Clostridioides Difficile Infections

Anton De Witte

Background

  • 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) o
    • Spores are transferred from environment to person, once in intestine convert to functional vegetative, toxin-producing forms à 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)

Presentation

  • 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

Evaluation

  • 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

Management

  • 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 (nonsevere 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 ID +/- GI

First Recurrence:

  • First line: PO Fidaxomicin 200mg BID x 10 days
  • Second line: Vancomycin Taper (PO 125mg QID x 14 days à PO 125mg BID x 7 days à PO 125mg QD x 7 days à 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 ID, 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
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