C Diff

Clostridioides difficile Infections – Matthew Meyers


  • 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 toxins to causes colitis and diarrhea
  • Risk Factors: Antibiotic use (during use or typically up to 1 month after use), age >65, hospitalization, PPI use, enteral feeding, obesity, stem cell transplant, chemo, IBD, cirrhosis



  • Spectrum from asymptomatic carrier to fulminant colitis with toxic megacolon
      • Non-severe disease: watery diarrhea (>3 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: above + hypotension/shock, ileus (rare), or megacolon
  • Recurrent disease: 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


  • Several options for lab testing but we have algorithm at VUMC: 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
  • Obtain KUB at least; prefer CT if suspicious for severe disease 
  • 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
  • Indications for EGS consult: intestinal perforation, toxic megacolon - 7 cm diameter in colon or >12 cm diameter in cecum
  • Do not repeat stool testing – 50% remain positive after treatment up to 6 weeks later
  • Initial episode with non-severe disease: Vancomycin 125 mg (some GI providers use 250) PO QID x 10 days or fidaxomicin 200 mg PO BID x 10 days (less recurrence, more $$$)
  • Initial episode with severe disease: above and, if not improving after 3-5 days, consider both oral vanc and fidaxomicin, consider longer course than 10 days based on severity of disease and improvement
  • Initial episode with fulminant disease: vancomycin 500 mg PO QID AND metronidazole 500 mg IV q 8 hours
  • If ileus, consider use of rectal vancomycin and fecal microbiota transplant
  • Surgery: EGS consult if any of the following are present:
    • Hypotension, lactic acidosis (>2.2), WBC > 20,000, Fever >= 38.5C, ileus, abdominal distension, peritoneal signs, admission to MICU, mental status changes, end-organ failure, or failure to improve after 3-5 days
  • Recurrent disease:
    • First – oral vancomycin as above (pulse-tapered regimen) or fidaxomicin
    • Second – vancomycin (pulse-tapered), fidaxomicin, or combo vancomycin rifaximin
    • Third – consider fecal microbiota transplant (currently on hold per FDA mandate)