Clostridioides difficile (formerly Clostridium difficile) is a Gram-positive, spore-forming, anaerobic bacterium that produces two major toxins: toxin A (enterotoxin TcdA) and toxin B (cytotoxin TcdB). Some strains additionally produce binary toxin (CDT). The disease results from disruption of normal gut microbiota, typically by antibiotics, allowing C. difficile spores to germinate, proliferate, and produce toxins that damage colonic epithelium causing the characteristic pseudomembrane formation. The hypervirulent NAP1/BI/027 strain, which produces increased toxin levels, has been associated with severe disease, fulminant colitis, and increased mortality.
CDI presents along a clinical spectrum from asymptomatic colonization to mild diarrhea, severe colitis with bloody diarrhea, fulminant colitis, toxic megacolon, and bowel perforation. Risk factors include recent antibiotic use (especially clindamycin, fluoroquinolones, third-generation cephalosporins, broad-spectrum penicillins), advanced age, hospitalization, immunosuppression, gastric acid suppression with proton pump inhibitors, prior CDI, and severe comorbidity. The disease is increasingly recognized in community settings without traditional risk factors. Recurrence affects 20-30% of patients after initial episode, increasing to 40-65% after multiple recurrences.
Diagnosis requires both clinical suspicion (≥3 unformed stools/24 hours) and laboratory confirmation. Modern algorithms use two-step testing: nucleic acid amplification testing (NAAT/PCR) for toxin gene detection followed by toxin EIA (or glutamate dehydrogenase plus toxin EIA), avoiding overdiagnosis of mere colonization. Treatment paradigms have evolved significantly: metronidazole is no longer recommended as first-line therapy. Oral vancomycin (125 mg four times daily for 10 days) or fidaxomicin (200 mg twice daily for 10 days) are first-line agents, with fidaxomicin showing reduced recurrence rates. For severe complicated disease, oral vancomycin plus IV metronidazole, with consideration of vancomycin enemas. Recurrent CDI is treated with prolonged tapered/pulsed vancomycin, fidaxomicin, or fecal microbiota transplantation, which achieves cure rates >90% for multiply recurrent disease. Bezlotoxumab, a monoclonal antibody against toxin B, reduces recurrence in high-risk patients.