90. IV to Oral Switch

In which Jame talks about the rationale for IVOS, evidence base for the pros and cons, and then finishes by giving the UK oral switch criteria an absolute rinsing.

Prep notes available here. 

Transcript

90. IVOS

Jame: [00:00:00] Hello, loyal listeners. Callum has once again abandoned us, but once again in his absence I will rise to the occasion. So, what are we going to talk about today? I'd like to talk about oral switching in general and my approach to it, of late. But before I do, let's get the nomenclature clear. You are not doing an IV to oral step down.

You aren't stepping down to anything because IV has never been proven to be superior to oral. Except by the way of dosing, of course. You're switching therapy from IV to oral to benefit the patient, hence IV to oral switch therapy. So now that we are switching, why would you do it? Why wouldn't you just keep them on IVs indefinitely or until the point of discharge at least?

Well, let's not pretend that there aren't advantages to IV therapy, [00:01:00] particularly if you want to get antibiotics on board at therapeutic dosage as quickly as possible. Think a life threatening sepsis, case. Then you'll get, time to, Maximal distribution of, , roughly about 5 minutes if you've got something that's just going to sit around in plasma.

Compare that to,, anything between 30 minutes and 2 hours for some antibiotics. That 2 hours is for cotrimoxazole, for example, compared to IV, which would be about 10 minutes. You have 100 percent bioavailability, by definition, whereas the bioavailability of oral medication is variable. depending on what you're using.

And you can give much higher doses with IV. So taking amoxicillin as an example, , the European guidelines for endocarditis suggest a weight based dosing. And so for, a 100 kilogram male, not, entirely unheard of, , you would be giving a amoxicillin dose of amoxicillin. [00:02:00] 20 grams a day and there's just no way that you would be able to give that Orally, so you can get Increased doses of the same antibiotic in ivy just because you don't have to worry about absorption kinetics.

And there are many more antibiotics that can be given IV, compared to oral, because most of the oral ones can be given IV as well. But there are many antibiotics like the aminoglycosides, for example, , and daptomycin and things like that, which are only available intravenously, , with a little asterisk, , next to that.

In terms of ease of dosing though, here we start to see things swing back to oral being. more beneficial to the patient. So for example, in, in terms of dosing, you can dose between one and four times a day , for oral. Any more than that, you're really going to have issues with adherence.

Whereas with IV, you can technically go up to about six times a [00:03:00] day, and with things like amoxicillin and benzopenicillin, we do sometimes do six times a day if we're wanting to try and maximize time over MIC. And there are, of course, extended infusion regimens that are now starting to become commonplace, particularly in intensive care.

But, as anybody who has worked in an ID ward will tell you, dosing six times a day is extremely difficult to do and leads to a lot of disturbed sleep for the patient and for the nursing staff also, who will no doubt be cursing your name if you ask them to give anything six times a day. When it comes to orals, of course, there's no risk of IV line complications, because by definition they don't need an IV line.

And there are benefits to be had in terms of expense and carbon and plastic. Let's talk about expense first. So I've pulled this data from the British National Formula, the BNF, on the equivalent [00:04:00] IV and oral dosings of three antibiotics, just to give you an example of the cost difference. So let's say you wanted to dose amoxicillin 500mg three times a day.

 Reasonably common dose, at least in the UK. That would be 21 pence per day, , for the oral, and 2. 88 for IV. Now, that's quite a lot more, maybe more than 10 times as expensive, but it's still pretty cheap in terms of costings. Let's do cotrimoxazole 960mg twice daily then, that's 46 pence orally, and 18 pounds 86 IV.

And lastly we'll take ciprofloxacin, and here we're comparing the 500mg BD IV. Oral regimen with a 400mg BDIV regimen. But if you think about the 70%, probably about the same dose of Cipro is hitting the bloodstream. 19 pence per day for oral versus 43. [00:05:00] 52 for IV. It's more than 20 times as expensive. Even putting to one side the cost of the pill or the injection, there's, , Advantages to be had in terms of reduced plastic and carbon usage, , when you move from, IV to oral.

And in terms of nursing time, I'm going to point you in the prep notes, , to a study which was a poster, , that was published, I think, in Jack AMR, comparing PrEP and admin time in the Royal Cornwall Hospital. So shout out to the authors from that, if you're, , listening. PrEP and admin for oral antibiotics was 2.

42 minutes, for IV bolus, 5. 53, and for IV infusion, 10. 27. Because when you're prescribing it, oral versus IV, you just click that, and then you, Send the order through at least on electronic prescribing, but then the nurse has to go and , make it up in some specified fluid, [00:06:00] maybe look up, how to prep the antibiotic, check it with someone else, go to the patient, double check everything, and then set up the infusion to administer it and then take it all down at the end of that.

And if they're doing that three or four times a day, you can imagine that's quite a lot of time. Whereas. The oral administration of the pills could have been done on the drug round along with everything else. So that's maybe a quick rundown of all the advantages of oral switching. You may be worried about the pharmacokinetics of it.

That time to, , therapeutic levels. Does that, matter? Well, I would say in stuff like life threatening sepsis, I would argue that it does matter and that the first dose of those should always be IV to get the antibiotics on board. There's not, as far as I know, a huge amount of evidence for this one way or the other.

In terms of the distribution, if you think about the PD target that you're trying to attain, if your PD [00:07:00] target is C max, , if you administered your antibiotic orally, you would get less of a C Max, because that delay in, sort of absorption, from the gut and first pass metabolism, that does lead to a lower C Max, and it varies by antibiotic.

But most antibiotics don't, , aren't concentration dependent. Aminoglycosides are. Daptomycin is. Both of those , are, given IV only. For beta lactams, it's time over MIC that matters. And so that won't be, shouldn't be significantly affected for dose equivalents, regimens going oral versus IV.

And for almost every other antibiotic, it's AUC over MIC, which is the PD target. And that's a combination of the. drug C Max and the half life. I'm simplifying all this a little bit. But that sort of differential time to C Max administering IV compared to oral is unlikely [00:08:00] to result in a significant difference of target attainment of most PD targets.

So that's my sort of pharmacokinetic Explanation for why I think aural should be used up front in anything other than life threatening infection, if they are a possible option. So that's a PSA on why aural switching is a good idea. I doubt the audience needed to be persuaded of that. But this is, as much ammunition to use in your own practice as anything else.

But, Do we have any nationally approved guidelines on when to oral switch? Well, I'm pleased to say that in the UK, at least we do, and we have done since January of 2023. In the PREMDOS I've linked to the UK Health Security Agency, our public health body, guidance on IV oral switch or IVOS criteria. This was produced by consensus involving a bunch of different participants from all over the country, and it's It, on the face [00:09:00] of it, it's a sort of flow chart about what they think are good ideas to make sure are in place before IV to oral switching.

I wish I could recommend it, but I'm about to tear it to pieces. , so if you want to, , pause the recording and go and have a quick look at it, and then you'll be able to see what I'm talking about if you haven't seen it already. So my main issue is with it is that it is way too conservative and has been written by people who clearly think that IV is superior to oral in some way and I would argue that there's no,, argument for that we haven't just discussed and refuted in the previous part of the show.

So the flowchart starts by asking does your patient have an infection that may require special consideration and the list of it is bloodstream infection. Empyema, endocarditis, meningitis, osteomyelitis, severe or necrotizing soft tissue infection, septic arthritis, or an undrained [00:10:00] abscess. My issue with this is that three of those, bloodstream infection, bone and joint infection, and endocarditis, all have excellent oral antibiotic data.

We've got the POET trial, we've got Aviva, , there are multiple, , studies of Bacteremias , using, oral agents, all of which were non inferior, , to IV. I would further argue that empyema are source control issues, not necessarily oral antibiotics aren't good enough issues, and efforts should perhaps focus on controlling the source, getting a surgeon or an interventional radiologist to drain said abscess or emphyema, as opposed to pontificating on the superiority of IVs over oral on no data whatsoever.

The next part is concerning the enteral route. Is the patient's GI tract functioning? No problem there. Is the patient's swallow or enteral tube [00:11:00] administration safe? No problem there. Are there any significant concerns over patient adherence to oral treatment? I would argue that there is a No hard and fast rule there.

You may have patients in whom you are Concerned about adherence to therapy. You may also be worried about those people absconding if you keep them on IVs People want to leave the hospitals for lots of different reasons and in that kind of group Transitioning them to orals is a risk mitigation strategy that you may wish to consider.

Flowchart be damned And then the last part is, has the patient vomited in the last 24 hours? Now, I don't want vomiting patients to be given oral antibiotics, but neither do I think that if they have vomited 23 hours and 55 minutes ago, that transitioning them to oral therapy is necessarily a bad thing.

As long as you think you've got on top of the vomiting or the nausea, which can also mean that [00:12:00] patients can't take antibiotics, then I think it would be fine to at least consider it. The second, next part is , clinical signs improving. Are there, signs and symptoms of infection improving? If yes, keep going down the flow chart.

If no, reassess in 24 hours. Again, this seems to be based on the erroneous assumption that IV is superior to oral. And that the patient would be safer if they are maintained on that, , and past the first dose of IVs, which I think is justifiable in, in cases like sepsis, I don't really know why you wouldn't consider oral switching as long as the oral regimen offers equivalent cover to the IV regimen it's replacing.

And lastly, the last part before , you, , Oral switch them , if they pass is three infection markers. Has the patient's temperature been between 36 to 38 for the past 24 hours? Is their news [00:13:00] score decreasing? Is their white count trending towards the normal range? And is their CRP decreasing? I have problems with just about all of those, and I'm sure you can have your problems with that too.

Having normothermia for the past 24 hours I feel is too restrictive. They're clearly using fever as a surrogate for non control of the infection, but if the patient is clinically improving and they happen to still be spiking fevers, I don't think that's necessarily a contraindication for oral switching.

I'm thinking particularly about pyelonephritis. Infected kidneys or inflamed kidneys are very pyrogenic. They throw off lots of prostaglandins, and I can think of several cases I've been involved in where the patient has clinically improved, but remained febrile over the Several days after that clinical improvement, that's caused confusion with the home clinical team and they phoned up for, , advice about what antibiotics to escalate to.

And my [00:14:00] response has been, don't escalate anything, or we'll switch the patient and send them home. And sometimes they've also had a little mini lecture about the word escalation, but that's a talk for another day. News or early warning score system, their OBS, , getting better, their news decreasing.

Fair enough, , I understand why that's in there. White count normalizing. I would argue that's nice to see, but by no means essential. There are patients who will, have a raised white count that will, , remain raised, even if you treat the infection or not. Thinking about certain hemo, haematology, oncology patients.

Or those people on steroids. And lastly, CRP decreasing. I have no idea how this wound in here, but the CRP is increasingly becoming the bane of my life. People are pointing to modest changes in CRP and using that as a justification for continuing IV antibiotics, despite the patient clinically improving.

A recently published ad, article by Brad [00:15:00] Svelberg and Twitter friends in, , CMI, , speaks to this phenomenon in more eloquence than I would be able to muster in this podcast episode, so I have linked to it in the show notes. Suffice it to say that I don't think the CRP should be used as a marker, and if you are getting better and eating and drinking and taking all your food and everything else is improving but your CRP has gone from 50 to 70.

I don't regard that as enough of a reason not to oral switch the patient. This checklist was clearly written by consensus of the clinical practice in the UK at the time and as a consequence of that I feel it has incorporated the prejudices of that consensus. And seems to be based on the assumption that IV is superior to oral.

And again, there's no evidence to support that notion and copious amounts of evidence to suggest otherwise. [00:16:00] In defense of the checklist, it does advocate oral switching to be considered, and I quote, from first dose of IV antimicrobial with formal review completed within 48 hours and daily thereafter, unless clearly documented exemptions, end quote.

So they do seem to be saying, moving from the give. 48 hours of IV and then oral switch to suggest that you could consider switching earlier. These days I'm switching from, virtually the first dose of antibiotics, and if I have somebody on a highly bioavailable antibiotic, I'm Not transitioning them to IV if I find that they are bacteremic, , for example, so say I have a You know somebody who I'm treating for a UTI and I have them on something that's highly bioavailable like Coltrimoxazole, Ciprofloxacin, And then I find that they're bacteremic.

I'm not, , switching to [00:17:00] IV and then waiting for the sends and , then oral switching at that point. If they are clinically improving, I'm changing nothing. Ditto for streptococcal bacteremia. This, happened , on my recent service. I had somebody who had a really nasty pneumonia and they were on amoxicillin.

And they had a blood culture that was eventually positive for strep pneumo. And the only thing that I did was I doubled the amoxicillin dose from 500 to a gram. But I kept them on orals because I felt that was in their best interest. And although they, , still felt quite rubbish, they were not deteriorating.

They were clinically improving. And so I just kept them on orals. I didn't bother going back. I feel that this is the correct approach. I feel this is the most evidence based approach. And if you are thinking the same and are interested in implementing more evidence based oral switch criteria [00:18:00] that are still based on the HSA criteria, I have included in the show notes a sort of draft, it's not live yet, in my local antimicrobial guidance of our IV to oral switch criteria, which are still in, in for review, but it might give you a few ideas about how you are going to structure your own IVAS criteria if you are involved in guideline development in your local area.

Alright, that's it for today. See you next time.