What is the treatment for a patient with a Clostridioides difficile (C. diff) polymerase chain reaction (PCR) A/B positive result?

Treatment of C. difficile PCR A/B Positive

For a patient with a positive C. difficile PCR A/B test and diarrhea (≥3 unformed stools in 24 hours), treat based on disease severity: oral vancomycin 125 mg four times daily for 10 days for both non-severe and severe initial episodes, or oral fidaxomicin 200 mg twice daily for 10 days as an alternative. 1, 2, 3

Critical Diagnostic Context

Before initiating treatment, confirm this represents active infection rather than colonization:

• A positive PCR test alone does not mandate treatment - diagnosis requires clinical signs and symptoms (diarrhea with ≥3 unformed stools in 24 hours) combined with laboratory confirmation 2
• NAAT/PCR testing detects toxin genes and is highly sensitive, but may detect asymptomatic colonization 2
• Asymptomatic patients with positive tests represent colonization and should NOT be treated 2, 4

Disease Severity Assessment

Classify severity to guide treatment intensity 2, 3:

Non-severe CDI:

• Stool frequency <4 times daily 3
• White blood cell count <15 × 10⁹/L 2
• No signs of severe colitis 3

Severe CDI:

• Temperature >38.5°C 3
• Hemodynamic instability 3
• White blood cell count ≥15 × 10⁹/L 1, 3
• Serum creatinine rise >50% above baseline 3
• Elevated serum lactate 3
• Pseudomembranous colitis on endoscopy or colonic wall thickening on imaging 3

Fulminant CDI:

• Hypotension or shock 3
• Ileus or megacolon 3
• Peritoneal signs 1

Initial Episode Treatment

Non-Severe CDI

First-line: Oral vancomycin 125 mg four times daily for 10 days 1, 2, 3

Alternative: Oral metronidazole 500 mg three times daily for 10 days (less preferred) 1, 2

The 125 mg vancomycin dose is as effective as 500 mg and significantly less expensive 5. Treatment courses are typically 10 days, though extending to 14 days should be considered for patients with delayed response, particularly those on metronidazole 1.

Severe CDI

First-line: Oral vancomycin 125 mg four times daily for 10 days 1, 3

Alternative: Oral fidaxomicin 200 mg twice daily for 10 days, especially for patients at high risk of recurrence 1, 3, 6

Fidaxomicin achieves similar cure rates to vancomycin but demonstrates significantly lower recurrence rates (13.3% vs 24.0%) 7, 8. However, this advantage is primarily seen with non-BI/NAP1 strains 6, 7.

Fulminant CDI

Recommended regimen: 1, 3

• Oral vancomycin 500 mg four times daily for 10 days PLUS
• Intravenous metronidazole 500 mg every 8 hours

If ileus present: Add rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema 1, 3

Recurrent CDI Treatment

First Recurrence

Preferred options: 1

• Oral vancomycin 125 mg four times daily for 10 days (if metronidazole was used initially) 1
• Oral fidaxomicin 200 mg twice daily for 10 days 1
• Vancomycin tapered and pulsed regimen (125 mg four times daily for 10-14 days, then twice daily for 1 week, once daily for 1 week, then every 2-3 days for 2-8 weeks) 1

Fidaxomicin reduces second recurrence rates significantly (19.7% vs 35.5% with vancomycin) in patients with first recurrence 8.

Second or Subsequent Recurrence

Recommended options: 1

• Vancomycin tapered and pulsed regimen 1
• Vancomycin extended regimen 1
• Fidaxomicin 200 mg twice daily for 10 days OR extended regimen (200 mg twice daily for 5 days, then once daily on alternate days for days 7-25) 1
• Fecal microbiota transplantation after ≥2 recurrences (3 total CDI episodes) 1

The extended fidaxomicin regimen demonstrates remarkably low recurrence rates (6% at day 90) 1.

Critical Management Considerations

Discontinue inciting antibiotics immediately if clinically feasible 2, 3

Avoid antimotility agents (loperamide, opiates) - these are contraindicated as they prevent toxin clearance and can worsen infection 2, 3

Discontinue proton pump inhibitors if not medically necessary 2, 3

Concomitant antibiotic use: If other antibiotics must be continued, fidaxomicin demonstrates superior cure rates (90.0% vs 79.4% with vancomycin) and fewer recurrences (16.9% vs 29.2%) 9

Surgical Intervention

Consider colectomy for 2, 3:

• Perforation of the colon
• Systemic inflammation with deteriorating clinical condition not responding to antibiotics
• Toxic megacolon
• Severe ileus
• Perform surgery before serum lactate exceeds 5.0 mmol/L 3

Common Pitfalls

Do not treat asymptomatic carriers - treatment with vancomycin temporarily suppresses colonization but leads to higher carriage rates 2 months later and is not recommended 4

Do not use metronidazole for severe CDI - it has higher failure rates 3

Do not rely on PCR results alone - always correlate with clinical symptoms 2

Hand hygiene requires soap and water - alcohol-based sanitizers are ineffective against C. difficile spores 3