Microbiota-based therapeutics in the treatment of recurrent Clostridioides difficile 🦠
@DrPaulGastro @Khanna_S @caterina_oneto
#MedTwitter #GITwitter #IDTwitter #ACG2022 #Cdiff
@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
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
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 👇🏽
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
NOT FDA approved (considered “experimental”)
Many ways to deliver #FMT
#FMT eliminated C. difficile AND restores the microbiota
Efficacy: 67-82%
Efficacy: 67-82%
#FMT beats antibiotics for rCDI
⭐️ We should be offering our patients with rCDI therapies that restore the microbiota
⭐️ We should be offering our patients with rCDI therapies that restore the microbiota
#FMT in the guidelines
Emerging microbiota restoration therapies for rCDI
⚠️FMT trials have lots of heterogeneity, including efficacy and safety assessments…
Enter LBPs!
⚠️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
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
Effective AND improves microbiota AND improves bile acids
CP101: broad consortium
Effective AND improves microbiota
Effective AND improves microbiota
VE303: 8 bacteria
Effective
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
@DrPaulGastro: explain that antibiotics are 1 part of the treatment;the other is to restore microbiome
A (relevant!) shameless throwback to #ACG2021
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