Clostridioides difficile infection

A 55 year old female presents to the emergency department with abdominal cramping, watery diarrhea, and low grade fever for 5 days. She was recently treated with ciprofloxacin for cystitis. She denies recent travel or contaminated food exposure. On examination, the abdomen is soft with mild tenderness and hyperactive bowel sounds. Vital signs show blood pressure of 120/80 mm Hg, pulse rate of 108 beats per minute, respiratory rate of 18 breaths per minute, oxygen saturation of 92 percent on room air, and temperature of 100.2 F. Laboratory studies show leukocytosis, and stool PCR is positive for Clostridioides difficile toxin genes. Diagnosis?

Diagnosis is Clostridioides difficile infection presenting as antibiotic associated colitis.

1. Definition

Clostridioides difficile infection is a toxin mediated inflammatory disease of the colon that occurs after disruption of normal gut microbiota, ranging from mild diarrhea to pseudomembranous colitis and fulminant colitis.

2. Etiology and Risk Factors

1. Caused by Clostridioides difficile, a gram positive, spore forming anaerobic bacterium
2. Most important risk factor is recent antibiotic use
3. High risk antibiotics include
• Clindamycin
• Fluoroquinolones
• Cephalosporins
• Penicillins
4. Other risk factors
• Recent hospitalization
• Advanced age
• Proton pump inhibitor use
• Immunosuppression

3. Pathophysiology

1. Antibiotics cause gut microbiome disruption
2. Leads to Clostridioides difficile overgrowth
3. Production of toxins A and B
4. Toxins inactivate Rho GTPases, causing
• Cytoskeletal disruption
• Loss of tight junctions
• Inflammation and colonic injury
5. Results in pseudomembrane formation in severe disease

4. Clinical Features

1. Watery diarrhea (≥3 loose stools in 24 hours)
2. Abdominal pain and cramping
3. Fever
4. Leukocytosis
5. Severe disease may present with
• Toxic megacolon
• Ileus
• Perforation
• Septic shock

5. Diagnosis

1. Suspect in patients with diarrhea and recent antibiotic use
2. Stool testing
• NAAT or PCR for toxin genes
• Often combined with toxin assays
3. Test only symptomatic patients
4. Colonoscopy may show pseudomembranes in severe cases

6. Severity Classification

1. Non severe disease
2. Severe disease
• WBC ≥15,000
• Serum creatinine ≥1.5 times baseline
3. Fulminant disease
• Hypotension
• Shock
• Ileus
• Toxic megacolon

7. Management

1. Discontinue the offending antibiotic
2. First line therapy
• Fidaxomicin preferred
• Oral vancomycin as alternative
3. Fulminant disease
• High dose oral vancomycin
• Add intravenous metronidazole
4. Recurrent infection
• Fidaxomicin or tapered vancomycin
• Fecal microbiota transplantation
5. Avoid antimotility agents

8. Complications

1. Toxic megacolon
2. Colonic perforation
3. Sepsis
4. Recurrent infection

9. Key Clinical Insight

Recent antibiotic use followed by watery diarrhea and leukocytosis strongly suggests Clostridioides difficile infection

10. Exam Level Pearls

1. Most common cause of antibiotic associated diarrhea
2. PCR detects toxin genes, not active toxin
3. Fidaxomicin is preferred first line therapy
4. Handwashing with soap is required as spores resist alcohol
5. Recurrence is common