What is the treatment for antibiotic-induced Clostridioides (C.) difficile?

Treatment of Antibiotic-Induced Clostridioides difficile Infection

For antibiotic-induced Clostridioides difficile infection (CDI), oral vancomycin 125 mg four times daily for 10 days is the first-line treatment for most cases, while fidaxomicin 200 mg twice daily for 10 days is an excellent alternative with lower recurrence rates. 1

Initial Management

1. Discontinue the inciting antibiotic if possible 2, 1

   • If the CDI is mild (stool frequency <4 times daily with no signs of severe colitis), discontinuing the inciting antibiotic and observing the clinical response may be sufficient 2
   • Monitor closely for clinical deterioration if this approach is taken

2. Assess severity to guide treatment choice:

   • Non-severe CDI: Fewer than 4 stools per day, no signs of severe colitis
   • Severe CDI: One or more markers of severe colitis (leukocytosis >15,000 cells/μL, serum albumin <3 g/dL, serum creatinine ≥1.5 mg/dL, or severe abdominal pain/distention) 2

Antibiotic Treatment Based on Severity

Non-severe CDI:

• First choice: Oral vancomycin 125 mg four times daily for 10 days 2, 1
• Alternative: Fidaxomicin 200 mg twice daily for 10 days 1, 3
• Note: Metronidazole (500 mg three times daily for 10 days) is no longer recommended as first-line therapy but may be considered in mild-to-moderate cases when access to vancomycin or fidaxomicin is limited 4

Severe CDI:

• First choice: Oral vancomycin 125 mg four times daily for 10 days 2, 1
• Alternative: Fidaxomicin 200 mg twice daily for 10 days 1

When oral therapy is not possible:

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

Management of Recurrent CDI

1. First recurrence:

   • Use the same regimen as for initial episode if vancomycin was used initially 2
   • Consider switching to fidaxomicin if metronidazole was used initially, as fidaxomicin has lower recurrence rates (9.3% vs 34.3%) 1

2. Second or subsequent recurrences:

   • Vancomycin 125 mg four times daily for at least 10 days, followed by a taper/pulse strategy (e.g., decreasing daily dose with 125 mg every 3 days) 2
   • Consider fidaxomicin for its lower recurrence rates 1, 4
   • Consider adjunctive bezlotoxumab (a monoclonal antibody against C. difficile toxin B) for patients with multiple risk factors for recurrence 4, 5
   • Fecal microbiota transplantation (FMT) should be offered to patients with frequently recurring CDI 4, 6

Special Considerations

1. If continued antibiotic therapy is required for the primary infection:

   • Use antibiotics less frequently implicated with CDI (parenteral aminoglycosides, sulfonamides, macrolides, tetracycline/tigecycline) 2
   • Consider extending the duration of CDI treatment 7
   • Fidaxomicin may be preferable due to its lesser effect on gut microbiome 7

2. Proton pump inhibitors (PPIs):

   • Review and discontinue unnecessary PPIs as they may increase risk of CDI and recurrence 2, 1

3. Infection control measures:

   • Place patients in a private room with en suite facilities when possible 2
   • Hand hygiene with soap and water (alcohol-based sanitizers do not kill C. difficile spores) 2
   • Contact precautions until 48 hours after diarrhea resolution 1

4. Surgical evaluation:

   • Consider surgical consultation for patients with:
     • Perforation of the colon
     • Systemic inflammation not responding to antibiotics
     • Toxic megacolon
     • Severe ileus 2, 1

Monitoring and Follow-up

• Monitor for symptom resolution (decreased stool frequency, improved consistency) within 3 days of treatment initiation 1
• Follow patients for at least 8 weeks after treatment to assess for recurrence 1
• For high-risk patients receiving antibiotics after CDI treatment, consider prophylactic low-dose oral vancomycin (125 mg once daily) 1

Emerging Treatments

• Defined microbial biotherapeutics as alternatives to FMT 8
• Bacteriophages and their derivatives 5
• Small-molecule agents without bacteriolytic activity 5

Remember that CDI treatment has evolved significantly, with metronidazole no longer recommended as first-line therapy and increased emphasis on preventing recurrence through appropriate antibiotic selection and adjunctive therapies.