John Damianos, M.D. Profile picture
Oct 23, 2022 26 tweets 15 min read Read on X
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

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More from @john_damianosMD

Oct 27
Gastroparesis with @BMoshiree

#MedTwitter #GITwitter #ACG2024 @AmCollegeGastro Image
Prevalence of gastroparesis-like symptoms: 1.3% worldwide, 3.7% in the US Image
Working up gastroparesis-like symptoms Image
Read 21 tweets
Oct 26
Treatment of upper gastrointestinal bleeding

#MedTwitter #GITwitter #ACG2024 @AmCollegeGastro Image
✅Erythromycin
❌Metoclopramide Image
Image
Image
❓PPI Image
Image
Read 15 tweets
Mar 14
A master class on prokinetics from @NGMJournal! Here is a summary! 🧵👇

⚡️🎈〽️🪠🫀💩🚄🧠✳️🗯️💊📰🚽🔌🧪💡🧲📊🔎

#MedTwitter #GITwitter #motility #pharmacology

onlinelibrary.wiley.com/doi/full/10.11…
Image
Pyridostigmine & neostigmine
⚡️cholinesterase inhibitors
🧠pyrido should not cross the blood-brain barrier
🚽evidence in chronic idiopathic constipation and acute colonic pseudo-obstruction
🫄pregnancy class C; excreted in breastmilk
🫀cholinergic side effects, esp bradycardia Image
Acotiamide
⚡️inhibits cholinesterase and enhances ACh release via muscarinic receptors
🎈enhances gastric emptying and accommodation
🔥NERD & FD
🫄no safety data
💊side effects: nausea, abdominal distension, constipation Image
Read 20 tweets
Dec 15, 2022
I gave a talk on inpatient bowel regimens today for the @YaleMed @YaleIMed residents and students, with additional 💎s on outpatient #constipation. Here are the slides!

💩 💩 💩

#MedTwitter #GITwitter #motility #MedEd @YaleIM_Chiefs @MayoClinicGIHep
Most inpatients require a bowel regimen. Our patients typically have most of the risk factors for #constipation!
#Constipation is more about symptoms than frequency! 🚽

It’s also a *symptom* (like chest pain), so need to figure out what’s causing it and treat accordingly.
Read 20 tweets
Dec 13, 2022
💨The gut microbiota generates ~0.2L–1.5L of gas per day
💨>99%: hydrogen (H2), carbon dioxide (CO2), & methane (CH4)– *odorless*
💨foul smell of gas from <1%: sulfur–containing gases hydrogen sulfide (H2S), methanethiol (CH3SH), dimethyl sulfide [(CH3)2S] + volatile compounds
🦠bacteria in the colon ferment substrates that are not digested or absorbed in the upper GI tract (e.g. carbohydrates, proteins, fats)
🦠produce short-chain fatty acids, branched-chain fatty acids, ammonia, N-nitro compounds, phenolic and indolic compounds, and various gases
Read 15 tweets
Oct 23, 2022
Summarizing our learning at #ACG2022 today! 🧑‍🎓

@tinahamd @AmCollegeGastro #MedTwitter #GITwitter
💎 GI bleeding🩸
💎#IBD
Read 8 tweets

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