111. An Exasperating Expansion on Endocarditis, Part 1

In this episode, Callum and Jame discuss the latest evidence base for endocarditis assessment & management, focusing on the ESC 2023 guidance. 

• Epidemiology! 
• Prophylaxis! 
• How to take a blood culture! 
• A long and complicated comparison of the Duke-ISCVID and Duke-ESC criteria that doesn’t really matter because they’re both as good as each other! 

AND MORE

…in part 2 because this is a 2-parter sorry 

SEE YOU NEXT TIME! 

Transcript

Jame: 0:18

Callum, how are you doing?

Callum: 0:20

I'm doing good. I was thinking about this episode and I thought that I had a pun but I realised that I had insufficient evidence for it, or, i. e.

Jame: 0:30

Oh, Callum, you're breaking my heart, with these terrible puns. so let's talk about broken hearts, Callum. Let's talk about the European Society for Endocarditis 2023 update.

Callum: 0:42

2023, James, but it's 2025.

Jame: 0:44

It is, oh my God, I thought you were going to say it's 2024. Oh, I'm so old. Oh, that does not make me feel good. Yes, that's true. And this sort of episode has been in the tank for a little while. It was initially a teaching session that I gave to local trainees in Nade Oshawa Infirmary South. So if any of you are listening, you can delete this episode unlistened. But I would keep it going in the background and just turn the sound off so that the download statistics count. Thank you very much. but. Yeah, one of our early episodes was an endocarditis episode and was recorded before the 2023 update. So, uh, I think we wanted to have a little chat, about the relevant differences between that episode and this. So that was episode what, Callum?

Callum: 1:31

It is episode numbers, 11, which is suspecting infective endocarditis, where we talked through the definition, causes of organisms, risk factors, signs, symptoms, diagnostics, and the Duke's criteria. And then number 12, which was managing infective endocarditis, where we talked through severity assessment, indications for surgery, treatment options by organism and innovations in practice.

Jame: 1:54

We're not going to cover that stuff because we've covered it in the previous episodes. This is just going to be an update episode, so we're not going to go everything through everything from scratch. If you want an overview of endocarditis. Go and listen to that.

Callum: 2:06

so in the show notes, Jane, you've put them all in. So I guess, that's a good reference document, because back at the beginning when we did episode 11 and 12, I have to say that we didn't really make notes because they're all just coming out of our brains. but now as the loyal listener has demanded higher quality content, we've been making these show notes on notions. So, although we won't talk about them, if you want an overview, you can go and have a look at that and I'll accompany the episodes that we've mentioned that you should go have

Jame: 2:34

Yeah. Okay. Fair enough.

Callum: 2:35

since 2021, when those episodes were released, it's still the same organisms. and most of the things are very similar, but there are some, I guess. Current controversies in practice and disagreements between guidelines, and it's worth being aware of those because this is definitely one of those areas where you'll have patients that are very complicated and getting a management plan isn't always

Jame: 3:01

No, no. I mean, hence why, regardless of what guideline you consult, one of the recommendations will usually be discuss these patients in endocarditis MDTs made up of cardiologists, cardiothoracic surgeons, and infectious disease doctors and microbiologists who are interested in the management of such cases.

Callum: 3:24

That's key, and that comes across in all the guidelines.

Jame: 3:27

So as a brief reminder, Cal, what organisms are causing infective endocarditis usually?

Callum: 3:32

Yeah, so in the ESC guidance they give us a bit of rundown epidemiology in Europe, but obviously it'll depend on where you're practicing. As you might expect, well, I guess in the literature there's always been this debate about whether Staph aureus or beta haemolytic strep are the most common cause. And so in this it's 31 percent staph aureus, 17 percent oral streptococci, so that's our veridans strep. And it varies by species, so then 11 percent Coagulase negative Staphylococci, and then other, which includes Enterococci, so Enterococcus faecalis, Hasex, so Haemophilus, And the other four, and there's an episode on that linked in the notes, and then other gram negatives. So, those are things like serratia are more common amongst the gram negatives, pseudomonas, seruginosa, and klebsiella species. And then fungi. Yeah, and the organisms will vary on what the clinical syndrome is.

Jame: 4:23

Yeah, I know. Though we've run through and named just about every bug that you can think of. This is predominantly a disease of gram positive organisms. So you lump staff, strep and intros together. You've got what, 80, 85 percent of all endocrinitis,

Callum: 4:38

so we've got a couple of questions here. so I guess, prevention is better than cure. who should be offered prophylaxis against infective endocarditis? And what are the recommendations from different organizations? Is there any evidence to support any one position? Jim,

Jame: 4:55

I'm glad you asked that, Callum, because this is a question which has a storied history, and I think we've centered upon an answer, and the ESE 2023 guidance is got probably, I think, the right answer. position. So prophylaxis for endocarditis started way back in 1955 and the American Heart Association produced a guideline which recommended the use of prophylaxis following invasive dental procedures and this continued unchallenged, I think, for Several decades until about from the UK context, we're talking about 2006 when the British Society for Antimicrobial Chemotherapy, one of our infectious disease societies in the UK, recommended prophylaxis for high risk patients only. And at that point the cardiology societies in the UK opposed that and they say we, we don't think that that's a good idea. We still want, prophylaxis for everybody. let's have a look at the evidence and they referred it to NICE for adjudication. And, NICE go and start taking a look at it. In 2007, AHA actually restrict their recommendation for prophylaxis to high risk patients and invasive dental procedures only. And then one year later, NICE recommend a complete scrapping of antimicrobial prophylaxis in the UK for endocarditis. And I remember this coming in and I remember it being controversial at the time. Do you remember it, Cal? Are you still at medical school, you young whippersnapper? Are you?

Callum: 6:38

I don't remember it though.

Jame: 6:39

Fine. Well, it caused quite the kerfuffle when it first came out and because that was not even BSAC were recommending that, but NICE had this thing at the time where they were only going to take evidence from RCTs. They had this policy where if you had retrospective data or cohort study data, blah, blah, blah, they didn't care. It was RCTs or nothing. So it was a very purist interpretation of the evidence base. we will revisit this later, Callum. But, so that NICE said, you haven't done an RCT and so we're not going to recommend it. And so they, they removed, that. In 2009, the ESC adopted the same policy as AHA, so high risk patients, invasive dental procedures only. And then in 2016, NICE sort of rolled back their recommendation to prophylaxis as not routinely recommended, and that caused loads of confusion. And so people started moving away from NICE's position. So making it even more local, Cal, in 2018, the S D C E P, the Scottish Dental Clinical Effectiveness Program, which is about dental clinical practice, obviously, in Scotland, so pretty small fry. From an international perspective, they advise that, and I quote, the vast majority of patients increased risk of endocarditis will not be prescribed prophylaxis. However, for a very small number of patients, it may be prudent to consider antibiotic prophylaxis in consultation with the patient and their cardiologist or cardiac surgeon. And they listed some risk groups which were identical to ESC and AHA groups, and NICE later approves this position. I've got a link to the evidence base for antimicrobial prophylaxis and endocarditis to a paper that summarizes all of this, including the timeline. And they've got a brilliant, table of what the risk is of endocarditis, per dental procedure and who is, and who is suitable for, prophylaxis. So the numbers that we're going to quote here are NNP or number needed to prevent a case of endocarditis. So the NNP is similar to the NNT, and the high risk procedures are oral surgery. Dental extractions and other invasive dental procedures and the NMPs for those three things are 45, 125 and 1, 500 respectively. And then for moderate risk and low risk procedures, there's very little difference with or without antibiotic prophylaxis. and so, why would you not want to just give antibiotics to everyone, I ask you, Callum, as if you don't already know, well, that would amount to quite a lot of antimicrobial usage in the community. And we actually already have defensive measures in place for transient bacteremia, which is what all but the most high risk invasive dental procedures would cause. So this is mostly a prophylaxis against mouth organisms, isn't it? And every time you brush your teeth, you get a transient bacteremia. Every time you floss. Every time you chew. food, you will get a transient bacteremia. So you are kind of used to alveolitic streps entering your bloodstream, and your body is usually pretty happy completely murdering them the second they enter the blood. And so the, that low level bacteremia, If your dental procedure is doing the same thing or conferring the same amount of low level bacteremia, you're probably going to be able to deal with it on your own, and there's not much point in giving you antimicrobial prophylaxis. And then I'll end by pointing out that there's a meta analysis of about 36 studies, including 21 trials, investigating the effect of antibiotic prophylaxis on the incidence of bacteremia following dental procedures. And they showed that prophylaxis reduces the incidence of bacteremia, but not a statistically significant protective event against endocarditis in case control studies. So, on the basis of all that, the ESC have recommended, in specific risk groups, which are people that have had endocarditis in the past, or prosthetic material in their bodies, or congenital heart disease, or LVADs, and they've said that for high risk procedures, to, give antibiotic prophylaxis, but for everybody who doesn't fit those criteria, and are having moderate or low risk procedures, not to bother. And there's a little table that we've got in here about what to use, and it's everything that you would have thought would be useful for strep. So amox, kefazolin, keflexin, keftraxone, macrolides, doxycycline, that kind of thing.

Callum: 11:34

that's really helpful. particularly getting that history behind what's going on, because, it does seem like something that's changed a bit.

Jame: 11:41

in the course of our careers, are my career at least Callum?

Callum: 11:45

Some people's careers, yeah, and, the prevention, is obviously much, much better than cure, so, do that. We're not saying don't floss or brush your teeth, because obviously those are important,

Jame: 11:55

No. Just in case you were wondering.

Callum: 11:57

do, do floss, please.

Jame: 11:58

but now I have a question for you, Callum.

Callum: 12:01

Uh oh.

Jame: 12:03

And the question is, What are the most common symptoms in, endocarditis? Mm-hmm

Callum: 12:10

So again, I think this is from the ESC guidance and, they helpfully differentiate it out. So 78 percent of people presenting will have fever. Important to note that means that 22 percent of people won't. 65 percent of people will have a murmur, so 35 percent of people won't have a murmur and 27 percent of people will present with heart failure. So it's worth bearing in mind, for those, patients, there's a whole lot of other symptoms that people might present with and settings where you should be considering infective endocarditis and the differential. So they've got a table, and that's from something called the Euroendo

Jame: 12:50

Yeah. Well, it's from the ESE guidance, but they've taken it from the Uruwendo registry, so

Callum: 12:55

yes, table s1 and it will vary by, the clinical presentation of whether it's prosthetic valve, or native valve or cardiac implantable electronic device.

Jame: 13:06

So what, that's pacemakers, LVADs, other stuff?

Callum: 13:10

Yeah, defibrillators.

Jame: 13:12

Yeah.

Callum: 13:13

and the reason it differs is because you've got different organisms. So, staphylococcus aureus, infective endocarditis, just to take an example, it's an acute presentation, they run well, they're bacteremic, they've got a fever, they have classic signs of infective endocarditis. in drug users, you'll see this, they'll have the embolic events, they'll have the, cutaneous manifestations. Whereas something like an endococcal bacteremia, where it's generally a more elderly patient or in a prosthetic setting, often they don't have fever, often they don't present with, sepsis because of the lack of the, virulence of the organism. So I guess why I'll stick away from the clinical features is that you need to have a quite a high index of suspicion, and particularly in things like embolic events or there's just systemic infection. Or you've got a set organism is the other,

Jame: 14:08

Yeah.

Callum: 14:09

particularly in patients that are high risk. So they defied the risk factors into cardiac risk factors. So similar to the prophylaxis groups, but not exactly the same. So the risk factors they give us previous effective endocarditis. valvular heart disease, prosthetic heart valve, central venous arterial catheter, transvenous cardiac implantable electronic device, and congenital heart disease. Jayme, what are the non cardiac risk factors?

Jame: 14:38

They are a central venous catheter, people who inject drugs, the immunosuppressed, recent dental or surgical procedures, recent hospitalization, and hemodialysis patients.

Callum: 14:51

So, yeah, I recommend going to the guidelines, which we've linked to, and looking at that table of symptoms, because there's a lot that we haven't mentioned. Also worth considering, it's easy to say, list off all the symptoms that suggest it, but I think it's also worth, just like we talked about meningitis of Fiona, and we were talking about those four key symptoms,

Jame: 15:11

you're on first name terms with Dr. Miguel, aren't you?

Callum: 15:13

them. And, a key thing there that I take away from that is. that actually, the classic symptoms often aren't there. So, sometimes you see people saying, Oh, well, we don't, we're not worried about infective endocritis here. Or maybe they don't write that down, but in their head they're thinking, well, they've not got fever. So I'm not worried about infective endocritis, because everybody has infective endocritis, much like a fever.

Jame: 15:36

Yeah, or everybody's got Rothspots and Janeway lesions, and so they don't have that, so therefore there's no endocarditis present,

Callum: 15:43

How often do you do ophthalmoscopy looking

Jame: 15:45

never, never Callum. Like, somebody's got endocarditis, bad enough that they've got Roth spots, but I've not detected the bacteremia and they've not got a lesion detectable on echo? No man, I'm not, I'm not Roth spotting my way to the diagnosis, I'm not house here.

Callum: 16:01

I really want a retinal camera and I can just get perfect retinal images on

Jame: 16:05

Well, I mean, that's the other thing is that my ophthalmoscopy skills have, completely fallen off a cliff since I passed paces.

Callum: 16:14

will be

Jame: 16:14

Yeah, I know. And that was a long time ago. So, you know, ditto looking for papilledema in my hypertensive headache patients, et cetera, et cetera. I just don't think it's worth,, maintaining that skill when there's other more high yield, investigations or assessment criteria, that you could, use.

Callum: 16:32

So I'm talking about, yeah, so we've got all these symptoms, but how would you, how do you, you know, is there some sort of score? I've heard of this thing called the Duke's criteria, and I've heard of modified Duke criteria, but what are the modified, modified Duke criteria? The so called second breakfast of infective endocarditis.

Jame: 16:52

Well, I'm glad you asked me that Callum, because, the Duke criteria. I don't know when they first, came out, but then they were modified and those modifications were called the modified, modified due cri, the modified due criteria. And what do we do with the modified due criteria? We modified it once more to make it more accurate. That's what we use at Callum. But. It wasn't just one organization that did it. It was two organizations that did it. So, ESC have produced their version of the Modified Duke Criteria, called the ESC Modified Duke Criteria. And ISCVID, the International Society for Cardiovascular Infectious Disease, have also produced their version of the Duke Criteria, called the ISCVID Modified Duke Criteria. And the ESC guidance, of course, only mentions their own one, because they're not going to go promoting somebody else's, Modified Duke Criteria, if they can get away with it. And I know what you're wondering, what are the relevant differences between those two. Well, I am happy to report that in terms of performance, accuracy, there doesn't seem to be much of an effect. So I found this paper from 2023, which again, we will link to. It's in CID. and they conclude, and I quote, the 2023 Duke ISCVID and 2023 Duke ESC clinical criteria show improved sensitivity for A diagnosis compared to the 2015 criteria. However, this increase in sensitivity comes at the expense of reduced specificity. That's for both of them, and there doesn't seem to be all that much difference in performance between the two. So pick whichever one you like, and I've got a little table there again from that paper. So for comparison, Cal, the 2015 ESC, 2023 ESCFID, and 2023 Dukes have positive predictive values of 97, 92, and 92 percent and negative predictive values of 88, 90, and 90 percent respectively.

Callum: 18:52

And just for the loyal listeners, so we, we talked in our previous episode about the modified root criteria, and we came up with a scoring system to get your head around, the major and the minor criteria and the pathological ones. So I think you got five points for a pathological. You got, three and a half for a major and one for a minor, and it meant that, it all worked out in terms of how many you needed, and you needed to get a score of, five or more to make the diagnosis. What is modified about the Modified Modified Duke Criterion? Now we're calling it Modified Modified, that's not what it's called, they're called, as James, as James said, the, there's the 2023 ESC, European Society of Cardiology, and the 2023 ISCVID

Jame: 19:32

Yeah,

Callum: 19:33

What is the change?

Jame: 19:35

the difference is, I think some of the, Organisms that are considered to be high risk of change. they've rolled in enterococcus, vaca, I think, into the highly likely, the differences are listed in the, paper, the CID paper that I'm going to, put in the pre notes.

Callum: 19:54

So, it seems like the changes, there's been quite a few different changes over time. In 2015, ESC integrated, G PET CT for diagnosis of prosthetic valve infective enteritis. Good luck getting that depending on where you work. And then in 2023, the I-S-C-V-I-D, they made further, changes, so they adjusted the microbiological criteria. They broadened the application of PET CT in native valve and CIED, lead infections, and introduced new surgical evidence as a major criteria. and that was validated against the 2015 ESC guidance, which showed it performed better. So then in 2023, the ESCs updated So that's more recent than the, ISC VID one, they had five new notifications, three of those mirrored the ISC ones, so encompassing changes to the cardiac predisposition criterion, microbiology and imaging. They also had two other modifications, one was identifying vowel thickening as a distinctive feature of infective endocarditis. Okay. and also incorporating hematogenous osteoarticular complications into the vascular phenomenon criteria.

Jame: 21:12

Yeah, so that's the discitis

Callum: 21:15

Yeah, but I guess, if it's osteoarticular complications, it could be other sites as well. And, quite commonly see in certain patient groups with infective endocrinitis. So it all makes sense. And I think what we do in the show notes is we'll put together what the current criteria are just linked to the MD calc. And in some ways, who cares what's changed? Just use the most recent one. There you go.

Jame: 21:38

Yeah. Well, I mean, I think, you know, frankly,

Callum: 21:41

Nobody's memorizing

Jame: 21:42

moving advantage is that, it's good. Duke has made it into MD calc. That's the one I'm going to use because that's the one I got on my phone. Do you know what I mean? And if there's no difference, if there's no advantage in using EFC over, it's good. I'm just going to use the one that I've got the quickest access to.

Callum: 22:01

For me, the main issue with these is just that, in the UK accessing, or at least locally, accessing a PET CT is nigh on

Jame: 22:10

Yeah,

Callum: 22:11

And so it's just a resource setting. If you're working in a setting where you've got easy access to investigation, I'm sure it's very useful.

Jame: 22:17

do you want to talk about blood cultures Cal?

Callum: 22:19

So we just talked about jukes and microbiological criteria. So blood cultures, so You know the SC guidance states that they want free and you know It goes about saying free high volume well filled Pairs of blood cultures of aerobic and anaerobic bottles and they asked for them at 30 minute intervals which kind of always surprises me when this gets rolled out again because when I've seen the studies looking at yield of blood cultures My understanding is that doing it at different sites and time, one, doesn't increase your yield, two, increases your rate of contamination, because we know that the first couple of mils of blood are most likely to be contaminated with organisms on the skin, and three, is obviously, three episodes of venipuncture for a patient, and sometimes patients are very difficult to bleed, and that's very, that may be six needles going into that person's skin, that's, very difficult. rather than one? it has to be, to me, quite a big benefit to justify

Jame: 23:19

in their defense Cal they're trying to identify persisting bacteremia and they have dropped the recommendation on different sites. They don't care anymore you are going to have to jab them three times.

Callum: 23:31

I also did wonder about the different sites. they've got infective endocrinosis, but just of the left arm.

Jame: 23:36

Yeah. Well, I mean, I

Callum: 23:37

Just of the right leg.

Jame: 23:38

I think they have paid attention to that criticism and removed it because, it doesn't make sense because blood just goes wherever it goes.

Callum: 23:45

also hard enough getting blood cultures done

Jame: 23:47

Well, I think the, what I would have done if I'd had my druthers is I would have started with a double culture and said get four bottles off and then wait 30 minutes. Ideally, and then take another set off, and that's your three. And if you can wait another 30 minutes before starting antibiotics, so be it. But at least then you've got, four, four bottles and off. Or even taking a dump tube first. So that first couple of mils goes into the coag or something like that. But, but they haven't gone that deep.

Callum: 24:21

the coag first is it's non sterile bottled and,

Jame: 24:24

Well, you know what's also not sterile Callum, is your skin, no matter how well you prep it.

Callum: 24:30

Yeah, that's true. You can get divert devices which you can put onto venipuncture kits now for taking blood cultures which will be sterile and take the first couple of mils

Jame: 24:38

Ah, yeah, yeah.

Callum: 24:39

that's preferable. I guess we usually say take six sets of blood cultures if the patient's stable and you're not in a rush and do it spaced out. But, doing multiple blood cultures, I'd probably say something like do two sets at a time and do three times maybe. But yeah, I guess there's a difference between, this person's bacteremia trying to identify in general sepsis and infective endocarditis where you're looking for a persistent bacteremia. We know that bacteremia isn't there all the time in some patients. Anyway, that's not, we can go back to bacteremia, but there's already an episode on that. They recommend doing peripheral over central, so, I guess taking it from a central line, there's a higher risk of contamination, and particularly in infective endocarditis, if there's prosthetic valves, getting coagulase negative, staff or other skin organisms is even harder to interpret I'm always surprised they don't make a recommendation about wearing a surgical face mask when taking, blood cultures as well. I was thinking about that when you see, virid and strep as contaminants in blood cultures, or CSF. It's often, come from the operators. on moral flora when they've read on to the tuber coughed or something or

Jame: 25:47

had a case like that the other day. A patient who had blood cultures taken. They had an E. coli. In their urine, and they grew a strap, a mouthy strap of some description in their blood culture bottle, what to do. And I just assumed either it was from them brushing their teeth or the operator had sneezed on the patient before taking the blood culture and ignored it.

Callum: 26:08

and that's fine if a patient is clearly got an urinary tract infection, but if you're really clinically worried about infective endometriosis, he's very hard to ignore that organism. And even if it's mixed, so it's, I think here, more critical than normal to ensure the sterility and aseptic non touch technique when you're doing your blood cultures. And some other things they talk about in the wiki guidelines, which if you've not read, it's a useful thing, although they don't make that many recommendations because they say there's insufficient

Jame: 26:37

Yes. at this point we need, we should introduce them, Cal. So like, what are the wiki guidelines?

Callum: 26:42

Well, the wiki guidelines are a recent endeavor, and they are a group that are trying to set up guidelines that are continually updated rather than waiting for, the next major update, and that can be years and years and years, and they are taking a sort of more consensus based approach to guideline development. So, not really the same backing of these major groups, but I guess have a bit more, How would you say flexibility and they can put things out a bit quicker, potentially. I've the infective endocarditis ones are worth having a look

Jame: 27:13

Yeah, very, if only for the evidence based summaries alone, which are just excellent.

Callum: 27:19

they are excellent. and I think it's interesting reading that in conjunction with something like the ESC guidance, because it doesn't agree. And, I think as a more junior training, you might think, Oh, guideline sees X. So I will do X. But I think particularly with these guidelines and this condition, because there is quite a lot of uncertainty in the literature and the data, it isn't like that. And certainly locally, we don't definitely all agree with what the ESC guidance says. And you, you ended up looking at different guidelines and seeing which recommendation makes the most sense for your patients. So the ESC guidance. The AHA guidance. Also, the Dutch swab guidance are really useful. I often go to that. So they're the same people that did the excellent penicillin allergy, I think 235 page documents that we referred to in our penicillin allergy

Jame: 28:06

Yeah. Yeah.

Callum: 28:07

episode. so anyway, back to, back to the topic. So time to positivity of blood cultures.

Jame: 28:14

Yeah. So they divide it by organism and they start with Staph aureus. so they. Evidence based for time to positivity, there's three studies with different cut offs. So, how quickly does your blood culture flag for what eventually is identified as a staph aureus? And can we use that to predict the likelihood that they have endocarditis? So for the first study, less than 14 hours, less than or equal to 14 hours. Sensitivity 74%, specificity 57, so not great. Time to positivity less than 12 hours. Prevalence. in this study was 25 percent versus 8. 5 percent for more than 12.

Callum: 28:58

Wait, so I, have you lost me there? Can you

Jame: 28:59

So it's three different studies. One reported sense and spec, one reported prevalence.

Callum: 29:05

So what do you mean? So when you say over 12 hours prevalence, 8. 5 percent less than 12 hours, 25 percent prevalence, what

Jame: 29:12

I mean, in inpatients whose time to positivity was less than 12 hours, a quarter of them had endocarditis, 75 percent did not. And for more than 12 hours, 8. 5 percent of them had endocarditis. So you've got a, Sort of tripling of the prevalence, so to speak. And then lastly, time to positivity more or less than, 11.5 hours. That cutoff had a sensitivity of 89% and specificity of 72, so that performed a little bit better. So you, if you tighten up the time to positivity, so it's 12 hours or 11 and a half hours, you get better performance. Do you see what I mean?

Callum: 29:53

Yeah. Yeah. So the quicker, again, it summarizes as saying the quicker is positive. It's suggestive of infective endocarditis. Although to me, it just suggests, the quicker it's positive, the higher the bacteria load in the specimen that you've taken. So it is reflective of the burden of the bacteremia, isn't it? The bacteria ones in the tube don't know where they've come from. But I, guess, like the conitis being an intervascular infection, you would generally expect to have a higher rate of bacteria in the blood.

Jame: 30:23

I suppose the important thing to note, having gone through all that, is that with other organisms, you don't identify that relationship. So for streptococci, they didn't identify any relationship of time to

Callum: 30:35

Hmm.

Jame: 30:36

But with enterococci, there's, they quote one study, A time positive to fewer than 11. 6 hours, sensitivity 93%, specificity 51%., So, in your endocarditis population, most of them will go positive within 11 and a half hours.

Callum: 30:55

Yeah. That makes sense. So if you, I guess it would be good to see the other statistics, I'd probably like to see a, a negative predictive value for enterococcal blood cultures being positive greater than 12

Jame: 31:08

Yeah, I know. Well, if you want that, Cal, you better, go and read the wiki guidelines, because I didn't note it down here, did I?

Callum: 31:14

but I, I guess it's useful to, if your enterococcus is coming up on blood cultures, 48 hours later, it doesn't, it does seem to, that, that to me suggests that that's making it less likely that it's an effect of endocarditis, although that on its own, it's, it's not really not a clincher, is it? You're also quoting some literature here saying that the volume of blood, increases the yield. I don't think we need to say more about that then.

Jame: 31:37

no, but let's finish with that last bit about battery mid detection rates, because that's worth knowing, I think.

Callum: 31:43

So the first set, and I think we talked about this in the bacteremia episode.

Jame: 31:46

but I don't think we have these precise numbers, so

Callum: 31:49

yeah, so this is for infective endocritis, obviously slightly different from just general bacteremia. But your first set of body cultures, you should pick up 65 percent of bacteremia with infective endocritis. Second set, 80%. Third set, 96%. Which heartens me because whenever I speak to people on the phone and complain about not having sent enough blood cultures, I quote 3 sets giving you 95%. So, yeah, I remember it as like 65,

Jame: 32:15

Two thirds, 1895. I think that's like a nice, easy to, to remember, as

Callum: 32:21

It's definitely a balance, if you've got that really acutely unwell patient or septic or you're worried about them. then, I guess we have to say, you just, that they recommend at least two sets of blood cultures before antibiotics. And I think that's a reasonable ask, even in A& E resus. Nobody's so busy that when, they're going to get floods anyway, so just, get

Jame: 32:39

Yeah, I mean, good luck going into the emergency department or an SDEC or an EMU and not getting a cannula stuck in and getting a load of blood taken off you. Do you know what I mean? You can't take two more bottles.

Callum: 32:51

yeah. I, I went in once with, I think I'd hit my head and just concussed and broken my

Jame: 32:55

Oh, that explains a lot actually, yeah,

Callum: 32:57

And yeah, and then, they were, they came and they were like, we're going to put cannula and take some blood. So it's No, like it's off. I don't want to can you like,

Jame: 33:06

for your, for your sore head.

Callum: 33:08

yeah, and it obviously didn't need it, but it just becomes part of the routine,

Jame: 33:12

You, you go into the machine and the machine will do what it will do. You'll probably get a chest x ray as well if you don't, if you don't push back against it.

Callum: 33:20

at my MDRTB? So the, I think maybe just to wrap up this first part of this, what looks like it's going to be a two

Jame: 33:27

Yeah,

Callum: 33:27

based on how long we've talked already, this quick update, It's on brand, Isn't it So let's finish talking about culture negative infective endogynitis, So we've got those organisms that we've just talked about, and you're likely to go those in blood cultures. And I guess this label is applied when, your blood cultures are negative. And the main differential diagnosis is the sort of, fungi, the hastics. or people that have had prior antibiotics and got one of the usual organisms. And then there's a whole list of other things. So, Brucella species. So we think about that quite a lot in patients that have had the epidemiological exposure, particularly the Middle East. or drinking, unpasteurized milk, which is obviously becoming more common, in large parts of the world. Q fever, coxiella bernetti. So again, the epidemiology of that exposure to farm animals and in the countryside, although some studies suggesting it can be carried, 12 miles downwind. So, don't really need that exact risk. So, Martinella as well, so, again, quite hard to diagnose, needs molecular diagnostics. Trephinema whipli, Mycoplasma, Legionella, and then some Mycobacteria, so Mycobacterium Chimaera particularly in prosthetic valve. and for all of these, because they're hard to grow in normal culture media, you're looking at doing things like serological investigations. Now, some of those are very complicated. So, for example, diagnosing Q fever isn't straightforward. or molecular diagnostics, PCR, particularly of valve tissue is a key microbiological diagnostics, but you'd only do that if you've got surgery. We'll come on to

Jame: 35:02

So, I mean, I note that 16S RNA is listed as an option or 18S for fungi. Bye. for every single one of these, which is great, that does rely on you having the tissue to send as well, so it's like a post op diagnostic, and,

Callum: 35:16

And you don't really want to be to that state. I think often those ones are the one where they go in for the cardiac surgery because they had valve filler impairment or something. And nobody was really expecting infective endocarditis. And then the surgeon's phoning you and saying, Oh, I went in and actually the valve endocarditis. So we're sending you some tissue. The other thing to say is that, my personal experience has been that, hasics are always labelled as this, cause of culture negative infective endocarditis. But all the times I've seen them, we've grown them on culture pretty easily. things like aggregatobacter, cardiobacterium, eichenella, and kingella, which is the asics and anamophilus, they actually grow pretty well in blood cultures. And maybe that's a reflection of having better diagnostics now with our automated blood

Jame: 36:00

yeah, I think the blood culture bottles that we're using these days are better for the fastidious, organisms. than they used to be, and so they'll flag, and then maybe you'll get a bit of a steer, when, once you do your gram stain as to what's going on. And actually the lab BMSs are great at figuring out what to grow, what to grow these organisms on based on their colony, their, appearance,

Callum: 36:26

it's usually in the SOP for these sort of organisms, so it should be happening automatically. If you're wondering what, when I said Hasek there and ran through those organisms, what I was talking about, episode 32 is all about Haemophilus and episode 35 is Arriving at Hasek, which I think is one of my favorite names of our episodes because it makes absolutely no sense,

Jame: 36:46

Yeah. it's certainly on brand for the podcast, isn't it?

Callum: 36:49

And there's a lot of stuff we mentioned that we haven't covered yet, but exciting things coming soon. Yeah, I guess we've run through there. Just to summarize, we've answered some of the questions. We talked, James talked a lot about the prophylaxis and the history of that, so thanks for that. We talked about the signs and symptoms and when they are present. We talked about the modified modified criteria, the second breakfast of infective endocarditis. And then we've started talking about diagnostic modalities. And all we managed to talk about was the, what cultures and culture negative causes. we will come back, shortly and tell you all about diagnosis with the echocardiograms, And then surgery, antimicrobial therapy, and a little, tidbit on antimicrobial susceptibility testing adding on what we talked about in those AST episodes that you've been avidly listening to recently.

Jame: 37:43

Perfect. See you next time.

Callum: 37:46

Cheerio.

Jame: 37:48

Is that second breakfast thing a Lord of the Rings pun,