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ID:IOTS - Infectious Disease Insight Of Two Specialists
Join Callum and Jame, two infectious diseases doctors, as they discuss everything you need to know to diagnose and treat infections. Aimed at doctors and clinical staff working in the UK.
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ID:IOTS - Infectious Disease Insight Of Two Specialists
100. AST: Rapid Identification and Molecular AST. The BCID2 & Vitek Reveal with BioMérieux
Jame is joined by Kate from BioMérieux as they take a deep dive into the BCID2 and the Vitek Reveal, 2 new devices used for rapid identification and antimicrobial susceptibility testing of blood culture isolates.
Note: This episode was produced in collaboration with BioMérieux. An honorarium received from them will be donated directly to charitable causes.
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Kate, how are you doing?
Kate:I'm good. How are you?
Jame:I'm fine. Kate, you are, this is a very special episode that we are recording in collaboration with BioMérieux. Why don't we start by introducing BioMérieux and then we can introduce BioMérieux.
Kate:Oh, very clever. Yeah. So, BMRU is a family owned company and it's been established over 60 years now. So, the family history itself goes all the way back to Louis Pasteur. where one of the Maria families to study with him. And yeah, they've been established in core microbiology for 60 years and developing out and taking on new technologies. So moving into MALDI TOF, PCR and that kind of thing. But yeah, really supplying core microbiology diagnostics and rapid diagnostics to microbiology labs across. The globe.
Jame:and your work for BioMérieux in particular.
Kate:So I am the senior product manager And I look after the blood cultures and automated AST products. So working with the marketing team joined the company just over three years ago as an account manager and then moved into marketing just over two years ago. So really looking after those products, speaking to customers and making sure we're getting our message out there to, to show what we can do.
Jame:I think the main way that people will know BioMérieux is that they are the manufacturers of the Vitek 2, and we will have released an episode based on the Vitek 2 with your colleagues earlier. So that episode covered that, kind of main application. We're talking about a couple of new technologies which may be coming into a lab near you soon, which are related to the Vitek 2 in terms of identification and, antimicrobial susceptibility testing. So what are we going to be talking about today?
Kate:So we're going to be talking about the BCID2 panel, which is one of our BioFire panels. And we're also going to be talking about the Vitek reveal, which is that AST diagnostic for rapid sensitivity results for blood cultures.
Jame:Perkitt. All right, let's start with the BCID2. Before we do, I think we probably need to talk a little bit about the BioFire platform. So people might have been working in a service which has access to the respiratory BioFire, which is a PCR that we use to diagnose respiratory infections. But the BioFire platform, briefly, what is that about?
Kate:So the BioFire platform, really all of the panels are based on syndromic testing. And what that means is rather than testing for one target they're testing for a range of targets associated with the syndrome. So, for example, the BCID2 panel, which we'll talk about a bit more, looks at all of those common targets for a bloodstream infection. The respiratory panels would look at both bacterial and viral targets to try and guess As much information as they can from a test rather than ruling one thing in or one thing out. It's more of a a wider approach. It's a really simple instrument..
Jame:I'm assuming that the BioFire is a standardized machine with a standardized PCR media. And then the primers are the only thing that's varying. So there's a RESP panel and the, that's got all the RESP primers in it. And then there's. This one, BCID, which has BC blood culture identification primers for a bunch of different bugs, but the the stuff that sample goes into doesn't vary a lot. Is that true.
Kate:Yeah. Yeah. So the BioFire platform is a really nice benchtop system. And basically it does two rounds of PCR. There's a little pouch. That's set up. And then depending on what you're looking for, we've different panels for respiratory infections or for joint infection. Panels as well.
Jame:Okay, and the BCID is the blood culture. Identification panel. So it goes into this sort of standardized way of doing a PCR that's high throughput and relatively high yield as well. Is that
Kate:That's right. Yeah. So the BCID2 panel looks at those blood culture infections. The setup is standard across the board. And you just need very little of the sample, which makes it very suitable for testing high value samples like CSFs and that kind of thing.
Jame:Okay. And BCID 2 implies that there was a BCID 1? Is that true? Is this the second iteration?
Kate:absolutely true. Yes. So there was a BCID so with no one and it was developed then to add more targets to it. So more organisms and more resistant markers.
Jame:So like you said, that you've expanded it since BCID one. Are you looking for,'cause A-P-A-P-C-R can only find what it has a primer for. So what are those primers in the BCID two.
Kate:So for the BCID2, we're looking at the most commonly isolated organisms from bloodstream infections. So we're going across gram negative bacteria, looking at kind of the usuals, Enterobacterioles, Haemophilus influenzae, Neisseria meningitis, To mention a few gram positives, like your staphs, your streps, your enterococci as well as some yeasts as well, including cryptococcus. So they're for the organisms and then there's also some resistance markers in there as well to look for carbapenems for colistin resistance, ESBLs, resistance, and as well.
Jame:Okay, so methicillin resistance in all organisms. Can it tell if it's specifically from a staph aureus or is it just like,
Kate:Yeah, so built into the software, it will only report a resistance mechanism if it has detected the associated appropriate organism. So, you're, it's going to try and take the guesswork out of it and not cause any confusion. So, you get really nice reports actually that will tell you the organism and the associated resistance marker
Jame:so it wouldn't report ESBL in a gram positive
Kate:no.
Jame:Particularly for the carbapenemases now? Because, I mean, there's hundreds of ESBL genes and carbapenemase genes, but there's, with carbapenus in particular, there's the big five. Is it just looking for the big five or is it looking for, is it more broad than that?
Kate:No, it's just looking for the big five. I suppose it's a numbers game, really. As you said, like with PCR, you can't look for something or you can't look for everything. You're just, focusing it. So it's really trying to capture the most commonly seen resistance, the most commonly seen organisms. With this, you'd assume that there's going to be follow up testing then as well, if there is anything weird or wonderful. Going
Jame:So I suppose this is not to be used in isolation. The blood culture, time to talk about the sample. I think that you're actually putting into this. So the sample is a blood culture that's just flagged positive. Is that right? Yeah, a blood culture bottle. So it's not like you're not only going to do the BCID2, you're going to continue to culture. And I suppose that will provide confirmation of whatever you find on the PCR panel. This is just giving you early detection.
Kate:Yeah. I suppose like any laboratory test is nothing is taken in isolation. And as you say, with a positive blood culture, there's going to be a gram stain. There's going to be culture as a standard of care and any additional sins,
Jame:So, and so in terms of the. Workflow this setting up of the BCID will be happening at about the same time. The gram stain is being done. What?
Kate:Yeah, so it depends. A lot of labs would have different algorithms. So you would imagine that a really busy microbiology lab will do a gram stain as well. But for some labs usually maybe out of hours, they might just do the BCID2 depending on their on call staff or depending on their working hours, they might just do the BCID2 and then follow on. But you would see that full. battery of tests being done on every blood culture by the end of the sample process.
Jame:Whilst we're talking about the sample prep We know that blood culture sensitivity is sort of effect by affected by the bottles being over or under filled. How? Sensitive is the BCID to PCR to that?
Kate:Well, I think what's wonderful about the BCID 2 is that it's done on a positive blood culture. So the only impact you're going to see from an underfill usually leads to like a false negative where you're not going to actually have to do a BCID 2 and the overfill then is more usually associated with a contamination. So you might just guess. an identification then of a staph species that isn't going to specie it down to a staph aureus. You'll probably get a staph epi. So you're not really going to see an impact for the blood fill volumes. Obviously you know the quality of the result is only reflective of the quality of the sample. But you're not going to see an impact across any sensitivity or anything. Once an organism is there and it grows up and the bottle flags positive, you're going to capture it. Capture it if it's on that panel.
Jame:and I suppose the other when I'm thinking about causes of a false Transcription positive blood culture that are not, that then are culturing negative. Two things are, the patient is got a leukocytosis, and these the white blood cells are chewing up all the, producing all the CO2, and actually there's no infection there, in which case the BCID will test negative. And, Things that are rapidly growing and dying fast, like streptococci strep pneumo in particular. So I wonder that the strep pneumo, of course the bugs are all dead, and so they won't grow, but the DNA and RNA would still be in the sample. So would that test positive?
Kate:That will. Yeah. Yeah, so it is because it's genetic material. Yeah, so you will still get the positive on the PCR. You may not get the growth on your culture. Okay. That's that's interesting. That's a tick in the box for the BCID two I feel. we've talked about the bugs that can ENT and the resistance genes, and you seem to have targeted at the kind of beta lactam, beta laces, high yield ones associated with the six sort of pathogens that cause the lion's share of resistance in the world. We've talked on the podcast before that, acinetobacter, Pseudomonas, MRSA, Strep pneumoniae, E. coli and Klebsiella pneumoniae are causing most of the antimicrobial resistance, about two thirds, and then two thirds of that is beta lactam and quinolone resistance. Is there any quinolone resistance detection going on, or is it just concentrated around methicillin resistance? ESBL, CARBAPED, collistatin resistance. And VAC, yes. Okay. Yeah, so no Quinlivan resistance at the moment but I know our R& D teams are working away. So who knows what the future will hold.
Jame:Oh, well. A BCID3, no doubt. That's it. Yeah. fine. In terms of sensitivity and specificity, what did you get?
Kate:The overall, yeah, so the overall performance is over in the 95, 96 percent of sensitivity and specificity. So it is, you know, highly sensitive and specific. I think what really helps with this is because it is on a culture as opposed to a neat sample. There's quite a lot of organism there as well To true, How quickly do you get the result back? So just about 45 minutes. So this, to set it up is only a couple of minutes hands on. And then the test will run for about 45 minutes and then your result is there and ready to go.
Jame:I see. So it's not all that much slower than doing a gram stain. In the first place, which is maybe why some centers have said, okay, we're just going to do the BCID2 instead. exactly. Yeah, okay. And can you run a single sample at a time or do you have to wait and batch them through?
Kate:No, so it's random access the system itself. So you'll just need a slot for each pouch. So depending on the size of instrument, but no, you can absolutely just pop it in and start going depending on when the bottles come up.
Jame:Okay,
Kate:You're not having to wait. Yeah.
Jame:Are there any downsides to the BCID2, apart from cost that you can think of? Any issues implementing it in a lab that people might want to think about? It's quite a straightforward one. And I think, the benefits that you get in terms of that speed of results probably outweigh the cost, but there is like with any sample as it's PCR based. So it's only looking for what you tell it to look for. So I think, if you're implementing anything like that, that you have, that has to be in your mind just in case. the result isn't what you expected or you get a negative result and you're seeing something on a gram that it's not, like anything else, it's not a silver bullet. So I think when these are being implemented, obviously the laboratory will be trained around this and awareness around this and how to interpret anything that may come up, but anything in the lab can cause, an unexpected finding. So I think it's just that, because sometimes you see with BioFire for any of the panels it's so quick and easy and you do see these results coming out that it's. You know, we have to remember that it's not going to capture everything. It's only going to look for what we tell it to. So just to keep that in the mind. But other than that, we've seen it perform really well. We've seen labs implemented with non microstaff with microstaff in terms of how easy it is. So yeah. that's the advantage of the BioFire platform is that a lot of the variants has been taken out of it. And that's why it's popular, respiratory BioFire and now this as well. Who's it, been approved by, for use by the FDA, the EMA, whoever needs to approve it? Yeah, so it's fully approved. It's FDA approved. It's IVD or I'll have to check that which one. Yeah, but it's absolutely approved across the board. We obviously have a very strict registration here for the UK and for Ireland for the EU as well. So it's it's approved across the board And it's being used in the UK at the moment.
Kate:Yes. Yeah. Yeah. So it has. Yeah. It's news in a number of sites. Actually we've seen this being implemented now in some kind of hub and spoke models Which is bringing micro to non micro labs which is really interesting. I'm looking forward to see how that develops for certain sites. I think what's really nice about the BCID2 is actually, if you think about a gram stain, I mean, I was in a lab for 15 years and it's the very, You basics of micro but it can take quite a lot of training to get people competent and comfortable to report on them. And if people are on antibiotics and the bugs do weird and wonderful things and look unusual on a gram stain to actually have somebody trained To set up A-B-C-I-D two is very straightforward and you don't need that years of experience. So when you're talking about taking it out of a micro lab, it's much easier to let the instrument do the work for you and give you a nice report than have the pressure of that interpretation if you don't have the experience and skills in a lab.
Jame:Good. So that's the BCID 2. You may have access to that You may have access to that soon, but let's talk about the Vitek reveals. This is borrowing from Vitek's good name. But it's antimicrobial susceptibility testing device primarily, whereas the Vitek 2 is both ID and sensitivity testing. This just does sense testing. Is that right?
Kate:Yeah, that's right. Yeah. Yeah. So it is borrowing on Vitek's name. It's the latest addition to the family but it is bringing, I suppose this rapid AST to, to that Vitek family. Whereas as you've spoken about that Vitek is more around routine workflow.
Jame:Well let's talk about the reveal then. Does it stand for anything? Okay.
Kate:No, it doesn't. No. So it came, the name came it was originally developed by Specific Diagnostics. So it came to us as Reveal,
Jame:Ah, I see gotcha. Okay then, so the reveal, what is it and how does it work?
Kate:So the Vitek Reveal is, as you said, it's for rapid AST, so it's for rapid antimicrobial susceptibility. It's also done in a positive blood culture. So you're already that bit faster because you're not trying to grow up the organism. And what's really exciting about it is it's brand new technology in that it's it's a colorimetric sensor and it's detecting a color change based on the growth of the bacteria. So it will give a SENS result in about five and a half hours from a blood culture, from a positive blood culture. So instead of waiting, you know, overnight to get a sensitivity result, you're really talking about same day. depending on when the bottle comes up.
Jame:But I guess you'll have to know what organism it is because you will need to know the breakpoints to use. So, presumably you will have obtained that either through a Molditov or a Vita 2 ident or a BCID 2 ident, something like
Kate:Yeah. Yeah. So the BCID2 would obviously give you that result that bit faster. Some people will do a kind of a reduced incubation MALDI as well. But what's really nice is that you can actually get the test up and running. So if you have, for anyone who's in a lab, who sees a nice test. juicy coliform on a gram as we'd call it. You can get it up and running and it'll run away and then it'll hold the interpretation until you put in your identification. So you could really work in tandem to your ID.
Jame:Okay then, so when you're, doing this, are you taking a sample of blood directly from positive culture, same as the BCID 2,
Kate:so you're taking it from the bottle directly from the bottle. So you can take, you only need 200 microliters for the BCID2. And then it's even a smaller volume. It's about 50 microliters for the reveal and just making up a dilution. Yeah. So you're really taking just small amounts.
Jame:And so when you make up your dilution what do you then do with it?
Kate:So what it does is it looks, the actual plate itself looks like a standard 96
Jame:well plate, yeah. I'm familiar to plenty of PhD people, so
Kate:yeah, so it's exactly like that. So we use like a special pipetter to load it into a plate like that and sit a sensor on top of which really for all intents and purposes looks like a little lid with little coloured dots on it. Seal it up and then pop it into the plate. to the instrument.
Jame:and in the wells are different sort of reagents or different concentrations of antibiotic
Kate:different concentrations of antibiotic. Yeah, so we'll have a positive control with no antibiotic and then spread across the remaining 95 wells, you'll have different concentrations of different antibiotics. And the sealing part is really important to seal that lid on because what it does is it makes sure that the sensors are just detecting growth or no growth in that individual. Well, so it's about assessing the growth in each well, as opposed to an overall picture, if that makes
Jame:Yeah, and so say the antibiotic targets the organism, presumably there'll be no growth, no color change, blah, blah, blah. If there is growth what's causing the color change? What are the bugs doing?
Kate:So it actually works off volatile organic compounds which was kind of new, I think, to the world of microbiology in terms of using them. When I did a look, it's more associated with like breath tests and that. So it's a normal release based on respiration. So the. Yes, the microorganisms release them. We release them as you're respiring. So that's what it's detecting. So it's more around the growth.
Jame:So this is so this is like the bacteria's poop and your sort of waste products and your the colorimetric analyte is binding to those volatile organic complements, creating color change. And that's what you're detecting.
Kate:Yes, yeah, in a very nice poop
Jame:Okay. No, I like that. Rainbow poop. Fantastic. Maybe that's maybe that's what you should have called this device. Right on. Okay. Okay. Yeah I can sort of get that. And then so that you've, when you've got growth you get this color change because of the volatile compounds reacting with whatever the reagent is that's in the in the well. And presumably you've got different wells for different concentrations that are mapped onto the MICs of various bugs. And yeah. And then, so once you get the iodine. You get the sensitivities. How long does this take this?
Kate:The actual colour change is mapped every 10 minutes. So what you'll see is if the organism is growing, they'll see that colour change that's so you can get some of those results in about three hours and the instrument will actually release them as they become available. So if you have the ID in, you'll get that in about three hours. The full run takes eight. But what we're seeing is an average of about five and a half hours. From kind of evaluation from real world use.
Jame:gotcha. So, but even eight hours is quicker than a other sensitivity testing method. So the Vitek 2 I have in my head 12 to 18, but I might be out of date
Kate:so the Vitek, actually the Vitek 2 can give you a result for some of the gram negatives in about six to eight hours. But I think because it's more generally used for standard workflow, it's usually given. The overnight, it fits into to a workflow. But yeah, certainly with the reveal and what's nice as well is that it's standardized. So it's not like doing just diffusion one where you're trying to be very strict on times and everything. The instrument will just do the work for you.
Jame:yeah, true enough, for the uninitiated, if you're doing sensitivities through the old fashioned way, which is you do an agar plate and you put some disks on, the time at which you measure the zones of inhibition around those disks really matters and can affect, particularly if they're on the cusp, the difference between sensitive and resistant. If there's growth up to the disk, it's fairly obvious, but yeah. Okay, then the. Reveal what can it do every organism that we've got, or is it again limited to intrabacteriales, important gram positives, and organisms like that.
Kate:so at the moment we have a gram negative panel. So that covers 10 gram negative. So again, looking at those most commonly isolated organisms
Jame:Does it do Pseudomonas?
Kate:it does do Pseudomonas. So it does Pseudomonas aeruginosa and Acinetobacter bomanii as well as well as the E. coli, Klebs, Citrobacter And Enterobacter cloacae as well.
Jame:So you're getting about 95 percent of all gram negative infections by concentrating on those two non fermenters and eight of the top, the top eight enterobacterialis.
Kate:Yeah, so trying to capture those as best as possible. We don't currently do the ground positives. Obviously it's in the pipeline, but I think if you sit it next to BCID2, if you're capturing your VREs or your MRSAs. With that, you're probably capturing another big cohort of potential resistance that you'd be concerned about. Whereas I think with the gram negatives, there's a bit more variability. as we said earlier, you captured the big five for the carbapenemases. We have the ESBL, but there's other things at play, which makes, I think the gram negative sends a little bit more. Difficult to predict. So it's nice to have No,
Jame:my next question is your BCID2 is identifying resistance mechanisms. Is the reveal just doing. sends a resistance to the bugs. It's not identifying the mechanism of resistance.
Kate:so it will give you I suppose it'll call it an ESBL or it'll call it a carbapenemase, but it's not giving you the mechanism
Jame:Yeah, but it's just saying it's meropenem R, so I'm calling it a carbapenemase produced, or a carbapenem resistant organism, or a carbapenem resistant, et cetera, et cetera. But it's not saying, yeah, and if it's third generation kephalosporin resistant, it's saying, well, this must be an ASBL or an APC. But it doesn't know any more than that. It's just inferring from the resistance profile.
Kate:Yes. Yeah. Yeah. So it'll give you that, that MIC and give you a category,
Jame:And how many antibiotics is it testing? Like, say for an E. coli, what is it actually pitting it against?
Kate:So it's covering quite a lot. I'm looking at it here. Do you want me to count them and ask me again?
Jame:Well yeah. How many is it covering? What are the what antibiotics is this going to test against if I were to put an E. coli into the machine?
Kate:Yeah. So it's it's testing over 25 antibiotics. So it's covering the, your first generation, ampicillin right up to artipenem Keftolazenteazobactam is on there. Keftazavi is on there.
Jame:What about the Trojan horse? Kephideropal.
Kate:No, it's not on there yet. I'm saying yes because I know the UCAS guidance is around broth microdilution for, so it's one of those
Jame:Yeah, it is. I don't know, I think once UCAST has advised broth microdilution, it's really difficult to walk it back. So, I mean, who knows if that'll ever get approved for maybe an e test or something like that. But yes, okay, fine, so it's from Keftazavi, Meropenem, Ertopenem, all the way down to the So that's a pretty wide spectrum of beta-lactams, quinolones, cotrimoxazole
Kate:yeah, so I'm just looking here. So yeah, so we've amication as Trinam is on there. Gent is on there. Cipro Tiggy Coltramoxel, Tobramycin. Cofox is there. I'd say that's more around
Jame:oxen. Yeah, that's probably for amnesty detection. Yeah. I mean, when I'm thinking about gram negative infection, I'm wanting to treat it with a beta lactam, a quinolone, cotrimoxazole, or an aminoglycoside, if I can. These are the four things I trust for serious infection. And so they're all represented there in that panel. And, tigacycline, we all know that it's, got its issues. But except for bacteremia and maybe also UTI, I think it's got its place as a reserve antibiotic, not as a as an everyday one, but it's good to have in your back pocket, I
Kate:yeah. I think what's nice about it, this is that, you have those hard hitters up there and you have those combination antimicrobials, but you also have, the more, the like ampicillin, if you could treat it with ampicillin, I know it was going to be effective rather than putting a patient on meropenem, then at least you're going to know that and do that confidently, When you talk about people with bloodstream infections and potential sepsis making sure that you can de escalate just as confidently as escalate, I think is an important point, something that sometimes the focus goes to escalation rather than
Jame:I suppose particularly if you're I don't know if you know about how people have been implementing this, but I suppose this is, I can see a role for the Vita reveal in situations where you need to know the sense as fast as possible, and that automatically leads me to think people in intensive care with sepsis and, being on the right antibiotic might be the difference between you. Life and death, they may already be on something broad spectrum if you only test against the new stuff, the cool stuff, the broad spectrum stuff, and you don't trust against, say, ampicillin or, amoxicillin. if you've got an E. coli that's sensitive to amoxicillin, you could well argue that should be the antibiotic that they're on. Penicillins are, beta lactams, and beta lactams are besta lactams. Yeah. Okay then. And in terms of the we've talked about the turnaround time have you compared this in terms of its ability to detect antimicrobial resistance in organisms against, say, the Vitek 2 and found it to be comparable? Or is there any, are there any sort of holes? Is it not as good at detecting It's not Coltrane moxizole resistance, to give an example, in E. coli compared to the Vitek etc.
Kate:No, I mean, it's performed really well when it's been compared to the standard of care. Again, over 95 percent in the essential agreement and category agreement. And what we've seen is in some of the sites who've looked at this, a really good comparison to their standard of care, be that just diffusion or by tech. So performing really well. Which is good.
Jame:Good. You got any data about how it compares against the Phoenix or the Microscan? Or is that too much of an opportunity for you to rinse your opponents?
Kate:I would never. No, we have no, I would never. No. So we have not in the UK but I know a European colleague is there is a paper due to be published that looked across across the board at looking at a couple of different options. So I don't have any data on it, But I'm expecting it to continue to perform well.
Jame:for the loyal listener the, there are three big antimicrobial susceptibility testing devices, BioMérieux, Vita2, Benton Dickinson's, Phoenix, and the Microscan, which I forget the company that is responsible for it, but anyway, those big three there are differences in sensitivity testing between them. They've each got individual holes where they're not as good compared to the reference standard. It's not specific to any one, all three are have sort of defects compared to the other two. So yeah, so interesting. So again, the BCID2 and the. Reveal may be coming to a lab near you soon. Anything else to say?
Kate:No, I just think it's really exciting that we have, the opportunity to bring these new technologies into labs. I think as a an ex lab rat myself who saw some of these come in, I think it's really exciting. Helps from the lab perspective and hopefully it helps you guys on wards get results that bit faster and Ultimately is going to help those patients in the bed, which is the goal overall
Jame:Yeah, I yeah, and particularly I'm on clinical service at the moment and I'm keenly aware that there are some situations where we are really just waiting for the sensitivities to come through and sometimes, there's a bit of a delay, sometimes there's a wait, just depending on when it initially flagged positive, et cetera. And that can be quite frustrating, to give you an example, somebody had an E. coli bloodstream infection and source unknown. And they were on Colmoxaclav, and this person was quite old. And that's fairly standard where I work to be on something like that. But. They were clinically well and I was tempted to oral switch them and I wanted to put them onto cotrimoxazole and the kind of pushback was, we don't know if it's sensitive to cotrimoxazole. And my argument was, we don't know it's sensitive to comoxaclav, which isn't quite true because they've symptomatically improved. The patient had no resistance data. There was no prior cultures or anything like that. And, but I would argue in that in, in that case that. Codrum is just as reasonable an option as as Colmox would be, and lower risk of C. diff diarrhea. And so we made the switch, but if I'd had the SENS in my hand, I wouldn't have had to have that discussion with the team. We've just been able to implement it right away. So getting that information into the hands of a clinician as quickly as possible, I think is an unalloyed good. And maybe the, reveal in time or technology comparable will replace the existing Vitek 2s and Phoenixes and micro scans of the world. So even if you don't, your lab doesn't adopt this for, cost reasons or workflow reasons right away, this technology may be coming into your clinical practice over the next few years. So one to watch out for.
Kate:Absolutely.
Jame:Kate, thank you very much for your time. No,