Thread by @john_damianosMD

Microbiota-based therapeutics in the treatment of recurrent Clostridioides difficile 🦠

@DrPaulGastro @Khanna_S @caterina_oneto

#MedTwitter #GITwitter #IDTwitter #ACG2022 #Cdiff

Pathogenesis of CDI
1. Disruption of #microbiome (antibiotics) ▶️ loss of colonization resistance
2. Colonization
3. Spore ▶️ vegetative ▶️ toxin
4. Recurrence cycle or restoration of microbiota

Antibiotics control acute disease, but do not protect against recurrence

rCDI disrupts the #microbiome

Antibiotics and rCDI

CDI treatment @AmCollegeGastro vs IDSA/SHEA

The vegetative form makes TOXIN. Antibiotics affect the vegetative state, NOT the spore form.

What affects the spore form? A healthy #microbiome!

Next-generation therapies address the microbiota

Bezlotoxumab: monoclonal antibody targeting B toxin (give during antibiotic treatment for CDI)

Contraindication: heart failure

Bez ⬇️ risk of recurrence by ~10% (NNT 10- even lower in higher risk patients!)

High risk features 👇🏽

Fecal microbiota transplantation: targets the underlying pathophysiology of rCDI— dysbiosis

NOT FDA approved (considered “experimental”)

Many ways to deliver #FMT

#FMT eliminated C. difficile AND restores the microbiota

Efficacy: 67-82%

#FMT beats antibiotics for rCDI

⭐️ We should be offering our patients with rCDI therapies that restore the microbiota

Safety concerns of #FMT

Now also need to consider SARS-CoV-2 and #Monkeypox

#FMT in the guidelines

@Khanna_S summarizing bezlotoxumab and #FMT

Emerging microbiota restoration therapies for rCDI

⚠️FMT trials have lots of heterogeneity, including efficacy and safety assessments…

Enter LBPs!

LBPs are microbiome supplementation with FDA approval

RBX2660: broad consortium

Effective AND restores microbiota

RBX2660 also improves bile acid profile to more favorable ⬆️ secondary bile acids that inhibit spore form

SER-109: firmicutes spores

Effective AND improves microbiota AND improves bile acids

CP101: broad consortium

Effective AND improves microbiota

VE303: 8 bacteria

Effective

Trial comparison

9 in 10 did not meet trial criteria. Need more data!

@DrPaulGastro summary:

@Khanna_S: explain to patients that metronidazole and vancomycin are BROAD-SPECTRUM, so not only destroy C diff, but also healthy microbiota that will prevent recurrence of CDI
@DrPaulGastro: explain that antibiotics are 1 part of the treatment;the other is to restore microbiome

A (relevant!) shameless throwback to #ACG2021

https://twitter.com/john_damianosMD/status/1453101864606568451