65. FIS highlights 1 - SNAP trial, AMR musical, S. aureus update, IPC in LMIC

Join Jame, Callum and Pals for a discussion on some highlights from FIS 2023: https://microbiologysociety.org/event/full-events-listing/federation-of-infection-societies-fis-conference.html

Mentioned in episode:

UCHL HLH protocol and referral details: https://www.uclh.nhs.uk/our-services/find-service/medical-specialties-1/hlh-service
SNAP trial: https://www.snaptrial.com.au/
SNAP trial email: snap-trial@unimelb.edu.au
SABATO (pre-print) https://www.medrxiv.org/content/10.1101/2023.07.03.23291932v1

RESISTANCE/The Mould that Changed the World: https://www.mouldthatchangedtheworld.com/

Transcript

0:00

Hi everyone, welcome to the Idiot's Podcast, that's infectious disease insight of two specialists. I'm James, that's Callum, and we're going to tell you everything you need to know about infectious disease. Soon may the editing come to discontinue the tase, oh son. One day when the CRP's done, we'll take our leave and go. The Federation of Infection Societies Conference is the largest UK hosted international infection conference. It is a must attend for anyone working in infection prevention and control, infectious diseases, clinical microbiology and biomedical science. This year, in 2023, the Microbiology Society hosted PHIS and they partnered with the Healthcare Infection Society, HIS, and the British Infection Association, the BIA, to develop the programme. Over three days, the programme was held in Edinburgh, Scotland, and this year, Jayme and I, Callum, were luckily able to attend with the support of the BIA. Whilst at the conference, we took the opportunity to interview some of the attendees at the conference to find out what take home messages they would have. And we're delighted to be able to share them with you today. Please excuse James voice, he was quite ill. I'm here with Dr. Anna Goodman to talk about the SNAP trial. Anna, how are you doing? I'm well, thank you very much. Enjoying this? Yeah, it's great. It's been amazing. I went to a particularly good session this morning on HLH, but we need to remember three things. Fever, ferritin, and falling counts, so something to take home with you from this meeting. Yeah. I really wanted to HLH one because we've seen a few cases in, in Nadosh Royal Infirmary and you know each time not really knowing a huge amount about what to do for it, but yeah. So they also directed us all to the UCLH have a guideline on their, on HLH, on their website that is available to anyone. And they have an MDT that people can refer to. Mm. I think we've used that. And in Sheffield as well. I didn't know they had a guideline though. I'll see if I can find that and put it in the show notes. But I, I wanted to bring you on because you are involved with the SNAP trial. And at FIS Dr. Cash presented the results of Sabato the last sort of big Staph aureus RCT that we've had. We'll be releasing a podcast episode on that later. But biggest trial. Ever in staff aureus, which is still ongoing and they're still recruiting is the snap trial. So what is the snap trial? So it's a staff aureus network platform and it's a global platform When you say it's ongoing and still recruiting. We're only just opening actually in the UK It's been live in many other countries in Australia, New Zealand Israel, Singapore, and Europe, the Netherlands have just opened, South Africa as well. So it's very much still opening and the graphs are getting steeper for the recruitment, which is exciting. They already have more than 1, 500 participants in the trial, and we're aiming for 7, 000. And the idea is to try different regimes. There are three different arms, and one of the arms has three parts to it. But essentially, to try and establish what the best treatments are for Staph aureus bacteremia. And what are the components of those arms? So the simplest is probably the adjunctive clindamycin arm. So that, in that, people who have Staph aureus bacteremia, early in their treatment, so you have to be within, 72 hours of your blood culture being positive are randomised to have clindamycin or not. It's open label, so it's on top of whatever treatments they're currently having, on top of whatever the home team's giving, and the idea is that it's not based on antibiotic susceptibilities, you're looking at the toxin. Potential antitoxin effect so five days of oral clindamycin or IV clindamycin, depending if you're on orals or IVs, on top of whatever you're giving. I anticipate many people at the beginning will be on IV. And then the second part, which ideally they go into at the same time, but it might be slightly later, is based on what their antibiotic backbone is, and that's based on what their antibiotic susceptibilities are. So that has to be available for that part. Where, if it's MRSA, they would have received vanco vancoadapto with or without kefazolin, and the test is to see if kefazolin can offer some synergy. If they have MSSA, traditional MSSA, but actually it has to include It excludes people who are penicillin susceptible, so it's MSSA but not those who are penicillin susceptible. Yes, but not PSSA, which I don't know about in your practice. I view it as very mythical. Well, it does exist. I mean, we don't test for it, but yeah, I'm sure it's out there somewhere. So, so in the MSSA arm, people get flucloxacillin or cafazolin. And it's looking at which of those two agents are... More effective, associating with lower mortality. It's interesting from Achim Kasch's talk yesterday He showed that 44 percent I think of the participants in his trial were on IV kefazolin So it's very much used as a first line drug in Europe in a way that I think in the UK We don't have that familiarity, but all the sites taking part in SNAP have it on formulary And then PSSA are the penicillin susceptible staph aureus. They're about 15 percent of the Methicillin susceptible group, so it certainly exists and the issue in many labs is that because they don't Report it and it then becomes difficult to establish But some some areas will will not release the report, but they know if it's penicillin susceptible or resistant Approximately based on the Vitek or automated methods to be in the PSSA arm you need to use manual methods that has to be to be certain that it's penicillin susceptible because we will then be randomizing to penicillin or fluoxacillin. So we want to be a hundred percent certain that that isolate is susceptible to penicillin if you're going to be entering someone into that arm. And is that a gradient test, like an e test, or is it just a standard agar plate with a penicillin disc? So it's a specific penicillin disc looking for specifically to be a hundred percent certain. We haven't mentioned at all. There's another whole part, which is the early oral switch. So when the patients get So you recruit the patients early in the hospital stay in the first, within the first 72 hours from their blood culture. But when they hit day 7 or day 14, you can then assess if potentially They would be able to be recruited to an early oral switch arm. The Day 7 arm is focusing on those people with perhaps a lower risk back, staph aureus bacteremia. It excludes those, for example, with a prosthetic, a prosthetic valve that you may wish to or endocarditis that you may wish to be certain that they receive 14 days of intravenous therapy. treatment. Yeah. And the day 14 it then has broader inclusion criteria. So people can be assessed at day seven and then reassessed at day 14, or they can just be assessed at one of those time points appropriate to their clinical scenario. I guess there would be getting a minimum of 28 days or, or, or more. So it still won't change their duration. You give the same duration you would normally give. It's merely focusing on whether that treatment's going to be intravenous or oral from that time point. Randomized and open label. So what's that randomized? And you would, the patient, the participants and yourself would know obviously what they're receiving. And what oral agents are you, or are you not specifying any and it's the person's choice, the clinician's choice? So it's designed to be a pragmatic trial. So it's, there's a table of recommendations. Particularly because someone, hopefully many of these people will already be in a backbone arm, so for example, they're on cafezolim, the clinician may want some guidance as to how to already step that down. So there is a guidance table, but the idea is it should fit with your usual practice and should be clinician driven decision making and prescribing. Sounds amazing. If people want to, you know, if people think about getting their center involved now that it's in the UK, how would they go about doing that? So we do have an email that's mrcctu. snap. I hope I've said that correctly or they can contact myself. Perfect. Dr. Goodman, thanks for coming on the show. Hello, it's Callum here, live at FIS again, 2023, and I'm joined by Dr. Megan Perry. Hello, hello, hello. Welcome to the podcast. Thank you. How is your phys going so far? I'm having a lovely time. Thank you. And what are some highlights or, or key learning points that you've, you've got gathered from the conference? I really enjoyed the he monk session about fungal infections. That was really very systematically. We went through all the different diagnostics and, and I enjoyed the kind of broad overview. I'm totally fascinated by PKPD and I always feel I should know more about it. So I have tremendous respect for Jane. We all do. We all do. And but there was a great debate about the pros and cons of personalized dosing. Mm-Hmm. in that session, and but it was quite pretty focused on critical care, and I would have liked to have talked a bit more about kind of community and antimicrobials, but I think maybe that's just far too far down the pathway. But I enjoyed the discussion of, like population based dosing so that we could maybe end up in a scenario where we're dosing not just on weight, but on more routinely on renal function and on protein levels and and That and I kind of like the idea from a stewardship perspective that if we make it a little bit more complicated to prescribe Antibiotics, then maybe people might make it might think a little bit harder. That's a bit cheeky, but James is smiling What do you think James? Agree, can you hear me Callum? The PKPD, it was, it was set up as a pro condomate, and it took me a while to realise that the guy who was pro was actually the pro guy because he was you know, commiting all these trials, the most recent of which has been the MERCI trial on meropenem extended infusion versus standard dosing in intensive care, which was negative with a one gram dose, so that's not exactly what we're doing these days, but it was at the time the trial was set up. And no difference in what I would call hard outcomes. I think the better evidence for PK PD dual salt atomization is in side effect reduction. So, if you think about the Horford nomogram for aminoglycosides. Moving from three times a day to one time a day, but keeping the dosage the same. That did no, made no difference to efficacy, but the side effects profile became much better. And I think that that is a much more convincing argument for using PKPD based dosing than Improving outcome by improving time over M. I. C. Because I think the evidence between target attainment and the patient are actually getting better is a lot shakier than we like to admit. I was going to say the other thing I thought came out of the session that was so interesting that even we had these two amazing experts, but there wasn't hardly any literature that was able to be cited about. What dose is the best dose to use to prevent the, or to try and decrease the emergence of antimicrobial resistance? And, and, and, when you start thinking about that... As a, you know, how to design those kind of studies is, is a bit overwhelming because all the different factors that would have to be taken into account, but I think that that's the next step within the PKPD kind of argument that will have a significant sway if we're going to change the way we use antibiotics. Yeah, yeah. And I also think that the advantage will only be really detectable in the seriously sick. I think that on the wards, I, I don't know that there is some magical dose that we would be able to give to the patient that would improve their outcome, I think intensive cares. The population that's most likely to benefit and they really talked about that. It's the intensive care, but right at the beginning, like, and that, you know, that, you know, they were just like, you've got to get it right within the first 24 to 40 hours. And then, and then after that, if you're kind of having to wait two days to kind of get your bug back and get your your actual TDM back, then, you know, it's, it's not going to be effective. So I think there's, yeah, there's different outcomes. So there's the. I guess the outcome of the, you know, the patient surviving and then there's the outcome of the side effects, and then there's the outcome of the, of AMR emergence. And all of those need to be taken into account as we go forward. But it was great. It was a really good session. Yeah. I liked it and I felt like they actually were arguing with each other, like it was properly pro con. Well, I'm sad to have missed that, and the problem with conferences in general is that there's just too much good stuff to do, isn't there? And one of the things that I'm going to miss this afternoon, which I'm very sad about, is your talk, Megan. So can you tell us a little bit about what exciting talk you're bringing to Fizz? So I'm going to be talking about a project that I've been working on now for seven years. And it's a project which is a musical about antibiotics and about antibiotic stewardship. And the idea came to me actually at a fizz in 2016 where I was watching. multiple stats about antimicrobial resistance and musing on the power of story versus stats and how we all love case reports because it's that kind of experiential learning. And I thought, well, story plus music within a musical, then we can really Maybe try and change people's hearts and minds in terms of their attitude towards antibiotics. And luckily we managed to persuade B Sec to, to fund us, and I managed to persuade a composer to write a musical about antibiotics, which wasn't the easiest part of things, but he is now... basically working full time on this musical because it's gone from being a kid's musical to a professional musical and next year we've got a I think six to eight week run in a theater off Broadway. Wow. I'm very excited. Wow. And it's been in the Edinburgh Fringe a couple of times, hasn't it? Yep. We've had two sell out runs in 2018 and 2022. Oh, you weren't going to bother to mention that, were you? Well, no, that was just a couple of sell out runs at the Edinburgh Fringe, don't mind me. Very much importantly want to say that I have not written this I have been like storyboarding and part of the kind of the development and I've had to kind of work through them, like the messaging that we really want to bring across but the words and the music and everything. And now we're brought on a new kind of award winning writer for the latest part of the script development. But the important thing I want to say about the Fringe productions is that we have a professional West End actors and actresses, and, but the course is all healthcare professionals and scientists. And I've had some of my colleagues here, Ian Lawrenson, who's a consultant microbiologist here in Lothian. has been part of it, Marcello Scopensini and many, many other very talented people have given up their time to come and perform in the chorus and, and be soldiers and doctors and patients and bacteria even. And they've, they've done a really beautiful job and made the musical as successful as it has been. Having seen it at the French bow fronts it was on and seeing both those colleagues there. It was very, very good. Jamie and I have some experience as being bacteria, but not in a musical, but only in art form. So on the podcast logo, that's what we are. Yeah. Not which, which bacteria we are, we won't reveal some artistic license has been taken with the Grammstein appearances. But yeah, thank you so much, Megan, for coming on and sharing some, some highlights and also a teaser. So what we'll try and do is get a link for the, for the musical. Is there a website that we can share? There is a website, a website, a website. Yeah, www. moldbuttchangedtheworld But, we're changing the name of the musical. Can you reveal that? Is that a secret? I will reveal it this afternoon, but I can reveal it now. It's going to be called Resist. But with a tagline of something to do with the kind of greatest invention of the 20th century, et cetera, and, you know, how it's changed, but that tagline has not been fully worked out yet. I feel a bit sad to say goodbye to them. Yeah. Well, for a good name is underneath the resistance. The more the change. Yeah, maybe. But you've got to imagine the Broadway lights. You know what? They might, might not, might cost a lot in lighting, but, and are you getting to go to, to Broadway to, to see it? I think I probably will. Damn. But I haven't fully decided. Well, we are the first to say Meghan Perry should get money to go to Broadway, to, to watch the musical that you've been heavily involved with and has had a big impact. Thank you very much, Callum. Thanks. Hello is Callum here again at Fizz 2023 Live. Joined by Dr. Simon Dur, consultant microbiologist. Well, Simon, you gave a talk yesterday that I attended and it was excellent. So what were you talking about? What were we hearing? Yeah, so the session was on updates of and management of staph aureus bacteremia and very good speakers there, including the, you know, the defendants of the sabbatical trial. So I followed that and it was looking at if there's anything that we can prevent healthcare associated staph aureus bacteremia and what's new in that field. So You know, there's a large majority of staph aureus that is either in hospital or people who have got staph aureus from in the community, but have had that healthcare association. And it's normally around 60 percent of staph aureus is there. So that's a huge patient population. People have looked at the kind of, I would say the easy or more established ones. So can you reduce kind of PVC associated staph aureus? Can you look at education of people, of healthcare workers hand hygiene, and those kind of three things have shown to reduce it, but that takes a lot of effort, a lot of continued effort, and actually when you look at surveillance programs, not much has changed overall. So can we take a different route, and can we look at other things that are maybe harder to prevent, and what would that look like, and what sort of patients would you want to Thanks. target for that intervention. Also, when we'd done our local study, we'd found that those with CBC or catheter related staph aureus bacteremia had a lot lower mortality or chance of metastatic disease. So actually, we'd argue, although somebody getting staph aureus bacteremia is bad, those are the less risk populations. So, perhaps you want to target a different population than those. And so you pose a question there. Do we have an answer to that question? So the answer to that question? Yeah. So we look to see, basically there's three categorizations of when you talk about staph aureus and healthcare, those, those are purely community. Those are purely hospital onset. And then there's the middle group, which is. Community Onset Healthcare Associated, and we looked at all those three different groups. So in the middle group, we found that actually, in that group, there was a higher proportion of those with skin and soft tissue infection, or with bone related staph aureus, and in the bone related group, they were associated with diabetes. So there's obviously a lot going on about how you, how you manage diabetic ulcers. So if you wanted to, that's even more of a reason to prevent infection in those groups. And then the skin and soft tissue infection as well. It's a bit obvious, but you, you, you said that you're more likely to have surgery in the last 30 days. So there's something about the, and the question was, and how do you prevent surgical related site infection? And whether you do things like looking at high risk procedures like your orthopedic or. Neurosurgery or Cardiothoracics and whether you do screening for Staph aureus and do decolonization pros and cons of that so maybe there's a Specific high risk population that you can target and do your intervention a bit better So that's that group, and the community onset group, actually, a lot of the sources are unknown. But there's an over representation of people who inject drugs as well, so that's all about, kind of community liaison with that population. And then for the hospital onset cases... Yeah, those are very difficult, actually, because most of the preventative measures have all been around line associated infections. And I think it's just, when it's not known, it's quite hard. So whether we just need to understand hospitals that are infections that are occurring in hospitals that aren't line related, how can we kind of understand that population a bit better? It was really interesting talk. And I guess what you're saying there to me sounds a bit like we know that infection prevention control is really important and staph aureus bacteremia is almost like the, the end point, isn't it? It's like down the stream. And then what we're looking at is actually the things at the very beginning preventing the, you know, diabetic ulcer, the, you know, the surgical wound infection, you know, what we see at the end of that is staph aureus bacteremia coming through and then that stuff about, you know, the unknown. Source patients. There was a talk on CT pet. Yeah Yeah Really interesting to say like actually just knowing where the source is is really important. Yeah. Yeah For sure. I know those are often the patients who are Hospital associated subs who had an unknown source had higher Transcript mortality than those who had like CBC related. So we probably just, you know, take the CBC out That's not to say that there's a population you have got lines that then develop complicated Saphorus bacteremia because that's obviously the risk is that you just ignore you think that they are low risk and maybe switch to orals But then you've actually got An underlying kind of metastatic SAB that's been undiagnosed. Yep. So, it's quite tricky isn't it when people, and then when you think about risk and when do you choose one treatment over the other? It was a great session on Saphiris Bacteremia. And thanks very much, Simon, for coming to, to share some of those sort of questions and potential answers. And, yeah, I think we're all, we're all excited to see what's next. Thanks very much, Simon. Hi, Callum and James. Ian Lawrenson here, consultant in Edinburgh. A few snippets of, of... Memories from FIS this year. It's been a great meeting of minds and old friends and more recent friends. This morning's, the Lowbury talk on Infection Prevention and Control was really inspiring from Professor Ali Granzy. Outlining the WHO approach and her history in that, looking at how we can prevent harms coming to our patients through healthcare associated infection, uh, and the global trends in that, and trying to prevent infection across the piece, not just in the high income, but also low income countries. Then there was a great talk by Thomas Williams on paediatric respiratory infection with the hits from invasive group A strep outlining the Paima to early this year With the resurgence of the M1 type, again, causing associated with empyema. And then there was an interesting vaccine talk on Klebsiella pneumonia, considering how we might address neonatal sepsis due to drug resistant Klebsiella pneumonia, and also... HAI in the older and more vulnerable groups, if a vaccine could be made, which is obviously a challenge in itself. And then, a number of great posters, but one I've just looked at suggested a quite a cool comment to put on to the results of urines with Staph aureus in them. Saying this can often be a contaminant, but also may be associated with severe infections. So, depending on the clinical setting to, to guide the interpretation management of this particular not uncommon result. Okay. And then yesterday, there was a great lecture on rabies by Mary Worrell. Fascinating about the vaccination programs and means to prevent and actually, but didn't say, and I went to the winter lecture of Edinburgh Infectious Diseases the night before on Monday evening for Professor Sarah Cleveland, and she was outlining how in fact, what we really needed was a strategy to vaccinate dogs to prevent human infection, but because of the lack of political leadership on this and perhaps the division of budgets between veterinary agricultural services and health, human health, that this wasn't being implemented in a systematic way globally, but yet it's highly cost effective. So that's a couple of thoughts on the various, some of the couple of talks that I've been on. Thanks very much for your podcast and carry on the good work. Bye. Thank you for listening to the Idiots podcast, the UK's premier infectious disease podcast. We are supported by the British Infection Association, but they do not have creative control over the episode content, so please don't blame them if we get something wrong. Questions, comments, suggestions, why don't you send them in to idiotspodcasting at gmail. com. Have a five star review in your pocket? Calum and I would love to have it. Please drop it in your podcast player of choice. We tweet at idiots underscore pod, and if you want to donate to support the show, there's a link to do so in the description. But until next time, I'm James, I'm Calum. See you then. Now that the episode's done, we hope you learned and had lots of fun. So go forth and treat people with some of what you now know.