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

Symptoms of Clostridioides difficile (C. diff) Infection

The primary symptom of C. difficile infection is diarrhea, defined as three or more unformed stools in 24 hours, which may be accompanied by abdominal pain, cramps, and systemic features in more severe cases. 1

Cardinal Symptoms

• Diarrhea: The hallmark symptom

  • Three or more loose/unformed stools in 24 hours 1
  • Stools typically take the shape of the receptacle or correspond to Bristol stool chart types 5-7 1
  • May be watery, foul-smelling

• Abdominal symptoms:

  • Abdominal pain and cramping 1
  • Abdominal distension 1
  • Tenderness on examination in severe cases 1

Systemic Symptoms (Indicating Severe Disease)

• Fever (core body temperature >38.5°C) 1
• Rigors (uncontrollable shaking with feeling of cold) 1
• Nausea 1
• Loss of appetite 1
• Malaise

Laboratory Markers of Severe Infection

• Marked leukocytosis (white blood cell count >15 × 10⁹/L) 1, 2
• Left shift (band neutrophils >20% of leukocytes) 1
• Rise in serum creatinine (>50% above baseline) 1, 2
• Elevated serum lactate 1
• Hypoalbuminemia (<2.5 g/dL) 1, 2

Severe and Complicated Presentations

• Pseudomembranous colitis: Visible on endoscopy as yellowish-white plaques on the colonic mucosa 1
• Toxic megacolon: Characterized by radiological signs of colonic distension with signs of severe systemic inflammatory response 1
• Ileus: Signs of severely disturbed bowel function including:
  • Vomiting
  • Absence of stool
  • Radiological signs of bowel distension 1
• Fulminant colitis: Severe inflammation potentially leading to:
  • Colonic perforation
  • Peritonitis
  • Septic shock 1

Important Clinical Considerations

1. Absence of diarrhea does not rule out C. diff: In surgical patients or those with ileus, diarrhea may not be present initially due to colonic dysmotility 1

2. Blood in stool is rare in C. diff infection and should prompt consideration of other diagnoses 1

3. Fecal incontinence may be part of the disease presentation 1

4. Post-infectious symptoms: After successful treatment, up to 35% of patients may experience transient functional bowel symptoms for up to two weeks, and 4.3% may develop post-infectious irritable bowel syndrome lasting more than three months 1

Risk Factors to Consider When Evaluating Symptoms

• Recent antibiotic exposure (especially clindamycin, fluoroquinolones, cephalosporins) 1, 2
• Recent hospitalization or healthcare facility exposure 2
• Advanced age (≥65 years) 1
• Proton pump inhibitor use 1, 2
• Immunocompromised status 2
• Serious comorbidities 1

Diagnostic Pitfalls

1. Do not test asymptomatic patients - laboratory testing alone cannot distinguish between asymptomatic colonization and clinical infection 1

2. Do not perform "test of cure" after treatment, as up to 56% of patients may asymptomatically shed C. difficile spores for up to six weeks after successful treatment 1

3. Recognize that symptoms may mimic other conditions such as post-infectious irritable bowel syndrome or antibiotic-associated diarrhea from other causes 1

4. Consider C. diff in patients with unexplained leukocytosis even without prominent diarrhea, especially in high-risk patients 2

The diagnosis of C. difficile infection requires both the presence of compatible symptoms (primarily diarrhea) AND laboratory evidence of toxigenic C. difficile or its toxins in stool, or colonoscopic/histopathologic findings demonstrating pseudomembranous colitis 1.