to Keftriaxone and, Chloramphenicol as well and carbapenems, like you're down that sort of rabbit hole, what would you be willing to try in the patient?

Fiona: 53:28

So probably the more likely, you've got somebody who cannot get venous access on for whatever reason. so quinolones, as we've said before, I think, are useful. Cotrimoxazole, is probably a useful

Jame: 53:39

Yeah, we've not mentioned that before, but for Listeria, isn't it the penicillin allergic alternative? Yeah. And

Fiona: 53:45

and obviously we use it for, toxo,

Jame: 53:47

mentioned amoxicillin, recently actually on, on Blue Sky where we are posting more we were talking about step down therapy. And I said, what about high dose amoxicillin? And I was. referred to a paper where people talked a lot about ampicillin penetrance, but not necessarily, and ampicillin being used as a alternative to putting somebody on BenPen, six times a day, putting them on ampicillin three or four times a day, and amoxicillin, but there was a mention that the PK of those two drugs are not exactly equivalent, they are slightly different.

Callum: 54:21

The other issue is that if you look at the UCAS guidance and there's some papers on, oral viability of amoxicillin being 60 percent and the time we need over MIC, I don't think people will tolerate or will be able to take the high doses of amoxicillin you need to get over that CSF barrier because there's so many steps to getting there. So when we're using IV. The amoxicillin for meningitis for listeria cover, we're looking at two grams, six hourly and, you just, people can't take that much.

Jame: 54:51

No, not least because you can't absorb more than 750 milligrams in in one go.

Callum: 54:56

I don't think that's going to be one of the options. you can barely get enough in the blood to treat bacteremia, let alone, getting enough into the brain. There, there is some papers that look at the area under the curve and CSF compared to serum and I will do a bit more of a deep dive in into that.

Jame: 55:13

and so to finish off, why don't we talk about the treatment of viral meningitis? We should be crowbarring acyclovir into every patient with a headache. Is that not right, Fiona?

Fiona: 55:25

Well, funny you should mention that. No, that is not correct. So obviously people know about acyclovir, with viral encephalitis. And this comes back to what we were saying right at the beginning about why it's important to tell the difference between encephalitis and meningitis. Acyclovir is life saving in herpes encephalitis. In meningitis, which as we said, most common causes enterovirus, acyclovir is not going to have any effect on that whatsoever. The second commonest causes are herpes viruses and you might think rationally acyclovir might have an effect, but there has never been a trial looking at acyclovir in viral meningitis or in herpes meningitis. There has slightly. There's been a trial, weirdly, been a trial looking at acyclovir in preventing recurrent HSV 2 meningitis. In which they admitted there's never been a trial actually looking for it in treatment. And it found that it was of no benefit in preventing recurrent episodes if you look at what people actually do, because we don't have a trial, there's a bit of equipoise. It's about 50 50, literally. usually, again, if you hammer down slightly more people might give it for VZV than give it for HSV. and that's about maybe 30, 70. and the bottom line is we don't know. And a lot, I suspect a lot of herpes meningitis is reactivation. So it's not primary infection. and that might be part of the reason why, it doesn't have as much of a effect. but yeah, the bottom line is there isn't really any evidence. And I think a lot of the time when people give it, we're treating ourselves rather than treating the patient. But equally, there is no evidence. So I might be wrong. Maybe there is. If somebody did a trial, maybe it would show a benefit.

Jame: 57:14

Has anybody done a retrospective review of, those that were given e psychobeer and those that weren't and seen how they differ in terms of outcomes?

Fiona: 57:22

so we tried that with the UK data. We didn't really have enough. You need quite a big, you probably need to combine a lot of studies really to get the power to show that, we tried that potentially there might have been a slight reduction of headache at three weeks, but it really wasn't big enough to show that. Show much at all because what you again your outcomes that you have to choose your outcome So I have put in grants to look at this and it's always been Rejected because it's not big enough for an issue. It doesn't kill people and you have to really choose your outcome So what outcome are you actually looking for? So you're probably looking for a quality of life outcome and what we do know is that viral meningitis does affect quality of life when compared to a population that don't have viral meningitis for at least a year after infection. and yeah, so there are things out there you can use, but yeah, it's difficult. So I personally don't give it, but that's not to say that if you do, I think you're wrong, contrary to what I said at the beginning, because actually there is no evidence there.

Jame: 58:20

Fair enough. what do you do then, for viral men?

Fiona: 58:23

For viral meningitis, it really is supportive treatment. analgesia, it is education, HIV testing is important as, Colin mentioned earlier. And I think a lot of it is actually letting the patient, what I do, I think the biggest thing is I tell the patient that you are not going to feel better within a week. and you have to accept that actually you might feel rotten for several weeks, if not months to come. And I think if you give patients advanced warning of that, then it doesn't come as quite as a shock to them because we get taught, Viral meningitis is a benign self limiting condition, but unfortunately that is not the lived experience. I don't think of patients.

Callum: 59:02

we locally have this debate quite often. with HSV meningitis, and we have just talked about meningitis, we haven't talked about encephalitis, and we'll need to come back to that at some point in the future. and it's important to differentiate

Fiona: 59:16

So exactly, and I would say sometimes, especially with the VZV, and I think this is why sometimes more people with VZV get it, is because it's sometimes a bit more difficult because you might have A somewhat more elderly patient who's got shingles, they've got some white cells in their CSF, and they're a little bit knocked off. And it's a bit more difficult to say for sure that they don't have encephalitis. And so I absolutely 100 percent would say err on the side of caution if you're at all concerned that the patient might have encephalitis, give them acyclovir. But if you've got a 20 year old who's sat up chatting to you and they've got a headache and some neck stiffness and some photophobia, they probably don't have encephalitis.

Callum: 59:50

Yeah, yeah, it's, it's not easy. We, I think, always have a debate about it. And obviously people have different opinions and it's difficult when you're in a data free zone, but the other way of thinking about it is that keeping someone in hospital for two, three weeks for IV cycle fear, you've got the risk of lines you've got the risks of the antiviral, which isn't that much, but I guess renal impairment could be one. You don't know it's going to help, but you know, you've got a different risk of harm. tricky. Hopefully we'll get more data and hopefully one of your grants will get approved soon. Any funders listening, please fund Fiona. because, everything you've been doing, um, so far has been really helpful. I guess we're coming to the close now is there anything else that we want, that

Fiona: 1:00:28

we haven't talked about steroids or adjunctive

Callum: 1:00:31

We haven't talked about serious at

Jame: 1:00:32

ah, okay, let's finish off on steroids. So, what's the evidence base for steroid use in this, uh, this condition? And what do you do personally?

Fiona: 1:00:41

So, the guidelines and what I do personally is I would give steroids, so we talk about giving dexamethasone at high doses, 10 milligrams, four times a day, and the evidence base for that a lot of it comes from paediatrics, so there's a huge evidence base in paediatrics in HIB, but as we've said, we don't really see HIB anymore. So if we're talking about adult patients now, the evidence base is in pneumococcal meningitis. So again, big study, big European study in the early 2000s looked at giving dex versus not Big mortality benefits, largely driven by that pneumococcal meningitis. There have been studies trying to reproduce that in resource poor parts of the world, so sub Saharan Africa, Vietnam. And they didn't show the same benefit. And so there's been all these new numbers studies trying to put all the different data together. And there is a Cochrane review, I think, 2015, 2016, that's looked at it. And the bottom line is that it probably does. benefit and it certainly benefits patients with pneumococcal meningitis and probably the setting in which I work so in the UK is probably most similar I think to the European setting which is where it was shown in the first instance. I'm a big believer in steroids and that is all about dampening down the cytokine response and the inflammation that we get with pneumococcal meningitis and that is where the mortality is and that is where we need to focus. Our efforts on treatment, I think, From that point of view,

Jame: 1:02:06

And if you were then discovering that the patient had Neisseria meningitidis, or, something that wasn't pneumococcus, what would you do? Would you continue the steroids at that point or would you stop them? Is it organism specific? It's

Fiona: 1:02:19

stopped them because I think the most evidence at the moment is for pneumococcal and what the Cochrane review did show was that there wasn't really any evidence of harm in other causes of meningitis. So in, I think there was maybe a slightly longer fever, but things like looking at G. I. bleeding or other infections that there wasn't any increase in that in meningococcal. Recently, there's been a little bit of talk about using steroids for listeria meningitis. Again, I don't think we've got the data, but there has been some retrospective studies from the Netherlands, which suggests there may be a benefit. but at the moment, I tend to just stop if it's not pneumococcal, and I continue it if it's pneumococcal. And I try and give it at the beginning when I've got antibiotics. So I think if you are thinking somebody's got meningitis so much that you're going to give them Keftraxone, you should give them steroids as well. and then just stop them if it's not that, because I don't think it Shows any harm.

Callum: 1:03:13

every time there's a listeria case and meningitis, luckily we have a big debate about treatment and mocs and gents and steris. a couple of things. To plug our people and directions, I'll ask you in a second Fiona, but given that this is the podcast, but we have done episodes on, and correct me if I'm wrong, James, we've done episodes on Strep, Pneumo, and Neisseria and Listeria. They're quite old now, so maybe not as comprehensive as more recent episodes have been, but I'll link those in the show notes, so you can go back and have a listen to those. And, before we started recording, Fiona, you were mentioning a couple of things coming up that might be useful, is there any other quick reference guides that people could go to who are looking for more of a

Fiona: 1:03:54

Yeah, so there will be, it's not quite there yet, but there is, for those who know on the British Infection Association website, if you look at the guidelines page, there are things called infection, quick reference guidelines. and there is one on neurological infections, which I've written along with a colleague in Manchester. but that will be useful, so that's just a single page flowchart, how to manage somebody with a suspected neurological infection.

Callum: 1:04:18

also mentioned there's the 2025 BIA Dilemmas Day, which is happening on the 23rd of January. What's that about?

Fiona: 1:04:27

So that is about, one of my other passions, which is mycobacterial infection. so TB, NTMs, anything you wanted to know is joint with the British Thoracic Society in Birmingham will

Jame: 1:04:38

in Birmingham. Yeah, I'll, be really interested to go to that actually, yeah.

Callum: 1:04:42

Yeah. Fiona's, you've got so many interests and, maybe we'll be on, we were lucky enough to have you back again in the future. so just to summarize, there, so we've, rapidly gone through, meningitis, both, bacterial and viral. We've talked about why this is important, a little bit about the epidemiology and how that's changed, how we define, things like meningitis, encephalitis and meningism, how it presents, so the signs and symptoms, what is and isn't useful and how hard this is to rule out clinically and the diagnostics in terms of things like blood cultures and HIV tests, PCR and blood, but also the lumbar puncture and the sort of. Both microbiological we should be getting on CSF and blood, and some of the issues around delayed lumbar puncture and imaging and the indications for that. And we're going to come back to that. And then, we've talked about how to treat it. So what the guidelines say and what antimicrobials we should be using a little bit more of a discussion around the evidence of where we're going next. and, briefly about the organisms and, the use of steroids, which we should be using. so thanks very much. for joining us Fiona, any closing thoughts, statements, things you want to point us towards, puns. I'm

Fiona: 1:05:58

but thank you very much for asking me, and I think yeah, my closing thoughts are just You need to think about it, so you need to consider it as a diagnosis when you see somebody who might, have confusion and fever, and no other reason. Don't automatically think that's a urinary tract infection, it could be meningitis, and you need to do a lumbar puncture to show that one

Jame: 1:06:18

I suppose everybody that meningism could just have a UTI, according to your paper.

Fiona: 1:06:23

Indeed.

Jame: 1:06:24

thank you. thank you very much, Fiona. It's been a Fiona McThrill. Sometimes there's a pun at the end.