What is the treatment approach for a patient diagnosed with a Clostridium (C.) diff infection?

Treatment of Clostridioides difficile Infection

For initial C. difficile infection, 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 metronidazole no longer recommended as initial therapy for adults. 1, 2

Initial Assessment and Severity Classification

Immediately discontinue the inciting antibiotic if clinically feasible, as this alone resolves symptoms in approximately 25% of mild cases. 1, 3

Avoid antiperistaltic agents and opiates completely—these medications promote toxin retention, worsen outcomes, and increase the risk of toxic megacolon. 1, 4

Classify disease severity based on:

• Non-severe disease: Stool frequency <4 times daily, WBC ≤15,000/μL, serum creatinine <1.5 mg/dL 1
• Severe disease: WBC >15,000/μL, serum creatinine ≥1.5 mg/dL (≥50% above baseline), signs of peritonitis, hemodynamic instability, or imaging showing colonic wall thickening 1, 4
• Fulminant disease: Hypotension, ileus, toxic megacolon, or serum lactate >5.0 mmol/L 1, 4

Treatment Algorithm for Initial Episode

Non-Severe Disease (Oral Therapy Possible)

• Oral vancomycin 125 mg four times daily for 10 days 1, 2
• Alternative: Fidaxomicin 200 mg twice daily for 10 days (FDA-approved, associated with lower recurrence rates) 5
• Metronidazole 500 mg three times daily is no longer first-line therapy in adults due to inferior cure rates 2

Severe Disease (Oral Therapy Possible)

• Oral vancomycin 125 mg four times daily for 10 days 1
• Alternative: Fidaxomicin 200 mg twice daily for 10 days 5

Severe Disease (Oral Therapy Impossible—Ileus Present)

• Metronidazole 500 mg IV every 8 hours 1, 4
• PLUS intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours via retention enema 1, 4
• AND/OR vancomycin 500 mg four times daily via nasogastric tube 1, 4

Treatment Failure (No Response by 72 Hours)

Escalate immediately if stool frequency does not decrease or consistency does not improve after 3 days, or if new signs of severe colitis develop. 4

• High-dose oral vancomycin 500 mg four times daily 4
• Add IV metronidazole 500 mg every 8 hours 4
• If ileus present, add rectal vancomycin enemas 500 mg in 100 mL normal saline every 4-12 hours 4
• Never continue metronidazole monotherapy for severe or resistant disease—vancomycin has superior cure rates 4

Surgical Intervention

Colectomy should be performed urgently in the following situations:

• Colonic perforation 1
• Toxic megacolon or severe ileus 1
• Systemic inflammation with deteriorating clinical condition despite maximal medical therapy 1, 4
• Serum lactate >5.0 mmol/L is a critical marker indicating need for surgery—operate before this threshold is exceeded 1, 4

Do not delay surgical consultation when clinical deterioration continues despite antibiotics—early surgery improves survival. 4

Recurrent C. difficile Infection

First Recurrence

• Treat the same as initial episode: oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days 1

Second and Subsequent Recurrences

• Oral vancomycin 125 mg four times daily for at least 10 days 1
• Consider a taper/pulse strategy: decrease daily dose by 125 mg every 3 days, then pulse dosing (125 mg every 3 days for 3 weeks) 1
• Fecal microbiota transplantation is highly effective for patients with multiple recurrent episodes who have failed appropriate antibiotic therapy for at least three episodes, with cure rates exceeding 80% 2

Critical Pitfalls to Avoid

• Never use metronidazole as first-line therapy in adults—it is no longer recommended due to inferior outcomes 2
• Avoid repeated or prolonged courses of metronidazole—cumulative neurotoxicity risk increases with extended use 4
• Do not test for cure—C. difficile can be detected for weeks after successful treatment; only test if symptoms recur 2
• Do not routinely test children under 12 months—colonization is common and asymptomatic in this age group 2

Pediatric Considerations

Fidaxomicin is FDA-approved for children ≥6 months of age with demonstrated efficacy and superior sustained response rates compared to vancomycin (68.4% vs 50.0%). 5