What is the antibiotic of choice for Clostridium (C.) infections?

Antibiotic Treatment for Clostridium difficile Infection

For Clostridium difficile infection (CDI), the antibiotics of choice are oral vancomycin 125 mg four times daily or fidaxomicin 200 mg twice daily for 10 days, with vancomycin being preferred for severe cases and fidaxomicin having lower recurrence rates. 1, 2

Treatment Algorithm Based on Disease Severity

Initial CDI Episode:

1. Non-severe CDI:

   • First choice: Vancomycin 125 mg orally four times daily for 10 days OR Fidaxomicin 200 mg twice daily for 10 days 1
   • Alternative (if access to vancomycin/fidaxomicin is limited): Metronidazole 500 mg orally three times daily for 10 days 1
   • Note: Avoid prolonged metronidazole courses due to risk of cumulative neurotoxicity 1

2. Severe CDI (defined as WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL):

   • Vancomycin 125 mg orally four times daily for 10 days OR Fidaxomicin 200 mg twice daily for 10 days 1

3. Fulminant CDI (hypotension, shock, ileus, megacolon):

   • Vancomycin 500 mg orally or via nasogastric tube four times daily 1
   • PLUS intravenous metronidazole 500 mg every 8 hours 1
   • If ileus present: Add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours 1

When Oral Therapy is Not Possible:

• Non-severe CDI: Metronidazole 500 mg intravenously three times daily for 10 days 1
• Severe CDI: Metronidazole 500 mg intravenously three times daily for 10 days 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 1

Treatment of Recurrent CDI

1. First recurrence:

   • If metronidazole was used initially: Vancomycin 125 mg four times daily for 10 days 1
   • If standard regimen was used initially: Consider tapered and pulsed vancomycin regimen OR fidaxomicin 200 mg twice daily for 10 days 1, 2

2. Multiple recurrences:

   • Vancomycin with tapered/pulsed regimen
   • Fidaxomicin 200 mg twice daily for 10 days
   • Consider fecal microbiota transplantation for patients who have failed appropriate antibiotic treatments 2

Clinical Evidence and Efficacy

Vancomycin has demonstrated clinical success rates of approximately 81% in clinical trials, with median time to diarrhea resolution of 4-5 days 3. Clinical trials showed vancomycin was effective against both BI and non-BI strains of C. difficile 3.

The 2018 IDSA/SHEA guidelines strongly recommend vancomycin or fidaxomicin over metronidazole based on high-quality evidence 1. This represents a shift from earlier guidelines that recommended metronidazole for non-severe cases.

Important Considerations

• Discontinue the inciting antibiotic as soon as possible to reduce recurrence risk 1
• Consider early surgical evaluation in fulminant CDI, especially with rising WBC count (≥25,000) or lactate level (≥5 mmol/L) 1, 2
• Monitor for recurrence for up to 2 months after treatment 2
• Implement infection control measures including hand hygiene with soap and water (alcohol-based sanitizers are less effective against C. difficile spores) 2

Pitfalls to Avoid

• Don't delay treatment in suspected severe or fulminant cases; start empiric therapy while awaiting laboratory confirmation 1
• Don't rely on metronidazole for severe CDI cases as it has shown inferior outcomes compared to vancomycin 1
• Don't use prolonged or repeated courses of metronidazole due to risk of cumulative and potentially irreversible neurotoxicity 1
• Don't forget to monitor elderly patients for renal function during and after vancomycin treatment 2
• Don't continue unnecessary broad-spectrum antibiotics as they increase risk of CDI recurrence 2

By following this evidence-based approach to antibiotic selection for C. difficile infection, you can optimize patient outcomes while minimizing the risk of treatment failure and recurrence.