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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.
[00:00:00]
Josh: Hello and welcome back to Communicable the podcast, brought to you by CMI communications, ed's Open Access Journal, covering infectious diseases and clinical microbiology. My name is Josh Davis. I'm an infectious diseases physician and clinical trialist based in Newcastle in Australia, and also an associate editor on CMI communications.
today I'm joined by my fellow editor Emily McDonald and our guest Steven Tong, , and I'll let them introduce themselves. Emily.
Emily: Hi everybody. Emily McDonald. I am an internist, in, Montreal Canada. I'm a clinical trialist as well, and I'm also an associate editor on CMI communications. over to you Steve.
Steve: Hi everyone. I'm Steve Tong. I'm an infectious diseases physician also in clinical trials based in Melbourne, Australia.
Thanks guys. great to have you here Today we're going to be discussing our top 10 papers in [00:01:00] infectious diseases from 2025. We were going to be recording this in, mid to late December, but.
Josh: time caught up with us and we're doing it in early January. so the three of us have each independently selected our top 10 lists. So we, we hadn't seen the lists until we, we all finished, uh, selecting them. The criteria we've used to select the articles, uh, that. Uh, firstly, they were published in a journal, um, during 2025.
So they can't just have been presented at a conference, for example, and that secondly, they have to meet one of these three criteria. They have to be, in our opinion, practice changing, paradigm shifting or dogma challeng. I also asked, Bassam Ghanem, who's an ID and AMS pharmacist trained in the US and Jordan, and currently working in Saudi Arabia to join.
He wasn't able to join us on the podcast, but he did provide me with his top 10 list. He's likely known to those of you on social media as antibiotic steward. in the days when [00:02:00] Id, Twitter was still a thing, he was very active on that and still is, I think, and Blue Sky as well. as you'd expect.
There's a lot of overlap between our four lists, but what makes it more interesting is that there are a lot of differences too. And I was reflecting on that and thinking it's probably not surprising given that there are many thousands of Id. Related papers published each year. So in fact, it's probably surprising that we chose a lot of the same ones independently.
if you wanna see the full top 10 lists that each of us have made, we'll publish those on the CM I COMMS website along with the show notes, and also on a new website called Clarity that we're working on. More on that another time. So rather than just each of us reading out our top 10 lists, we're gonna take turns briefly describing the articles we've chosen, why we chose them, and what we think the implications are for clinical practice.
There are a total of 23 papers chosen by one or more of us, and we won't have time to discuss all of those. So we've prioritized those that are chosen by at [00:03:00] least two of the four of us. so we're gonna start with Emily. By the way, I forgot to say these are not in any particular order of importance or, choice.
it's a bit random what order we're doing them in, but anyway, over to you, Emily, for your first trial.
Emily: Sure. Thanks Josh. I'll be talking about dots. I was looking at our spreadsheet dots, I think is the only. Trial of the 23 where all four of us selected it. and along those lines, dots was also presented on another commutable podcast.
Which was the microbiology, top papers. So that episode is gonna come out a little bit before this one, so I won't go into huge detail. We know Staph Aureus is a leading cause of bacterial death globally.
There's not a lot of randomized control trials about how to manage it for many years. and this is being challenged now. The standard of care has been long term, meaning four to six weeks of antibiotics. Often intravenous. This usually, often means placement of a temporary catheter, and [00:04:00] that of course has risks like thrombosis 5% and secondary bloodstream infections around 5%.
in some jurisdictions it also means prolonged hospitalization. I and Iatrogenesis, you'll hear me mention again and again on this podcast, when we keep people in the hospital, we do things to them. It's not always good. We stop their home medications, we keep them in bed, we give them bad food. you all see this in your practice.
So strategies that avoid this are really interesting. They're needed. One option is switching to oral antibiotics and studies looking at this approach are underway. And another option is treatment with a long acting antibiotic. So enter Dalbavancin, it has a terminal halflife of 14 days. So if you give a dose of 1500 milligrams on day one and day eight, this actually gives.
Plasma levels that are well above staph aureus, MIC for more than six weeks. So this study was an RCT and included patients with, complicated staph aureus bacteremia, or right side and endocarditis. important to note, this was for consolidation therapy, so you needed to have initial blood culture [00:05:00] clearance, and then patients were randomized to Dalbavancin,
Or six weeks of IV therapy. And it was at the recipe that I mentioned just previously. It was an open label, actually superiority trial, with DOOR as an outcome, that analyzed 200 participants. So just make sure to check out the definition of complicated bacteremia to see that the results of the study applied to your patient.
The final results show that the probability that a patient randomly selected from the Dalbavancin group would have a superior DOOR versus standard therapy was 47.7%. It did not demonstrate superiority of Dalbavancin treatment still for a secondary outcome. 73 of a hundred participants in the Dalbavancin group and 72 of a hundred participants in the standard of care group had overall clinical success.
And the lower bound of the 95% confidence interval was within the pre-specified margin. I would say healthily within the pre-specified margin of 20%, indicating that Dalbavancin met criteria for non-inferiority relative to standard [00:06:00] therapy. So I chose this article , because every time I'm on service, I actually use Dalbavancin probably once, for this indication. at one of the hospitals where I work, and that's the hospital where we manage a large population of patients, with no fixed address. And so I was happy to have some evidence supporting this practice.
I think the bottom line here is that this is an option for treatment, when you want or need to get someone out of the hospital. I would make sure the bacteremia is cleared before using this strategy personally. and knowing in the future of one dose is enough would be really helpful. As I have to say, I do have a significant number of patients that have not come back, for the second dose.
So, uh, that's my take on dots. Steve, Josh, you also chose it. what do you think?
Steve: Yeah, I think it's a great study as well, really potentially practice changing. Uh, a couple quick notes. on the Clarity website, there are a couple of additional indepth reviews about dots by, uh, and Sean also check those out.
One of the things they raised was that the door [00:07:00] outcome may have missed some of the potential advantages of Dalbavancin, and so in particularly the convenience and impact on everyday life of not having to have an IV line in that wasn't selected in their patient reported outcomes. My other thought was that if oral Switch does prove to be non-inferior to standard intravenous therapy, then oral switch will be a more cost effective option for most patients.
I think in my clinical practice I'm reserving Dalbavancin for patients who need prolonged therapy but are unlikely to be adherent to oral therapy.
Emily: Yeah, same.
Josh: Yeah, I agree. I think this is a really important, paper. It's, both paradigm shifting in the sense that it's the first long acting antibiotic trial in staph aureus bacteremia and, potentially practice changing.
I think a couple of things important to bear in mind is this is a highly selected group of staph aureus bacteremia patients. As Emily said, they have to have reached clinical stability before they were dosed with the Dalbavancin. And so I wouldn't want people to interpret this as meaning. [00:08:00] They can just treat staph bacteremia from the beginning with Dalbavancin and they have to have cleared their bacteremia and be improving.
and then secondly, I'd be interested to know what it would have shown if using oritavancin, which is the other long-acting Glycopeptide, which is the one that, I use in, in the hospital we work in, primarily because it has a longer half-life than Dalbavancin and may not need 2 doses.
But that trial's probably never going to happen now that this one has happened. just as an aside, I forgot to mention before that, all the three of us, all clinical trialists and therefore may have conflicts of interest with some of the papers we're describing. if we don't say anything, that means we don't, Emily, I know Dots was recruiting in Canada. Were you involved in that at all?
Emily: Yeah, I was an investigator on dots. We recruited, two patients to the trial. Yeah.
Josh: Cool. Alright, over to you, Steve for your, first paper.
Steve: So, my Pick was a harvest trial for TB meningitis. TB meningitis has a mortality of up to 50%.
The recommended treatments with standard [00:09:00] dosing of Isoniazid, Rifampicin, pyrazinamide, and ethambutol. However, CSF levels of rifampicin alone often undetectable actually with standard dosing of 10 milligrams per kilogram of rifampicin, and so high doses of rifampicin have been shown to increase CSF levels, and they've been associated in a number of phase two trials with improved clinical outcomes.
The investigators here gonna state that. We still really need larger studies to prove whether it works or not. And so they designed a phase three double-blind, randomized placebo controlled trial conducting Indonesia, South Africa and Uganda. Adult participants with TB meningitis were assigned to either standard for drug therapy with rifampicin at 10 milligrams per kilogram.
Or alternatively, they were assigned to the standard therapy, but with rifampicin and a dosing of 35 milligrams per kilogram, so substantially higher, for the first eight weeks, and then followed by completion of standard [00:10:00] therapy and dosing for the remaining nine to 12 months. Glucocorticoids are indicated in TB meningitis, and they were given in accordance with international guidelines.
And the primary outcome was six month mortality analyzed in a time to event method and reporting a hazard ratio. So they looked at 499 participants, 249 got the high dose and two 50 the standard dose. 109 of the 2 49 died with high dose. So 44% mortality rate compared to a hundred of two 50 with standard dose four.
So 40%. So the hazard ratio was actually 1.17 with confidence intervals of 0.89 to 1.54. So looked a bit worse in fact with high dose Rifampin. And this high dose was not beneficial in other pre-specified analyses of the primary outcome in any subgroups or in any of the secondary outcomes. So it's pretty clear story.
I think. the reason I chose this was that it's a important question of great clinical relevance. In fact, [00:11:00] after ESCMID Global when these results were first presented, in 2025, we had a patient at my hospital with TB meningitis and the treating team was going to use high dose rifampicin and we're able to advise them not to do so.
The trial really also highlights the importance of conducting high quality, well powered clinical trials to properly address questions like this, instead of relying on smaller studies, which because of the smaller sample size, are less reliable. The bottom line in my opinion is that we don't use high dose rifampacin and for TB meningitis, I think you both chose this one as well.
So, Josh, maybe you first, what were your thoughts?
Josh: I loved this trial as well. I saw it presented at ESCMID Global. Was it last year or the year before? and just simple, question, strong study design. Clear answer. I agree a key point for me is, you know, history is littered with practice change based on phase two trials, which then turn out to be.
Wrong when you do the [00:12:00] definitive trial. This was a huge effort. it's not a very common disease worldwide. a bit more common in the regions that they. Recruited in. but yeah, I agree.
I think it just closes the book on the question in my mind. the other interesting thing that came up at ESCMID is there was a, a trend towards increased mortality in those on higher dose. And why might that be? Partly it was they had more adverse effects, liver toxicity, for example. But there was also, they hypothesized it might be to do with the drug interaction between the steroids and rifampicin, which I think they're doing more work on the PK that they're gonna publish.
how about you, Emily?
Emily: Yeah, I completely agree with both of you. I also saw it presented at E really appreciated, you know, how difficult it is to run a trial, such as this. And, Absolutely. There's a lot of examples of phase two trials that when you run the phase three, the results are, the opposite or, quite different.
So once again, proving that we do need those [00:13:00] bigger phase three trials.
Josh: Cool. Alright, I'm gonna do the next paper. And this was a trial called the Step Up Trial, which is around treatment of bacterial vaginosis. So this is a common sexually transmissible infection that affects its. up to about 30% of women, during their lifetime.
So incredibly common. It's characterized by vaginal irritation and vaginal discharge, and it's caused by a shift of the usual vaginal flora away from lactobacilli towards anaerobes. the current treatment approach is focused on treating the affected woman, but not her sexual partner. And recurrence rates are over 50%.
So there have been previous small trials done, of treating the male partners as well, which is what this trial's about, which have not found benefit. but they were both small in number and also had a crucial difference, which we'll see in a sec, which is that they only used oral therapy for the male partners.
this trial was an open label multicenter, randomized trial conducted [00:14:00] at five clinics in Australia. They were sexual health clinics or family planning clinics. I don't know if you have family planning clinics. Um. In whatever country you're listening in, but they're, publicly funded clinics where people go to, get contraception basically.
Josh: and the trial was led by Professor Katrina Bradshaw, who's a sexual health specialist in Melbourne, and she's been a guest on this podcast discussing this trial previously. So the trial enrolled 164 women diagnosed with bacterial vaginosis who were in a monogamous relationship with a man. Along with their male partners.
So there were 83 couples who were randomized to standard care. the standard care being, the woman was treated with oral metronidazole or if she couldn't tolerate that or if it's contraindicated, she used topical vagina clindamycin instead. And 81 were randomized to standard care plus treatment of the male partner with oral Metronidazole plus topical penile clindamycin.
And they were both given twice a day for [00:15:00] seven days. the primary outcome, which was recurrence of bacterial vaginosis within 12 weeks occurred in 63% in the control group. And 35% in the partner treatment group. the p value on this, was less than 0.001. and this was stopped early at the first interim analysis after 150 couples had completed follow up.
Important to note, there was an originally planned 342 couples. Were going to be enrolled. and they pre-specified a pretty stringent stopping rule using the Haal PTO principle of a p value of less than 0.001. at the interim analysis, which very rarely happens when people set those really stringent stopping rules.
so the reason I chose this is I think this is practice changing as well as paradigm shifting. So it shifts the paradigm from just treating the female partner to treating both. and ideally this should be replicated, I think, in larger numbers of patients, in in other settings [00:16:00] because this has only been done in one country and, a small number of centers in that country, but I think it's a well-designed trial with a strong biological rationale and the potential to improve outcomes for millions of women globally each year. So the bottom line in my mind is that. guidelines should change even at the same time as other trials might be being conducted and that male partners of women with bacterial vaginosis should be offered treatment.
Josh: Steve, you chose this as well, and Emily, you didn't. Steve, why don't you tell us your thoughts first and then Emily.
Steve: Yeah, . I think it's, um, a challenging document. I don't know a lot about this area. it really opened my mind to this idea that, bacterial vaginosis could be a STI,
it was interesting if you were to be picky, I think there was, still quite a lot of missing data, like 18% for the primary analysis. But they did a number of sensitivity analysis and because the effects are so large, the results didn't change. I was surprised, I guess just how difficult this is to treat.
So in the [00:17:00] standard care group, 63% recurrence, that's really, uh, and even in the, partner treatment group, the recurrence rate was still 35%. One of the things perhaps in offering treatment to the male partners is that, there was 14% reported non-adherence in the men, and another 19% had missing adherence data.
So 33% when add those all up. So it's quite a bit of missing data there. and also not all partners are taking the therapy. I followed on and read up. They did a follow up study, where they asked questions about the partners in another 70, patients. and about 25% of them ended up being a bit lukewarm about whether they would recommend this approach to family or friends.
But more encouragingly, 96% of them agreed or strongly agreed that they would take both antibiotics again if my partner needed treatment again in the future. So obviously for this to work, the partners need to be adequately counseled, and adhere to the therapy as [00:18:00] well. Emily. You didn't choose it?
Yeah,
Emily: I didn't. I didn't choose it. I know not for any negative reason. I think it's gonna be the same answer for most of us when it comes to why we didn't choose a study, which was, if this was my top 20, it would've been a lot easier. 'cause there were a lot of good studies to choose from. I don't have any major criticisms.
was a small study. It was stopped early, but they had very stringent stopping rules as you mentioned, Josh. So yeah, I take no issue with the study. I think it was a great selection
Josh: in a way, it just makes you think it's obvious that STIs the partner needs to be treated like we would never treat a woman for chlamydia or gonorrhea and not try and treat a partner.
it's just the thinking in, in this condition has evolved so much over the years from it being just something that affects women to something that is an STI. And we didn't mention that there are, a lot of studies showing that, Men can harbor bacterial species in the distal urethra and under their foreskin that are associated with bv.
and then men that harbor those [00:19:00] bacteria are more likely to be partners of women with bv. So, it, it does make sense that it's an STI. It just took a long time to work it out 'cause it's not one organism.
I went back to their references and Catriona Bradshaw's. First publication in this area was like 20 years ago.
Steve: 2006. So it's been a long time coming.
Josh: Yeah. so onto your next paper, Emily.
Emily: Yes. Okay. I'm gonna be talking about the ESCUDDO trial. Hope I'm pronouncing that right. E-S-C-U-D-D-O. So for background, this is an HPV vaccination trial. We know that the HPV vaccine is efficacious, but it's, actually pretty underused around the world.
some of you. May recall that the vaccine schedule for HPV actually used to be three doses, and then two were recommended. The question this study addressed was whether one dose was as good as two. So in this study, girls, age 12 to 16 were randomly assigned one to one to one to one to receive one or two doses of bivalent [00:20:00] or non valent HPV vaccine.
And the primary outcome was the development of a new. Persisting HBV 16 or 18 infection between 12 and 60 months. they had a pre-specified non-inferiority margin of 1.25 infections per 100 participants. They enrolled 20,330 participants. The non-inferiority analysis showed that one vaccine dose was indeed non-inferior to two doses in preventing eight.
PV 16 or 18 infection. The rate difference between one and two doses of the bivalent vaccine was, minus 0.13. Infections per a hundred participants, less than zero point, 0 0 1 for non-inferiority, and the difference between one and two doses of the non valent vaccine was 0.21. Infections per hundred participants, again, p less than 0.001 for non-inferiority.
The vaccine effectiveness was at least a 97% in each of the four trial groups. So I chose it, because it was interesting to me. I was [00:21:00] actually, I think I was 15 when the vaccine came out. and at the time it wasn't covered in Canada. I actually remember personally trying to decide whether or not to pay for it.
and I remember the three doses was costly, and daunting. So I can imagine there are places in the world where that's similar for two doses. You know, I love high value medical care, so to me, testing whether you can get as good a result with less treatment is super important. Less resources, less cost, a lighter lift, to get the job done.
Cervical cancer is almost entirely preventable now, and so I really appreciated seeing the results of this study. It's potentially more accessible for resource limited countries, more accessible for anybody really. 'cause you have to take some time off of work or school to go and get the vaccine. and so, you know, giving one dose instead of two and seeing these results was great.
I. Personally, I think this should be adopted, into practice straightaway. Since such it was such a large trial. Josh, you also, chose this one. Steve, you didn't. Why and why not? Josh, why don't you go first?
Josh: I was hoping for a bit more spicy [00:22:00] conversation in the why and why not, but it's always gonna be.
Yeah, we like the paper just was a number 11 on our top 10 or whatever. maybe it won't be Steve. We'll find out. So. Yeah, I, liked this trial. I also think it should be practice changing. and it's high value care. I did note when I was reading around it that a lot of, Countries and guidelines have already had changed to a single dose even before this was published.
But, this obviously adds a lot of weight to the evidence that is not inferior. so yeah, I dunno a whole lot about this area either. except that to me it looked like a well-designed trial, the results of which should be applied. Steve, how about you?
Steve: Yeah, I disappoint you both.
I, I actually really like it too. And in fact, this should have been in my top 10. I hadn't read it properly prior. as you both said, it's well conducted. It's an important clinical and public health questions, convincingly answered. I'm not in this vaccine space, but the findings are compelling to me.
Interestingly, some of the commentary I read [00:23:00] around it was that these virus-like particles. Clearly are very immunogenic. And so that's potentially why one dose is as good as further doses that just generate such a good immune response.
Josh: Yeah, this is, I guess, a good example of when I saw Emily and Steve's lists.
There were, papers I saw that, oh, I missed that one. I didn't even know about that one. I would've chosen that. So that's why it's really good having, I guess, several different perspectives on generating these lists. okay. Over to you, Steve, for your next trial.
Steve: Okay, the next trial n tb. so this looks at Rifampin resistant, quinol and susceptible, tb, which is really difficult to treat.
We need more treatment options. Previously for these infections, we've used 18 to 24 month prolonged courses with drugs with multiple toxicities, including injectable aminoglycosides. There's been a six month course of bedaquiline, predominant and moxifloxacin, or B parm, which has shown to be non-inferior to standard therapy [00:24:00] in 2022.
And that's actually been an absolute game changer, truly a game changer. but the endTB group has now tested other regiments and reported in this year, 2025 in the New England Journal of Medicine. It's a phase three multi-country open label non-inferiority trial that tested five. Different nine month oral regimens against standard therapy for participants with Rifampin resistance, fluroquinolone susceptible pulmonary tb.
The primary outcome was a favorable outcome at week 73, defined as an absence of an unfavorable outcome and two consecutive negative cultures or favorable bacteria. Logic, radiologic and clinical evolution. There are approximately 120 participants assigned to each regimen. Three of the five regimens were found to be non-inferior.
The standard therapy achieved treatment success of 80%, and these three other regimens achieved treatment success of 85, 89 [00:25:00] and 90%. The three regiments all included bedaquiline, lin ide, and a fluoroquinolone. Need ox Ox. The BDA and sparing regimens, which both used delaminate, which were not non-inferior, so they're not recommended.
So the reason why I chose it, we see in my hospital about 80 to 90 cases of active TB per year, about two of these will be rifampicin resistant. So while it's uncommon, it does definitely have direct clinical relevance for me and my practice, and also across the world has even more relevance. The implications for me is that while BPAM may still be preferred and it's just what we're used to using now here, I think the endTB trial regimens provide more options including readily available drugs.
So the predominant in BAS, less available and more expensive. So the endTB options would particularly important in regions that can't access predominant. There's a great discussion on [00:26:00] Communicable episode 20 with one of the guests being the lead author, Lorenzo Guglielmetti, who talks about this endTB trial and also TB in general, and I highly recommend listen to go back to that.
Emily and Josh, what are your thoughts? Neither of you guys chose it, but did say we'll have to justify that now.
Emily: . No good reason, Steve. it looks like a really cool trial and, I like that they tested, so many different regimens. it's cool to see like some consistency in the results, in the sense that the laminated regimens were not non-inferior. and so I think it's great to have it on the list and I'm glad that you and Bassam both chose it.
So we got to talk about it. Josh.
Josh: obviously I think it's important and a good trial, I guess I didn't choose it because these, MDR TB trials I find a bit mind boggling, really confusing to read and, get my head across because I really rarely treat patients with M-D-R-T-B.
clinically probably [00:27:00] less frequently than, than even Steve was mentioning, a couple a year. and you know, the multiple. Treatment options, multiple drug combinations, are confusing. But I'm glad you chose and summarized it for us nicely, Steve.
Steve: I agree. It's confusing the same in different regimens, aren't there?
I do wanna add that, the WHO has actually now recommended those three regimens together with BPAM, so that, that's important.
Josh: Great. Okay. And then for those of you who might be getting tired of listening to us, don't worry, this is the last, paper I'm about to describe in detail.
And then we'll do some briefer things after this. So the, last trial I'm gonna talk about is called the Eagle One trial, which was a trial of a new drug class for gonorrhea. So Neisseria gonorrhea is increasingly antibiotic resistant. and the first line treatments evolved over the years from.
I recall we used to, in the Northern Territory, years ago, use amoxicillin as the treatment for gonorrhea, and that was the first line treatment elsewhere in the past. And that then evolved due to [00:28:00] resistance to azithromycin or ciprofloxacin and then to ceftriaxone. So injectable ceftriaxone is now, in most cases, the first line therapy often combined with azithromycin.
But now there's an increasing, proportion of, isolates that are resistant even to ceftriaxone and need other options, such as meropenem. Even for example. There've been no new drugs marketed for this condition for decades. And Gepotidacin, it took me a while to work on how to pronounce that, Gepotidacin is a novel drug class which inhibits bacterial, DNA replication.
and that was tested in this trial. So the Eagle One trial was a commercially sponsored trial. It was phase three, open label, non-inferiority Trial then enrolled 628 people aged over 12 years with uncomplicated urogenital gonorrhea. So they were randomized to standard care, which was a single intramuscular dose of Ceftriaxone, 500 milligrams, plus an oral dose of azithromycin, one [00:29:00] gram, or Gepotidacin three grams orally twice 12 hours apart.
the primary outcome was microbiological success, which was defined as negative urogenital cultures at the test of cure, which was conducted at between days four and eight. So the microbiological success outcome occurred in 91.2% of people in the control group and 92.6 in the treatment group, which met the predefined non-inferiority margin.
Notably, there were adverse effects occurred in 74% in the Gepotidacin group versus only a third, 33% in the control group. And most of these were mild to moderate GI symptoms. So about two thirds of patients in the Gepotidacin group got, GI symptoms, primarily nausea or diarrhea. Notably, nearly all of the participants, 92% were male, and three quarters of the participants were men who had sex with men.
so the generalizability that needs to be taken into [00:30:00] account. the reason I chose it is this is paradigm shifting. It's the, first in class, first, new drug for gonorrhea. and it's, practice changing. So the FDA in the United States approved Gepotidacin, and in December, 2025 for this indication, also worth noting another, new drug in parallel called XLE Floatin.
Which is a different drug class and a different mechanism of action, although also works on bacterial DNA synthesis. xLi Floatin was also approved in, December last year by FDA, and the trial describing that wasn't published till 2026, so that can't be in our top 10. yeah, so bottom line for me is we now have, an oral alternative to intramuscular ceftriaxone for gonorrhea, especially drug resistant gonorrhea.
Its place in guidelines is yet to be determined. should it be saved up for drug resistant cases? And in fact, how would you know that a person is drug resistant when they present? or should it be rolled out more widely? And I [00:31:00] guess patients will need to decide would they prefer diarrhea and nausea or a painful injection.
so, Emily, you also chose this. And Steve, you didn't. Emily, what are your thoughts?
Emily: Yeah, we, presented this, in our, post ESCMID kind of wrap up of the abstracts that were presented. So I was sensitized to it because I saw it presented. agree with you Josh. first in class gives an option for, resistant bacteria, so super interesting.
that was why I picked it.
And Steve,
Steve: yeah, I really liked it too. Just had fitted other things in ahead of this. I found it pretty compelling. As you said, it's led to FDA approval and I also noted that higher occurrence of GI side effects. I looked up the cost. It looks like it's about a thousand dollars per course.
Which is considerably more expensive than ceftriaxone and azithromycin. So be interesting to see once it gets marketed where this fits. I guess it's as it's produced and marketed by GSK, a big company, at least it won't be at risk of the underlying [00:32:00] company. Holding with sales aren't terribly strong.
Josh: Great point, Steve.
so if you're driving to work, listening to this podcast and you've arrived, don't get out of your car yet. because we've talked through, the six most consistently chosen papers among the three of us, plus Bassam, the four of us. But there are so many other amazing, papers in our list, and I'm sure.
There are others out there that we completely missed. so we didn't have time for a deep dive on all 23 papers, but I'm going to throw down a challenge to each of us to give a one-liner on three of the papers we chose that have not yet been discussed. So, I'm gonna go to you, Emily, first for your three, one liners.
The line might be a little bit long, but. One liner.
Emily: Okay, here we go. And, and Rapid fire succession CloCeBa by Etol, published in the Lancet where Cefazolin was found to be non-inferior to cloxacillin for the treatment of staph Aureus bacteremia, fewer adverse, events. Less risk of kidney injury.
This will change [00:33:00] practice for the treatment of Staph Aureus bacteremia. This study in the much larger Snap led by yourself, Steven Josh, were both presented at Esid and we look forward to the publication of Snap in 2026, which we know had consistent findings. Second, a study in Lancet Respiratory Medicine by Leal et al.
Looked at steroids for patients with non H-I-V-P-C-P. The primary outcome of day 28 mortality missed statistical significance. The long-term follow-up showed reduced mortality at 90 days and less mechanical intubation. So we should be giving steroids to patients with PCP. That is not HIV related as we do for HIV related PCP.
It saves lives. I also wanna highlight that we have a communicable episode coming up on this topic where we interview the study authors. So if the topics of interest to you keep an eye out for that episode coming out in a few weeks from now. My third and final study I decided to discuss was Doxy Pep.
Some people were really excited about this approach. Others are more hesitant and wonder about the impact on antimicrobial resistance, so I definitely wanted to mention it. [00:34:00] Basically, doxycycline post-exposure prophylaxis was effective in reducing bacterial STIs among a population of men who have sex with men and transgender women, including an open label extension study, which continued to show benefit.
It was well tolerated, acceptable to participants and prescribers, and there were no safety signals. So that's my rapid fire. Top three. Over to you, Steve.
Josh: Thank you. You can take a breath now, Emily. Steve, what are yours?
Steve: Okay, I've got four, but three of them are lumped in together. these three papers were from Stanford Group and published in 2025 in Nature, JAMA and Cell.
So big publications. Reporting a likely causative association between vaccination with a live attenuated herpes zoster vaccine and reduced risk of dementia. So they're not a clinical trial. but the authors took advantage of natural experiments in that in Wales and Australia, the live attenuated vaccine became available for individuals of a certain age cutoff and not to those.
On the other side of that cutoff, [00:35:00] they used a regression discontinuity design, comparing populations just on either side of that age cutoff. So these patients should have been very similar apart from that minor age difference. And they estimated that over the following seven years, having exhaustive vaccine reduced the absolute risk of a diagnosis of dementia by 3.5%, or relative risk reduction of 20%.
So this is really a big area I think that we need to keep our eye on. The second study is, Durkin Al, who reported on a phase two trial of Oz dvir in a controlled human infection model of dengue. This oral pan dengue virus serotype small molecule antiviral blocks the interaction between the dengue virus, non-structural proteins three and four B, and was tested in only 29 patients.
These patients were given low dose, medium dose, and high dose or placebo regimens, and then they underwent this dengue virus three serotype challenge. Viral levels were suppressed in a dose dependent manner, and [00:36:00] much fewer of the high dose recipients had a dengue rash. So this is an important study because it really advances the first dengue antiviral drug and moves this drug beyond in vitro and animal studies.
Over to Josh.
Josh: Yeah, thanks Steve. great, great papers, both of you. The last six. So, yeah, my three, the first one, penicillin in early syphilis, randomized trial in the New England Journal by hook etal. so in adults with early syphilis treatment with one dose of 2.4 million units, zaine, penicillin G was non-inferior treatment with three doses with regard to Serologic response six months after treatment.
And this was regardless of HIV status. So we can thus stop giving three doses of. Penicillin in early syphilis just because somebody has HIV, which is a, common practice still. second was a trial about the interruption of immunosuppression by opt in CID, in adults on immunomodulatory agents for rheumatic diseases, [00:37:00] a strategy of temporary interruption of immunosuppression when mild or moderate infections occur.
Is not better than continuation of the immunosuppression in terms of their risk of hospitalization for a severe infection. So we can tell our patients that there's no need to stop or withhold methotrexate, steroids, and biologics when they have a minor infection, such as an, upper respiratory tract infection or a UT And then finally this, I don't know how you pronounce it, but it's sort of written, swishy two, the Swishy two trial, published in the Lancer by Arundel Al. In adults with surgical wounds that are healing by secondary intention, particularly those who've had vascular surgery of the lower limb, which was most of the people in the trial.
Negative pressure wound therapy. So like vac dressings was no better than standard dressings in terms of. Time to healing or adverse events. And these dressings are heavily promoted by manufacturers and are really widely used. And so I think as physicians looking after these patients are involved in their care, we should [00:38:00] question the use of these dressings, and particularly in smaller wound defects.
so that brings us to the end of our, podcast. But as I mentioned, there are other papers we didn't discuss and we'll publish the lists on the CMI Comms website. so thanks for listening to Communicable the CMI Comms podcast. This episode was hosted by Emily McDonald and Josh Davis, editors at CMI Comms ESCMID's Open Access Journal. And our guest Steven Tong,
Josh: It was peer reviewed by Dr. Akshatha Ravindra of Kasturba Medical College, Manipal, India . And the theme music was composed and conducted by Joseph McDade. Don't forget, you can subscribe to Communicable wherever you get your podcasts, or you can find it on the CMI COMMS website. Thanks for listening and helping CMI, comms and Esid move the conversation in ID and clinical microbiology further along.
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