C. diff infection (mechanism of disease)

This is a flowchart on Clostridioides difficile (formerly Clostridium difficile), covering the etiology, pathophysiology, and manifestations.

ADDITIONAL TAGS:
Oral transmission of C. diff, which can form spores resistant to heat, antibiotics, acid
Hospital-acquired: via contaminated surfaces, medical equipment
Risk factors / SDOH
Cell / tissue damage
Structural factors
C. difficile infection
Medicine / nosocomial
Infectious / microbial
Biochem / molecular bio
Immunology / inflammation
Signs / symptoms
Tests / imaging / labs

Metabolic / hormonal
Genetics / hereditary
Flow physiology
Pathophysiology
Etiology
Manifestations
Clostridioides difficile (formerly Clostridium difficile) infects and causes inflammation in the colon
Releases toxin A (enterotoxin)
Releases toxin B (cytotoxin)
Binds to enterocyte brush border
Endocytosis
Conformational change exposing active domain
Glycosylates target proteins: Rac, Cdc42, RhoA
Disrupts cytoskeleton
↑ epithelial permeability
Induces apoptosis
Forms pores in endosomal membrane
Endosomal content enters cytosol
Damages cell
Enterocyte death
Watery diarrhea (3 stools / day)
+/- traces of mucus, occult blood
+/- characteristic odor
Dehydration
Cramping abdominal pain
Diffuse abdominal tenderness
Anorexia
Nausea
Fever
Typical symptoms, occurring 2-10 days after initiation of antibiotics
Paralytic ileus
Toxic megacolon
Perforation → peritonitits
Diffuse tympany on percussion
Abdominal distention
Constipation
(Bloody) diarrhea and vomiting
Sepsis → shock
Tachycardia
Tachypnea
Fever
Hypotension
Complications
Community-acquired: fecal-oral route
Recent antibiotics (clindamycin, cephalosporins, fluoroquinolones penicillin, macrolides others)
Destroys the normal intestinal bacterial flora that normally suppresses C. diff overgrowth
Gastric acid suppression
Proton pump inhibitors (-prazole)
Gastric acid bypass
Enteral feeding
Unsanitary drinking water
Advanced age
Severe illness
Recent hospitalization
Immune suppression
Inflammatory bowel disease