Подтвердите e-mail

Для публикаций, комментариев, реакций и сообщений подтвердите адрес.

←

Публикация

Antibiotic Steward 🅱️C🆔🅿️🌟

Wow! 🆕🔥🔴Multicenter OL NI RCT Oral fosfomycin (3 g once daily) was noninferior to continued intravenous therapy with carbapenems or BLBLIs when used as oral transition therapy for complicated UTIs caused by ESBL-producing Enterobacterales #IDSky #utisky academic.oup.com/cid/article-...

Fosfomycin as Oral Transition Therapy Versus Continued Intravenous β-Lactams for Complicated Urinary Tract Infections Caused by Extended-Spectrum β-Lactamase–Producing Enterobacterales: A Multicenter,...Switching from intravenous antibiotics to oral fosfomycin was noninferior to continuing intravenous therapy for complicated urinary tract infections causedacademic.oup.com
Обсуждение

2 прямых ответов · 21 сообщений

Jonathan Ryder, MD

Might be a viable PO transition option for ESBLs, although part of me wonders if 3 days of IV antibiotics are enough regardless, especially as patients already clinically improved. Notably, they used the old definition of cUTI. So 3 days is certainly enough for cystitis in someone with DM

Ответ для Jonathan Ryder, MD
Jonathan Ryder, MD

However, its notable 36% had pyelo and 25% had bacteremia....although I still think many of those could have received the longer end of 5-7 days IV, which would mitigate fosfo having any effect. Very possible fosfo was placebo in this trial. Would love to see sub-group of IV durations in BSI/pyelo

Ответ для Jonathan Ryder, MD
Jonathan Ryder, MD

If sub-groups of patients with BSI/pyelo showed good outcomes with fosfo transition at 3-4 days, that would be helpful. Admittedly, numbers will get quite small, but I'd still like to see how those are distributed in the study

Ответ для Jonathan Ryder, MD
José Molina

If there were PK/PD issues with fosfo, the problem might arise not on early TOC, but on relapses of non-cystitis UTI. In this subanalysis of patients switched to oral in FOREST trial, more relapses were observed with fosfo for bacteremic E. coli UTI. academic.oup.com/jac/article/... #IDSky #UTIsky

Ответ для José Molina
José Molina

Caveats: - FOREST was 100% bacteremic UTI - A lower dose of oral fosfo was used (3g/48h). - Definition of relapse was more strict, requiring a new isolation of E. coli with same phenotype. - Absolute risk difference still low (11%), so definitely an option to consider if no other options! #IDSky

Ответ для José Molina
Jonathan Ryder, MD

This is the very fascinating thing about the data on fosfo. By all means, there is enough data to suggest its a good option in certain situations, but then there is other data showing its nowhere near as good as firstline options, e.g., SCOUT trial. Very confusing www.thelancet.com/journals/lan...

Clinical and bacteriological effectiveness of three different short-course antibiotic regimens and single-dose fosfomycin for uncomplicated lower urinary tract infections in women (SCOUT): a pragmatic...Nitrofurantoin was the most effective treatment and single-dose fosfomycin the least effective treatment for UTIs. Adverse events were mild. The role of fosfomycin as a first-line antibiotic for uncom...www.thelancet.com
Ответ для Jonathan Ryder, MD
Philip Bejon

I think SCOUT says single dose fosfo was less good, there was no single dose nitrofurantion or pivmecillinam arm. Can assume they wouldn't have done gone well either. Two dose fosfo was similar in cure rates to nitro/piv, despite those being 5 and 3 day courses.

Ответ для Philip Bejon
Antibiotic Steward 🅱️C🆔🅿️🌟

The dose of fosfomycin matters, it seems like 3g q24h is more consistent with clinical success, but tolerability esp diarrhea might be an issue here

Ответ для Jonathan Ryder, MD
José Molina

In my view, fosfomycin may be that antibiotic slightly less effective but so more convenient in so many ways (oral route, unbeatable dosing, broad spectrum with low ecological impact...) Now we have data from many RCTs to better inform and engage patients in shared decission-making! #IDSky #UTIsky

Ответ для Jonathan Ryder, MD
bugsdrugs

I think the problem is how they use Fosfomycin. Its a drug that only has CLSI breakpoints for E coli. The study had numerous other organisms. Also, tge E coli isolates were more likely resistant to Fosfo than Nitrofurantoin

Ответ для Jonathan Ryder, MD
Geno Tai MD

Are the outcome definitions exactly the same? And objective ?

Ответ для Geno Tai MD
Jonathan Ryder, MD

Not all apples to apples. Editorial for this piece with a nice summary of available evidence for fosfomycin academic.oup.com/cid/advance-...

Ответ для Jonathan Ryder, MD
Chris Hopkins

Great to have this editorial, but it doesn't include this other very recent RCT (in press) on oral fosfo as transition after IV carbapenem. So adds extra weight to #4 in the table. #UTIsky www.ijidonline.com/article/S120...

Oral Fosfomycin after Carbapenems as De-escalating Therapy in Complicated Urinary Tract Infections: A Randomized Controlled TrialAntimicrobial resistance is a major global public health threat, driven by the rising prevalence of third-generation cephalosporin–resistant Enterobacterales (3GCRE). In 2021, drug-resistant infection...www.ijidonline.com
Ответ для Chris Hopkins
Jonathan Ryder, MD

Looks like the editorial was submitted before this RCT was published, so the table already needs updated!

Ответ для Jonathan Ryder, MD
Jason Gallagher

I was the editor for this and nudged them on that. Table 2 is how they addressed it. The design can't answer the question of whether 3 days of IV abx isn't enough, but at least it contributes to the body of knowledge that we can get them out of the hospital and on something oral early... even if 1/

Ответ для Jason Gallagher
Jason Gallagher

that oral therapy isn't really necessary. 2/

Ответ для Jason Gallagher
Jonathan Ryder, MD

Agree, it definitely adds interesting information. Always challenging when a trial is designed and the paradigm of the diagnosis definition changes during the trial or prior to publication!

Ответ для Jason Gallagher
bugsdrugs

@absteward.bsky.social can’t help but think this implies that shorter duration is probably sufficient rather than the oral fosfo is non-inferior to longer IV course. Who’s to say that A “skittles” /placebo arm of the trial could not have produced comparable results?

Ответ для bugsdrugs
bugsdrugs

@jonathanrydermd.bsky.social interested in knowing what you think

Ответ для bugsdrugs
Jonathan Ryder, MD

Agreed for the “cUTI” that were actually cystitis we know that’s the case. But a fair number of patients were sick which makes us wonder. Or maybe fosfo is fine at this stage with most infection gone anyway