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

Treatment of Clostridioides difficile Infection

For Clostridioides difficile infection (CDI), vancomycin 125 mg orally four times daily for 10 days is recommended as first-line treatment, with fidaxomicin 200 mg twice daily for 10 days as an alternative first-line option. 1

Initial Treatment Based on Severity

Non-severe CDI

• Vancomycin 125 mg orally four times daily for 10 days 1, 2
• Alternative: Fidaxomicin 200 mg orally twice daily for 10 days 1

Severe CDI

• Defined by: temperature >38.5°C, leukocytosis >15,000/mm³, serum creatinine rise >50% above baseline, pseudomembranous colitis on endoscopy, or signs of severe colitis on imaging 1
• Treatment: Vancomycin 125 mg orally four times daily for 10 days 1
• Note: Higher doses of vancomycin (250 mg or 500 mg qid) do not appear to provide additional clinical benefit for most patients with severe CDI 3, 4

Fulminant CDI

• For severe CDI with complications (perforation, systemic inflammation, toxic megacolon, severe ileus, serum lactate >5.0 mmol/L) 1:
  • Vancomycin 500 mg four times daily orally or via nasogastric tube PLUS metronidazole 500 mg IV three times daily
  • Surgical consultation for possible colectomy

Treatment of Recurrent CDI

First Recurrence

• Fidaxomicin 200 mg twice daily for 10 days 1
• OR Vancomycin in a tapered and pulsed regimen 1

Multiple Recurrences (≥2)

1. Vancomycin 125 mg four times daily for 10 days, followed by either a tapered or pulse regimen 1
2. Consider Fecal Microbiota Transplantation (FMT) after appropriate antibiotic treatments have failed 1, 5
3. Consider adjunctive bezlotoxumab 10 mg/kg IV once during antibiotic treatment for patients at high risk of recurrence 1

Special Populations

Pediatric Patients

• For children ≥6 months: Fidaxomicin is FDA-approved 1
• Alternative: Vancomycin 10 mg/kg/dose (max 125 mg) four times daily for 10 days 1
• Total daily dosage should not exceed 2 g 2

Patients Unable to Take Oral Medications

• Consider vancomycin via nasogastric tube or as retention enema 1
• Important: Parenteral vancomycin is NOT effective for CDI treatment 1, 2

Important Clinical Considerations

Monitoring Response

• Evaluate treatment response after at least 3 days of therapy 1
• Look for improvements in stool frequency and consistency
• Complete normalization of bowel habits may take several weeks despite clinical cure 1

Safety Considerations for FMT

• FDA safety alerts document transmission of pathogenic E. coli and potential transmission of SARS-CoV-2 through FMT 1
• Proper donor screening is essential 1

Adjunctive Measures

• Discontinue the inciting antibiotic as soon as possible to reduce recurrence risk 1
• Avoid antiperistaltic agents and opiates to prevent worsening of disease 1

Common Pitfalls to Avoid

• Using metronidazole as first-line therapy for severe CDI 1
• Failure to recognize fulminant CDI requiring urgent intervention 1
• Overuse of FMT before trying appropriate antibiotic regimens 1
• Inadequate duration of therapy 1
• Not administering vancomycin orally for CDI (parenteral administration is ineffective) 1, 2

Monitoring in Special Populations

• In patients >65 years, monitor renal function during and after treatment with vancomycin, as nephrotoxicity can occur 2
• Consider monitoring serum vancomycin levels in patients with inflammatory intestinal disorders or renal insufficiency who may have significant systemic absorption 2