What is the treatment for dysbiosis caused by Clostridium species?

Treatment of Dysbiosis Caused by Clostridium (Clostridioides) difficile

For initial Clostridioides difficile infection, oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days are the first-line treatments, with fidaxomicin preferred due to significantly lower recurrence rates. 1, 2

Initial Episode Treatment Algorithm

Non-Severe Disease (WBC ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL)

• First-line options:

  • Vancomycin 125 mg orally four times daily for 10 days 1, 2
  • Fidaxomicin 200 mg orally twice daily for 10 days (preferred due to lower recurrence rates) 1, 2, 3

• Resource-limited settings only: Metronidazole 500 mg orally three times daily for 10 days can be considered when vancomycin or fidaxomicin are unavailable, but has inferior efficacy 1, 2, 4

Severe Disease (WBC ≥15,000 cells/mL OR serum creatinine >1.5 mg/dL)

• Vancomycin 125 mg orally four times daily for 10 days 1, 2
• Fidaxomicin 200 mg orally twice daily for 10 days (alternative with lower recurrence) 1, 2
• Vancomycin demonstrated superior cure rates compared to metronidazole in severe CDI (97% vs. 76%) 1, 2
• Metronidazole use in severe or life-threatening CDI is strongly discouraged 1

Fulminant or Complicated Disease (Unable to Take Oral Medications)

• Vancomycin 500 mg orally four times daily PLUS intravenous metronidazole 500 mg three times daily 2
• Alternative: Intravenous metronidazole 500 mg three times daily PLUS vancomycin retention enema 500 mg in 100 mL normal saline every 4-12 hours 5, 1, 2
• Vancomycin can be administered via nasogastric tube (500 mg four times daily) or trans-stoma in surgical patients 5, 1
• Critical caveat: Intravenous vancomycin has no effect on CDI since it is not excreted into the colon 1

Recurrent CDI Treatment Algorithm

First Recurrence

• Fidaxomicin 200 mg orally twice daily for 10 days (preferred option) 5, 1, 2
• Alternative: Vancomycin as a tapered and pulsed regimen rather than a standard 10-day course 1, 2
• Treat as initial episode if disease has not progressed from non-severe to severe 5

Second and Subsequent Recurrences

• Vancomycin tapered and pulsed regimen: 5, 1, 2

  • 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 5, 1, 2

Long-Term Prophylaxis for Refractory Cases

• For elderly patients with frequently relapsing CDI who have failed FMT or where FMT is not available, prolonged vancomycin 125 mg once daily orally was effective in preventing further relapse 6
• Only 1 relapse occurred during 200 patient-months of follow-up on long-term vancomycin 6

Critical Management Principles

Discontinue Inciting Antibiotics

• Discontinue the inciting antibiotic agent(s) as soon as possible to reduce recurrence risk 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

Medications to Avoid

• Antiperistaltic agents and opiates should be avoided in all patients with CDI 5, 1, 2
• Avoid repeated metronidazole courses due to risk of cumulative and potentially irreversible neurotoxicity 1, 2

Treatment Response Monitoring

• Clinical response typically requires 3-5 days after starting therapy, particularly with metronidazole which may take up to 5 days 1, 2
• Evaluate treatment response daily, assessing stool frequency, consistency, and clinical parameters 1
• Do not perform a "test of cure" after treatment completion 1
• Approximately 20% of patients experience recurrence, with higher risk in elderly patients and those with continued antibiotic use 1, 2

Surgical Intervention

Total abdominal colectomy with ileostomy should be performed for: 5, 1

• Perforation of the colon
• Systemic inflammation and deteriorating clinical condition not responding to antibiotic therapy
• Toxic megacolon or severe ileus

Timing is critical: Surgery should be performed before colitis becomes very severe; operate before serum lactate exceeds 5.0 mmol/L 5, 1

Alternative surgical approach: Diverting loop ileostomy and colonic lavage combined with antibiotic treatment (intracolonic antegrade vancomycin and intravenous metronidazole) may be considered as a future alternative to colectomy 5

Common Pitfalls to Avoid

• Using metronidazole for severe disease (inferior outcomes compared to vancomycin) 1, 2
• Administering intravenous vancomycin expecting colonic effect (it is not excreted into the colon) 1
• Continuing antiperistaltic agents or opiates during active infection 5, 1, 2
• Delaying surgical intervention until lactate exceeds 5.0 mmol/L in fulminant cases 5, 1
• Using standard 10-day vancomycin courses for multiple recurrences instead of tapered/pulsed regimens 5, 1, 2