What is the recommended treatment for Clostridioides difficile colitis?

Treatment of Clostridioides difficile Colitis

For initial episodes of C. difficile infection, fidaxomicin 200 mg orally twice daily for 10 days is the preferred first-line therapy regardless of disease severity, with oral vancomycin 125 mg four times daily for 10 days as an acceptable alternative. 1, 2

Initial Episode Treatment Algorithm

Non-Severe Disease

• Non-severe CDI is defined by white blood cell count ≤15,000 cells/µL AND serum creatinine <1.5 mg/dL 1, 2
• First-line options:
  • Fidaxomicin 200 mg orally twice daily for 10 days (preferred due to lower recurrence rates of 13-17% vs 24-27% with vancomycin) 1
  • Vancomycin 125 mg orally four times daily for 10 days (acceptable alternative with 81-92% clinical cure rates) 1, 3
• Metronidazole 500 mg orally three times daily for 10 days should ONLY be used in resource-limited settings where vancomycin and fidaxomicin are unavailable 1, 2

Severe Disease

• Severe CDI is defined by white blood cell count ≥15,000 cells/µL OR serum creatinine >1.5 mg/dL 1, 2
• Use the same first-line regimens as non-severe disease: fidaxomicin 200 mg twice daily or vancomycin 125 mg four times daily for 10 days 1
• Vancomycin achieves 97% cure rates in severe disease compared to only 76% with metronidazole—metronidazole is strongly discouraged for severe CDI 4, 1
• Higher vancomycin doses (500 mg four times daily) may be considered in life-threatening cases, though evidence is limited 4, 1

Fulminant/Life-Threatening Disease

• Fulminant CDI is identified by hypotension/shock, ileus, toxic megacolon, or severe systemic inflammation 1, 2
• Combination regimen: Vancomycin 500 mg orally (or via nasogastric tube) four times daily PLUS intravenous metronidazole 500 mg every 8 hours 4, 1
• If ileus is present: Add vancomycin 500 mg in 100 mL normal saline per rectum every 4-12 hours as a retention enema 4, 1
• Critical point: Intravenous vancomycin is NOT effective for CDI because it is not excreted into the colon 1
• Surgical consultation should not be delayed: Total abdominal colectomy with ileostomy is indicated for perforation, refractory systemic inflammation, toxic megacolon, or severe ileus—ideally performed before serum lactate exceeds 5.0 mmol/L 4, 1

Recurrent CDI Treatment

First Recurrence

• Fidaxomicin 200 mg orally twice daily for 10 days is the preferred option 1, 2
• Alternative tapered-and-pulsed vancomycin 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 4, 1
• If metronidazole was used initially, standard vancomycin 125 mg four times daily for 10 days may be employed 1

Second and Subsequent Recurrences

• Preferred hierarchy:
  1. Fidaxomicin (standard or extended-pulsed regimen) 1
  2. Vancomycin tapered-and-pulsed regimen (as above) 1, 2
  3. Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 1, 2
• Fecal microbiota transplantation (FMT) is strongly recommended after at least 2 recurrences (i.e., three total CDI episodes) that have failed appropriate antibiotic therapy, with resolution rates of 70-92% 1, 5

Critical Management Principles

Essential Actions

• Discontinue the inciting antibiotic(s) immediately—this is the single most important modifiable factor to reduce recurrence 1, 2
• Avoid antiperistaltic agents and opiates in all CDI patients 4, 1
• Do NOT perform a "test of cure" after completing therapy—clinical improvement within 3-5 days is the appropriate endpoint 1, 2

Monitoring

• Clinical response typically requires 3-5 days after starting therapy 1, 2
• In patients >65 years of age, monitor renal function during and after treatment to detect vancomycin-induced nephrotoxicity 3
• For fulminant disease, escalate care immediately if severe abdominal pain, hypotension (systolic BP <90 mmHg), WBC ≥25,000 cells/µL, rising lactate ≥5 mmol/L, or altered mental status develop 1

Common Pitfalls to Avoid

• Never use metronidazole for severe or recurrent CDI—it has inferior cure rates and carries risk of cumulative, potentially irreversible neurotoxicity 1, 2, 6
• Never administer only intravenous vancomycin for CDI—it does not reach the colon 1
• Do not delay surgical consultation in fulminant disease—operate before lactate exceeds 5.0 mmol/L 4, 1
• Avoid repeated metronidazole courses due to neurotoxicity risk 1, 6
• Fidaxomicin was not associated with fewer recurrences in CDI due to PCR ribotype 027, and there is no evidence supporting its use in life-threatening CDI 4

Special Considerations

• Concomitant antibiotic use during CDI treatment is associated with lower cure rates (84.4% vs 92.6%) and extended time to resolution (97 vs 54 hours), but fidaxomicin remains more effective than vancomycin in this setting (90.0% vs 79.4% cure rate) 7
• For patients unable to take oral medications, use intravenous metronidazole 500 mg every 8 hours plus vancomycin retention enema 500 mg in 100 mL normal saline four times daily, transitioning to oral therapy once possible 2
• Vancomycin can be administered via nasogastric tube or trans-stoma in surgical patients with ileostomy or colonic diversion 1