What is the first line treatment for Clostridioides difficile (C. diff) infection?

First-Line Treatment for Clostridioides difficile Infection

Metronidazole is recommended as the first-line antibiotic for non-severe, first episode CDI, while vancomycin is recommended for first episode CDI of any disease severity. 1

Treatment Algorithm Based on Disease Severity

Non-Severe CDI (First Episode)

• Metronidazole 500 mg orally three times daily for 10-14 days 1
• This recommendation is supported by high-quality evidence showing similar mortality outcomes between metronidazole and vancomycin in non-severe cases 1

Severe CDI (First Episode)

• Vancomycin 125 mg orally four times daily for 10-14 days 1
• Patients with severe CDI treated with vancomycin have lower all-cause 30-day mortality compared to those treated with metronidazole 1

Fulminant CDI

• Vancomycin 500 mg orally four times daily, plus
• Vancomycin per rectum (500 mg in 500 mL saline as enema) four times daily, and/or
• Metronidazole 500 mg IV every 8 hours 1
• Prompt surgical evaluation should be obtained in patients with complicated CDI 1

Alternative First-Line Options

Fidaxomicin

• Fidaxomicin 200 mg orally twice daily for 10 days 1, 2
• Similar clinical cure rates to vancomycin (88% vs 85.5%) but with lower recurrence rates 1
• Recommended by IDSA guidelines as one of the first-line treatment regimens 1
• Best prescribed to patients with high risk of recurrence due to its lower impact on gut microbiota 1
• FDA approved for adults and pediatric patients 6 months of age and older 2

Determining Disease Severity

Non-Severe CDI

• Diarrhea without features of severe or fulminant CDI 1

Severe CDI

• Temperature >38.5°C
• White blood cell count >15,000 cells/mL
• Serum creatinine >1.5 mg/dL or increase of 50% from baseline
• Albumin <2.5 mg/dL
• 10 or more bowel movements within 24 hours
• Severe abdominal pain 1

Fulminant CDI

• Hypotension
• Shock
• End-organ failure
• Ileus
• Toxic megacolon
• Colonic perforation 1, 3

Important Considerations

• Discontinue the inciting antibiotic therapy if possible 1
• Do not perform "test of cure" after CDI treatment 1
• Vancomycin may increase the risk of vancomycin-resistant Enterococci (VRE) acquisition (31% vs 7% with fidaxomicin) 1
• Prolonged use of metronidazole may be associated with neurotoxicity, especially in patients with pre-existing liver disease 1
• Fidaxomicin has minimal systemic absorption and excellent in vitro activity against C. difficile 1

Treatment of Recurrent CDI

• For first recurrence: Use oral vancomycin 125 mg four times daily for 10 days, especially if metronidazole was used for the first episode 1
• For second or subsequent recurrences: Consider vancomycin in tapered and pulsed regimens or fidaxomicin 1
• Fecal microbiota transplantation (FMT) should be considered for multiple recurrences or refractory cases 1, 3

Pitfalls and Caveats

• Laboratory testing cannot distinguish between colonization and infection; only test symptomatic patients 1
• Metronidazole is not recommended for treatment of recurrent CDI due to risk of neurotoxicity 1
• Fidaxomicin may not be cost-effective for all patients despite its benefits in reducing recurrence 1
• The recurrence rate of CDI varies by region; it is lower in some Asian countries compared to Western countries 1
• Patients with fulminant CDI or toxic megacolon were excluded from most fidaxomicin studies 1