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

Symptoms and Causes of Clostridioides difficile Infection

Clostridioides difficile infection (CDI) is characterized primarily by diarrhea (three or more unformed stools in 24 hours) with no obvious alternative explanation, along with a positive laboratory test for toxigenic C. difficile or its toxins. 1

Clinical Manifestations

Common Symptoms

• Diarrhea: Defined as ≥3 loose stools in 24 hours, the hallmark symptom 1
• Abdominal pain and cramps 1
• Abdominal distension 1
• Fever (>38.5°C) 1

Severity Spectrum

CDI presents with varying severity:

• Mild to moderate disease: Diarrhea without systemic symptoms
• Severe disease: Marked by:
  • Leukocytosis (WBC >15 × 10^9/L)
  • Hypoalbuminemia (<2.5 g/dL)
  • Rise in serum creatinine (≥133 μM/L or ≥1.5 times premorbid level)
  • Fever >38.5°C 1
• Fulminant colitis: Occurs in 1-3% of cases but carries high mortality 1
  • Toxic megacolon
  • Colonic perforation
  • Peritonitis
  • Septic shock
  • Multiple organ failure

Complications

• Ileus (signs of severely disturbed bowel function) 1
• Pseudomembranous colitis 1
• Recurrent infection (occurs in 10-30% of cases) 1
• Increased hospital length-of-stay and mortality 1

Causes and Risk Factors

Primary Causes

1. Antibiotic exposure: The most significant risk factor 1, 2

   • Disrupts normal gut microbiota
   • Clindamycin carries particularly high risk 3
   • Risk increases with multiple antibiotics and longer duration 1

2. Healthcare exposure:

   • Recent hospitalization
   • Longer hospitalization duration 1
   • Nursing home residence 4

Additional Risk Factors

• Advanced age 1, 4
• Proton pump inhibitor use 1
• Chemotherapy 1
• Chronic kidney disease 1
• Use of feeding tubes 1
• Immunosuppression
• Previous CDI episodes (risk of recurrence increases with each episode) 1

Transmission

• Fecal-oral route 4
• Spores can persist in the environment 2
• Hypervirulent strains (particularly ribotype 027/NAP1) associated with increased severity and mortality 1, 2

Diagnostic Approach

Who Should Be Tested

• Only test patients with clinically significant diarrhea (≥3 loose stools in 24 hours) 1
• Testing should not be performed on formed stool 1
• "Test of cure" is not recommended after treatment 1

Diagnostic Testing

1. Laboratory confirmation options:

   • Nucleic acid amplification tests (NAAT) for C. difficile toxin genes 1
   • Glutamate dehydrogenase (GDH) screening followed by toxin A/B enzyme immunoassays (EIA) 1
   • Toxigenic culture (gold standard but time-intensive) 1

2. Alternative testing for patients with ileus:

   • Polymerase chain reaction testing of perirectal swabs (sensitivity 95.7%, specificity 100%) 1

Clinical Pearls and Pitfalls

Important Considerations

• CDI can mimic other conditions, including post-infectious irritable bowel syndrome 1
• Asymptomatic colonization is common, especially in healthcare settings 1
• Recurrent episodes are typically less severe than initial episodes 1
• Early identification allows prompt treatment and infection control measures 1

Common Pitfalls to Avoid

• Testing asymptomatic patients or those taking laxatives 1
• Performing "test of cure" after treatment (56% of patients shed spores for up to 6 weeks after successful treatment) 1
• Confusing recurrent CDI with functional bowel disorders 1
• Delaying treatment in severe cases, which can increase mortality 1

By recognizing the symptoms and understanding the causes of C. difficile infection, clinicians can promptly diagnose and treat this potentially serious condition, improving patient outcomes and preventing complications.