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

Treatment for Clostridioides difficile Infection

For initial C. difficile infection, oral vancomycin 125 mg four times daily or fidaxomicin 200 mg twice daily for 10 days is the recommended treatment, with fidaxomicin preferred for severe disease or high recurrence risk, while metronidazole is no longer first-line therapy. 1, 2, 3

Initial Episode Treatment Algorithm

Non-Severe Disease (Oral Therapy Possible)

• Oral vancomycin 125 mg four times daily for 10 days 4, 1
• Oral fidaxomicin 200 mg twice daily for 10 days is an alternative and may be superior for preventing recurrence 4, 2, 3
• Metronidazole 500 mg three times daily for 10 days is no longer preferred first-line therapy but may be used when vancomycin or fidaxomicin are unavailable 1, 5

Non-severe disease is defined as stool frequency less than 4 times daily with no signs of severe colitis 4, 1

Severe Disease (Oral Therapy Possible)

• Oral vancomycin 125 mg four times daily for 10 days 4, 1
• Fidaxomicin 200 mg twice daily for 10 days is increasingly recommended as first-line for severe disease 4, 3
• Higher vancomycin doses (up to 500 mg four times daily) have been used in fulminant cases, though evidence is limited 4

Severe disease indicators include: 4, 1

• White blood cell count >15,000/μL
• Serum creatinine rise >50% above baseline
• Fever, hemodynamic instability
• Elevated serum lactate
• Imaging showing colonic distension, wall thickening, or pericolonic fat stranding

When Oral Therapy is Impossible

For non-severe disease: 4, 1

• IV metronidazole 500 mg three times daily for 10 days

For severe disease: 4, 1

• IV metronidazole 500 mg three times daily PLUS
• Intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours (via retention enema) AND/OR
• Vancomycin 500 mg four times daily via nasogastric tube

Recurrent Infection Management

First Recurrence

• Treat the same as initial episode with oral vancomycin or fidaxomicin 4, 5

Second and Subsequent Recurrences

• Oral vancomycin 125 mg four times daily for at least 10 days 4
• Consider vancomycin taper/pulse strategy: decrease daily dose by 125 mg every 3 days, then pulse dosing (125 mg every 3 days for 3 weeks) 4
• Fidaxomicin 200 mg twice daily for 10 days is effective for preventing further recurrence 2, 3, 6
• Fecal microbiota transplantation (FMT) is highly effective after multiple recurrences despite appropriate antibiotic therapy 4, 3, 5

Adjunctive Therapy for Recurrence Prevention

• Bezlotoxumab (monoclonal antibody against toxin B) may be administered to prevent recurrence in high-risk patients, including those with severe CDI, immunocompromised status, or epidemic 027 strain 4, 3, 6

Fulminant/Complicated Disease

Surgical consultation should be obtained early for patients with: 4

• Perforation of the colon
• Toxic megacolon or severe ileus
• Systemic inflammation with deteriorating clinical condition not responding to antibiotics
• Serum lactate >5.0 mmol/L (operate before this threshold when possible) 4, 1

Medical management of fulminant disease: 4, 3

• High-dose oral vancomycin (500 mg four times daily) ± rectal vancomycin
• IV metronidazole 500 mg three times daily
• Consider fidaxomicin or tigecycline as part of combination therapy 3

Surgical options include: 4

• Total colectomy (traditional approach)
• Diverting loop ileostomy with colonic lavage (alternative to colectomy)

Critical Management Principles

What to Avoid

• Antiperistaltic agents and opiates should be avoided as they worsen outcomes 4, 1
• Do not use metronidazole for severe CDI when vancomycin is available 1

Antibiotic Stewardship

• Discontinue the inciting antibiotic if possible 4
• If antibiotics must be continued, switch to lower-risk agents (aminoglycosides, sulfonamides, macrolides, tetracyclines) 4
• Narrow antibiotic spectrum whenever possible 4

Monitoring Treatment Response

• Expect improvement within 3 days of starting therapy 4, 1
• Treatment failure is defined as absence of response after 3 days 4
• Consider surgical consultation early if clinical deterioration occurs despite maximal medical therapy 4, 1

Pediatric Considerations

For children 6 months and older: 2

• Fidaxomicin is FDA-approved with weight-based dosing
• Children ≥12.5 kg able to swallow tablets: 200 mg twice daily for 10 days
• Oral suspension available for younger/smaller children with weight-based dosing from 80-200 mg twice daily

Common Pitfalls

• Do not test for cure after treatment completion, as patients may remain colonized without active infection 5
• Do not use probiotics for prevention—not recommended by major guidelines 5
• Proton pump inhibitors are associated with CDI but evidence for discontinuation is insufficient; however, discontinue if not needed 4
• Recurrence rates remain 20-30% even with appropriate therapy, so counsel patients about this risk 7, 8