What antibiotics can be used to treat Clostridium difficile (C. difficile) diarrhea?

Treatment of Clostridioides 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 antibiotics for treating C. difficile diarrhea, with fidaxomicin preferred due to significantly lower recurrence rates. 1, 2

Initial Episode Treatment

Non-Severe Disease

• Vancomycin 125 mg orally four times daily for 10 days is highly effective for non-severe CDI (defined as WBC ≤15,000 cells/mL and serum creatinine <1.5 mg/dL) 1, 2
• Fidaxomicin 200 mg orally twice daily for 10 days is the preferred alternative, offering lower recurrence rates (13.3% vs 24.0% with vancomycin) 1, 3
• Metronidazole 500 mg orally three times daily for 10 days can be considered only in resource-limited settings where vancomycin or fidaxomicin are unavailable, but has inferior efficacy 4, 2

Severe Disease

• Vancomycin 125 mg orally four times daily for 10 days is the standard treatment for severe CDI (defined as WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL) 1, 2
• Vancomycin demonstrated superior cure rates compared to metronidazole in severe disease (97% vs 76%) 1
• Fidaxomicin 200 mg orally twice daily for 10 days is an equally effective alternative with lower recurrence rates 1, 2
• Consider increasing vancomycin dosage to 500 mg four times daily for 10 days in life-threatening cases, though evidence is limited 4
• Metronidazole use in severe or life-threatening CDI is strongly discouraged 4

Fulminant or Complicated Disease

• Vancomycin 500 mg orally four times daily PLUS intravenous metronidazole 500 mg three times daily for patients with fulminant CDI, ileus, or toxic megacolon 2
• For patients unable to take oral medications: intravenous metronidazole 500 mg three times daily PLUS vancomycin retention enema 500 mg in 100 mL normal saline every 4-12 hours 4, 2
• Vancomycin can be administered via nasogastric tube (500 mg four times daily) or trans-stoma in surgical patients with ileostomy or colonic diversion 4
• Note: Intravenous vancomycin has no effect on CDI since it is not excreted into the colon 4, 5

Recurrent CDI Treatment

First Recurrence

• Fidaxomicin 200 mg orally twice daily for 10 days is the preferred option 1, 2
• Vancomycin tapered and pulsed regimen is the alternative: 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, 2

Second and Subsequent Recurrences

• Vancomycin tapered and pulsed regimen as described above 1, 2
• Fecal microbiota transplantation (FMT) is strongly recommended after at least 2 recurrences that have failed appropriate antibiotic treatments 4, 1, 2

Critical Management Principles

Discontinue Inciting Antibiotics

• Stop the causative antibiotic as soon as possible to reduce recurrence risk and improve treatment outcomes 1, 2
• In non-epidemic situations with clearly antibiotic-induced non-severe CDI, it may be acceptable to stop the inducing antibiotic and observe for 48 hours before starting treatment, but monitor closely for deterioration 4

Avoid Harmful Medications

• Antiperistaltic agents and opiates should be avoided in all patients with CDI 4, 1
• Avoid repeated metronidazole courses due to risk of cumulative and potentially irreversible neurotoxicity 1, 2

Dosing Considerations

• Lower dose vancomycin (125 mg) is as effective as higher doses (500 mg) for non-fulminant disease and is preferred due to lower cost 6, 7
• The 500 mg dose should be reserved for critically ill patients or those with fulminant disease 6

Treatment Response Monitoring

• Clinical response typically requires 3-5 days after starting therapy, particularly with metronidazole which may take up to 5 days 4, 1
• Evaluate treatment response daily, assessing stool frequency, consistency, and clinical parameters 4
• Do not perform a "test of cure" after treatment completion 1
• Approximately 20% of patients experience recurrence, with higher risk in elderly patients and those requiring continued antibiotic use 1, 2

Special Populations

Elderly Patients (>65 years)

• Monitor renal function during and after treatment as nephrotoxicity risk is increased in this population 5
• Fidaxomicin may be particularly beneficial due to lower recurrence rates in elderly patients 4

Pediatric Patients

• Vancomycin 40 mg/kg/day in 3-4 divided doses for 7-10 days (maximum 2 g/day) 5
• Fidaxomicin is approved for patients ≥6 months of age 8

Surgical Intervention

Total abdominal colectomy with ileostomy should be performed for: 4

• Perforation of the colon
• Systemic inflammation and deteriorating clinical condition not responding to antibiotic therapy
• Toxic megacolon or severe ileus
• Surgery should be performed before colitis becomes very severe; operate before serum lactate exceeds 5.0 mmol/L 4