Classification of Clostridioides difficile Infection by Severity
Clostridioides difficile infection should be classified into three severity categories—mild-to-moderate, severe, and fulminant—using specific clinical and laboratory parameters that directly predict mortality and surgical intervention risk. 1
Mild-to-Moderate CDI
Mild-to-moderate disease is defined by:
- WBC < 15,000 cells/mL 2, 1
- Serum creatinine < 1.5 times baseline 2, 1
- Diarrhea without systemic signs of severe infection 2, 1
- May have mild abdominal pain and cramping 1
First-line treatment for mild-to-moderate CDI:
- Oral vancomycin 125 mg four times daily for 10 days 2
- Oral fidaxomicin 200 mg twice daily for 10 days (alternative, especially if high recurrence risk) 2
- Metronidazole 500 mg three times daily for 10-14 days is no longer recommended as first-line therapy in adults, though it may remain reasonable for select mild cases 2, 3, 4
Severe CDI
Severe disease is characterized by any one or more of the following:
- WBC ≥ 15,000 cells/mL 2, 1
- Serum creatinine ≥ 1.5 mg/dL or ≥ 50% increase above baseline 2, 1
- Serum albumin < 2.5-3.0 g/dL 1
- Age > 65 years 1
- Body temperature > 38.5°C 1
- ≥ 10 bowel movements within 24 hours 1
- Severe abdominal pain 1
- Evidence of pseudomembranous colitis on endoscopy 1
- ICU admission required 1
First-line treatment for severe CDI:
- Oral vancomycin 125 mg four times daily for 10-14 days (preferred) 2
- Oral fidaxomicin 200 mg twice daily for 10 days (alternative) 2
- If oral route not feasible: vancomycin 500 mg per rectum (in 500 mL saline as enema) four times daily AND/OR metronidazole 500 mg IV every 8 hours 2
Fulminant CDI
Fulminant disease represents life-threatening infection with:
- Hypotension or shock requiring vasopressors 2, 1
- End-organ failure 1
- Ileus 2, 1
- Toxic megacolon 2, 1
- Colonic perforation 1
- Septic shock 1
Treatment for fulminant CDI:
- Oral vancomycin 500 mg four times daily 2
- PLUS vancomycin 500 mg per rectum (in 500 mL saline) four times daily 2
- PLUS metronidazole 500 mg IV every 8 hours 2
- Multidisciplinary care is mandatory including critical care, surgery, gastroenterology, and infectious disease 2, 5
- Consider fecal microbiota transplantation if not responding to antibiotics within 2-5 days 2, 5
- FMT should be delivered via colonoscopy or flexible sigmoidoscopy as first dose 2, 5
- Surgical consultation for possible colectomy if medical management fails 1, 5
Recurrent CDI
Recurrent infection is defined as:
- Return of gastrointestinal symptoms due to CDI following initial resolution 1
- Occurring within 8 weeks after discontinuation of treatment 2, 1
- Affects 10-30% of patients after initial therapy 1
Treatment approach for recurrent CDI:
First recurrence:
- Repeat initial therapy with oral vancomycin or fidaxomicin 2
Second or subsequent recurrences:
- Vancomycin oral taper and pulse regimen: 125 mg every 6 hours × 1-2 weeks, then 125 mg every 12 hours × 1 week, then 125 mg every 24 hours × 1 week, then 125 mg every 48 hours × 2-8 weeks 2
- Fidaxomicin 200 mg twice daily for 10 days 2
- Fecal microbiota transplantation (highly effective for multiple recurrences) 2
- Bezlotoxumab (monoclonal antibody against toxin B) may be considered as adjunctive therapy in patients with high recurrence risk 6, 4
Critical Pitfalls to Avoid
- Never perform "test of cure" after treatment completion—over 60% of successfully treated patients remain C. difficile positive despite clinical resolution 7
- Do not use fidaxomicin for fulminant/complicated CDI—there are no data supporting its use in this setting 2
- Do not delay gastroenterology consultation in severe or fulminant cases—these are medical emergencies requiring immediate multidisciplinary involvement 5
- Consider post-infectious irritable bowel syndrome rather than recurrent CDI for mild symptoms after successful treatment 2, 7
- Treatment response may require 3-5 days after starting therapy, but escalation can be considered sooner based on disease severity 2