What is the recommended treatment regimen for an adult with confirmed Clostridioides difficile colitis, including dosing for mild versus severe disease, options for recurrence, and management of fulminant colitis?

Treatment of Clostridioides difficile Colitis

For initial CDI episodes of any severity, oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days are the first-line treatments, with fidaxomicin preferred due to significantly lower recurrence rates. 1

Initial Episode Treatment Algorithm

Non-Severe Disease (WBC ≤15,000/µL AND creatinine <1.5 mg/dL)

• First choice: Fidaxomicin 200 mg orally twice daily for 10 days 1, 2
• Acceptable alternative: Vancomycin 125 mg orally four times daily for 10 days 1, 3
• Resource-limited settings only: Metronidazole 500 mg orally three times daily for 10 days may be used when vancomycin and fidaxomicin are unavailable 1, 3

The distinction between non-severe and severe disease does not change the initial antibiotic choice—both fidaxomicin and vancomycin are appropriate for either severity level. 1 Metronidazole is strongly discouraged as first-line therapy because it has inferior efficacy, particularly in severe disease where cure rates are only 76% compared to 97% with vancomycin. 4, 1

Severe Disease (WBC ≥15,000/µL OR creatinine ≥1.5 mg/dL)

• Use the same regimen as non-severe disease: Fidaxomicin 200 mg twice daily or vancomycin 125 mg four times daily for 10 days 1, 3
• Do not increase vancomycin dose beyond 125 mg four times daily for non-fulminant severe disease—higher doses provide no additional benefit 1, 3

Fulminant Disease (hypotension/shock, ileus, or megacolon) – MEDICAL EMERGENCY

This is a life-threatening condition requiring immediate multidisciplinary care involving critical care, surgery, gastroenterology, and infectious disease. 4

Medical regimen:

• Vancomycin 500 mg orally (or via nasogastric tube) four times daily 1, 3, 5
• PLUS intravenous metronidazole 500 mg every 8 hours 1, 3, 5
• PLUS vancomycin retention enema 500 mg in 100 mL normal saline every 4-12 hours if ileus is present 1, 3, 5

Critical pitfall: Intravenous vancomycin alone is completely ineffective for CDI because it is not excreted into the colon. 1 The rectal vancomycin enema is essential when ileus prevents oral medication from reaching the colon. 1, 3

Surgical consultation: Obtain immediately when WBC ≥25,000/µL or lactate ≥5 mmol/L, as early surgery (before vasopressor requirement) reduces mortality. 2, 6 Total abdominal colectomy with end ileostomy is the recommended procedure for perforation, refractory systemic inflammation despite antibiotics, toxic megacolon, or severe ileus. 1, 7

FMT in fulminant disease: Consider conventional FMT in hospitalized patients not responding to standard antibiotics within 2-5 days of initiating treatment, delivered via colonoscopy or flexible sigmoidoscopy. 4 FMT is contraindicated in patients with bowel perforation, obstruction, or severe immunocompromise. 4

Essential Management Principles

• Discontinue the inciting antibiotic immediately whenever clinically feasible—this is the single most important modifiable factor to reduce recurrence. 1, 3
• Avoid antiperistaltic agents (loperamide, diphenoxylate) and opioid analgesics in all CDI patients, as they worsen outcomes and increase complications. 1, 3
• Do not perform a "test of cure" after treatment completion; clinical response within 3-5 days is the appropriate endpoint. 4, 1
• Clinical response typically requires 3-5 days after starting therapy, particularly with metronidazole which may take up to 5 days. 1

First Recurrence Treatment

If the initial episode was treated with metronidazole:

• Oral vancomycin 125 mg four times daily for 10 days 1, 3

If the initial episode was treated with standard vancomycin:

• Preferred: Fidaxomicin 200 mg twice daily for 10 days 1, 2, 3
• Alternative: Vancomycin tapered-and-pulsed regimen:
  • 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 (total duration 6-11 weeks) 1, 3

Adjunctive therapy: Bezlotoxumab 10 mg/kg IV as a single dose can be added during antibiotic therapy to reduce recurrence risk, but use cautiously in patients with congestive heart failure due to FDA safety warnings. 1, 2, 3

Second and Subsequent Recurrences

Treatment options (in order of preference):

1. Fidaxomicin 200 mg twice daily for 10 days (standard or extended-pulsed regimen: 200 mg twice daily for 5 days, then every other day for 20 days) 1, 2, 3

2. Vancomycin tapered-and-pulsed regimen as described above 1, 3

3. Sequential therapy: Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 1, 3

4. Fecal microbiota transplantation (FMT) is strongly recommended after at least 2 recurrences (i.e., 3 total CDI episodes) that have failed appropriate antibiotic treatments. 4, 1, 3 FMT achieves clinical resolution in 81-92% of patients compared to 23-40% with antibiotics alone. 2 FMT should be administered after completion of standard antibiotics, using appropriately screened donor stool. 4

Critical Pitfalls to Avoid

• Never use repeated metronidazole courses beyond 14 days due to cumulative, potentially irreversible neurotoxicity. 1, 2, 3
• Never use IV vancomycin alone for CDI—it does not reach the colon. 1, 2
• Do not use metronidazole for severe CDI—cure rates are significantly inferior (76% vs 97% for vancomycin). 4, 1
• Do not delay surgical consultation in fulminant CDI—operate before serum lactate exceeds critical thresholds and before vasopressor therapy is required. 1, 2, 6
• Do not forget rectal vancomycin in fulminant CDI with ileus—oral therapy alone will not reach the colon. 1, 3

Recurrence Risk Factors to Monitor

Patients at higher risk for recurrence include those who are elderly (>65 years), immunocompromised, have continued antibiotic use, multiple comorbidities, concomitant proton pump inhibitor use, or severe initial disease presentation. 1, 2 These patients should be considered for fidaxomicin over vancomycin and for adjunctive bezlotoxumab. 1, 2