From the Guidelines
The treatment of severe Clostridioides difficile (C. diff) infection should be escalated to vancomycin 500 mg four times daily by mouth or nasogastric tube, plus intravenous metronidazole 500 mg every 8 hours, as recommended by the most recent guidelines 1.
Key Considerations
- For severe C. diff, oral vancomycin 125 mg four times daily for 10 days is the standard first-line therapy, but for severe complicated cases, treatment should be escalated to vancomycin 500 mg four times daily by mouth or nasogastric tube, plus intravenous metronidazole 500 mg every 8 hours 1.
- If ileus is present, consider adding vancomycin enemas (500 mg in 100 mL normal saline) every 6 hours 1.
- Surgical consultation should be obtained for patients with toxic megacolon, perforation, or refractory disease.
- Supportive care including fluid resuscitation, electrolyte replacement, and discontinuation of unnecessary antibiotics is essential.
- Fecal microbiota transplantation may be considered in adults hospitalized with severe or fulminant C. difficile infection not responding to antimicrobial therapy, as suggested by the AGA 1.
Treatment Options
- Vancomycin 500 mg four times daily by mouth or nasogastric tube, plus intravenous metronidazole 500 mg every 8 hours 1.
- Fidaxomicin 200 mg twice daily for 10 days may be used as an alternative to vancomycin, but its use in severe complicated cases is not well established 1.
- Bezlotoxumab 10 mg/kg given intravenously once during administration of standard of care antibiotics may be considered as an adjunctive treatment, but its use is limited by the risk of congestive heart failure 1.
Monitoring and Follow-up
- Patients should be monitored closely after completing treatment, as recurrence occurs in approximately 20-30% of cases.
- Follow-up stool tests and clinical evaluation should be performed to assess treatment response and detect potential recurrence.
From the FDA Drug Label
1 INDICATIONS AND USAGE 1.1 Clostridioides difficile-Associated Diarrhea DIFICID® is indicated in adult and pediatric patients aged 6 months and older for the treatment of C. difficile-associated diarrhea (CDAD).
The recommended treatment for severe C. difficile is not explicitly stated in the provided drug labels. However, fidaxomicin (PO) is indicated for the treatment of C. difficile-associated diarrhea (CDAD) in adult and pediatric patients aged 6 months and older 2. The dosage for adults is one 200 mg tablet orally twice daily for 10 days, and for pediatric patients, the dosage varies based on weight 2.
- Key points:
- Fidaxomicin (PO) is used to treat CDAD.
- The dosage is 200 mg twice daily for 10 days for adults.
- Pediatric dosage varies based on weight. However, the provided information does not specifically address the treatment of severe C. difficile.
From the Research
Treatment Options for Severe C. difficile Infection
- The treatment of severe C. difficile infection includes management of severe sepsis and shock, pathogen-directed antibiotic therapy, and, in selected cases, surgical intervention 3.
- Vancomycin and fidaxomicin are considered the cornerstones for the treatment of C. difficile infection 4.
- Fidaxomicin has been shown to be noninferior to vancomycin in terms of clinical cure rates, and is associated with a significantly lower rate of recurrence of C. difficile infection 5.
- Metronidazole should be used only in mild-to-moderate disease in younger patients who have no or only few risk factors for recurrence 4.
Recurrent C. difficile Infection
- Bezlotoxumab infusion, a monoclonal antibody against C. difficile toxin B, may be considered as an adjunctive therapeutic strategy in addition to standard care for patients with several risk factors for recurrence 4.
- Fecal microbiota transplantation (FMT) should be offered to patients with frequently recurring C. difficile infection 4.
- In patients with inflammatory bowel disease, fidaxomicin led to resolution of C. difficile infection in 60.6% of patients, with 30.0% developing a recurrence at a median of 55 days 6.
Special Considerations
- Patients with severe C. difficile infection require early and aggressive treatment, including management of severe sepsis and shock, and surgical intervention if necessary 3.
- Critically ill patients require treatment by an interdisciplinary team, consisting of early surgical intervention in combination with drug treatment 7.
- Fecal microbiota transplantation (FMT) is an effective therapy for patients who do not respond to fidaxomicin, including those with inflammatory bowel disease 6.