Clostridioides difficile Infection, Including Pseudomembranous Colitis¶
Chapter 139 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- CDI is the most common healthcare-associated infection in the U.S., caused by toxigenic C. difficile spores disrupting colonic microbiota
- Diarrhea (watery/mucoid) with ≥ 3 unformed stools/day, fever, leukocytosis, and pseudomembranous colitis (PMC) are hallmark features
- Treatment algorithms prioritize vancomycin/fidaxomicin for initial episodes, with fecal microbiota transplantation (FMT) for recurrent cases
1. DEFINITION & OVERVIEW¶
Clostridioides difficile infection (CDI) is a colonic disease acquired primarily through antimicrobial use, leading to disruption of normal microbiota. It is the most common healthcare-associated infection in the U.S., with ~462,100 cases in 2017. Pseudomembranous colitis (PMC) is a severe form characterized by pseudomembrane formation in the colon.
Table 139-1 Relative Sensitivity and Specificity of Diagnostic Tests for CDI¶
| TYPE OF TEST | RELATIVE SENSITIVITYa | RELATIVE SPECIFICITYa | COMMENT |
|---|---|---|---|
| Stool culture for C. difficile | ++++ | +++ | Most sensitive test; specificity of +++ if isolate tests positive for toxin |
| Enzyme immunoassay for toxins A and B in stool | ++ to +++ | +++ | Rapid results, less sensitive than stool culture |
| Nucleic acid amplification tests for C. difficile toxin A or B gene in stool | ++++ | +++ | Widely used in U.S.; more sensitive than EIA |
| Colonoscopy or sigmoidoscopy | + | ++++ | Highly specific if pseudomembranes are seen |
1.1 Pathogenesis¶
Spores of toxigenic C. difficile are ingested, germinate in the small bowel, and colonize the colon. Toxins A and B disrupt epithelial integrity, causing diarrhea and pseudomembrane formation. Binary toxin CDT may contribute to pathogenesis.
1.2 Clinical Spectrum¶
Ranges from mild diarrhea to fulminant colitis with toxic megacolon, sepsis, and mortality. Asymptomatic colonization is common, especially in neonates.
2. EPIDEMIOLOGY¶
U.S. hospital CDI rates tripled 2000–2005; decreased by 24% 2011–2017. Community-associated cases remain stable. Risk factors include older age (>65), prior antibiotic use, hospitalization, and immunocompromise. Prevalence is 1–3% in community residents vs ≥ 20% in hospitalized patients >2 weeks.
2.1 Global Trends¶
NAP1/BI/027 strain (toxinotype III, ribotype 027) caused epidemics in North America and Europe. Fluoroquinolone resistance in this strain declined after restrictions in England (2006). Toxinotype V (ribotype 078) remains associated with high mortality.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
C. difficile is an obligately anaerobic, spore-forming gram-positive bacillus. Toxins A (enterotoxin) and B (cytotoxin) disrupt epithelial barrier function. Binary toxin CDT (related to C. perfringens) may contribute to pathogenesis. NAP1/BI/027 strain produces 16–23x more toxins and has high fluoroquinolone resistance.
3.1 Virulence Factors¶
Toxin B is more critical for disease than toxin A. Binary toxin CDT may enhance pathogenicity. Spores persist in environment for months and are resistant to disinfectants.
4. CLINICAL FEATURES¶
Diarrhea (watery/mucoid, non-bloody) is most common. 28% have fever, 22% abdominal pain, 50% leukocytosis. Severe cases present with toxic megacolon, sepsis, or acute abdomen. PMC shows confluent pseudomembranes in colon (Fig. 139-1).
4.1 Complications¶
Toxic megacolon (10% of patients), perforation, sepsis, and mortality (6.9% in 2005 Montreal outbreak). Fulminant CDI presents without diarrhea, mimicking acute abdomen.
5. DIFFERENTIAL DIAGNOSIS¶
Other causes of diarrhea (viral, bacterial, ischemic colitis, inflammatory bowel disease). Differentiate from other colitides using endoscopy and toxin testing. Exclude other infectious agents in immunocompromised patients.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis requires combination of clinical criteria: diarrhea + toxin detection (NAAT/EIA) or pseudomembranes on endoscopy. Stool testing is not recommended for asymptomatic patients. Confirm toxin presence with NAAT or GDH + toxin EIA.
Table 139-2 Recommendations for the Treatment of CDI¶
| CLINICAL SETTING | TREATMENT(S) | COMMENTS |
|---|---|---|
| Initial episode, mild to moderate | Fidaxomicin (200 mg bid × 10 d) or vancomycin (125 mg qid × 10 d) | Metronidazole less effective; use only for mild/moderate cases |
| Initial episode, severe | Vancomycin (125 mg qid × 10 d) or fidaxomicin | Indicators: leukocytosis ‡15,000/mL, creatinine ‡1.5 mg/dL |
| Fulminant CDI | Vancomycin + metronidazole + rectal vancomycin | Duration >2 weeks; consider surgery if no response |
| First recurrence | Fidaxomicin or vancomycin taper-and-pulse regimen | Fidaxomicin superior to vancom, metronidazole not recommended |
| Multiple recurrences | FMT (Rebyota/Vowst) or vancomycin + rifaximin | Bezlotoxumab for high-risk patients (age >65, immunocompromised) |
6.1 Diagnostic Algorithms¶
NAAT (PCR) is most sensitive. If NAAT+ or GDH+/toxin EIA–, treat for CDI. Endoscopy is rapid for suspected PMC but has low sensitivity for diagnosis.
7. MANAGEMENT & TREATMENT¶
Discontinue non-essential antibiotics first. Initial treatment: vancomycin (125 mg qid) or fidaxomicin (200 mg bid) for 10 days. Severe/fulminant cases require vancomycin + metronidazole. Recurrent cases: fidaxomicin (10 days) or vancomycin taper-and-pulse. FMT (oral capsules/enemas) for multiple recurrences. Bezlotoxumab (10 mg/kg IV) for high-risk patients.
7.1 Treatment Algorithms¶
- Discontinue non-essential antibiotics. 2. Use vancomycin/fidaxomicin for initial episodes. 3. For recurrences: fidaxomicin or vancomycin taper. 4. FMT for multiple recurrences. 5. Bezlotoxumab for high-risk patients.
8. PROGNOSIS & COMPLICATIONS¶
15–30% recurrence rate. Severe complications: toxic megacolon (10%), perforation, sepsis, and mortality (6.9% in 2005 outbreaks). Fulminant CDI has 30-day mortality of ~11%. Recurrent CDI may require FMT or rifaximin.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: No specific contraindications for vancomycin. Pediatrics: Neonates may have asymptomatic colonization. Elderly: Higher risk for severe disease. Immunocompromised: Higher recurrence risk. PPIs may increase risk but not definitively implicated.
10. KEY POINTS & CLINICAL PEARLS¶
- Discontinue non-essential antibiotics first. 2. Use NAAT for rapid diagnosis. 3. Fidaxomicin reduces recurrence better than vancomycin. 4. FMT is effective for recurrent CDI. 5. Bezlotoxumab prevents recurrence in high-risk patients. 6. Avoid antiperistaltic agents/opioids. 7. Monitor for toxic megacolon in severe cases.