What is CIP (Clostridioides difficile infection)?

Clostridioides difficile Infection (CDI): Definition and Management

Clostridioides difficile infection (CDI) is defined as a clinical picture compatible with CDI and microbiological evidence of toxin-producing C. difficile in stool, without reasonable evidence of another cause of diarrhea, or pseudomembranous colitis diagnosed during endoscopy, colectomy, or autopsy. 1

Clinical Presentation

CDI presents with a spectrum of symptoms ranging from:

• Mild to moderate diarrhea: Loose stools (Bristol stool chart types 5-7) with ≥3 stools in 24 hours or more frequently than normal for the individual 1
• Severe disease: Marked leukocytosis (>15 × 10⁹/L), decreased blood albumin (<30 g/L), or rise in serum creatinine (≥133 μM or ≥1.5 times premorbid level) 1
• Complicated/fulminant disease: Hypotension, shock, ileus, toxic megacolon requiring ICU admission, colectomy, or resulting in death 1

Other clinical manifestations may include:

• Abdominal pain and distension
• Fever
• In patients with ileostomies: increased output, nausea, fever, and leukocytosis 1
• In patients with ileal pouch anal anastomosis: increased stool frequency 1

Epidemiology and Risk Factors

CDI is the most common cause of healthcare-associated infectious diarrhea, accounting for up to 50% of antibiotic-associated diarrhea cases 1. Key risk factors include:

• Antibiotic exposure: Highest risk with clindamycin (OR 2.12-42), third-generation cephalosporins (OR 3.84-26), fluoroquinolones, and broad-spectrum penicillins 2, 1
• Age ≥65 years 2
• Healthcare exposure: 64.7% of cases are healthcare-associated 2
• Proton pump inhibitor use 2
• Comorbidities: Inflammatory bowel disease, chronic kidney disease, immunodeficiency 2
• Previous CDI history 2

Diagnostic Approach

CDI should be suspected in patients with:

• ≥3 unformed stools within 24 hours
• Not taking laxatives
• Recent antibiotic exposure or healthcare facility contact

Diagnostic testing should include:

• Enzyme immunoassays for glutamate dehydrogenase and toxins A and B, or
• Nucleic acid amplification testing 3

Important: Do not test asymptomatic patients or perform "test of cure" after treatment, as up to 56% of patients will asymptomatically shed C. difficile spores for up to six weeks 2

Treatment Recommendations

Treatment should be based on disease severity and whether it's an initial or recurrent episode:

Initial Episode, Non-severe CDI:

• First-line: Oral vancomycin 125 mg four times daily for 10 days 2, 1
• Alternative: Oral fidaxomicin 200 mg twice daily for 10 days 4
• Note: Metronidazole is no longer recommended as first-line therapy for adults 3

Initial Episode, Severe CDI:

• First-line: Oral vancomycin 125 mg four times daily for 10 days 1
• Alternative: Oral fidaxomicin 200 mg twice daily for 10 days 4

Initial Episode, Fulminant CDI:

• Vancomycin 500 mg orally/nasogastric tube four times daily plus
• Intravenous metronidazole 500 mg three times daily 1
• Early surgical consultation for possible colectomy or diverting loop ileostomy with colonic lavage 1, 5

Recurrent CDI:

• First recurrence: Oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days 6
• Multiple recurrences: Consider fecal microbiota transplantation (FMT), which has 70-90% cure rates 5, 6
• Adjunctive therapy: Bezlotoxumab (monoclonal antibody against C. difficile toxin B) may be considered for patients with multiple risk factors for recurrence 6

Prevention Strategies

• Antibiotic stewardship: Use antibiotics only when necessary and select lower-risk options 2
• Hand hygiene: Soap and water (preferred during outbreaks) or alcohol-based products 2, 3
• Contact precautions: Isolation of patients with CDI 2
• Environmental cleaning: Use sporicidal agents 2
• Avoid unnecessary proton pump inhibitor use 2

Special Populations

Immunocompromised Patients

Immunocompromised patients (solid organ transplant recipients, cancer patients, HIV/AIDS patients) have higher risk of CDI due to:

• Frequent hospitalization
• Antibiotic exposure
• Immunosuppression
• Altered gut microbiota 1

Inflammatory Bowel Disease (IBD) Patients

• CDI symptoms may mimic IBD flare
• Higher risk of severe outcomes including mortality
• Consider CDI in any IBD patient with worsening symptoms 1

Important Caveats

• Do not treat asymptomatic carriers as this may increase risk of C. difficile carriage following therapy 1
• Do not repeat testing during the same episode as this increases false-positive results 1
• Do not use antimotility agents in severe cases as they may precipitate toxic megacolon 1
• Consider early surgical consultation for patients with severe or fulminant disease 1
• Monitor treatment response daily and evaluate after at least 3 days of therapy 1