What is the treatment for Clostridium difficile (C. difficile) colonitis?

Treatment of Clostridium difficile Colitis

For non-severe 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; metronidazole is no longer recommended as first-line treatment. 1, 2

Disease Severity Classification

Before selecting treatment, classify disease severity using objective laboratory criteria:

• Non-severe CDI: White blood cell count ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL 1, 2
• Severe CDI: White blood cell count ≥15,000 cells/mL OR serum creatinine ≥1.5 mg/dL 1, 2
• Fulminant CDI: Hypotension, shock, ileus, or megacolon 2

The European Society of Clinical Microbiology and Infectious Diseases also includes marked leukocytosis, elevated creatinine (>50% above baseline), or decreased albumin (<30 g/L) as markers of severe disease. 1

Treatment Algorithm by Severity

Non-Severe Disease (Initial Episode)

First-line options (both have strong recommendation with high-quality evidence):

• Oral vancomycin 125 mg four times daily for 10 days 3, 1
• Fidaxomicin 200 mg twice daily for 10 days 3, 1, 4

Fidaxomicin offers lower recurrence rates compared to vancomycin (except for PCR ribotype 027 strains), making it preferable when available despite higher cost. 3, 2

Metronidazole 500 mg three times daily for 10 days should only be used when access to vancomycin or fidaxomicin is limited, and only for non-severe disease. 3, 1 This represents a significant change from older guidelines—metronidazole is no longer first-line therapy.

Severe Disease (Initial Episode)

Oral vancomycin 125 mg four times daily for 10 days is the treatment of choice. 1, 2

In severe disease, vancomycin demonstrated a 97% cure rate versus only 76% for metronidazole, making metronidazole use strongly discouraged in this setting. 1, 2 Consider escalating to vancomycin 500 mg four times daily for 10 days in particularly severe cases. 3, 2

Fulminant Disease

High-dose oral vancomycin 500 mg four times daily PLUS intravenous metronidazole 500 mg every 8 hours 2

If oral administration is not possible due to ileus, add vancomycin retention enemas (500 mg in 100 mL normal saline four times daily) or administer vancomycin via nasogastric tube. 3

Intravenous tigecycline 50 mg twice daily for 14 days may be considered as salvage therapy, though this carries only marginal strength of recommendation. 3

Recurrent C. difficile Infection

First Recurrence

Treat as initial episode unless disease has progressed from non-severe to severe. 2 Fidaxomicin 200 mg twice daily for 10 days is preferred due to significantly lower rates of second recurrence. 3, 2

Second and Subsequent Recurrences

Use either:

• Vancomycin tapered and pulsed regimen: Start with vancomycin 125 mg four times daily for 10 days, then gradually taper (e.g., 125 mg twice daily for a week, then once daily for a week, then every 2-3 days for 2-3 weeks) 3
• Fidaxomicin 200 mg twice daily for 10 days 3, 2

Critical Management Principles

Immediately discontinue the inciting antibiotic if clinically feasible—this is the most important initial step. 1, 2 However, when patients require concomitant antibiotics for other infections, be aware that this compromises both initial response and durability of cure. 5 In such cases, fidaxomicin demonstrates superior efficacy over vancomycin (90.0% vs 79.4% cure rate with concomitant antibiotics). 5

Avoid antiperistaltic agents and opiates—these worsen outcomes and increase complications including toxic megacolon. 1, 2

Assess clinical response by 72 hours; if no improvement, escalate therapy immediately rather than waiting to complete the initial 10-day course. 1, 2 Treatment response typically requires 3-5 days. 1

Do not perform "test of cure" after treatment completion—only test symptomatic patients. 1, 2

Common Pitfalls to Avoid

Never use repeated or prolonged courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity, particularly concerning in elderly patients. 1

Do not use higher doses of vancomycin (500 mg four times daily) for non-severe disease—the 125 mg dose is equally effective and less expensive. 3, 6

Do not continue ineffective therapy—if the patient shows no improvement by day 3-5 on metronidazole, escalate to vancomycin rather than completing the full 10-day course. 1

Surgical Intervention

Total abdominal colectomy with ileostomy is indicated for:

• Perforation of the colon 3, 2
• Systemic inflammation with deteriorating clinical condition despite maximal antibiotic therapy 3, 2
• Toxic megacolon, acute abdomen, or severe ileus 3, 2

Operate before disease becomes very severe—serum lactate >5.0 mmol/L is a marker suggesting surgery should be performed urgently. 3, 2 A future alternative may be diverting loop ileostomy with colonic lavage combined with intracolonic antegrade vancomycin and intravenous metronidazole, though this requires further validation. 3