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Clostridioides Difficile Infections

Anton de Witte


  • Clostridioides difficile is the causative bacteria for antibiotic-associated colitis
  • Always consider C. diff in a hospitalized patient with unexplained leukocytosis
  • Microbiology: Anaerobic gram-positive, spore-forming, toxin-producing bacillus
  • Outside colon, exists in spore form – resistant to heat, acid, and antibiotics (why we must wash our hands)
  • Spores are transferred from environment to person, once in intestine convert to functional vegetative, toxin-producing forms susceptible to antibiotics
  • To be pathogenic, must release toxin (A+B) to cause colitis and diarrhea
  • Risk Factors: Antibiotic use (during use or typically up to 1 month after use), age >65, hospitalization, enteral feeding, obesity, stem cell transplant, chemo, IBD, cirrhosis, ± PPI use (no clear causal relationship)


  • Spectrum from asymptomatic carrier to fulminant colitis with toxic megacolon
  • Asymptomatic carrier: 20% of hospitalized patients (50% of adults in long term care facilities)
  • Non-severe disease: watery diarrhea (>3 unformed stools in 24 hours), lower abdominal pain, nausea, ± fever, leukocytosis (WBC >15,000)
  • Severe disease: diarrhea, diffuse abdominal pain, abdominal distention, fever, lactic acidosis, AKI (Cr > 1.5), marked leukocytosis (sometimes >40,000)
  • Fulminant disease: Severe criteria + hypotension/shock, ileus (rare), or megacolon (>7cm colon diameter and/or >12cm cecum diameter)
  • Recurrent disease (relapse > reinfection): resolution of symptoms on therapy followed by reappearance of symptoms within 2-8 weeks after stopping therapy; (Up to 25% of patients have recurrence)
  • If symptoms never resolve, consider refractory C. diff or alternative diagnosis


  • Stool PCR for toxigenic strains (very sensitive, can detect asymptomatic carriers w/o toxin production); with reflex EIA (enzyme immunoassay) for toxins A and B (specificity of 99%)
    • PCR (+)/Toxin (-) = carrier
    • PCR (+)/Toxin (+) = treat
    • PCR (-) = no treatment
  • Imaging
    • Nonsevere disease: no imaging necessary
    • Severe or fulminant disease: CT a/p with oral and IV contrast
  • Endoscopy: Typically used when alternative diagnosis is suspected; not warranted for classical symptoms, positive laboratory tests, or clinical response to treatment


  • Contact precautions until at least 48 hours after diarrhea resolves
  • Classify patient disease severity to guide treatment algorithm
  • Do not repeat stool testing – 50% remain positive after treatment up to 6 weeks later
Clinical Condition Treatment
Non-fulminant disease
Initial episode (non-severe or severe)

-First line: PO Vancomycin 125mg QID x 10 days OR PO Fidaxomicin 200mg BID x 10 days

-Second line: (only for non-severe disease in low-risk patients): PO Metronidazole 500mg TID x 10-14 days

Recurrent episode

Consult GI

First Recurrence:

-First line: PO Fidaxomicin 200mg BID x 10 days

-Second line: Vancomycin Taper (PO 125mg QID x 14 days PO 125mg BID x 7 days PO 125mg QD x 7 days PO 125mg q72h x 2-8 weeks)

-Adjunctive therapy: IV Bezlotoxumab 10mg/kg x1

Second or Further Recurrence:

-Same as above

-Consider Fecal Microbiota Transplantation (FMT)

Fulminant disease
Fulminant disease

Consult GI and EGS

Ileus Absent:

-PO Vancomycin 500mg QID + IV Metronidazole 500mg TID

Ileus Present

-Same as above + consider Vancomycin enemas 500mg q6h

Consider colectomy or FMT