• 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

Metronidazole

• 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

Vancomycin

• 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

Fidaxomicin

• 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

Teicoplanin

• 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

• 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