Clostridioides Difficile Infections

Kayley Josephs

Background

  • Clostridioides difficile (C. diff) is the bacteria that causes antibiotic-associated colitis.
  • One of the most common healthcare associated infections.
  • 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 spores are inside the intestine -> convert to functional vegetative, toxin-producing forms (susceptible to antibiotics).
  • C. diff releases toxins (A+B) that cause colitis and diarrhea.
  • Risk Factors: antibiotic use (within the last 30 days), age > 65, recent hospitalization, enteral feeding, chemo, IBD, cirrhosis, PPI use.

Presentation

  • Spectrum from asymptomatic carrier (no clinical symptoms) 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, abdominal pain, abdominal distention, fever, lactic acidosis, AKI, marked leukocytosis (sometimes > 40,000).
  • Fulminant disease: Severe criteria + hypotension/shock, or megacolon (> 7cm colon diameter and/or > 12cm cecum diameter).
  • Recurrent disease: resolution of symptoms on therapy -> reappearance of symptoms within 2-8 weeks after stopping therapy (up to 25% of patients).
    • Persistent symptoms despite therapy -> 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/B (up to 99% specificity). 
    • PCR (+)/Toxin (-) = asymptomatic carrier vs low production of toxin (use clinical judgement to decide whether to treat).
    • PCR (+)/Toxin (+) = treatment required.
    • PCR (-) = no treatment required.
  • Imaging 
    • Non-severe disease: no imaging necessary.
    • Severe or fulminant disease: CT A/P with oral and IV contrast.
  • Endoscopy: Typically performed when alternative diagnosis is suspected that requires visualization +/- biopsy of bowel mucosa.

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 up to 6 weeks after treatment.

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 14d -> PO 125mg BID x 7d -> PO 125mg QD x 7d -> PO 125mg q72h x 2-8wks)
  • 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 + Vancomycin enemas 500mg q6h (can be stopped once ileus resolves)

Consider colectomy or FMT

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