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
Pharmacotherapy
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
- Fecal transplantation is recommended for multiple recurrent C difficile infection
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