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

Treatment of Clostridioides difficile Diarrhea

For initial episodes of C. difficile infection, use oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days as first-line therapy, with treatment selection based on disease severity and access to medications. 1, 2

Disease Severity Classification

Assess severity immediately to guide treatment selection:

• Non-severe CDI: White blood cell count ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL 2
• Severe CDI: White blood cell count ≥15,000 cells/mL OR serum creatinine >1.5 mg/dL 3, 2
• Fulminant CDI: Signs of septic shock, peritonitis, ileus, toxic megacolon, or serum lactate >5.0 mmol/L 3

Initial Episode Treatment

For Non-Severe CDI (Oral Therapy Possible)

• First-line: Vancomycin 125 mg orally four times daily for 10 days 1, 2, 4
• Alternative: Fidaxomicin 200 mg orally twice daily for 10 days 1, 2, 5
• Important: The standard 125 mg dose of vancomycin is as effective as higher doses (500 mg) for non-severe disease, with no difference in cure rates or complications 6, 7

For Severe CDI (Oral Therapy Possible)

• First-line: Vancomycin 125 mg orally four times daily for 10 days 3, 2
• Alternative: Fidaxomicin 200 mg orally twice daily for 10 days 2
• Note: Higher vancomycin doses (500 mg four times daily) have not demonstrated superior clinical outcomes in severe CDI 2, 6

For Patients Unable to Take Oral Medications (NPO Status)

• Recommended regimen: Intravenous vancomycin 500 mg every 8 hours PLUS vancomycin retention enema 250-500 mg in 100-500 mL saline four times daily for 10 days 1, 2
• Critical point: Intravenous vancomycin alone is completely ineffective for CDI because it is not excreted into the colon 1, 4
• Transition: Switch to oral vancomycin 125 mg four times daily or fidaxomicin 200 mg twice daily once the patient can tolerate oral intake 1

Recurrent CDI Treatment

First Recurrence

• If metronidazole was used initially: Vancomycin 125 mg orally four times daily for 10 days 1, 2
• If vancomycin was used initially: Consider fidaxomicin 200 mg twice daily for 10 days (associated with lower recurrence rates) 2, 8

Second or Subsequent Recurrence

• Option 1: Vancomycin in a tapered and pulsed regimen (e.g., decreasing daily dose by 125 mg every 3 days, then 125 mg every 3 days for 3 weeks) 3, 2
• Option 2: Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 2
• Option 3: Fidaxomicin 200 mg twice daily for 10 days 2
• Fecal microbiota transplantation: Recommended after at least 2 recurrences have failed appropriate antibiotic treatment 1, 2

Critical Management Principles

Discontinue Inciting Antibiotics

• Stop the causative antibiotic(s) as soon as possible—this is essential for reducing recurrence risk 1, 2
• For mild CDI (stool frequency <4 times daily, no severe colitis signs) clearly induced by antibiotics, stopping the antibiotic alone may suffice with close observation 3

Avoid Harmful Medications

• Never use antiperistaltic agents or opiates—these can worsen colitis and increase complications 3

Monitor High-Risk Patients

• Patients >65 years of age have increased risk of nephrotoxicity with oral vancomycin 4
• Monitor renal function during and after treatment in elderly patients, even those with normal baseline function 4
• Patients with inflammatory bowel disorders may have significant systemic absorption of oral vancomycin and require serum level monitoring 4

Surgical Intervention

Consider urgent colectomy for:

• Colonic perforation 3
• Toxic megacolon or severe ileus not responding to medical therapy 3
• Systemic inflammation with clinical deterioration despite antibiotics 3
• Timing is critical: Operate before serum lactate exceeds 5.0 mmol/L for better outcomes 3

Common Pitfalls to Avoid

• Do not use metronidazole for severe or recurrent CDI—it has lower cure rates than vancomycin and risk of cumulative neurotoxicity with repeated courses 1, 2
• Do not perform "test of cure" after completing treatment—this is not recommended 1, 2
• Do not administer only IV vancomycin for CDI—it does not reach the colon and is ineffective 1, 2, 4
• Do not use higher vancomycin doses routinely—125 mg four times daily is as effective as 500 mg for most patients 6, 7

Treatment Response Assessment

• Expect improvement in stool frequency or consistency within 3 days of starting therapy 3, 9
• Treatment failure is defined as absence of response after 3 days 3
• If response is delayed, consider extending treatment duration to 14 days 1
• Approximately 20% of patients experience recurrence, with higher risk in elderly patients and those requiring continued antibiotic use 1