80. A Poem on POET

Join us for this special 80th episode celebrating Jame's favourite trial.

https://www.nejm.org/doi/full/10.1056/NEJMoa1808312

Prep notes (including the images referred to in the poem) here. 

Special thanks to the Wikiguidelines Endocarditis crew for their work summarising the evidence this poem was based on. 

Transcript

Callum: 0:00

Welcome to the IDIOTS Podcast. It's my pleasure to introduce this special episode where Jane McCrae will be taking us through the POET trial in just under six minutes. This is a presentation he prepared for the recent BIA Spring Conference, and I enjoyed it so much, I asked if he would share it with you, our dear, loyal listeners.

Jame: 0:45

Thank you, BIA. I'm here to talk to you today about Iversen et al. 
It came out quite a while ago in January 2019, challenging the dogmas of oral versus IV. 
But before I vent by a Venflon hating tablet loving spleen, first I feel the need to step right back and set the scene. 
The year was 1945 when accepting the Nobel Prize was Alexander Fleming, the greatest Scot who's not alive. 
Back then, endocarditis, well, it wasn't all that great. Pre antibiotics, it's a 0 percent survival rate, and that led some doctors to parlay in a hypothecate that a course of antibiotics might set these unlucky buggers straight. 
First they tried sulfonamides, cousins of cotrimoxazole, or at least one half of it, you can look it up. But damn it, all if the bug drug MICs were simply far too high, and despite best efforts, only 4 percent survived. 
Next they tried penicillin, which they knew had low MICs, but did have to go in IV, but what success! At 70% to far the best of all that they so far test...ed. 
And then with pen already on side, they thought they'd try a macrolide: Erythromycin, not well absorbed. High volume of distribution leading to the low plasma levels that doth blight its reputation. For mycoplasma, he's your drug. But staph and strep are hardy bugs and biofilms in a plasma site? This bug drug combo, isnae right! 
Even then though? Still not great. 25 percent survival rate. 
So think about this little tale that I have to you folks regaled. What do you think it's all aboot? The drug you're choosing? Or the route? 
This is to this very day the only data that we've got to say that IV beats out oral, dose for dose and shot for shot. But ladies and gents, it is quite tricky to displace a dogma most sticky. 
Even just a few years ago for BSI to suggest PO was quite the challenge to the status quo. Most bosses would just say no and whisper "troublemaker, yo", to their colleagues as you walked home. 
IV clearly beats PO. IV's safer, they'd be moaning. Even if the preliminary data you'd show them, they'd dismiss you as a showman. Cohort studies had them groaning. The idea was so spicy it got mined by House Harkonnen. 
So think about endocarditis, a bacteremia with the abscess in the middle of your chest. It needs long courses, quite a pest, of IV drugs, cause they're the best, are they not? 
Well, let's stare at some case reports, because there, we can see some good success. A few claim 100%, "But Jame", I hear you folks decry, "Case reports, I guess they're fine, but low quality, don't waste my time". Well, here's some data befitting your station, in the realm of observation...al studies and a case cohort included in this fine report. 
Success rates equal IV and even in some cases are much better with PO. But I can see from your faces "This data just won't do for me. Don't you have an RCT?" 
Well, yes I do. In fact, have three. 
The first two are quite interesting, to read later, I am recommending, but now I think three minutes in, it's time to mention Iverson 2019, the final trial. But I promise this one's worth your while! 
Patients over 18, native or prosthetic valves, left side lesions, gram pos bugs, 10 days of an IV salve, then randomized to either pills or continuing on IV. But there was no blinding, which group you were in was plain to see: but surely that should help IV? 
Six month primary outcome, a mix of unexpected death or surgery, or emboli or blood infection recurrent. 
And is there a difference to be drawing? 
I think you know where this is going. 
Average switch from IV to PO was at day 17, and from that point on, the groups start to diver statistically the OR 0.72 with CI crossing 1.0 in favor of oral treatment - but non significant sums. 
Though when followed out two five years, well, feast your eyes on this, My dears! 
The lines continue to depart. The OR becomes significant. And if I may summarize this rant, Oral's awesome, IV's pants! 
So that's my story. Told you in all its glory. But now that I've declared myself a member of the tablet faction, I'd like to summarize this diatribe with a final call to action. You can trump these tablets, and you can shill these pills. And early vein decannulation's where you can get your thrills. For each genus, there's regimens published in ESC. And if confused, just use Linez plus Rif, it cures all three! A stable patient can be switched, and you can send them home. But stay away from moxiflox, it's still a quinolone. 
With all of you evangelizing, the limit is the sky! 
My loyal oral army. My Pharma Uruk Hai. 
Go monkey with those medicines. Oh fly, my pretties, fly. 
And if I asked if you got this from a Scotch ID:IOT, tell them aye. 
I thank the BIA, apologise for my poor timing. I don't know if I took more than my while. And also to the audience for this incessant rhyming. But then again: they did call it the POET Trial.