Should an adult with ulcerative colitis hospitalized for severe bloody diarrhea and imaging‑confirmed colitis, who has a positive Clostridioides difficile PCR but a negative toxin assay, be treated for C. difficile infection according to guidelines?

Treatment of C. difficile in Hospitalized UC Patients with Positive PCR but Negative Toxin

Yes, treat for C. difficile infection with oral vancomycin 500 mg four times daily for 10 days while continuing corticosteroids for the ulcerative colitis flare. 1, 2

Rationale for Treatment Despite Negative Toxin

The most recent British Society of Gastroenterology guidelines (2025) mandate that all hospitalized UC patients with acute severe colitis undergo C. difficile screening, and when diagnosed, treatment should be initiated regardless of the specific testing methodology used 1. The 2019 BSG guidelines explicitly state that if C. difficile is diagnosed during acute severe UC, you should "treat with oral vancomycin 500 mg 6 hourly for 10 days and continue steroids" 1.

The key clinical principle is that PCR-positive results in a symptomatic patient with bloody diarrhea and colitis warrant treatment, particularly in the high-risk context of active inflammatory bowel disease. 3, 4

Why PCR-Positive Matters in This Context

• PCR detects the organism's genetic material and is more sensitive than toxin assays, which can have false-negative rates of 15-30% 1
• In a UC patient with severe bloody diarrhea and colitis on imaging, a positive PCR indicates clinically significant infection that requires treatment to prevent fulminant disease 4, 5
• The negative toxin assay does not rule out pathogenic C. difficile in this clinical scenario—the patient meets criteria for severe disease (bloody diarrhea, colitis on CT, hospitalization required) 3, 2

Treatment Protocol

Immediate Management

• Start oral vancomycin 500 mg four times daily for 10 days 1, 2
• Continue IV corticosteroids (hydrocortisone 100 mg every 6 hours OR methylprednisolone 60-80 mg daily) for the UC flare 1, 2
• Discontinue any inciting antibiotics if clinically feasible 3, 4
• Avoid antiperistaltic agents and opiates to prevent toxic megacolon 4, 2

Concurrent UC Management

• Do NOT withhold corticosteroids—the UC flare requires simultaneous treatment 1, 2
• Provide thromboprophylaxis with low-molecular-weight heparin 1, 2
• Conduct daily senior gastroenterology review with monitoring of stool frequency, FBC, CRP, and U&E 1
• Perform flexible sigmoidoscopy within 48 hours to assess UC severity, obtain biopsies for CMV testing, and evaluate for deep ulceration 1, 3

Day-3 Assessment for UC Response

Apply objective criteria to determine if rescue therapy is needed for steroid-refractory UC:

• >8 bowel movements per day OR 3-8 movements with CRP >45 mg/L predicts 85% steroid failure 1, 2
• If these criteria are met, initiate rescue therapy with infliximab or cyclosporine while continuing vancomycin for C. difficile 1, 6

Critical Monitoring Parameters

For C. difficile Response

• Clinical improvement should occur within 3-5 days of starting vancomycin 4
• Monitor stool frequency, WBC count, and CRP in severe cases 4
• Treatment response is defined as decreased stool frequency or improved consistency after 3 days with no new signs of severe colitis 4

For UC Complications

• Daily abdominal examination and imaging if transverse colon diameter exceeds 5.5 cm (toxic megacolon) 3, 2
• Pericolic fluid on CT is a marker of severe inflammation warranting surgical consultation 3
• Emergency surgical evaluation is required for peritoneal signs, free air, hemodynamic instability, or clinical deterioration after 3-5 days 3, 6

Common Pitfalls to Avoid

• Do not delay treatment while awaiting repeat testing—the combination of positive PCR, severe symptoms, and UC flare mandates empiric therapy 3, 4
• Do not stop corticosteroids when treating C. difficile—both conditions require simultaneous management 1, 2
• Do not use metronidazole as first-line therapy—vancomycin is the preferred agent for severe CDI 4
• Do not perform full colonoscopy in fulminant colitis due to perforation risk; flexible sigmoidoscopy is safer 1, 3

When to Escalate

Indications for surgical consultation:

• Fulminant C. difficile (shock, ileus, megacolon) requires vancomycin 500 mg orally/NG four times daily PLUS IV metronidazole 500 mg every 8 hours 4, 5
• Failure to respond to rescue therapy within 7 days for UC 1, 6
• Toxic megacolon, severe hemorrhage, or perforation 1, 3
• Serum lactate >5.0 mmol/L indicates severe disease warranting urgent colectomy 3