Treatment of Clostridioides difficile Infection (C. diff)
For initial C. diff infection, oral vancomycin 125 mg four times daily for 10 days is recommended as first-line therapy regardless of disease severity, with metronidazole 500 mg three times daily for 10 days as an alternative for non-severe cases only. 1
Treatment Based on Disease Severity
Non-severe C. diff Infection
- Metronidazole 500 mg orally three times daily for 10 days is recommended for first, non-severe CDI episodes 1
- Vancomycin 125 mg orally four times daily for 10 days is recommended for first CDI episodes regardless of severity 1
- Fidaxomicin 200 mg orally twice daily for 10 days is suggested as an alternative for first CDI episodes 1, 2
- Metronidazole should be limited to initial episodes of mild-moderate CDI due to increasing treatment failures 1
Severe C. diff Infection
- Vancomycin 125 mg orally four times daily for 10 days is the treatment of choice 1, 2
- Fidaxomicin 200 mg orally twice daily for 10 days is an effective alternative with lower recurrence rates 2, 3
- Criteria for severe CDI include: leukocytosis (WBC >15,000/mm³), serum albumin <30 g/L, or rise in serum creatinine ≥1.5 times premorbid level 1, 2
Fulminant C. diff Infection
- Vancomycin 500 mg orally four times daily with intravenous metronidazole 500 mg three times daily 1
- When oral treatment is not possible, intravenous metronidazole combined with intracolonic or nasogastric vancomycin is recommended 1
- Early surgical consultation is advised for patients with systemic toxicity 1, 4
Treatment of Recurrent C. diff Infection
First Recurrence
- Vancomycin 125 mg four times daily for 10 days is recommended, especially if metronidazole was used for the first episode 1
- Fidaxomicin 200 mg twice daily for 10 days is suggested, particularly when vancomycin was used for the first episode 1
- Avoid metronidazole for recurrent episodes due to lower sustained response rates 1
Second or Subsequent Recurrences
- Vancomycin in a tapered and pulsed regimen (125 mg four times daily for 10-14 days, then twice daily for 7 days, then once daily for 7 days, then every 2-3 days for 2-8 weeks) 1
- Vancomycin followed by rifaximin (400 mg three times daily for 20 days) 1
- Fidaxomicin 200 mg twice daily for 10 days 1, 3
- Fecal microbiota transplantation after appropriate antibiotic treatment for at least 2 recurrences 1, 5
Special Populations
Pediatric Patients
- For non-severe first episode or first recurrence: metronidazole (7.5 mg/kg/dose, max 500 mg) three or four times daily for 10 days OR vancomycin (10 mg/kg/dose, max 125 mg) four times daily for 10 days 1
- For severe or fulminant infection: vancomycin (10 mg/kg/dose, max 500 mg) orally or rectally every 8 hours, with or without IV metronidazole 1
- For multiple recurrences: vancomycin extended regimen or adjunctive fecal microbiota transplantation 1
Important Considerations
- Discontinue the inciting antibiotic as soon as possible, as continued use significantly increases the risk of CDI recurrence 1, 2
- Avoid repeated or prolonged courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity 1
- Fidaxomicin has been shown to have lower recurrence rates compared to vancomycin but may not be superior in Asian populations 1, 6
- Vancomycin may increase the risk of vancomycin-resistant Enterococci (VRE) acquisition compared to fidaxomicin (31% vs 7%) 1
- Avoid antiperistaltic agents and opiates as they may mask symptoms and worsen disease 2
- Hand hygiene should be performed with soap and water rather than alcohol-based sanitizers, as alcohol does not kill C. diff spores 2
Treatment Algorithm
- Assess disease severity based on WBC count, serum albumin, and creatinine levels
- For non-severe first episode:
- For severe first episode:
- For first recurrence:
- For multiple recurrences: