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

Treatment of Clostridioides difficile Infection

Oral vancomycin 125 mg four times daily for 10 days is the recommended first-line treatment for initial C. difficile infection regardless of disease severity. 1, 2

Initial Episode Treatment by Severity

Non-Severe CDI

• Vancomycin 125 mg orally four times daily for 10 days is preferred for all initial episodes, including non-severe cases 1, 2, 3
• Fidaxomicin 200 mg orally twice daily for 10 days is an effective alternative with lower recurrence rates 1, 2, 4
• Metronidazole 500 mg orally three times daily for 10 days may be used only for non-severe first episodes when vancomycin or fidaxomicin are unavailable, though this is increasingly discouraged due to inferior outcomes 1, 2

Severe CDI

• Vancomycin 125 mg orally four times daily for 10 days remains the treatment of choice 1, 2, 3
• Fidaxomicin 200 mg orally twice daily for 10 days is an acceptable alternative 1, 2
• Severe disease is defined by: elevated white blood cell count (>15,000 cells/μL), low serum albumin (<3 g/dL), or rising serum creatinine (≥1.5 times baseline) 1, 2, 3

Fulminant CDI

• 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 due to ileus, use vancomycin 500 mg in 100 mL normal saline four times daily via nasogastric tube or retention enema, combined with IV metronidazole 1
• Early surgical consultation is mandatory for patients with hypotension, shock, ileus, toxic megacolon, or peritonitis 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 CDI Treatment

First Recurrence

• Vancomycin 125 mg four times daily for 10 days is recommended, especially if metronidazole was used initially 1, 2, 3
• Fidaxomicin 200 mg twice daily for 10 days is preferred when vancomycin was used for the initial episode due to significantly lower recurrence rates 1, 2, 4
• Metronidazole should be avoided for recurrent episodes due to lower sustained response rates and risk of cumulative neurotoxicity 1, 2

Second and Subsequent Recurrences

• Vancomycin 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, 3
• Fecal microbiota transplantation (FMT) should be considered for multiple recurrences that have failed appropriate antibiotic treatments 2, 5
• Bezlotoxumab (monoclonal antibody against C. difficile toxin B) may be administered to prevent recurrences in high-risk patients 2, 5

Pediatric Treatment (≥6 months to <18 years)

Non-Severe or First Recurrence

• Vancomycin 10 mg/kg/dose (maximum 125 mg) orally four times daily for 10 days 1, 3
• Metronidazole 7.5 mg/kg/dose (maximum 500 mg) orally three times daily for 10 days is an alternative 1

Severe or Fulminant Disease

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

Multiple Recurrences

• Vancomycin extended tapered regimen (weight-adjusted, same schedule as adults) 1
• FMT should be considered 1

Critical Management Principles

Antibiotic Stewardship

• Discontinue the inciting antibiotic as soon as possible to reduce recurrence risk 1, 2, 3
• Avoid repeated or prolonged courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity 1, 2

Infection Control

• Hand hygiene must be performed with soap and water, not alcohol-based sanitizers, as alcohol does not kill C. difficile spores 1, 2
• Place patients in private rooms when possible 3

Monitoring Considerations

• In patients >65 years of age, monitor renal function during and after treatment as nephrotoxicity risk is increased 6
• Clinically significant serum vancomycin concentrations can occur with oral administration in patients with inflammatory intestinal mucosa; consider monitoring levels in patients with renal insufficiency or those receiving concomitant aminoglycosides 6

Common Pitfalls to Avoid

• Do not use metronidazole for severe or recurrent CDI due to inferior efficacy 2
• Do not delay treatment while awaiting diagnostic confirmation in patients with severe disease 2
• Do not use parenteral vancomycin for CDI treatment—it is ineffective as oral vancomycin is not systemically absorbed and acts locally in the colon 6
• Avoid antiperistaltic agents and opiates as they may worsen disease 3