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Communicable takes on hot topics in infectious diseases and clinical microbiology. Hosted by the editors of CMI Communications, the open-access journal of ESCMID, the European Society of Clinical Microbiology & Infectious Diseases.
Communicable E59: Ask me anything – EUCAST
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[00:00:00]
Nav: Hello, and welcome back to Communicable, the podcast brought to you by CMI Communications, ESCMID's open access journal covering infectious diseases and clinical microbiology. My name is Navaneeth Narayanan. I am a clinical associate professor and infectious disease pharmacist at Rutgers University in New Jersey in the US, and an associate editor at CMI Comms.
I'm joined by my co-host, Thomas Tängden, fellow editor at CMI Comms. Thomas is a professor and senior consultant of infectious diseases at Uppsala in Sweden and is part of the expert group authoring ESCMID's treatment guidelines for MDR gram-negative infections.
Thomas: Hi, we're excited to welcome three experts guests today for a new episode series called Ask Me Anything.
This will be a mailbag episode where we have experts join us and answer questions from you. We're lucky to have the chairs and former chair of two major global antimicrobial susceptibility testing standards organization, [00:01:00] EUCAST and CLSI. Our first two guests are the current and former chair of EUCAST, Sören Gatermann and Christian Giske.
Sören is the current chair of EUCAST and head of medical microbiology at the Ruhr University in Bochum in Germany. He is also the head of the National Reference Center for Multidrug-Resistant Bacteria in Germany and the chair of the National AST Committee for Germany. Christian is the head of the AMR and Hospital Acquired Infections section at the European Center for Disease Prevention and Control, ECDC.
He served as chair of EUCAST between 2016 and 2024, and immediate past chair from 2024 to 2026. He is also professor of clinical bacteriology and senior consultant physician at the Karolinska Institute in Sweden. Welcome both of you.
Sören: Yeah. I'm Sören Gatermann. Hi to everybody.
Very nice to be here.
Christian: Yes, pleasure to be here. Thank you.
Nav: And our final guest is Professor Amy Mathers. Amy's bit of my boss I'm gonna indulge a bit on, [00:02:00] introducing her. I think Amy's just one of my most favorite people. she's a really brilliant physician, microbiologist, researcher, lab director person, that I truly enjoy working with through CLSI.
right now she serves as the chair of the CLSI Antimicrobial Susceptibility Testing Subcommittee. She's a professor of medicine and pathology and the associate director of clinical microbiology at the University of Virginia in the United States, and she was also formerly the medical director of antimicrobial stewardship at the University of Virginia as well.
And lastly, she serves on the panel for a very well-known guidance, the IDSA guidance on the treatment of antimicrobial-resistant Gram-negative infections. Welcome, Amy. It's so nice to have you.
Amy: Thank you so much. I'm excited to be here, Nav, Thomas, Christian, and Sören.
Nav: So as our listeners know, we get to know each other a little bit with the, break the ice question so Thomas, what was your either favorite movie, TV show, or book as a kid? Not your sophisticated stuff now as an adult, but as a kid what did you enjoy?
Thomas: [00:03:00] it didn't change, Nav. It's the same now. I was very open-minded. I would say anything that involved action I would enjoy, like Batman or Superman, anything like that.
What about you, Nav?
Nav: I'm right on the money with that as well. I truly enjoyed, Teenage Mutant Ninja Turtles, the cartoon, when I was little, so much so that I would watch it and because you weren't streaming it, I would cry after it was done 'cause I wanted to watch more. So my kids have no idea what it means for it to just come once a week and then go away, Amy, what about you?
Amy: I grew up in a little bit of a Dungeons & Dragons household, so I'm a big fan of The Hobbit or Lord of the Rings, but still action.
Nav: It's a bit of a theme here so far. Let's see. Sören, what about you?
Sören: It's a little bit different. I had to look this up again. It is actually a book series, that I liked as a kid, and it's called The Forester's Lodge.
v-very interesting. it's a bit about biology, so maybe that's why I'm a mycologist today. It's
Thomas: a good starting point. what [00:04:00] about you, Kristian?
Christian: Actually, I was a great fan of, Twin Peaks, and I even, re-seen it. I was such a fan that I even considered, what it would take to become a naturalized, US citizen so I could become an FBI agent.
So I was very inspired by Agent Cooper, including his, hairstyle and everything and, ~uh,~ I was all into that. And that also led me into, a lifelong relation to David Lynch as well.
Amy: Christian, fun fact, I live in David Lynch's old house in Charlottesville, Virginia, so you have to come visit me.
Fantastic. That would
Nav: enlighten me. Thank you.
,
Nav: I think Christian's gonna make you an offer, Amy, now for your house, wow, very cool.
All right. Thank you all. we did solicit questions as Thomas said, from our listeners, from just members out in the world. but before we get into that , if you can from both the EUCAST and CLSI perspective, give us a brief overview of how it's organized.
Who are the members, that are involved with the organizations, [00:05:00] and how you come to a decision for setting breakpoints and these susceptibility testing standards.
Sören: We have a steering committee, at EUCAST with, people interested in antimicrobial susceptibility testing and antibiotic usage. and, these people come from, all over Europe. then we have two temporary positions which are just offered on a two years term for people from other places in the world, from other NACs.
So we have, 13 people total in our steering committee, and this, is a small group if I compare this to CLSI, for instance. But we also have other subcommittees like AFST for fungal susceptibility testing, AMST for mycobacteria we also have, ~uh, ~VETCAST. The financing is done via ECDC, and this is why Christian is here today, of course.
he [00:06:00] gives the money, that was joking. And by ESCMID and, So we are a pretty small group and, we have a lot of work to do. that is quite true. But anything to add from your side, Christian? Because Christian is the former chair and, he has chaired EUCAST for so long, he should be knowing every intricacy that's within EUCAST.
Christian: I think you covered it well, Sören. I think could, emphasize that we also have this, network of, National Antimicrobial Susceptibility Testing committees, the NAST, as they are called, and they also form, a general committee which meets, once per year. so additionally, we use the countries quite a lot for, the public consultations, to get their views on specific issues. And also even the sub-committees have this same structure with, a general committee.
So is like an overarching, structure all the related committees.
Sören: and of course, setting of breakpoints is a very complex thing, and , [00:07:00] we of course consider experimental data, which is also PK/PD, which comes from experiments with animals and, this gives you an idea where, a cutoff could be set.
then of course we want validation during clinical studies. And, I think this is very similar to CLSI
Amy: So, the same but different, I would say for CLSI. CLSI is a standards development organization, much like EUCAST, and, it has a large footprint in lab medicine as a standard development organization, even though we're gonna just talk about susceptibility testing today. CLSI writ large is a volunteer-led organization, so we don't get paid for all the work that we do.
We just, show up to do it, because it's a lot of fun. And on that note, we're always looking for more volunteers that are interested in helping us set breakpoints. and I would say that we are looking to do stuff for the United States, but also [00:08:00] internationally. Technically, from the susceptibility testing committee, we meet yearly in the United States somewhere.
and we have working groups where the work gets done. All meetings are open to the public, minutes are publicly posted, after the meeting. We also use the same group of people, ID physicians, microbiologists, pharmacists, both clinical and research, and, take consultation from a lot of different opinions.
Representatives are from the professions, government, and then we also have industry representatives from both pharma and, the diagnostic companies that make susceptibility testing platforms participate and weigh in and help us, understand the impacts of the decisions that we make. We do have in place pretty strict conflict of interest about who can vote and who can't, on various topics.
I would say just again, as a susceptibility breakpoint, we also weigh the same things, the PK/PD, the clinical micro, the bug, the type of infection, all [00:09:00] into how we decide how to set a breakpoint. The structure's slightly different in that we'll have ad hoc working groups that will take on a very, niche topic, maybe a specific agent or a specific bug, and what agents to test it against and that's called an ad hoc working group.
We take people from all over that have expertise, whether they're involved in CLSI and ask them to help us out to come to the best decision, and then that answers up to depending on the topic, a methods working group or a breakpoint working group or a texts and tables issue. And then those all answer and everything gets voted on at the level of the, antimicrobial susceptibility testing committee or subcommittee, and then gets published annually in the M100.
as, Amy pointed out, , the meetings are open, which is, different from what EUCAST has. And just to emphasize that, the part which partly corresponds to this is the public consultation system in EUCAST, but it's not like a [00:10:00] direct democracy where you can, , get, your comment and the response immediately.
Christian: But, at least it's a possibility with all major decisions, that there is a public consultation, and it's like a forced peer review process. So there will be a response to all the posted comments . So that's, the way of interacting directly in addition to the organization also, offering basically, possibility to contact by email or to comment on various issues.
it's a different way of organizing the interaction with the public, so to speak.
Thomas: Okay. That's a nice brief description about your organizations
Let's move to the unfiltered questions from the mailbag. the first question is, The more we lower or remove breakpoints, are you worried that we are at a place where there's no effective drugs? What do you say to people who say, ' I've effectively treated patients with this for years.'" And there are some examples here, like gentamicin for Pseudomonas infections, oral cephalosporins for [00:11:00] gram-negative resistant bloodstream infections,
What's your comment on this?
Sören: neither CLSI nor ma- make drugs ineffective. they just are effective or they are not effective and, It appears to me that the clinical experience in using some of these drugs are in situations where, it is not absolutely clear that there is a really serious infection going on.
The bug you found may relate to colonization and then if you treat colonization with some drug, you may see, something happening or not, and the patient gets better, not because of the drug, but in spite of it. , So I think, both organization try to find evidence for the drug that can be used if the drug can be used in a certain situation, and then we require [00:12:00] that the diagnosis of the condition is according to the current standards.
And, I think this must be taken into account, and this is what I ask all the people who tell me you have removed the drug." and they tell me that it has always been working, then I ask them, "Do you have really the MIC versus outcome correlation?"
They don't usually. Do you have the data that in these cases the patients really had an infection? They usually do not have the data and, then, try to explain that the breakpoints should also be valid for real severe infections, and this is what we are looking for.
And I think both organizations are not convinced that gentamicin as monotherapy will work in pseudomonas. There's enough data to show that it doesn't and, the [00:13:00] same is true for other examples you gave.
Christian: I think Sören raises here several of the important, issues, and also to stress this issue, which is sometimes misunderstood, that we don't consider clinical data. We do, but we have to relate clinical data to, as Sören pointed out, MICs.
We need to know does the susceptibility testing mean anything for the clinical outcome. Not only if the, clinical outcome appears to be favorable, but also if it is in fact related to, some kind susceptibility level. So quite clear. I think in addition to the points that were made, there is also the issue that sometimes people use something in combination therapy, and then we don't really know what's happening and what is the active component, et cetera.
So , I think over the years, since many of us have also been working, in clinical labs, we have been also very much, thinking about the antimicrobial stewardship [00:14:00] implications. We try to save some drugs that were in fact not really making the cut in terms of the susceptibility like colistin, like aminoglycosides, for, systemic therapy, non-UTI essentially.
And I think the way we did it was we introduced the bracketed breakpoints, which was to, suggest that there is a caveat. You need to use it in combination if you want to be successful, when using it. You should avoid using it in monotherapy. I think this, was, an attempt to do something along these lines because clearly, of course, it's not like we are dismissing drugs for fun.
I think we are all finding it, particularly painful with some of the drugs to dismiss them when we know that there is a great demand for them, et cetera. But sometimes this is very tricky when you see that it doesn't add up, at least not for systemic, therapy in monotherapy. And then I think we have, to weigh in the patient [00:15:00] safety dimensions as even more important, and we need to think about can we still convey some useful information about susceptibility, but still respecting that there is a caveat to the statement.
The laboratory cannot simply promise too much. That comes down to this feeling that, what we are stating actually means something. We believe that what we are measuring actually has a predictive value.
Yeah. I would agree with all of that. I would also say that, you know- New drugs are not coming fast enough, and salvaging old drugs and thinking about the way and the context in which they get used, which is something Christian just mentioned.
people aren't giving colistin for the worried well probably at this point, but they are giving it for severe infections when there's nothing else to give. And I think we all felt somewhat uncomfortable knowing that the therapeutic window on colistin is largely closed. So we all handled it actually [00:16:00] the same or slightly different.
Amy: You can't really achieve colistin killing by itself even at high dose, but there is a value potentially in testing it in that if it's very high, it's very unlikely to be effective in any way, so it's just toxicity. So is there a way to parse and communicate to physicians who are interpreting these or labs who are putting the results out, caveats around the breakpoint?
And I think that's what we've really been doing. And then some of the data just looks so uncertain or so unlikely to actually have and Pseudomonas, which was mentioned , and there's other alternative agents that maybe we can just say, "You know what? We should convey to people that is probably not a good idea, even in combination in most settings."
Systemically, it's not gonna help your patient, and it could do harm. And so eliminating that breakpoint. But one breakpoint that, [00:17:00] I mean you and I, Nav, had tons of anxiety and, reflux over was amox-clav. Amoxicillin/clavulanic acid, the only, available form of that drug in the US is oral.
And so I don't think that people are coming in with septic shock and getting oral amox-clav. And so we felt like trying to salvage that for end of therapy, that there was enough data in clinical trials showing that might have a role, that was probably worth salvaging with footnoting.
Don't use this for septic shock, but potentially it has a role in mop-up therapy. Or Christian pointed out, Stenotrophomonas, for example, and levofloxacin. I would not give that drug alone because of a whole bunch of caveats, Steno quickly becomes resistant on therapy, a whole host of different issues.
And so we put a caveat in consider for combination therapy and hoping that [00:18:00] some of this gets conveyed from the microlab to the clinician, as a way to try to salvage some of these drugs and the way that they're actually being used in modern medicine. And so I think it's nuanced, but we've all been involved in killing off breakpoints, and it doesn't feel good.
And , I think the thing I hear the most about as chair of this committee is the Burkholderia. we are regrouping and trying to come up with a different approach to potentially evaluating that bug and what agents might be effective to help patients who get, say, a contaminated product bacteraemia.
Christian: So if I may briefly add to this, it's an excellent summary, Amy. when we start questioning some of the old breakpoints, like for instance, colistin, I think quite oftentimes we have this, ~uh,~ high-income country perspective, and many of us are also involved in different, writing treatment guidelines and other things.
And it's obvious to us that people wouldn't want to use colistin in [00:19:00] case this is a more severe infection, or they would prefer, for instance, to use some of the, novel agents. But sometimes if we don't have these caveats in the tables, then in many low and medium income settings, people would not make a bigger effort to, obtain the novel agents because they would say we have colistin.
That's our backbone. We continue to use it. it can be reported as susceptible." So we need also to nudge this development, and to take into account that the patient safety must apply everywhere and for all patients and that, even in areas where there might be less knowledge about treatment guidelines and other aspects, we also have a responsibility to do something.
And to me, that part is quite important and I realize still that there are so many countries in the world where the, carbapenemase-producing, organisms are treated with colistin. And that's really a concern and something that we need to [00:20:00] improve, by how we, communicate, in the breakpoint tables, but also, in other settings.
Sören: is not only true for low and middle-income countries but also for high-income countries, that in some places, people have just learned that colistin exists, and then they are taking that for each and every infection with a carbapenemase-positive strain.
it is really important to make them aware of the fact that there are better drugs even in high-income countries. This is necessary.
Amy: Yeah. , My philosophy a little bit is if the lab doesn't test it, the clinician doesn't think about it. Generally, of course, that's not true in a, well-funded academic medical center.
But, I think that testing bugs against newer agents is really critical to get it on the radar of the treating physician. And so that's part of the mission.
Nav: . Thank you all. that adds a lot of, helpful [00:21:00] context. along the lines of, looking at breakpoint reassessment the procedures for that, maybe we can start with you, Amy. why does it take so long to update breakpoints for older drugs? When a newer drug comes out, in many instances, CLSI breakpoints shortly follow, FDA approval in the US. but obviously for older drugs, the reassessment of breakpoints, can take quite a bit of time.
So why is that, Dr. Mathers? can you give us some insight?
Amy: We're a volunteer-led organization, I'll start with that. And so we are trying to prioritize. We have a rubric for when to evaluate a breakpoint. and if there's new emerging resistance that's noted so that the breakpoint needs to be reassessed, or most importantly, if there's clinical outcome data that's showing that the breakpoint might be wrong, I think that takes the highest priority.
So that's why we reevaluated piperacillin-tazobactam for both Enterobacterales and Pseudomonas recently. and so I think it's a clinical prioritization. [00:22:00] We, for example, reevaluated all the Stenotrophomonas breakpoints recently, and that was because there's more Steno being seen in the United States than there was, several years ago, and the same for Acinetobacter.
And so it just takes a long process, and then the problem is there's no new data. Nobody's doing a clinical trial, on levofloxacin and Stenotrophomonas, and so we're going back to old data or back to the amoxicillin-clavulonate, right? Those data were mostly from the '70s, '80s and some in the '90s.
But it's old clinical trial data, and it's less than perfect, and it was before modern-day PK/PDs so you're trying to stitch together this kind of like convoluted evaluation to come up with what your best guess is. and it's definitely sausage making, when you're looking at old breakpoints, if nobody's done anything sort of modern day.
So those are some of the reasons why I would say the aminoglycosides got recently evaluated because a new kid came on the block, plazomicin. And so [00:23:00] we evaluated it with modern techniques and, that made it look like tobramycin was really great. but the issue was is tobramycin was evaluated by the old rule.
So we took a modern-day lens to it. And so some of those things prompt it but it just takes a lot of volunteer time and getting through the literature and pulling it all together and coming up with what you think is your best guess Maybe it takes so long 'cause I talk for a really long time
Nav: No, that, that's perfect, Amy. Thank you. what about you guys EUCAST? I'm sure you've heard this as well.
Sören: Yes, we can subscribe to everything Amy has said. this is absolutely true. Try to find some real good clinical data on cefazolin, for instance. you'll end up with very old
Let me call that reports. These aren't trials, what we would call trials today. these are just reports, and they typically lack the [00:24:00] correlation between MIC and outcome, because at that time they only said it was susceptible and we took it, and then it was fine." And if you look into the publication, you won't find what susceptible meant at that time.
so it is really hard to find some data you could base a breakpoint on. so that sometimes I think the same happens in CLSI, but sometimes you are, left with breakpoints that are just based on tradition, not on real data. And if we have those breakpoints that are based on tradition, tends to take the approach that we set the breakpoints to the ECOFF.
If we really believe that the drug can be used against this bug, then we would set the breakpoint to the ECOFF saying that it becomes less likely that it will [00:25:00] work if there's a resistance mechanism, meaning that the MIC is above the ECOFF. this is why we sometimes go to the ECOFF which then seems for people that we take away the breakpoint for many organisms, has happened recently with co-trimoxazole and actually there was no man's land between the, ECOFF and the real resistant ones.
Sören: And if there are very few isolates, we can't take away the drug from too many patients because there are very few infections with strains in that region and we can't increase the resistance rate too much Because there are no isolates, so that won't change anything. this is why sometimes there may be these big changes or perceived big [00:26:00] changes which just don't change anything indeed.
But this is about the old drugs and how EUCAST then modifies or revises breakpoints
Christian: historically, we still revised many breakpoints for old agents. And in a way, you could say that the old agents group in... you can group them in many ways, obviously, but at least one of the ways of grouping them is those where people have bothered about, and succeeded in generating, somehow some PK/PD data, and it has been, a little bit more actively developed.
And then you have others, such as, macrolides or trimethoprim and trimethoprim sulfa, as Sören just mentioned, which I think is a great example of the tradition-based breakpoints, where there has not really been any such, data. and of course, it is painful to reopen sometimes, old agents because you know you're not going to find anything.
I was part of the CLSI working [00:27:00] group working on amoxicillin and amoxicillin, clavulanic acid, and I'm still so impressed by all of the work that, Paul Edelstein did with this, and it was really an heroic effort to identify information. But it's so hard to find any useful, clinical data with the old agents, and studies were so heterogeneous as said, not related to MICs or exposure.
So it's highly difficult to work on those. But what I think is a little bit astonishing still is that, in the case of trimethoprim and trimethoprim sulfa, although, as Sören pointed out, almost no strains were in that area between, the old breakpoint and the new breakpoint, which was ECOFF-based, there was still a reflex to feel that we had taken away something and we had reduced the stewardship flexibility, which was actually untrue.
And we even described that this was the case, that it would not have a major implication on [00:28:00] susceptibility reporting. It would, , remove some scenarios where, there was a discord between trimethoprim and trimethoprim sulfa. It would also, resolve, some problems of logic and our feeling that it was a very unsubstantiated breakpoint.
but regardless of whether this actually had a very limited, impact on the resistance levels, it was still felt as, we were doing something, which was not good for stewardship. So I think it also illustrates that, When you do these processes, it is really important maybe even to start with that message that this is not going to have a great, impact on stewardship.
and that message might have to be repeated a couple of times. But of course, even if it has an impact, one has to be very transparent and say that, "Yes, this will, impact so and but it's still considered necessary for patient safety reasons or whatever, ~uh,~ could be." So in that regard, we [00:29:00] could maybe, improve how it's communicated.
But certainly revising breakpoints for all agents is very painful, and you have to invest lots of time looking for something which you know already from the outset that it will not be great. and it feels like not a great way of spending your time, to be honest.
And I think clear from this discussion is that the clinical breakpoints really make a big difference in clinical practice sometimes, and it raises a lot of questions from clinicians who are not themselves involved in clinical breakpoint setting, and that communication is also key in this.
that's a nice bridge to the following question, from Australia. it goes like this: "The I category has caused a lot of confusion among doctors in Australia, where most labs have switched over to the EUCAST in the past few years. I get regular calls from GPs saying that a particular organism has no available susceptible antibiotics, interpreting I as not susceptible, and usually this applies [00:30:00] to Pseudomonas with ciprofloxacin.
Thomas: Given that I actually mean susceptible dose dependent, why not change this label to SDD or similar, which would mean that you had three categories: S susceptible, SDD susceptible dose dependent, and R resistant. So this question is for EUCAST.
Sören: Yes, of course it's for EUCAST. It's quite clear.
Amy: We have SDD, just to be clear.
Sören: There are three categories. namely S susceptible with a standard dose, I susceptible with increased exposure, usually increased dose, and R resistant. So this is exactly what was asked for. the only difference is that, EUCAST has a different opinion on SDD. susceptible dose dependent relates to each and every breakpoint.
Each and every breakpoint is dose dependent. use a lower dose [00:31:00] than those that are licensed, and the bug will not react. So every susceptible breakpoint is based, on a specific dose. Then in some drugs there's a high licensed dose, and for this high dose there should be another breakpoint.
what I gather from, this question of course is that we could have used another letter instead of the I, to better explain this. And, this was, during Christian's time think there was, a long discussion within EUCAST and within the NACs, I think more than one consultation, on the I.
Sören: And then finally it was decided that we stick with the letter I mainly because some IT people felt that it would take them too long to use [00:32:00] another letter at this place. I can't understand this because everything is a byte, but, this is not my realm. this was the final reason to leave it with the letter I , and now I will reveal something quite interesting. this goes actually back to Sören's great loyalty of, not trying to throw me under the bus or anything when he should have done that because, in fact, Sören proposed to use the letter H, and he was quite, insisting on using the letter H for a very long time.
Christian: I think during a dinner in Ismaning outside of Munich, I finally managed to convince him that, there were so many practical implications, and we wanted these definitions to be possible to use instantly. and this was also one of the reasons why, this was, desirable to rebrand the I, but only partly rebranding the I because this had already been one of the meanings of I.
the problem was [00:33:00] that we took away the other meanings of I, which was the buffer category, part, in principle, and also the I which you use when you don't really, know, what to do and this type of thing, which is an R or maybe something which is, an R light, but anyhow, let's avoid it.
Christian: So that was where we were coming from, and we were trying to narrow down the meaning of the I, so we would be able to instantly use the I still in the way that it had gradually been used by our committee. I think one of the bad things that actually happened, which coincided with the introduction of the SIR, definitions was, ~uh, uh,~ a certain virus, that, ~uh, ~struck the world and, had people worried about completely different things.
And it was very difficult to get people at that time to engage in what would have been needed, which was quite broad informational campaigns, and that would have to be done [00:34:00] locally, nationally. It was impossible for the UK Steering Committee to do all of that. But think in retrospect, one could say that it's always difficult to first unlearn and then learn to use the same concept in a different way.
So I think in that sense, still insisting on a different letter might have been better. But meanwhile, as the years have gone by, many countries have actually succeeded quite well with this. But it has been necessary to do education and training to achieve it, and that's what we were hoping would happen.
But it didn't happen because all of the countries were occupied with other things, and I think this is also one of the main reasons why it utterly failed. But going forward, I would, certainly advocate ignoring the IT problems and maybe going for a different letter because it's very difficult to rebrand something.
So that's a long [00:35:00] story, but just to say that Sören was certainly not responsible for this, and he even advocated the other perspective, and, I would take the full responsibility for this one
Sören: thank you. Thank you, Priscilla . Thank you. And, to our EUCAST listeners out there EUCAST is planning, a worldwide survey for all the NACs, to get an impression how the perception of the new letter and how people are coping with the new meaning of the I in the different countries.
And I've heard different messages from different countries. Some of them are already using different designations which should not happen, because just imagine you use a Y instead of the I just to pick some letter, and another country uses an X, [00:36:00] then you will have problems in comparing those, statistics and surveillance studies from two different countries.
So we won't see H in Germany anytime
Sören: soon? Not one- No. Actually, the German NAC decided against having a national H just Germany. We discussed that, but the arguments were the same I just mentioned. we would have severe problems in, comparing our data with international data.
Amy: I think it's just a challenge across the board, right? How do you convey this complex information to a micro lab with varying levels of knowledge to get it over to a clinician with varying levels of knowledge about how to prescribe antibiotics? I think we're all challenged with it.
And I agree with Sören's comment that, like, all breakpoints are- Dose-dependent, right? They're all based on certain dosages. I [00:37:00] think we have used susceptible dose-dependent in cases where we haven't used it universally. I think Pseudomonas and ciprofloxacin is a great example, of susceptible dose-dependent.
But, we just haven't used it across the board. But in places where we're really stretching and you have to be giving high dose and we're hoping that it calls out looking at that bug/drug combination. And then, of course, the yeast folks are using that for all caprata, just to convey that if you are actually treating a systemic infection, a serious infection, you really need to be using high-dose fluconazole, for example.
So there are instances where we're liberalizing susceptible dose-dependent, but we also-- I haven't talked too much about this, but at CLSI, I also have the FDA. And for devices, to clear FDA, there is an issue around minor errors, that is a little more forgiving and not all bugs and drugs behave themselves.
And so EUCAST has really highlighted that issue with area of technical uncertainty, which I [00:38:00] think is helpful to call out. But we have lumped some of the technical uncertainty into the eye too when there's just issues where the bug and the drug might not completely behave at a very clean cutoff, MIC or disk zone.
Amy: And so that's also lumped in I, which makes it a little bit more forgiving for the diagnostic manufacturers to get product cleared or for us to come up with a disk zone that works for everybody because those become minor errors rather than major errors or very major errors, which is one of the issues that we really run into if we just have a susceptible and resistant, category.
So I think that's, another highlighted difference between the two groups, and how we use intermediate for both things. high dose and, is it intermediate? Is it susceptible? Is it resistant? It's not testing completely, clearly.
Sören: Yes. but the problem of course with that different meanings for one letter is that the recipient of the information does not know what [00:39:00] the laboratory meant.
Amy: That's correct. Agree with you, Soren. Like I think that is the problem, that those are meshed together. so Good communication between clinicians and labs. And I think- Yeah ... for most people, like the questioner said, intermediate means I ain't gonna use it. I don't know.
Right? That's what a lot of people think intermediate means. I need help if I'm gonna try to use it, and so that essentially means for the average practitioner, I'm probably not gonna use that drug. And I can see why that's been need for a lot of education, but not necessarily wrong approach.
Nav: Amy- Yeah. No, I- ... that's my favorite interpretation, I think. I equals I ain't using this, so that's- I think we should- It's the right letter. I think we should propose
Sören: that
Nav: to go into the M100 as the new definition for I. Yeah. Based on this. So it's
Sören: lovely.
Thomas: So I could be the new R, the next version.
Sören: Yeah.
Thomas: No, but I completely agree with everything you just said, from a stewardship perspective or someone who, works a lot with guidelines, I can [00:40:00] certainly, recognize what the questioner said about this being confusing to many people including ID specialists, where we've had some interpretation of results and also because it is continuously, it feels minor updates and suddenly you get an I where you used to get an S without knowing the background for it.
So it's definitely something we need to communicate about.
I think as Amy said, the one letter to summarize a whole bunch of complex information is just always gonna be hard. So the efforts much appreciated in trying to, simplify that and then make that useful for folks.
our next question, is directed technically to EUCAST, I would obviously, very much want Amy to chime in, from a CLSI perspective. So quote, " I would like to see EUCAST breakpoints informed by clinical trial data, not theoretical considerations, PK modeling, or animal models.
Nav: Just like clinical guidelines, if a breakpoint is based only on observational data or modeling, perhaps it can be [00:41:00] flagged as a weaker recommendation and lower level of evidence than if it is based on RCT data." What are your thoughts on that?
Sören: I would like to see clinical data for each and every breakpoint, but we do not have these clinical studies which really cover the whole range of MICs . This is impossible this is why we need the experimental data
Amy: Yes, we would all love RCT data. My first thought though was like, there's, ethics issues, right? Like enrolling somebody that you know has, an MIC that's probably not achievable based on the in vivo PK/PD or Monte Carlo is slightly ethically an issue.
And then also when new drugs come forward or old drugs come forward, especially new drugs, you might not have resistance mechanisms that you've identified and, it's very hard to get that outcome by MIC [00:42:00] data, in part because of the ethics. Like even when we looked at like these giant observational databases, and you have resistant isolates and you wanna look at what was the outcome by resistant isolates, most clinicians, once they find that the MIC is too high and it's testing resistant, will change therapy.
So you can't even really get observational data, and that's correct. That's what we should be doing. We shouldn't be offering, things that we think aren't gonna work to patients even if they're in a trial. I agree. I would love to see more data outcomes by MIC, but for severe infections especially, the ethics aren't great.
Christian: I think this is again a good opportunity to remind that everything which is done in the breakpoint committees, and I know both how CLSI is working since many years back and definitely EUCAST, is based on clinical data. So it is a misunderstanding, a very common one, that, the breakpoints are not based on clinical data.
And I would say it's one [00:43:00] of the most common misconceptions that we are only basing the breakpoints on MIC distributions and PK/PD. It's very clearly described in all SOPs that clinical data is what we are actually most interested in having. It's just that clinical data in relation to susceptibility levels or antimicrobial exposure, that's the part where it gets trickier with older agents.
basically some, quite easy conceptual rules, is that our first question, in terms of the clinical data is can the wild type, i.e., those bacterial strains without resistance mechanisms be treated? Is there clinical data to support that? if the answer to that is yes, then we know at least that the wild type is susceptible.
The difficulty is starting when you have the low-level, resistance or non-susceptibility or slightly a non-wild type, . so what happens there? Are they still [00:44:00] treatable? Can we achieve, high enough exposure so we can ignore this type?
Christian: And then comes a lot of things as Amy pointed out also. is it ethical to, try out something if we think theoretically at that MIC level you won't even reach that level in the plasma, even at the Cmax?
Is it then ethical to even try the agent? of course, for many non-severe infections, there is also a great contribution of the immune system, and there are plenty of factors that could, explain why someone would respond. So I would challenge those who say that we are not using clinical data to come up also with, more of a theoretical framework to actually, go into the details and start suggesting more creatively w-what we could do.
But I think certainly we need to consider all the time also can we have more innovative, design? [00:45:00] Can we design, the, non-RCTs in a better way so that they will be more informative? These are things we can clearly, think about and plenty of people could contribute to that, and I think all of us would definitely welcome that.
But please let's just kill the myth that the breakpoints are not based on clinical data because that's simply untrue. But the breakpoints cannot be based on non-informative or poor clinical data or heavily biased clinical trials. a badly designed clinical trial could be, in fact, quite misleading.
it's not like it's always better than nothing. And I think that's just important, also to consider that it's not like always if we have something which resembles clinical data despite biases, that's what we're going to go with. I think that's going to lead us in the wrong place.
Amy: Yeah, Christian, I totally agree, Our revisit of salmonella and lowering was the PKPD should work, the drug should [00:46:00] work. but we were seeing clinical failures within the realm of what was considered we're constantly looking for data that shows that an MIC breakpoint might not be correct in a particular clinical scenario, and taking that and ingesting that, and that is the largest motivator, I think, of revisiting breakpoints back to one of the other questions.
And in the setting of salmonella typhi, there were failures within the susceptible, and the community came forward with that data and it was-- it's been a great process to, to be able to revisit some of those breakpoints, and I think those are much more accurate and better breakpoints now.
And that has the added complex of that's an intracellular organism, so it has to get into a human cell to then get into the bacteria, so it's probably one of the issues that's going on there , in vitro data may not represent the actual infection. Trying to keep these breakpoints as living things is what think of them as,
Thomas: of course everyone wants clinical RCTs give robust evidence but, like you just pointed out, it's not even only about dosing, it's about [00:47:00] severity of illness, the site of infection, what tissue concentrations do you get where the bacteria reside?
So it's simply not realistic to have clinical data supporting everything. We need also these modeling techniques to figure out what would happen if we change dosing or what would happen if we consider protein binding or tissue penetration of this particular drug.
Sören: I completely agree with that, even in, some licensing studies for new drugs, people use or tend to use susceptible organisms, even with the very new drugs that are intended for usage in carbapenemase, positive organisms.
They still use, typical UTI organisms in their licensing studies, and the problem then is that we know that it will work in bugs without a resistance mechanism, but this is not where the, drugs are used, in clinical practice. They will be used in carbapenemase [00:48:00] positive strains. I always try to ask for studies that then use carbapenemase positive strains in these new drugs.
This has been done for some, but for others, it has not , and we still see cases, and these only give you the information that it will work on bugs you will never use this is why we need a framework of different methods or concepts to come to something we agree upon that this is a breakpoint And this includes clinical and theoretical data
Thomas: Thank you everyone. Here's a somewhat more detailed question from Dublin, so you need to pay attention now. we recently validated cefiderocol 30 microgram discs for 20 days as per EUCAST guidelines. We used the recommended quality control strains, and while all the E. coli results were within [00:49:00] the target range for that quality control organism, they were all at the upper end of that range.
This is something we never seen before with a validation, and we are wondering whether we can accept these results. Validation was performed by several different scientists exactly the same process, and we also decided to validate cefiderocol discs from another company to see how that performed.
The re- results were better with not as many falling in the upper range. Who wants to take on that question?
Amy: I'd take it on. It's a tricky drug to test. And my heart goes out to this group and appreciate the question because we had the same issue. And the problem is that iron chelation and the amount of iron in your, agar is probably having a huge impact. And we looked across three different brands of agar and found, different results even to the point where it was susceptible versus resistant.
And so looking at your QC organism and the [00:50:00] range in that QC, it's good that you looked at a second disk, but you might also look at a second agar. And I think the question just highlights a great lab that's paying great attention to the importance of quality control. , I think breakpoints get all the glamour and the shine, but actually good QC in the lab so that you know that your lab is putting out good quality results so that clinicians can take action is so central to clinical microbiology.
So I appreciate the question, and we had the same issue, and it's, that drug is very susceptible to varying concentrations of probably not just iron, but iron especially. And that's not necessarily regulated across media manufacturers. That's what we found was the issue and, have a publication on it.
Sören: When I saw that question of course, asked the EDL, the EUCAST Development Lab with Erica Matuschek, who's heading that lab, and she gave exactly the same answer. There's even a warning on the EUCAST homepage on [00:51:00] the combination of some agar with some disk.
I just wanted to point out that, in the EUCAST website, you can, ask those questions directly to the EUCAST system.
there on each and every page you have the opportunity to enter your questions . And if you pick the right page to ask the question, it will go directly to the people who are experts in the subject
Nav: Thank you both . I didn't realize that , you could ask those questions. I'm gonna send a lot of questions just your way, Soren,
so my next question, please behave yourselves, everyone, 'cause this is a question about two things. One, a discrepancy between CLSI and EUCAST, which I can't believe that exists. And two, it's about everybody's favorite drug, fosfomycin. Why are the breakpoints for fosfomycin so different between EUCAST , and CLSI? And I will preface this saying we do work very hard to try to harmonize when possible. Our goal is not to be different, for the sake [00:52:00] of being different.
Christian, you look like you're itching , to get in this.
Christian: Yes, I cannot wait to get started with this. No, but, I can tell you a little bit about the EUCAST process, which was also, among the last things that I was working on, towards the ends of my period as a chair. And I think what is important to understand and acknowledge fosfomycin is that there is such a vast, difference in activity of the drug versus E.
coli and versus, Klebsiella, Pseudomonas, Acinetobacter. It's not like a small difference. So the epidemiological cutoff value of E. coli is four, and for Klebsiella it's 128, for Pseudomonas and, Acinetobacter, I believe on top of my head it might even be 256, or maybe it was changed, but anyhow, it's much, much higher.
And, , I think gradually, when we started receiving, MIC data of slightly, better quality because this drug is also not uncomplicated to test, and you need to pay [00:53:00] attention to a number of factors. but we realized that this, general breakpoint at 32, which we had previously, did not really fit with E.
coli because, we did not have any either clinical or PKPD data to suggest that, if you have between the ECOFF of E. coli , and 32, that you can treat an E. coli at least with monotherapy, use of the drug. And there was no clinical, data to, corroborate this, whatsoever. So we felt that this was in itself a problem.
And obviously that breakpoint at 32 would totally bisect all of the other populations, so it would be an impossible value. So that's when we started considering, can we have a bracketed breakpoint for some of these, , to suggest that If it is, let's say, wild type to Klebsiella less than or equal to 128, you can use, fosfomycin in combination therapy.
However, we did not see any such signal [00:54:00] that, ~uh,~ whether it was 128 or 256, ~uh,~ mattered much. ~Uh, ~and , the data was also difficult to assess overall on whether it was useful to add fosfomycin or not. We are not in any place stating that it could not be theoretically useful or maybe in some strains it's, ~uh,~ it's greatly helpful in increasing the killing.
That's quite possible. So we were just saying that we don't believe that there is a lab test that can predict this, and that's why we ended up with this pretty radical, decision maybe that, ~uh,~ with E. coli we went with almost, ~uh,~ an ECOFF-based breakpoint, which was quite low. And for all of the others, it didn't really make much sense to have a breakpoint at one twenty-eight because we didn't think that would predict anything.
So I understand that many people previously like to have one breakpoint for fosfomycin at thirty-two, and then they would do their gradient test, which we, by the way, don't [00:55:00] know how well that works because, ~uh,~ that has not been, ~uh,~ also properly assessed and particularly not for tricky species like, ~uh,~ Klebsiella, Pseudomonas, Acinetobacter.
So I feel, ~uh,~ while ~uh,~ I could accept that it was a mistake, ~uh,~ to not, ~uh, uh,~ find a new letter for the I group, ~uh,~ I still feel that this decision made a lot of sense, ~uh, uh,~ from, ~uh, uh,~ lots of perspectives and ~uh,~ it was, ~uh, uh,~ consistent with the data. And you pointed out initially, Nav, I think there has been a strong tendency to work towards harmonization and to really, ~uh,~ see if we can, ~uh,~ agree on values And in my new role now, I have to say , I really even more appreciate having comparable data from different regions.
So when you're working with surveillance it makes a lot of sense to have, ~uh, ~data which is comparable. So there are plenty of, ~uh,~ advantages of this. But to my knowledge, maybe, ~uh,~ fosfomycin has not been assessed to that [00:56:00] degree ~uh,~ recently, ~uh,~ by CLSI. So maybe one of the reasons why there is a discrepancy is also because, ~uh,~ it has not been under a detailed process.
Amy: So Christian, we did look at it not that long ago, and you'll probably remember this. We, like you just said, only focused on E.
coli because it was urine, and we did not feel you could test accurately or it was meaningful to test any other species. I personally... this is not the, ~uh,~ views of the CLSI necessarily, but I personally think fosfomycin is like this ancient microbial warfare molecule, and that almost all bacteria on the planet have a FosA gene, so they're ready to like deal with fosfomycin 'cause it's this tiny little molecule.
And so yes, the MICs for many species are really high. E. coli does not have a FosA generally unless it gets it from a plasmid in Europe. So we felt like the colonies in the zone made a big difference in the E. coli that we were looking at, so we have that different reading interpretation guide where we pay attention to the colonies in the zone and you [00:57:00] guys don't.
Again, you guys had Pseudomonas at the time and had Klebsiella that you were having to deal with, which if anybody's ever tested a disc with fosfomycin and Kleb pneumo, you will see colonies in the zone because that FosA is variably expressed. I 100% agree with Christian. I don't know what to do with that clinically.
Does it mean anything? I don't know. But, ~uh,~ the test isn't helpful. You could probably use it maybe, but I don't know. The other issue is, we only had oral fosfomycin until, a few months ago, so now we are going to have to deal with it because, ~uh,~ FDA just approved IV fosfomycin for E.
coli and Kleb pneumo. So I don't know what we'll do, but we are probably going to be evaluating those breakpoints in 2027 and figuring out what in the world we're gonna do. And I agree with you, combination therapy, I don't know, how is this really gonna be used for severe infections outside of the urinary tract.
So we'll see. And its only indication is urinary tract ~uh,~ in the US. So we'll take a look at it and, ~uh,~ we will get back [00:58:00] to you. But I think it's a really good example of we looked at it for oral E. coli, E. faecalis only, while EUCAST had it for a lot more indications-
then they change-- You guys changed what you thought about it, now we get another swing at it.
So they're just coming at different times, and that's one of the reasons we might have differing breakpoints actually.
Christian: Yeah, thank you for the reminder about that, ~uh, ~Amy, because I was mostly referring now to systemic, ~uh- ~
use of Fosfomycin. But for certainly I do remember that for the oral, ~uh,~ fos- this is also in itself an interesting concept, right?
That, ~uh, uh, ~sometimes, ~uh, uh,~ when, ~uh,~ the agent has the same name, regardless of whether it's, ~uh, uh,~ oral compound or IV, it becomes like, ~uh,~ you believe that whatever is applying for one situation also applies for the other one. But, ~uh,~ like with amoxicillin, for instance, ~uh,~ it's completely different ballgame whether it's, ~uh, uh,~ oral or IV.
So ~uh, uh, ~it's not really helpful that they have the same name, ~uh,~ for the oral and the IV because it [00:59:00] confuses quite a lot, and I think fosfomycin is a good example of this. But let's see when this IV, ~uh,~ thing comes up and other indications because then you will also need to consider so what happens beyond E.
coli and, and Klebsiella if it's not only for uncomplicated UTI but for all these other indications. So I think, ~uh,~ maybe it still holds true that process is ahead of you, and it might end up, ~uh, ~if not at the same level, then at least, ~uh,~ you will run into some of these problems, ~uh,~ with the very high ECOFFs, I think.
Amy: Yeah. I think it's gonna be a hard drug.
Sören: That'll be hard and I think this is this is also why we set, ~uh, uh,~ the breakpoints for UTI only and E. coli only. And the study, the only study that used IV fosfomycin at that time for treatment of then had E.
coli mostly, and those E. coli had MIC of, ~uh,~ four or [01:00:00] below. And then we found it hard to set a breakpoint at 32. And this is why we ended up with a breakpoint where it is for fosfomycin. But I think it will be fun seeing how CLSI deals with
Nav: Thank you all. Yeah, it's nice.
Having EUCAST there at the CLSI meetings I think is always very collaborative and interesting to hear the perspectives. And so I think we'll hear a lot more about fossil mycin soon. So let's-- make the last few questions, ~uh,~ a little bit of a lightning round.
I will tell you These are hard questions, so let's see how you do and I will say e- everyone has mentioned, a paper here, a paper there.
We'll make sure that the links to the literature is in the show notes. There are some great references that many of you have written some phenomenal papers that I think will shed ~uh,~ some light on this.
A question here, in the context of, therapeutic drug monitoring for beta-lactams and other drugs as well, where MICs, are indexed to that exposure how important are MICs when antimicrobials [01:01:00] test, quote, "susceptible"?
Should this be considered in any way clinically or from a PK/PD perspective? ~Uh,~ Christian, I know you had a great paper on this ~uh, ~I'll turn it to you to take a first shot at this.
Christian: Yes. ~Uh, ~so there is this, ~uh,~ paper w- where Johan Matthon is the first, ~uh,~ author "Facts and fables about MIC." And I think the main concept of that one is, yes, the MIC could, ~uh,~ potentially matter, but only if it's, ~uh,~ above the epidemiological cutoff value. So there is no need to consider an MIC below the ECOFF because the granularity of the assay is not great and the reproducibility, so that will only lead you into problems.
But if you have, ~uh,~ let's say a corridor between the ECOFF and the S breakpoint, then you can still consider the MIC in that corridor. But what you need to pay attention to is always the variability of the assays. You will need to inflate your, ~uh,~ value at least with one dilution step, and potentially more if you're [01:02:00] pretty bad at MIC testing.
briefly now that In case someone needs a you can always provide them that, ~uh,~ even based on this diffusion, you can infer because you can say if it is below the ECOFF, you could give them the value which is the ECOFF, and they can use that in their TDM calculation.
And if the only thing you know is it's susceptible, then they can also consider using the, ~uh,~ S MIC breakpoint. And that's actually a pretty good way of, ~uh,~ providing someone with something which is helpful, not just stating to them that you cannot have an MIC value, but actually giving them something else instead that they can use in the TDM because it is going to be necessary to have some value to put in.
~Uh,~ oftentimes we did this in the hospital where I was previously working and I think that worked quite well for many and it was quite well accepted.
Thomas: Okay. S- ~uh,~ so we're gonna end with a fungal theme. ~Uh,~ first question is from Austria. How should rare yeast be correctly tested, interpreted, and [01:03:00] commented on? There's a EUCAST guidance document, but in my opinion, it isn't very informative or doesn't really offer any practical guidance.
Christian: Should I take this one, Sören? Because was after all I was after all, ~uh,~ a member of the, ~uh,~ AFST for a number of years until very recently, and I was also part of writing that document. And I think that if you go through it, ~uh,~ it actually provides you with some, ~uh,~ cutoff values that you can use, ~uh, ~in case you test, ~uh,~ rare combinations ~uh,~ yeast, ~uh,~ versus different, ~uh,~ agents, ~uh,~ that are typically ~uh,~ clinically relevant.
So I find it a little bit, ~uh,~ puzzling that this document is not seen as providing guidance because I think, ~uh,~ you may have some detailed comments or disagree with some of the values or something like this, but to say that it doesn't provide any guidance, I think is a bit harsh on the document. But what I would recommend still is that if someone has very specific views on this [01:04:00] document, I'm absolutely sure that the AFST subcommittee would be very happy to look at those comments,
~Uh, uh,~ but it certainly contains, ~uh,~ also cutoff values, ~uh,~ that are not supposed to be used for SIR classification, but still give some guidance on how to i-interpret the usability, usefulness of the drug
Amy: I would just comment. I agree that it is potentially helpful guidance. You're flying blind, and CLSI does have a antifungal susceptibility testing. But the rare yeast part of the question makes me a little bit anxious. I don't know which rare yeast they're referring to, and you just have to be very careful once you start testing really rare yeast and how you interpret those.
But I do think that the document that Christian's referenced can be quite informative as, I think, the CLSI trying to provide some guidance in this area where there's not a lot of known, of course, clinical outcomes or even PK/PD for these organisms, and we barely have ECOFFs for some of the rare yeasts.
So I do think [01:05:00] it's very challenging for clinicians and for patients that get infected with a rare species. But just be careful when you're testing them out in the real world that you really know what you're doing and how you're interpreting it, so you're not putting out incorrect information into the chart
Thomas: Okay, thank you. ~Uh,~ time for the last question. It's a good one regarding the absence of data and guidance. What should we do with fungal or bacterial organisms that do not have clinical breakpoints? Should we adapt breakpoints from other organisms or use ECOFFs, for example?
Amy: Yeah, so I think it dovetails onto the yeast question, especially rare yeast, right? So when you have very few organisms, I think you just have to be in consultation with the person who's taking the data from you if you're generating said data in the clinical microbiology lab. And data is not always better than no data, because if you're giving something misleading out of the lab that can be problematic. What I will say is for some of the rare organisms, we have two different documents at CLSI [01:06:00] and we tier our break points. Some of them are in the M100 And that's a standard.
We have a guideline document, an M45, where there's just a lot less data, and it is basically at the ECOFF, and a new version of that is coming out in January. And we've added some new organisms like, ~uh,~ Achromobacter, for example. And so where we don't have, much in way of how that organism is killed but have some ECOFFs that have been generated, and so trying to come up with how you would interpret that and give clinicians a reasonable estimate of what to do with that,
Sören: In EUCAST we have a document for bacteria that is called When There Are No Breakpoints and, ~uh,~ this is a description of what can be done if you have isolated an organism. you should first make sure that it is clinically relevant and then you have to do an MIC and go with that. part of the question was Could you go with [01:07:00] ECOFFs?
If you have an ECOFF, you are in a very good situation because you know that the organism can be tested by standard methods. And this makes it easy. If then the MIC you you found is within the wild type, you could say, "Okay, this is wild type." What you still have to find out is if the MIC is in a region where other breakpoints, other MIC of susceptible organisms can be found.
Then you could say, "Okay, maybe we can use this drug to treat that patient." The real problem comes if the last update of your MALDI-TOF spits out some, ~uh,~ unheard organism and then you have to find out if, ~uh,~ you can obtain data in the literature that are more or less reliable if not you have to live with it and then see what other people have done when they [01:08:00] treated this very uncommon organism. This, by the way, will be part of the new version of the guidance document when there are no breakpoints.
Nav: Thank you all for that insight. It's always fun when I have you guys, ~uh, ~to talk with around these ~uh,~ challenging issues. ~Uh, ~thank you so much for joining us for making the time today, for sharing your insights on these clinically standards from EUCAST and CLSI.
~Uh,~ and I just wanted to leave the last messages to you guys.
So
Sören: my message is just look at our website. There are frequent updates and subscribe to the EUCAST News. There's a newsletter and you are informed if something on the website except for typos, changes
Christian: So from my side, first of all, I'm very happy that, ~uh,~ although I have, ~uh, uh,~ retired from, ~uh, uh,~ the AST committee work, I'm still invited. So that's greatly appreciated that I'm still allowed to have some opinions [01:09:00] something which, ~uh,~ has been on my mind for a long time is that ~uh,~ it's good to have more people engaged in, ~uh,~ AST questions, and also more interaction between various stakeholders, ~uh, uh,~
and maybe also joint workshops to discuss more broadly about how to solve some of these, ~uh,~ challenges but sometimes when I've seen comments that come in public consultations, ~uh,~ they also tell me that n-not always have people, ~uh,~ read or tried to understand, ~uh, ~the basic concepts, ~uh,~ before having opinions about things.
And that's, of course, ~uh,~ very understandable that, ~uh, uh,~ you may have other things on your mind . But sometimes I feel also that we all can do better if we have a more, ~uh,~ humble and curious approach and try to understand, so how could they possibly have, ~uh,~ thought about this?
~Uh,~ could be, ~uh,~ rephrased into something more positive and more collaborative. So that would be something I would wish to see.
Amy: [01:10:00] Thanks for having us. This was a great discussion, and thanks for the great back and forth Thomas, and Soren and Christian.
It's been great to spend an hour with you. I would say that CLSI, we publish every year, so it's a little bit of a different cadence. But our documents are freely available now on the website, and please use them and stay informed. And if you are that uber interested person, we are always looking for volunteers and come participate we need your opinion.
We need your insight. We need to understand how these breakpoint changes are affecting everyone. So with that, thank you so much for your interest
Nav: . Thank you so much to our guests, ~uh,~ Sören Gaderman in Bochum, Germany, and Christian Jyske in Stockholm, Sweden, both from EUCAST, and Amy Mathers in Charlottesville, Virginia in the United States from CLSI.
And thank you for listening to Communicable, . This episode was hosted by Thomas Tängdén in Uppsala, Sweden, and Navaneeth Narayanan in New Brunswick, New Jersey, both associate editors at CMI [01:11:00] Comms, ESCMID's open access journal. It was edited by Angela Huttner, executive producer of Communicable.
Theme music was composed and conducted by Joseph McDade. Any literature we've discussed today can be found in the show notes. You can subscribe to Communicable wherever you get your podcasts or find it on ESCMID's website . Thank you for listening and helping CMI Comms and ESCMID move the conversation in ID and clinical microbiology further along.
Nav: Thank you guys. Christian, can you just say your last name for me? The proper way so I can try to be as true to your nature as possible.
Christian: It would be Jyske.
Nav: Jyske. Okay. I've heard Angela say it, and I'm like I need to be cool like Angela and say it as properly as possible, so all right.
~ ~