First-Line Treatment for Clostridioides difficile Infection
For initial C. difficile infection, use oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days, regardless of disease severity. 1, 2
Treatment Selection Based on Current Guidelines
The 2021 IDSA/SHEA guidelines represent a significant shift from older recommendations:
- Vancomycin 125 mg orally four times daily for 10 days is now the preferred first-line therapy for both non-severe and severe CDI 1, 2
- Fidaxomicin 200 mg orally twice daily for 10 days is an equally acceptable first-line alternative with the advantage of lower recurrence rates (13.3% vs 24.0% with vancomycin) 1, 2, 3
- Metronidazole is no longer recommended as first-line therapy for initial CDI, though older 2009 European guidelines did recommend it for non-severe disease 4, 1, 5
Why This Represents a Change from Older Practice
The 2009 ESCMID guidelines recommended metronidazole 500 mg three times daily for non-severe CDI and vancomycin only for severe disease 4. However, more recent evidence demonstrates:
- Vancomycin shows superior clinical cure rates compared to metronidazole, particularly in severe CDI (OR 0.46,95% CI 0.26-0.80) 2
- In non-severe CDI, while mortality outcomes are similar between metronidazole and vancomycin, vancomycin is now preferred based on overall efficacy 1
- Prolonged metronidazole use carries cumulative neurotoxicity risk 1, 2
Disease Severity Definitions
Severe CDI is characterized by any of the following 1:
- Temperature >38.5°C
- White blood cell count >15,000 cells/mL
- Serum creatinine >1.5 mg/dL
- Albumin <2.5 mg/dL
- 10 or more bowel movements within 24 hours
Fulminant CDI includes 1:
- Hypotension or shock
- End-organ failure
- Ileus or toxic megacolon
- Colonic perforation
Special Considerations for Fidaxomicin
Fidaxomicin offers specific advantages in certain clinical scenarios:
- Lower recurrence rates make it particularly valuable for patients at high risk of recurrence (age >65, ongoing antibiotic use, proton pump inhibitor use) 1, 2
- Less impact on gut microbiome: VRE acquisition occurs in only 7% with fidaxomicin versus 31% with vancomycin 2
- Particularly useful when concurrent antibiotics are needed for other infections, as it preserves more of the normal gut flora 2
- FDA-approved for patients 6 months and older 3
Critical Management Steps
Discontinue the inciting antibiotic immediately if clinically feasible—this is a strong recommendation that significantly influences recurrence risk 1, 2
Avoid common pitfalls:
- Do NOT use IV vancomycin for CDI treatment—it is not excreted into the colon and is ineffective 2
- Do NOT perform "test of cure" after completing CDI treatment 1
- Do NOT use metronidazole for severe CDI under any circumstances 1, 2
When Oral Therapy Is Not Possible
For patients unable to take oral medications with severe CDI 4:
- Metronidazole 500 mg IV three times daily PLUS
- Vancomycin 500 mg via nasogastric tube four times daily and/or
- Vancomycin 500 mg retention enema in 100 mL normal saline every 4-12 hours
Treatment of First Recurrence
For first recurrence, treat the same as initial episode unless disease has progressed from non-severe to severe 4, 1:
- Oral vancomycin 125 mg four times daily for 10 days, especially if metronidazole was used initially 1
- Consider fidaxomicin given its lower recurrence rates 1
For second or subsequent recurrences, use vancomycin in tapered/pulsed regimens or fidaxomicin, with fecal microbiota transplantation considered for multiple recurrences 1, 5, 6