What are the treatment options for Clostridioides difficile (C. diff) infections?

Treatment Options for Clostridioides difficile Infection

Fidaxomicin 200 mg twice daily for 10 days is the preferred first-line treatment for non-severe initial C. difficile infection due to superior sustained clinical response rates and lower recurrence rates. 1

Classification and Initial Treatment Selection

Non-severe CDI

• First-line: Fidaxomicin 200 mg orally twice daily for 10 days 1
• Alternative: Vancomycin 125 mg orally four times daily for 10 days 1
• Limited use: Metronidazole 500 mg orally three times daily for 10 days (only when fidaxomicin and vancomycin are unavailable or for patients ≤65 years old) 2, 1

Severe CDI

Severe CDI is defined by one or more of the following markers:

• Hypotension or shock
• Ileus or megacolon
• White blood cell count >15,000/mm³
• Serum creatinine >1.5 times baseline
• Serum albumin <3 g/dL

Treatment:

• Vancomycin 125 mg orally four times daily for 10 days 2
• For severe complicated CDI: Vancomycin 500 mg orally four times daily plus intravenous metronidazole 500 mg every 8 hours 1
• If ileus present: Add rectal instillation of vancomycin 500 mg in 100 mL normal saline every 4-12 hours 2, 1

When Oral Therapy Is Not Possible

• Intravenous metronidazole 500 mg three times daily for 10 days 2
• Plus intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours and/or vancomycin 500 mg four times daily by nasogastric tube 2

Management of Recurrent CDI

First Recurrence

• Fidaxomicin 200 mg twice daily for 10 days OR
• Fidaxomicin 200 mg twice daily for 5 days followed by once every other day for 20 days 1
• If fidaxomicin unavailable: Vancomycin 125 mg four times daily for 10 days 2, 1

Second or Subsequent Recurrences

• Vancomycin 125 mg four times daily for at least 10 days with consideration of a taper/pulse strategy 2
• Consider fecal microbiota transplantation (FMT) after appropriate antibiotic treatment for at least 2 recurrences (70-90% success rate in preventing further recurrences) 1, 3
• Consider bezlotoxumab 10 mg/kg IV once during antibiotic administration, particularly for immunocompromised patients 1

Special Populations

Pediatric Patients (6 months to <18 years)

• For children weighing at least 12.5 kg and able to swallow tablets: Fidaxomicin 200 mg tablet orally twice daily for 10 days 4
• For children unable to swallow tablets: Weight-based dosing of fidaxomicin oral suspension 4
• Metronidazole can be used at 7.5 mg/kg/dose (maximum 500 mg) three or four times daily for 10 days 1

Monitoring Treatment Response

• Improvement is typically expected within 2-3 days of starting appropriate therapy 1

• If no improvement occurs within 48-72 hours:

  1. Reassess severity
  2. Consider alternative or additional treatments
  3. Evaluate for complications (toxic megacolon, perforation)

• For patients on metronidazole: Monitor for peripheral neuropathy with prolonged therapy 1

• For patients over 65 years on vancomycin: Monitor renal function during and after treatment 1

Infection Control Measures

• Hand hygiene with soap and water (alcohol-based sanitizers are less effective against C. difficile spores) 1
• Contact precautions including isolation and use of personal protective equipment 1
• Thorough environmental cleaning with sporicidal agents 1
• Discontinue the inciting antibiotic as soon as possible 1

Emerging Therapies

• Fecal microbiota transplantation (FMT) has shown 70-90% success rates for recurrent CDI and is increasingly being studied for severe and fulminant CDI with promising results 3
• FMT should be particularly considered in elderly patients with severe or fulminant CDI who are poor surgical candidates 3

The treatment landscape for C. difficile has evolved significantly, with fidaxomicin and vancomycin now preferred over metronidazole for initial episodes. The management approach should be guided by disease severity, recurrence status, and patient-specific factors to optimize outcomes and reduce the risk of complications.