94. BSAC OPAT conference 2024

Jame regales Callum with tales of his online adventure to the BSAC OPAT conference. Listen in to hear some updates on: implementation of OVIVA; subcutaneous antibiotics; and the BSAC OPAT good practice guidelines

Notes for this episode here.

Transcript

Jame: 0:18

Callum, how are you doing?

Callum: 0:20

Good, yeah, I think I'm ready. for you, to start, so Oh, Pat are on then, James. Pat are on.

Jame: 0:33

What a coincidence that is, Callum, because what are we discussing today?

Callum: 0:37

Well actually I had an incident recently, very confusing. One of my friends got a new dog, I'd never really met a dog before.

Jame: 0:45

You've never met a dog before. Callum,

Callum: 0:48

shake his hand and talk to it, and eventually the owner was like, this is what you do. And I was like, Oh, Pat, the dog.

Jame: 0:56

And what a coincidence that is, Callum, because what are we discussing today?

Callum: 1:00

Oh Pat,

Jame: 1:01

Yes, I attended the National OPAT Conference run by BSAC, the British Society of Antimicrobial Chemotherapy, on the 8th of November, 2024. It was hosted in Liverpool. I didn't go, that's a bit far away from me, but I did attend online and there's a few sort of bits and bobs that I thought were worth discussing on the show.

Callum: 1:22

worthy of the listener's attention.

Jame: 1:24

Well, if that pun wasn't then, and I think we both agree that it was not then the conference breakdown is. So, the conference had loads of stuff in it, but I've only taken notes on the stuff that kind of interested me, and so forgive everybody who presented at the conference that we're not going to discuss we're just going to highlight the cool stuff that I took notes on so this will not be a comprehensive teardown of every single session. Will we get started, Cal? Okay.

Callum: 1:58

Yes.

Jame: 1:59

Yeah, you're not nervous, you don't want to put on that piece of headwear that you wear that lets you deal with your anxiety attacks, your cope hat.

Callum: 2:08

Right. Cool Pat. That's quite good,

Jame: 2:11

Yeah. We should have made that the entering pun. Okay. So the first session was evaluating the safety and tolerability of oral antibiotic regimens in orthopedic infections, lessons learned and current perspectives. And this was by Antonia Scoby Anter, as am GHI from the Royal National Orthopedic Hospital, which is in Middlesex. in a place called Stanmore. So they were just talking about their sort of implementation of Aviva the big oral versus IV in orthopedic bone and joint infections, which was non inferior. And after that was published in, I think, about 2019, there was a lot more, enthusiasm about using highly bioavailable oral agents in orthopedic bone and joint infection. And they had an image which I screenshotted and I've put in the the prep notes about their sort of pre and post Aviva implementation of what antibiotics they used. And it's interesting to see. So they're, The Pre's in blue here, Calum, and the Post is in red, and they were using lots of Keftraxone, lots of Tycoplanin, and a moderate amount of Daptomycin and Ertopenum beforehand, and afterwards, all of that sort of dropped precipitously, and they were using lots more. There's Big six were Cotrimoxazole, Amox, Clinda, Doxycycline, and Cipro and Rifampicin. And Cipro and Rif were the backbone of what they were using, particularly for Staphylococcal bone and joint infection. And they had a 75 percent IV to oral switch rate, which I thought was pretty impressive in the post op period. And they were talking about another couple of things that they were doing. There Their, it's, their trust is a bit unconventional in that the Orthopaedic hospital is in its own, trust. And so they, when they were doing the oral prescribing they used a standardized letter to say to the GP, these are what we would like the patient to go on. So they didn't do the prescribing themselves, which is the thing that they did. They were doing when they were using lots of IVs and they used to standardize later to delineate the roles and responsibilities because they had teething issues for the GPs wrote back saying we don't normally prescribe this stuff. We don't want to do it. And they had some data on side effects. and tolerability, and I don't think there was any surprises there, but I included a screenshot as well for people to look at. Their overall side effect rate with orals was about 37%, which I thought was quite a lot, but they were just listing just everything. Every possible side effect, and there were some that were worse than others, like Quinlones, for example. But it is cheap, so they have, their real world outcome data was similar to IV at about a year. They analysed it in the post implementation period and reduced cost of about 2, 800 per patient, reduced length of stay by four days and fewer line complications in the oral switch group for obvious reasons. So you know, all very good and they finished by commenting on the MHRA fluoroquinolone alert. Thank you. Which went out earlier this year, I think. And they make the point that the side effects that people are worried about, like aortic dissection and all that sort of stuff, It's all observational, but because quinolones have an effect on matrix metalloproteinases that's well documented and is the reason that they can cause tendinitis, it's got a biological plausibility to it, but they also make the comment that is this high risk? If you work out the number needed to harm, it's about 11, 000 for aortic dissection for quinolone use, and that's with the long term quinolones that they are using. Compare that to risk of upper GI bleed with aspirin. The NNH is one in either 2, 7 5 to 1,429, and we're not stopping the use of aspirin. And upper GI believe, is a fairly serious side effect. Same with anaphylaxis, with Tyco Palin, NNH is 1700 to 2200. So they, they make the point that, yes, this may cause the art dissection, but you have to balance that against the benefits, the equivalent to the patient, particularly in this. Yeah.

Callum: 6:39

It's interesting, the notes that you've put together here, particularly the slide on tolerability, and I was just reading through that there, and it seems that there's a higher rate of tolerability of monotherapy compared to combination therapy where they're combining things like fluoclonalone with say rifampicin or cotrimoxol with other antibiotics with a higher rate of those in combination therapy needing to have either a dose reduction, a switch or an early stop compared to those in monotherapy. And it's just quite useful just looking through the list of antibiotics there as well, just seeing from the monotherapy agents as you said, there's a high rate of side effects, but you almost a side effect if you can tolerate it nausea that can be tolerated or other side effects that patients can tolerate, I guess is less. Concerning the, when they can't tolerate and you have to switch actually the small numbers, but fairly low tolerability compared to some of the other monotherapies there.

Jame: 7:41

Well, I think over a long enough timescale, a lot of people are going to get myelosuppression with Loneslid, that's true of Coltrane too.

Callum: 7:48

Yeah, it actually coach them off. So it was in the monotherapies most highly tolerated. So Some interesting again, small numbers, but this is useful, to reflect on their practice and for others.

Jame: 8:03

But people can dig through it and see what they like.

Callum: 8:05

Thanks for sharing.

Jame: 8:07

The next thing was it was titled Revisiting Oral Antibiotic Options for the Treatment of ABSSSI. That's Acute Bacterial Skin and Skin Structure Infection. This is a guy called John Cunliffe from Wirral University Teaching Hospital, but I'll be honest with you, Calum, this was the sponsored session, and it could well have been titled Delafloxacin is really good for skin and soft tissue infection, and was sponsored, I think, by the people that make Delafloxacin. But it was actually quite a good overview of the kind of options that we've got for skin and soft tissue infection. As skin stuff is the number one reason for referral to, to OPAT and previously. Before people started getting more comfortable with oral agents, most of them would be treated with Keftraxone. And then after daptomycin became cheaper, daptomycin became an option. Tycoplanin. was the other big hitter that we were using. And I know some OPATs have moved away from that as daptomycin has become cheap enough that all that fuss with levels and that requirement to load which not a lot of OPATs can do just becomes a bit too fussy and a bit too difficult. when you're moving to orals, and when you're using highly bioavailable orals, you need to think about what are the considerations? One that he really highlighted, he was talking about things like susceptibility, bioavailability, tissue penetrance, stuff that we've covered on the on the show, but one thing that he did point out was adherence and a brilliant statistic that he mentioned was that QID regimens, so six hourly dosing regimens There's about 51 percent adherence to those, and timing compliances in keeping to a relative spacing between those doses, even if you do manage to take it four times a day, is about 40%. I don't know what counted as a lack of compliance but if you take it with meals and then once at bedtime, your dosing will not be precisely six hourly. Does that count? Because I wouldn't really consider that to be a lack of compliance, really but the 51 percent adherence is notable, particularly because the standard treatment for skin soft tissue infection in the UK is fluke loss, which does have to be taken four times a day. And then he went through the choices of other agents that we've got, the sort of newer things that we've, a lot of them aren't new that we have been using linozolid pristinomycin, which is quinupristin, dalfripristin's oral friend. It's an oral streptogram, and you do have to import it from Europe, but you can get a hold of it. We use it a lot for bone and joint infection in Adolphe Royal Infirmary South. Cotrimoxazole, which is an off label indication but I have to say I use it a lot for, in my clinical practice, particularly when I'm working on our local SDEC, same day emergency care unit. And then he talked about Delaphloxacin, this new ish quinolone which has a very wide spectrum of action. I screen grabbed the spectrum here but Staph, Strep, Enterococcus faecalis all covered. A bunch of Gram negatives are including Pseudomonas and Enterobacterioles, and then It's got a license for sort of cap and skin, scuff, tissue infection. It is more active in vitro against staph aureus than moxifloxacin. And they all, he also pointed out that it is active in acidic pH in biofilm. So if you've got, abscess formation. That might be something to consider. I don't know if there's any clinical data to back that up. And the, I think the reason that I wanted to talk about this was that I don't know a lot about delafloxacin and I haven't used it a lot. And it was good to get a primer on the drug in general, rather than it be something that I was going to, I wasn't going to leave the OPAC conference and instantly start handing out delafloxacin to everything with a pulse. And then the. The ADRs, again, I screen grabbed this, but the it seems to be more well tolerated than other Quinloans and in particular doesn't have significant QT prolongation compared to the others.

Callum: 12:34

Yeah, it's useful to have that as another option. Again, it's in some of the guidelines. I think we've mentioned it on the pod briefly before. So yeah, you can have a look at the show notes that James put together there. It might be an option. I guess it's pretty broad spectrum, isn't it? So it's not ideal for skin soft tissue infection where you just want really staph or strep cover.

Jame: 12:55

Yeah, but you can think about complicated situations where there is gram negative involvement your diabetic foots, your this is your that's where it might be a tool in your toolbox,

Callum: 13:08

and it's got pseudomonas cover as well.

Jame: 13:11

So it is. And then there was a session that I was desperate to attend and rushed my mid afternoon dog walk to get back in time for which was subcutaneous OPAT experiences from Western Australia and this is from Laurence Manning who works out of Perth and the I know that there's quite a lot of subcut, or data, on subcut administration of antibiotics that emerges out of France. And he opened, by saying, why why would you want to do this? The obvious idea is that if you have an injecting drug user and you don't want to leave a long line in them, then you may want to use subcut access. Some people have difficult access. It involves the plastic of a cannula, or a pic. It's meant to be less painful. And there are some PK advantages in terms of a slower absorption and then you get less of a peak, but maybe you get a long sort of tail of time over MIC. And so they presented some French data. Mostly it was the same antibiotics kept coming up again, Keftraxone, Ertepenem, and Tycho. So the sort of backbone of of OPAT therapy. And they presented some PK data for Keftraxone, which I thought was very impressive. So compared to IV, very similar time over MIC curves, although admittedly a smaller peak, but I would argue that with beta latins that doesn't matter so much. And the SO2 for ertapenem. And some data for tycoindapto. And I've screenshotted all this. And they mentioned that a crossover trial has just been published with Daptomycin, and there's if you look at the Tycho Dapto sort of image that I've got, the thing in the bottom right is that, but I've not pulled the DOI from that just yet, Cal. And then they talked about their own experience in Perth, and they had some details on what they gave, which was usually a gram, of either Ertopenum or Keftraxone or 0. 8 of a gram of Tycoplenum. And it was diluted in 50 ml of normal saline and that was administered through a subcutaneous flexible catheter over 30 minutes. So it does take a bit of time, you just can't, it's not a subcutane injection like semaglutide, where you just shove it in your belly and you keep on with your day. It still does need somebody who can put it through the catheter and the patient needs to sit for half an hour. And they usually injected it into the belly or the thigh or the back places like that. And they had a little map a little diagram of where they were injecting it into. And they also mentioned that they were trialing the use of benzathine penicillin which is used for the treatment of syphilis and kefazolin. So syphilis is a problem in some communities in Western Australia, notably the indigenous Australians. And if they can give it through subcutaneous access, they can also if their PK data is to be believed can give it 10 weekly. So that is that's much easier than getting them in. Every two to four weeks, however often you need to give it, three weeks. Yeah, so ten weekly, and it's less painful, so people are more likely to come back. Because people not coming back is a big problem.

Callum: 16:37

So that's in comparison to IM, which should be the standard route,

Jame: 16:40

Yeah, yeah, which is quite sore.

Callum: 16:43

Interesting.

Jame: 16:45

And so that was good in the ended by publishing their regimens, which is really what I've said there, but also daptomycin eight milligrams per kilogram daily, or 12 milligrams per kilogram, 48 hour, depending on the indication. I. I think but yeah interesting to see and I, I kind of, I think subcutaneous antibiotics, it's not the done thing in the UK, but I think that's just because of a lack of local experience and all it takes is somebody to to start doing it and then the dam will break.

Callum: 17:18

Yeah, I guess you would need the support of your pharmacist and a protocol for doing it as well,

Jame: 17:23

Well true, but I mean, A, you can just nick the Australians protocol because they've done all the hard work for us and B, the French have done all the PK data which the Australians have based all their stuff off, so you can just nick the French and Australians PK data and away you go. When it comes to dosing equivalency, the only issue is that Keftraxone you can only give a gram. Is that enough? It's certainly not for a complex Staph aureus infection. I don't think it would be, but

Callum: 17:50

they're going to look at that next in your chart that says next step, so you get two gram and they've got n equals 15 next to it.

Jame: 17:55

yeah, so they're, that's their thing is that can you actually give two grams and then, because you don't want to set up to infusion could you do that? And that would expand its sort of use case as well. So, interesting, subcut antibiotics from the Australians and probenicid boosted beta lactam regimens from the New Zealanders. The Southern Hemisphere is strong with OPAT and COPAT.

Callum: 18:20

What about Northern Ireland, James?

Jame: 18:21

well, The OPAT experience from Northern Ireland, a lot of the stuff that was presented was here's how we've implemented OPAT in this bit of the world, and there was someone from Malaysia as well later on, and there was someone from Northern Ireland, and it was really interesting the stuff that Eileen Dorgan, consultant microbiologist at Antrim Hospital, was saying, but a lot of it was just here's how we were implementing it locally. The one thing that they did say, which I was very interested in, was that they were using aminoglycosides with OPAT, because that's something that we've been trying to implement locally. in the hospital at home world and they were actually using it sort of amikacin and tobramycin with complex respiratory patients such as people infected with NTMs and CF and bronchiectatics and I was very interested to see what their experience with that was. But I don't know if I just wasn't paying attention, but I'm not sure they said all that much more apart from we're using it. I didn't get an understanding of what the regimens they were using was and how they were dealing with the monitoring issue. But it was interesting to note that because if I remember rightly in NAIDOF Roiling Firmly North, there was a reluctance to use aminoglycosides in the OPAT setting

Callum: 19:34

tricky, we haven't done it at all. It's been done for select patients of NTM, so it's certainly not normal, and it's run into problems. Not infrequently, so I guess it's not your go to, but it can be done.

Jame: 19:49

Aye. Aye. And then the last thing that we'll comment on was the BSAC OPAT good practice recommendations a first look, which was presented by Ann Noble, infectious disease consultant at NHS Lanarkshire. And she was going over the, good practice recommendations which were being revised. So there's a set from BSAC that's already out and they were in revision and they were making. Recommendations around five domains, service structure, patient selection, antibiotics and devices, monitoring and monitoring outcome, and clinical governance. And she was went over the sort of recommendations, so for example, for service structure, have a formal structure and have an MDT and don't be afraid to use telemedicine and self administration at home and stuff like that if the patient can be trained up. Which we do quite a lot of, down here in Nadov South, we particularly with our respiratory population teach people to administer their own antibiotics so they can have Keftazidime two or three times a day, that kind of thing. And then there were comments around patients who inject drugs, frail elderly people, integration with hospital at home and then for the antibiotics and devices they were talking about expanding the use of Copat, which I think we would be in favour of, subcutaneous antibiotics, paying attention to what the French and Australians are doing, and then, with one eye on, dalbovancin, or dalbovansin, depending on how you pronounce it. Prefer your C's, soft or hard. Coming off patent in 2027 or 2028, I forget which, Callum. But you know, in a few years, that long acting glycopeptide is going to be available through generics manufacturers. And then, that has the potential to turn around how we are doing things. using glycopeptides in the OPAT setting so maybe tycoplainin having fallen out of favor because of the monitoring issues. Well, they are not an issue with long acting glycopeptides. So maybe that'll come back into fashion. And they did make a mention about polyfusers or the use of infusion devices. And The stability data. So as you're probably aware Callum, the stability data in the UK has to be more than 95 percent stable at the 24 hour period, which means that some antibiotics which are given in polyfusers like meropenem in other countries are not given in the UK because they don't meet this criteria. But we're the only people using that 95 percent cutoff. Most people are using 90. And so there was chat about whether we should shift that goalpost, because it means that we're not using stuff that is used in another country. And I think really, if you have 6 grams of meropenem in your polyfuser, and at the end of 24 hours you have 5. 4 grams worth has gone into the patient, I think that's going to be enough to take care of most infections that you're using it against. Do you know what I mean?

Callum: 22:56

and who set that target of 95 percent compared to

Jame: 22:59

I think that target has been set by BSAC, but maybe that's on the advice of some government agency, like the Health Security Agency. I don't know where it came from, honestly, Callum. You're catching me out and shooing me up for the charlatan I am in front of

Callum: 23:14

You can write it and tell

Jame: 23:16

in front of the loyal listeners. So thanks a lot for that, you monster.

Callum: 23:19

Well maybe someone we could ask who might know the answer, like the BSAC president that may or may not have recently been interviewed on this podcast and talked about OPAT.

Jame: 23:29

well, I mean, if only you two were tight chums and you could send him a quick email and then append it to the end of this episode, that's more work for you. I'm not doing it. And that's really about all I had to say, Cal. It was a really nice conference to go to. It's like all the BSAC conferences, they're cheap, they're available online I always learn a lot, and the OPAT, there's loads of research going on in the OPAT domain, which I suppose we don't really cover because we're more aimed at going over the basics, but the, I always felt, as a trainee and even now as a consultant, that the BSAC conferences are really worth attending.

Callum: 24:09

That's great. thanks for feeding back our OPAT correspondent, Jane McCray. And We'll come back to BSAC in the near future as you may have heard about on our last episode,

Jame: 24:22

Lovely. See you again, Cal.