Clostridium difficile infection is commonly associated with antibiotic treatment and is one of the most common nosocomial infections.
Symptoms usually start on days 4-9 of antibiotic treatment, but may also occur up to 8-10 weeks after discontinuation of antibiotics.
Discontinuation of antibiotics may be the only measure needed for patients with only mild diarrhea, no fever, no abdominal pain nor a high WBC count.
Cessation of antibiotics allows for reconstitution of the normal colonic microflora and markedly reduces risk of relapse.

Principles of Therapy

  • The first step in otherwise healthy patients is to stop the offending antibiotic
  • Discontinuation of antibiotics may be the only measure needed for patients w/ only mild diarrhea, no fever, no abdominal pain nor a high white blood cell (WBC) count
    • Cessation of antibiotics allows for reconstitution of the normal colonic microflora & markedly reduces the risk of relapse
  • Antibiotic therapy specific for C difficile should be given to the following:
    • Patients w/ severe diarrhea or colitis
    • Elderly patients
    • Patients w/ multiple concomitant illnesses
    • Patients in whom antibiotics cannot be discontinued
  • Treatment for C difficile should be started if colitis is evident & diarrhea continues despite discontinuation of precipitating antibiotic
    • If w/ fulminant C difficile infection & clinical condition deteriorates despite antibiotic therapy, surgical treatment w/ total abdominal colectomy or a diverting loop ileostomy w/ colonic lavage is recommended
  • Oral route of administration is preferred because C difficile remains w/in the lumen of the colon & does not invade the mucosa
  • Opiates & antidiarrheal medications should be avoided because impaired intestinal motility can worsen toxin-mediated disease
  • Proton pump inhibitor use should also be reviewed

Duration of Therapy

  • Antibiotics are generally given for 10-14 days
    • Normalization of stool consistency & frequency may take weeks after clinical response
  • Prolonged treatment may be necessary for patients w/ severe colitis or those w/ underlying gastrointestinal (GI) conditions



  • Oral Metronidazole is the 1st-line therapy for C difficile infection
    • Not to be used in severe disease, complicated course, or in multiple recurrences
  • Intravenous (IV) Metronidazole may be used for patients who are too ill to tolerate the oral form
    • If ileus is present, consider the addition of Vancomycin via nasogastric tube or nasal small-bowel tube
  • Efficacy in treating C difficile-induced diarrhea is comparable w/ oral Vancomycin
    • Oral Metronidazole is preferred because of concerns about Vancomycin-resistant enterococci


  • Considered 2nd-line therapy because of concerns regarding the development of Vancomycin-resistant enterococci
  • May be used for therapeutic failure of Metronidazole & in patients who cannot tolerate Metronidazole
    • Treatment w/ Metronidazole should have been given for at least 5 days before considering therapeutic failure
    • Superior to Metronidazole in patients w/ severe C difficile infection
  • Preferred for pregnant patients
  • Poorly absorbed from the intestines, which results in high concentrations in the intestines along w/ fewer adverse effects
  • IV Vancomycin is not effective


  • As effective as Vancomycin but w/ fewer secondary recurrences

Other Agents

Bacitracin (Oral)

  • Less effective than Vancomycin or Metronidazole
  • Given at 25,000 u PO every 6 hours x 10 days


  • As effective as Vancomycin but there is concern regarding the development of resistant enterococcal strains

Cholestyramine, Colestipol

  • Binds C difficile toxins
  • Results of studies have been variable
  • Binds Vancomycin & should therefore not be used concomitantly w/ this drug

Biologic Agents & Other Therapies

  • Includes immunoglobulins, monoclonal antibodies, & probiotics Saccharomyces boulardii & Lactobacillus GG
    • S boulardii is inadequate when used as single therapy for C difficile infection
    • More studies are needed before these can be recommended
  • Other therapies include rectal instillation of anaerobic bacteria & rectal enemas of feces from healthy relatives
    • Fecal transplantation is recommended for multiple recurrent C difficile infection
      • Consider a fecal microbiota transplant if w/ third recurrence after a pulsed Vancomycin therapy

Treatment of Relapses

  • Mild relapses often resolve spontaneously & do not require antibiotics
  • For first recurrence, drug previously given may be reused
    • Oral Vancomycin or Fidaxomicin is preferred if severe or multiple recurrences of C difficile infection

Other Relapse Regimens

  • Metronidazole 500 mg PO 6 hourly x 10 days followed by Cholestyramine 4 g PO 8 hourly + Lactobacillus 1 g PO 6 hourly x 4 weeks
  • Vancomycin taper:
    • 125 mg PO 6 hourly x 1 week, then 12 hourly x 1 week, then 24 hourly x 1 week, then every other day x 1 week then every 3 days x 2 doses
    • Taper inhibits C difficile vegetative cells but preserves colonic flora
  • Vancomycin pulse therapy:
    • 125 mg PO q2 days or 500 mg PO every 3 days x 3 weeks
    • Used for the second recurrence of C difficile infection
  • Vancomycin high dose w/ S boulardii
    • 250-500 mg PO 6 hourly x 10 days followed by S boulardii 500 mg PO 12 hourly x 4 weeks
  • Patients w/ >10 episodes of recurrent diarrhea may need long-term therapy

Supportive Therapy

  • Administer fluids & electrolytes to rehydrate & maintain hydration
    • Please see Diarrhea - Infectious Management Chart for specific therapy
  • Diarrhea may resolve w/ conservative management in approximately 15-23% of otherwise healthy patients
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