What is the treatment for colitis without Clostridioides (C.) difficile?

Treatment of Colitis Without C. difficile

For colitis without C. difficile, treatment depends on the underlying etiology: inflammatory bowel disease (IBD) requires corticosteroids as first-line therapy, with IV hydrocortisone 100 mg every 6 hours or IV methylprednisolone 60-80 mg daily for acute severe colitis, while other infectious causes require pathogen-specific antimicrobial therapy. 1

Acute Severe Ulcerative Colitis (Non-C. difficile)

Initial Management

For patients presenting with acute severe ulcerative colitis (≥6 bloody stools per day AND systemic toxicity), commence treatment immediately without delay: 1

• IV hydrocortisone 100 mg every 6 hours OR IV methylprednisolone 60-80 mg daily 1
• Low molecular weight heparin prophylaxis 1
• Consider withholding 5-ASA agents 1
• Obtain baseline investigations including stool microbiology to exclude C. difficile and other infectious causes 1

Do not delay steroids while awaiting stool culture results. 1

Day 3 Assessment

Daily senior gastroenterology review with FBC, U&E, and CRP is mandatory throughout the hospital stay. 1 Treatment escalation depends on stool frequency and inflammatory markers:

If ≥3 bowel movements per day AND CRP >45 mg/L: 1

• Continue IV steroids
• Consider flexible sigmoidoscopy with biopsies for urgent histology, specifically assessing for CMV colitis 1
• If CMV colitis is diagnosed, treat with IV ganciclovir 5 mg/kg every 12 hours for 3-5 days, then oral valganciclovir 900 mg every 12 hours for 2-3 weeks 1

If <4 bowel movements per day for 2 consecutive days: 1

• Switch to oral prednisolone 40 mg daily
• Commence thiopurine if not already receiving 1

Second-Line Rescue Therapy

For patients not responding to IV steroids by day 3, two equally effective options exist: 1

• Infliximab: Accelerated dosing is beneficial, though optimal regimen remains unclear 1
• Ciclosporin: Head-to-head trials demonstrate equivalent efficacy to infliximab 1

When using infliximab for acute severe UC, combination therapy with azathioprine has synergistic effects, raising infliximab levels and reducing antibody formation. 1 Azathioprine or mercaptopurine should be started during hospitalization and continued after discharge. 1

Surgical Considerations

Emergency colectomy is indicated for: 1

• Continued systemic toxicity despite medical therapy
• Severe abdominal pain
• Suspicion of toxic megacolon or perforation 1
• Deep ulceration on endoscopy (associated with poor outcome) 1

CT imaging is preferable to abdominal X-ray if severe complications, notably perforation, are suspected. 1

Other Forms of Non-C. difficile Colitis

CMV Colitis

CMV colitis carries extremely high mortality (nearly 70% in severely ill immunocompetent patients, even worse in immunocompromised). 1 The association between IBD and CMV colitis should be considered, as patients with both conditions experience up to seven times higher in-hospital mortality. 1

Treatment: 1

• IV ganciclovir 5 mg/kg twice daily for 3-5 days
• Transition to oral valganciclovir 900 mg twice daily for remainder of 2-3 week course
• Continue corticosteroids if underlying IBD present 1

Surgical intervention (subtotal or partial colectomy) is indicated for toxic megacolon, fulminant colitis, perforation, or ischemia. 1

Checkpoint Inhibitor-Induced Colitis

For mild colitis (Grade 1-2): 2

• Supportive therapy with oral hydration, bland diet without lactose or caffeine
• Anti-diarrheal agents (loperamide)
• Low-fiber diet and spasmolytics 2

For severe cases (Grade 3-4): 2

• Corticosteroid treatment is mandatory
• Refractory cases may require off-label biological therapies (infliximab or vedolizumab) 2

Other Infectious Colitis (Non-C. difficile)

For infectious colitis from other pathogens: 3

• Use antibiotics with narrowest effective spectrum
• Adjust based on culture results
• Avoid antiperistaltic agents and opiates as they may worsen the condition 3

Common Pitfalls

Critical caveat: Patients with IBD are at independent risk for C. difficile infection, and immunomodulators are independent predictors of severe C. difficile-associated disease. 1 Always exclude C. difficile before attributing symptoms solely to IBD flare, as co-infection significantly worsens outcomes. 1

Pneumocystis jirovecii prophylaxis should be given to patients on ≥20 mg prednisolone. 1 Screening for tuberculosis, hepatitis B and C, HIV, and VZV is required before starting second-line immunosuppressive therapies. 1