What is the treatment for Clostridium (C. diff) infection?

Treatment and Diagnosis of Clostridioides difficile Infection

Diagnosis

Test patients who have ≥3 unformed stools in 24 hours and are not taking laxatives, using either enzyme immunoassays for glutamate dehydrogenase and toxins A and B, or nucleic acid amplification testing. 1

• In children, only test those >12 months of age with prolonged diarrhea and risk factors 1
• Toxigenic culture remains the gold standard, though PCR and enzyme immunoassays offer faster results with high specificity and sensitivity 2
• Clinical response should be the primary measure of treatment success rather than repeat stool testing 3

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Disease Severity Classification

Severity classification drives treatment decisions and must be assessed immediately:

Non-severe CDI:

• Stool frequency <4 times daily 4
• White blood cell count <15×10⁹/L 3
• No signs of severe colitis 4

Severe CDI (presence of ≥1 of the following):

• Temperature >38.5°C 4
• Hemodynamic instability 4
• Leukocyte count >15×10⁹/L 4, 5
• Serum creatinine rise ≥50% above baseline or ≥133 μM 4, 5
• Serum albumin <30 g/L 5
• Elevated serum lactate 4
• Pseudomembranous colitis on endoscopy 4
• Colonic wall thickening on imaging 4

Fulminant CDI:

• Hypotension or shock 4
• Ileus or megacolon 4
• Signs of peritonitis 3

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First-Line Treatment

Non-Severe CDI

Vancomycin 125 mg orally four times daily for 10 days is the recommended first-line therapy for non-severe CDI. 4

• Fidaxomicin 200 mg orally twice daily for 10 days is an alternative, particularly for patients at high risk of recurrence 4, 6
• Metronidazole 500 mg orally three times daily for 10 days is less preferred and no longer recommended as first-line therapy in adults 4, 1

Severe CDI

Vancomycin 125 mg orally four times daily for 10 days is the recommended first-line therapy for severe CDI. 4, 5

• Fidaxomicin 200 mg orally twice daily for 10 days is an alternative, with evidence suggesting fewer secondary recurrences compared to vancomycin 5, 3
• Metronidazole has higher failure rates in severe CDI and should not be used 4

Fulminant CDI

For fulminant CDI, use oral vancomycin 500 mg four times daily PLUS intravenous metronidazole 500 mg every 8 hours. 4

• If ileus is present, add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema 4

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Critical Management Principles

Discontinue the inciting antibiotic immediately if possible—continued use significantly increases risk of recurrence. 5, 3

• If continued antibiotic therapy is required, choose agents less associated with CDI 4
• Avoid antiperistaltic agents and opiates as they may mask symptoms and worsen disease 5, 3
• Discontinue unnecessary proton pump inhibitors in high-risk patients 4

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Treatment of Recurrent CDI

First Recurrence

Treat based on severity using vancomycin 125 mg orally four times daily for 10 days or fidaxomicin 200 mg orally twice daily for 10 days. 4, 5

Second and Subsequent Recurrences

Vancomycin 125 mg orally four times daily for at least 10 days, followed by a tapered and pulsed regimen. 4, 5, 3

Alternative regimens include:

• Vancomycin followed by rifaximin 3
• Fidaxomicin 200 mg twice daily for 10 days 3

Multiple Recurrences

Fecal microbiota transplantation (FMT) is strongly recommended for multiple recurrent CDI unresponsive to repeated antibiotic treatments. 4, 3

• FMT should be offered after at least two recurrences, or after one recurrence with risk factors for further episodes 3
• FMT should be given upon completion of standard antibiotics, ideally stopped 1-3 days before conventional FMT 3
• Prevention of CDI recurrence following FMT ranges from 70% to 90% 3
• In mildly or moderately immunocompromised adults, conventional FMT is suggested 3
• In severely immunocompromised adults with recurrent CDI, fecal microbiota-based therapies are not recommended 3

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Surgical Management

Consider colectomy for perforation, systemic inflammation with deteriorating clinical condition not responding to antibiotics, toxic megacolon, or severe ileus. 4, 5, 3

• Surgery should be performed before serum lactate exceeds 5.0 mmol/L 4, 3
• Total colectomy has been traditional, but diverting loop ileostomy with colonic lavage is emerging as a viable alternative with potentially lower mortality 5

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Pediatric Considerations

For children with non-severe CDI, metronidazole or vancomycin for 10 days is recommended. 4

• For severe or fulminant CDI in children, use vancomycin orally or rectally every 8 hours, with or without metronidazole IV for 10 days 4
• For recurrent CDI in children, consider vancomycin extended regimen or fecal microbiota transplantation 4
• Fidaxomicin is FDA-approved for pediatric patients ≥6 months of age 6
• Weight-based dosing for fidaxomicin oral suspension ranges from 80 mg (2 mL) twice daily for 4-7 kg to 200 mg (5 mL) twice daily for ≥12.5 kg 6

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Infection Control and Prevention

Hand hygiene with soap and water is required, as alcohol-based hand sanitizers are ineffective against C. difficile spores. 4, 5

• During outbreaks, soap and water is superior to alcohol-based products 1
• Good antibiotic stewardship is a key strategy to decrease CDI rates 1
• Contact isolation strategies and environmental controls are essential 2

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Common Pitfalls

• Do not use metronidazole for severe CDI—it has higher failure rates 4
• Do not repeat stool testing to assess treatment response—use clinical improvement 3
• Treatment duration may need extension beyond 10 days in patients with delayed response 4
• In patients with inflammatory bowel disease and CDI, symptoms may overlap, making assessment challenging 3
• The Infectious Diseases Society of America does not recommend probiotics for prevention of CDI 1