What is the treatment for Clostridioides difficile (C. diff) infection?

Treatment for Clostridioides difficile Infection

Oral vancomycin 125 mg four times daily for 10 days is the first-line treatment for all initial C. difficile infections regardless of severity, with fidaxomicin 200 mg twice daily for 10 days as an equally effective alternative that offers lower recurrence rates. 1, 2, 3

Initial Episode Treatment

Non-Severe Disease

• Non-severe CDI is defined as WBC ≤15,000 cells/mL and serum creatinine <1.5 mg/dL 3
• 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 equally effective alternative with significantly lower recurrence rates (preferred when available) 1, 3, 4
• Metronidazole 500 mg orally three times daily for 10 days may be used only for non-severe initial episodes in younger patients with few risk factors for recurrence, though it is increasingly considered inferior 1, 2, 5

Severe Disease

• Severe CDI is defined as WBC ≥15,000 cells/mL, serum creatinine >1.5 mg/dL, or low serum albumin 1, 2, 3
• Vancomycin 125 mg orally four times daily for 10 days is the treatment of choice 1, 2
• Vancomycin demonstrated superior cure rates compared to metronidazole in severe CDI (97% vs. 76%) 3
• Fidaxomicin 200 mg orally twice daily for 10 days is an effective alternative 1, 2

Fulminant Disease

• Fulminant CDI presents with hypotension, shock, ileus, toxic megacolon, or peritonitis 1
• Vancomycin 500 mg orally four times daily PLUS intravenous metronidazole 500 mg three times daily is the recommended regimen 1, 2
• When oral administration is not possible, use vancomycin 500 mg in 100 mL normal saline four times daily via nasogastric tube or retention enema, combined with IV metronidazole 500 mg three times daily 1
• Early surgical consultation is essential for patients with systemic toxicity, perforation, or toxic megacolon 1, 2
• Subtotal colectomy with end ileostomy is the established surgical procedure, though loop ileostomy with colonic lavage is emerging as a colon-salvage alternative 1

Recurrent C. difficile Infection

First Recurrence

• Fidaxomicin 200 mg orally twice daily for 10 days is the preferred option for first recurrence, particularly when vancomycin was used initially 1, 2, 3
• Vancomycin 125 mg four times daily for 10 days is recommended if metronidazole was used for the initial episode 1, 2
• Avoid metronidazole for recurrent episodes due to lower sustained response rates and risk of cumulative neurotoxicity 1, 3

Second and Subsequent Recurrences

• Vancomycin tapered and pulsed regimen is recommended: 125 mg four times daily for 10-14 days, then 125 mg twice daily for 7 days, then 125 mg once daily for 7 days, then 125 mg every 2-3 days for 2-8 weeks 1, 3
• Fecal microbiota transplantation (FMT) is strongly recommended after at least 2 recurrences that have failed appropriate antibiotic treatments 2, 3, 5
• Bezlotoxumab (monoclonal antibody against C. difficile toxin B) may prevent recurrences in high-risk patients when given as adjunctive therapy 2, 5

Pediatric Treatment (≥6 Months of Age)

Non-Severe or First Recurrence

• Metronidazole 7.5 mg/kg/dose (max 500 mg) orally four times daily for 10 days OR vancomycin 10 mg/kg/dose (max 125 mg) orally four times daily for 10 days 1
• For children weighing ≥12.5 kg who can swallow tablets: fidaxomicin 200 mg orally twice daily for 10 days 4

Severe or Fulminant Infection

• Vancomycin 10 mg/kg/dose (max 500 mg) every 8 hours for 10 days, with or without IV metronidazole 1

Multiple Recurrences in Children

• Vancomycin extended regimen (same tapering schedule as adults, weight-adjusted) 1
• Fecal microbiota transplantation (FMT) should be considered 1

Critical Management Principles

Essential Actions

• Discontinue the inciting antibiotic agent(s) as soon as possible to reduce recurrence risk 1, 2, 3
• Clinical response typically requires 3-5 days after starting therapy 3
• Do not perform a "test of cure" after treatment completion 3

Important Pitfalls to Avoid

• Avoid antiperistaltic agents and opiates in patients with CDI 3
• Avoid repeated or prolonged courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity 1, 2, 3
• Do not use metronidazole for severe or recurrent CDI due to lower efficacy 2
• Do not delay treatment for severe CDI while awaiting diagnostic confirmation 2

Infection Control

• Hand hygiene must be performed with soap and water rather than alcohol-based sanitizers, as alcohol does not kill C. difficile spores 1, 2
• Implement strict infection control measures including contact precautions 2

Monitoring and Follow-up

• Approximately 20% of patients experience recurrence, with higher risk in elderly patients and those with continued antibiotic use 3
• Recurrence can be due to either relapse or reinfection 5