Best Strategies in Recurrent or Persistent Clostridium Difficile Infection

Background: Clostridium difficile infection (CDI) is the primary cause of antibiotic-associated colitis and 15-25% of nosocomial antibiotic-associated diarrhea. Its clinical manifestations can range from mild diarrhea to toxic megacolon, bowel perforation, septic shock, and death. Over the past decade, more virulent strains have become increasingly common causes, and the incidence of CDI has risen, especially in elderly patients. These developments have led to an increase in recurrent CDI, which is more difficult to treat. This review focuses on recurrent CDI and its treatment.

Methods: MEDLINE review using search terms Clostridium difficile, Clostridium difficile infection, recurrent Clostridium difficile infection.

Results: A first recurrence may be treated with the same regimen as the first episode. Metronidazole 500 mg q 8 h for 10-14 days is the drug of choice for moderate infection, and vancomycin 125 mg q 6 h for 10-14 days is the drug of choice for severe CDI. Metronidazole should not be used for treatment of subsequent recurrences because of potential neurotoxicity and hepatic toxicity. Second recurrences should be treated with an oral vancomycin course and taper: 125 mg q 6  h × 10-14 days, 125 mg q 12 h × 7 days, 125 mg q 24 h × 7 days, 125 mg q 48-72  h × 2-8 weeks. Alternative agents are fecal bacteriotherapy, a "rifaximin chaser," nitazoxanide, probiotics, and intravenous immunoglobulin. Fidaxomicin has been approved recently. Monoclonal antibodies against C. difficile toxin remain investigational.

Conclusion: Treatment of recurrent CDI remains challenging. Because of the lack of high-quality studies, recommendations for treatment are based on expert opinion. Metronidazole and vancomycin are the mainstays of treatment for both the initial infection and the first recurrence. For second recurrences, a vancomycin course plus taper is recommended. For subsequent recurrences, treatment options are many, with no one approach being entirely satisfactory. New drugs (fidaximicin) and treatments (monoclonal antibodies against the causative toxin) appear promising.