Why is rifaximin used in Clostridioides difficile infection (CDI)?

Rifaximin in Clostridioides difficile Infection Management

Rifaximin is primarily used as an adjunctive therapy for recurrent Clostridioides difficile infections (CDI), particularly after standard treatment with vancomycin, to prevent further recurrences by preserving gut microbiota while maintaining activity against C. difficile. 1, 2

Role in CDI Treatment Algorithm

First-Line Treatment

• Rifaximin is NOT recommended as first-line therapy for initial CDI episodes
• First-line treatments according to current guidelines are:
  • Fidaxomicin (preferred if resources allow) 1
  • Vancomycin as an acceptable alternative 1

Recurrent CDI Management

Rifaximin's primary role is in managing recurrent CDI:

1. First Recurrence:

   • Oral vancomycin (if metronidazole was used initially)
   • Fidaxomicin
   • Vancomycin in tapered and pulsed regimen (if standard vancomycin was used initially) 2

2. Second or Subsequent Recurrences:

   • Vancomycin followed by rifaximin (chaser therapy)
   • Vancomycin in tapered and pulsed regimen
   • Fidaxomicin (standard or extended-pulsed regimen)
   • Fecal microbiota transplantation 1, 2

Evidence for Rifaximin in CDI

The IDSA/SHEA guidelines cite a small randomized controlled trial where rifaximin (400 mg three times daily for 20 days) was given immediately after completing standard CDI therapy. In this study, CDI recurrences occurred in 15% of patients given rifaximin compared to 31% given placebo (P = .11) 1.

Additional evidence from smaller studies shows:

• Success rates of 53-73% in treating recurrent CDI 3, 4
• Rapid symptom resolution (within 36-48 hours) in some cases 5
• Effectiveness as a "chaser" therapy after vancomycin course 6

Mechanism of Action and Benefits

Rifaximin offers several advantages in CDI management:

• Minimal systemic absorption (non-systemic antibiotic)
• Preserves gut microbiota better than alternative treatments 1
• Maintains activity against C. difficile while allowing restoration of normal gut flora 1

Important Considerations and Limitations

1. Resistance concerns:

   • Monotherapy should be avoided due to potential for resistance development 1
   • Higher MIC values for rifampin predict poorer response to rifaximin 3
   • Some treatment failures are associated with high-level resistance (MIC >256 μg/ml) 6

2. Patient selection:

   • Most effective when used after a course of standard therapy (vancomycin) 1, 6
   • May be considered for mild-to-moderate CDI resistant to metronidazole 4

3. Administration:

   • Typical dosing: 400 mg three times daily for 2-3 weeks following standard CDI therapy 1, 3, 4

Conclusion

Rifaximin serves an important role in the management of recurrent CDI, particularly as an adjunctive therapy following standard treatment with vancomycin. It should not be used as monotherapy or first-line treatment but can be valuable in preventing further recurrences in patients with multiple episodes of CDI.