What is the recommended treatment for Clostridioides difficile (C-diff) infections?

Treatment of 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 as first-line therapy, regardless of disease severity. 1, 2

Initial Episode Treatment

First-Line Options

• Vancomycin 125 mg orally four times daily for 10 days is the standard first-line treatment 1, 2, 3
• Fidaxomicin 200 mg orally twice daily for 10 days is equally effective for initial treatment and offers a significant advantage with lower recurrence rates (15% vs 25-31% with vancomycin) 2
• Both agents have strong evidence supporting their use for initial episodes, with treatment selection based on availability and cost considerations 1, 2

Disease Severity Classification

• Non-severe CDI: WBC ≤15,000 cells/mL and serum creatinine <1.5 mg/dL 1
• Severe CDI: WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL 1
• The same dosing regimen (vancomycin 125 mg four times daily or fidaxomicin 200 mg twice daily) applies to both non-severe and severe CDI 1, 2

Critical Action

• Discontinue the inciting antibiotic immediately to reduce recurrence risk 1, 2

Dosing Considerations

Standard Vancomycin Dosing

• Do not use higher doses of vancomycin (500 mg four times daily) for severe CDI, as they have not shown significant differences in clinical outcomes compared to standard 125 mg dosing 1, 4, 5, 6
• The 125 mg dose achieves fecal concentrations far exceeding the MIC90 for C. difficile, even in patients with frequent stools 7
• Higher doses are more expensive without added benefit 6

Treatment Duration

• Standard duration is 10 days for all initial episodes 1, 2
• Consider extending to 14 days if clinical response is delayed 1, 2
• Clinical response is expected within 3-5 days after starting therapy 2

Fulminant CDI

For fulminant disease (hypotension, shock, ileus, or megacolon):

• Vancomycin 500 mg orally or via nasogastric tube four times daily 2
• Add intravenous metronidazole 500 mg every 8 hours 2
• Consider vancomycin retention enema 500 mg in 100 mL normal saline every 6 hours if ileus is present 2

Recurrent CDI Treatment

First Recurrence

• Fidaxomicin 200 mg twice daily for 10 days is the preferred option 2
• Alternative options include prolonged tapered and pulsed vancomycin regimen or vancomycin 125 mg four times daily for 10 days 1, 2

Second or Subsequent Recurrence

• Vancomycin in a tapered and pulsed regimen 1
• Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 1
• Fidaxomicin 200 mg twice daily for 10 days 1
• Fecal microbiota transplantation (FMT) is strongly recommended after at least 2 recurrences that have failed appropriate antibiotic treatments 2

Special Populations

NPO Patients or Ileus

• Intravenous metronidazole 500 mg every 8 hours plus vancomycin retention enema 500 mg in 100 mL normal saline four times daily 1, 2
• Transition to oral vancomycin or fidaxomicin once oral intake is possible 1, 2

Pediatric Patients (≥6 months to <18 years)

• Vancomycin 10 mg/kg/dose orally four times daily (maximum 125 mg per dose) 2
• Fidaxomicin weight-based dosing for 10 days 2, 8
• For pediatric patients weighing at least 12.5 kg and able to swallow tablets: fidaxomicin 200 mg twice daily 8

Critical Pitfalls to Avoid

What NOT to Do

• Do not use metronidazole for severe or recurrent CDI due to lower cure rates compared to vancomycin 1, 2
• Do not administer only intravenous vancomycin for CDI, as it is not effective for colitis treatment 1, 2, 3
• Do not perform a "test of cure" after treatment completion 1, 2
• Do not use antiperistaltic agents or opiates in patients with active CDI 2
• Do not use repeated or prolonged courses of metronidazole due to neurotoxicity risk 1

Monitoring Considerations

• Monitor renal function in patients >65 years of age during and after treatment, as nephrotoxicity risk is increased 3
• Consider monitoring serum vancomycin concentrations in patients with renal insufficiency, colitis, or those receiving concomitant aminoglycoside therapy 3
• Approximately 20% of patients experience recurrence after initial treatment, with higher risk in elderly patients and those with continued antibiotic use 2