Treatment of Clostridioides difficile Infection
Oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days are the recommended first-line treatments for Clostridioides difficile infection (CDI), with metronidazole now considered only as an alternative for non-severe cases. 1, 2, 3
Treatment Based on Disease Severity
Non-Severe CDI
- Vancomycin 125 mg orally four times daily for 10 days is recommended as first-line therapy 1, 2, 3
- Fidaxomicin 200 mg orally twice daily for 10 days is an effective alternative with lower recurrence rates 1, 2
- Metronidazole 500 mg orally three times daily for 10 days may be considered as an alternative, but should be limited to initial episodes of mild-moderate CDI due to increasing treatment failures 1, 2
Severe CDI
- 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 1, 2
- Criteria for severe CDI include: leukocytosis (WBC >15 × 10^9/L), serum albumin <30 g/L, or rise in serum creatinine (≥133 μM or ≥1.5 times premorbid level) 2
Fulminant CDI
- Vancomycin 500 mg orally four times daily with intravenous metronidazole 500 mg three times daily is recommended 1
- When oral treatment is not possible, intravenous metronidazole combined with intracolonic or nasogastric vancomycin is recommended 1, 2
- Early surgical consultation is advised for patients with systemic toxicity 1, 2
Treatment of Recurrent CDI
- For first recurrence: vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days 1, 2, 3
- For second or subsequent recurrences: vancomycin with a tapered and pulsed regimen or consideration of fecal microbiota transplantation (FMT) 4, 1, 2
- Vancomycin extended regimen: standard dose for 10-14 days, then twice daily for a week, then once daily for a week, then every 2-3 days for 2-8 weeks 4
Pediatric Treatment Considerations
- For non-severe first episode or first recurrence in children: metronidazole (7.5 mg/kg/dose, max 500 mg) or vancomycin (10 mg/kg/dose, max 125 mg) four times daily for 10 days 4, 3
- For severe or fulminant infection in children: vancomycin is recommended (10 mg/kg/dose, max 500 mg) 4
- For children with multiple recurrences: vancomycin extended regimen or consideration of FMT 4
Important Clinical Considerations
- Discontinue the inciting antibiotic as soon as possible to reduce the risk of CDI recurrence 1, 2, 3
- 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 1, 2
- Fidaxomicin has been shown to have lower recurrence rates compared to vancomycin but may not be superior in certain populations 1, 5
- Fecal microbiota transplantation has high cure rates in patients with multiple recurrent episodes who have received appropriate antibiotic therapy 6, 7
Treatment Pitfalls to Avoid
- Metronidazole is no longer recommended as first-line therapy for adults due to increasing treatment failures and potential neurotoxicity with prolonged use 1, 6
- Vancomycin capsules must be given orally for CDI treatment; parenteral administration is not effective for CDI 8
- Avoid repeated or prolonged courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity 1
- Monitor renal function in patients >65 years of age during and after treatment with vancomycin, as nephrotoxicity can occur even with oral administration 8