What is the treatment for Clostridium difficile infection (CDI)?

Treatment of Clostridium difficile Infection

For initial episodes of CDI, use oral vancomycin 125 mg four times daily for 10 days as first-line therapy regardless of severity, as this has replaced metronidazole due to superior efficacy. 1, 2

Disease Severity Classification

Severity classification guides treatment intensity and monitoring:

• Non-severe CDI: Stool frequency <4 times daily, white blood cell count ≤15,000 cells/μL, serum creatinine <1.5 mg/dL, and no signs of severe colitis 3, 1, 2

• Severe CDI: Presence of one or more of the following: temperature >38.5°C, hemodynamic instability, leukocyte count >15×10⁹/L, serum creatinine rise >50% above baseline, elevated serum lactate, pseudomembranous colitis on endoscopy, or colonic wall thickening on imaging 1, 2

• Fulminant CDI: Hypotension or shock, ileus, megacolon, hemodynamic instability, or signs of peritonitis 1, 2

Initial Episode Treatment Algorithm

Non-Severe CDI (Oral Therapy Possible)

• First-line: Vancomycin 125 mg orally four times daily for 10 days 1, 4
• Alternative: Fidaxomicin 200 mg twice daily for 10 days, especially for patients at high risk of recurrence 1
• Less preferred alternative: Metronidazole 500 mg three times daily orally for 10 days (relegated to alternative status due to vancomycin's superior efficacy) 1, 2, 5

Severe CDI (Oral Therapy Possible)

• First-line: Vancomycin 125 mg orally four times daily for 10 days 1, 4
• Alternative: Fidaxomicin 200 mg twice daily for 10 days 1

Fulminant CDI

• High-dose oral vancomycin 500 mg four times daily PLUS intravenous metronidazole 500 mg every 8 hours 1, 2
• If ileus present: Add rectal vancomycin 500 mg in 100 mL normal saline every 4-12 hours as retention enema 1, 2
• Alternative route if oral impossible: Vancomycin 500 mg four times daily by nasogastric tube 3

Recurrent CDI Treatment Algorithm

First Recurrence

• Preferred: Fidaxomicin 200 mg twice daily for 10 days 1
• Alternative: Vancomycin in a tapered and pulsed regimen 1
• Consider: Bezlotoxumab 10 mg/kg IV once as adjunctive therapy for patients at high risk of recurrence 2

Second and Subsequent Recurrences

• Vancomycin 125 mg four times daily orally for at least 10 days, followed by tapered/pulsed regimen (example: decreasing daily dose by 125 mg every 3 days, then pulse dosing of 125 mg every 3 days for 3 weeks) 3, 1
• Consider fecal microbiota transplantation for multiple recurrences that have failed appropriate antibiotic treatments 1, 5

Surgical Management Indications

Colectomy should be performed urgently in the following situations 3, 1, 2:

• Colonic perforation
• Systemic inflammation and deteriorating clinical condition not responding to antibiotic therapy
• Toxic megacolon
• Severe ileus
• Serum lactate >5.0 mmol/L (surgery should be performed before lactate exceeds this threshold)

Critical Management Principles

Discontinue Inciting Antibiotics

• Stop the causative antibiotic immediately if possible 3, 1
• For mild CDI clearly induced by antibiotics, stopping the antibiotic alone may be sufficient with close observation for clinical deterioration 3
• If continued antibiotic therapy is required for another infection, consider agents less associated with CDI 1

Concomitant Antibiotic Use

• Concomitant antibiotics compromise CDI treatment outcomes, reducing cure rates (84.4% vs 92.6%) and extending time to resolution (97 vs 54 hours) 6
• Fidaxomicin is superior to vancomycin when concomitant antibiotics are necessary, with cure rates of 90.0% vs 79.4% and 12.3% fewer recurrences 6

Medications to Avoid

• Avoid antiperistaltic agents and opiates, as they worsen outcomes by promoting toxin retention and increasing risk of toxic megacolon 2, 7
• Discontinue unnecessary proton pump inhibitors in patients at high risk for CDI 1

Special Considerations

Infection Control

• Hand hygiene with soap and water is required, as alcohol-based hand sanitizers are ineffective against C. difficile spores 1

Monitoring

• Monitor closely for clinical deterioration, especially in patients where antibiotics were stopped without specific CDI treatment 3
• Nephrotoxicity occurs in 5% of vancomycin-treated patients, typically within one week after completion of treatment (median day 16), with higher rates (6%) in patients >65 years 4

Treatment Duration

• Standard duration is 10 days for initial episodes 3, 1, 4
• Treatment duration may need extension beyond 10 days in patients with delayed response to therapy 1

Alternative Agents

• Teicoplanin 100 mg twice daily can replace oral vancomycin if available 3