What are the symptoms of Clostridium difficile (C. diff) infection?

Symptoms of Clostridioides difficile Infection

Watery diarrhea (≥3 unformed stools in 24 hours) accompanied by abdominal cramping is the hallmark presentation of C. difficile infection, though the clinical spectrum ranges from mild diarrhea to life-threatening fulminant colitis. 1, 2

Mild to Moderate CDI

Gastrointestinal Symptoms:

• Watery, non-bloody diarrhea (typically ≥3 unformed stools per 24 hours) 2, 3
• Abdominal pain and cramping ranging from mild to moderate intensity 1, 2
• Hyperactive bowel sounds due to increased intestinal motility and inflammation 4
• Abdominal distension may be present 4
• Stool frequency <4 times daily in mild cases 1

Systemic Features:

• Dehydration and electrolyte imbalances with prolonged diarrhea 2
• Fever may be absent or low-grade in mild cases 1

Severe CDI

The following clinical and laboratory markers indicate severe disease: 1

Laboratory Abnormalities:

• White blood cell count >15 × 10⁹/L (marked leukocytosis) 1
• Serum creatinine ≥133 μmol/L or ≥1.5 times premorbid level 1
• Serum albumin <2.5 g/dL (hypoalbuminemia) 1
• Marked left shift with band neutrophils >20% 1
• Elevated serum lactate 1

Clinical Features:

• Fever >38.5°C (core body temperature) 1
• Rigors (uncontrollable shaking with chills) 1
• Increased abdominal cramping and pain 1
• Hemodynamic instability or signs of septic shock 1
• Bloody stools may occasionally be present 2

Fulminant/Complicated CDI

This represents 1-3% of all CDI cases but carries high mortality: 1

Critical Warning Signs:

• Absence of diarrhea may signal progression to fulminant infection 1
• Hypoactive or absent bowel sounds indicating ileus development 1, 4
• Signs of peritonitis: decreased bowel sounds, abdominal tenderness, rebound tenderness, guarding 1
• Signs of ileus: vomiting and absent passage of stool 1
• Vasopressor requirements 1
• Organ failure with increased serum lactate 1

Imaging/Endoscopic Findings:

• Pseudomembranous colitis on endoscopy 1
• Distension of large intestine 1
• Colonic wall thickening with low-attenuation mural thickening 1
• Pericolonic fat stranding 1
• Ascites not explained by other causes 1
• Toxic megacolon (radiological distension plus severe systemic inflammatory response) 1

Important Clinical Pitfalls

Atypical Presentations:

• Surgical patients with ileus may present without diarrhea initially, making diagnosis challenging 2
• Immunocompromised patients may have less pronounced symptoms and atypical presentations 4
• Patients with inflammatory bowel disease (IBD) may have overlapping symptoms with an IBD flare, complicating diagnosis 4, 2

Progression Patterns:

• Early CDI typically presents with hyperactive bowel sounds and watery diarrhea 4
• As severity increases, bowel sounds may become hypoactive or absent if ileus develops 4
• The absence of diarrhea in a patient with suspected CDI should raise concern for fulminant disease with ileus 1

Recurrent Disease:

• Recurrence develops in 10-30% of cases after initial therapy 1
• Patients with 1-2 previous episodes have 40-65% risk of further recurrences 1
• Recurrent episodes are typically less severe than initial episodes 1

Clinical Context

Risk Factor Recognition:

• Recent antibiotic exposure (especially clindamycin, ampicillin, amoxicillin, cephalosporins) 5, 3
• Recent healthcare facility exposure 3
• Long-term care facility residents with antibiotic exposure in previous 30 days 2

Systemic Consequences:

• Hypoalbuminemia increases severity because serum albumin binds C. difficile toxins A and B, impairing their cellular internalization 1, 2
• Systemic toxin effects result from toxins spreading into the bloodstream, not just local colonic inflammation 1