What is the initial treatment for a patient with a confirmed diagnosis of Clostridioides difficile (C diff) infection?

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, with fidaxomicin preferred due to significantly lower recurrence rates. 1

Initial Episode Treatment Algorithm

First-Line Therapy

• Fidaxomicin 200 mg orally twice daily for 10 days is the preferred treatment for all initial CDI episodes regardless of severity, as it significantly reduces recurrence rates compared to vancomycin 1, 2
• Vancomycin 125 mg orally four times daily for 10 days remains an acceptable alternative with proven efficacy (81-92% clinical cure rates) and is appropriate for both non-severe and severe disease 1, 2, 3
• The distinction between non-severe (WBC ≤15,000 cells/mL and creatinine <1.5 mg/dL) and severe disease (WBC ≥15,000 cells/mL or creatinine >1.5 mg/dL) does not change the initial antibiotic choice between fidaxomicin and vancomycin 1

When Metronidazole May Be Considered

• Metronidazole 500 mg orally three times daily for 10 days should only be used in resource-limited settings where vancomycin or fidaxomicin are unavailable, and only for non-severe CDI 1
• Metronidazole has inferior efficacy compared to vancomycin, particularly in severe disease (76% vs 97% cure rates) 1
• Avoid repeated or prolonged metronidazole courses due to risk of cumulative and potentially irreversible neurotoxicity 1, 4

Fulminant/Life-Threatening CDI

Defining Fulminant Disease

Look for these specific clinical features: 5

• Hemodynamic instability or septic shock
• Signs of peritonitis (decreased bowel sounds, abdominal tenderness, rebound, guarding)
• Signs of ileus (vomiting, absent stool passage)
• Marked leukocytosis (WBC >15,000/mm³) or marked left shift (bands >20%)
• Serum creatinine rise >50% above baseline
• Elevated serum lactate
• Imaging showing colonic distension, wall thickening, or pericolonic fat stranding

Treatment Regimen

• Vancomycin 500 mg orally four times daily PLUS intravenous metronidazole 500 mg every 8 hours 1, 2
• If ileus is present, add vancomycin 500 mg in 100 mL normal saline per rectum every 4-12 hours as a retention enema 5, 1, 2
• Vancomycin can be administered via nasogastric tube (500 mg four times daily) if oral route is compromised 5, 1
• Critical pitfall: Intravenous vancomycin has NO effect on CDI since it is not excreted into the colon—never use IV vancomycin alone 1, 2

Surgical Intervention

• Perform total abdominal colectomy with ileostomy for: perforation of the colon, systemic inflammation with deteriorating clinical condition not responding to antibiotics, toxic megacolon, or severe ileus 5, 1
• Operate before colitis becomes very severe—ideally before serum lactate exceeds 5.0 mmol/L 5, 2

Recurrent CDI Treatment

First Recurrence

• Fidaxomicin 200 mg orally twice daily for 10 days is the preferred option 1
• Alternative: Vancomycin 125 mg four times daily for 10 days if metronidazole was used initially 1, 2
• If standard vancomycin was used initially, use a prolonged tapered and pulsed regimen 1, 2

Second and Subsequent Recurrences

• Vancomycin tapered and pulsed regimen: 1, 2, 4
  • 125 mg four times daily for 10-14 days
  • Then 125 mg twice daily for 7 days
  • Then 125 mg once daily for 7 days
  • Then 125 mg every 2-3 days for 2-8 weeks
• Fecal microbiota transplantation (FMT) is strongly recommended after at least 2 recurrences that have failed appropriate antibiotic treatments 1

Critical Management Principles

Essential Actions

• Discontinue the inciting antibiotic agent(s) immediately as this significantly reduces recurrence risk 1, 2
• Antiperistaltic agents and opiates should be avoided in all patients with CDI as they worsen outcomes and increase complications 5, 1, 2
• In non-epidemic situations with clearly antibiotic-induced non-severe CDI, it may be acceptable to stop the inducing antibiotic and observe for 48 hours before starting treatment, but monitor closely for deterioration 5, 1

Treatment Response Monitoring

• Clinical response typically requires 3-5 days after starting therapy, with metronidazole potentially taking up to 5 days 1, 3
• Median time to resolution of diarrhea is 4-5 days with vancomycin 3
• Evaluate treatment response daily by assessing stool frequency, consistency, and clinical parameters 1
• Do not perform a "test of cure" after treatment completion 1

Special Considerations

• Concomitant antibiotic use during CDI treatment is associated with lower cure rates (84.4% vs 92.6%) and extended time to diarrhea resolution 6
• When patients require concomitant antibiotics, fidaxomicin demonstrates superior cure rates compared to vancomycin (90.0% vs 79.4%) 6
• Recurrence occurs in approximately 18-25% of patients after successful initial treatment 3, 4
• Fidaxomicin may be particularly beneficial in elderly patients due to lower recurrence rates 1