Clostridioides Difficile Colitis

Clostridioides difficile colitis results from toxin-producing C. difficile overgrowth following disruption of normal colonic flora, most commonly by antibiotic exposure (virtually any antibiotic, though clindamycin, fluoroquinolones, and broad-spectrum cephalosporins carry particularly high risk), causing a spectrum from mild diarrhea to life-threatening pseudomembranous colitis and toxic megacolon. A leading cause of healthcare-associated diarrhea.

Watery diarrhea (sometimes with mucus, rarely grossly bloody), abdominal cramping, fever, and leukocytosis, typically developing during or within several weeks of antibiotic exposure. Severe disease features marked leukocytosis (often above 15 x10⁹/L), significant renal impairment, hypoalbuminemia, and hypotension; fulminant disease includes toxic megacolon (colonic dilation above 6 cm with systemic toxicity), ileus, or perforation, a surgical emergency.

• Stool testing: a two-step approach is standard, given neither test alone has ideal sensitivity/specificity, glutamate dehydrogenase (GDH) or PCR as a sensitive screen, followed by toxin EIA to confirm active toxin production in GDH/PCR-positive samples (PCR alone can detect toxigenic colonization without active toxin-mediated disease, risking overdiagnosis and overtreatment if used in isolation)
• Testing should only be sent on unformed stool from a patient with clinically significant diarrhea, not for surveillance or in asymptomatic patients
• CT abdomen for suspected fulminant disease (colonic wall thickening, dilation, pericolonic stranding); flexible sigmoidoscopy showing pseudomembranes supports diagnosis where testing is equivocal

• Stop the inciting antibiotic where feasible
• Non-severe disease: vancomycin 125 mg PO qds for 10 days, or fidaxomicin 200 mg PO bd for 10 days (increasingly preferred first line given lower recurrence rates, where cost/availability allow); metronidazole is now generally reserved for settings where vancomycin/fidaxomicin are unavailable, given inferior efficacy
• Severe disease (WCC above 15 x10⁹/L, or creatinine 1.5x baseline): vancomycin 125 mg PO qds for 10 days (higher-dose oral vancomycin, e.g. 500 mg qds, considered in fulminant disease)
• Fulminant disease (hypotension, ileus, megacolon): oral/NG vancomycin 500 mg qds PLUS IV metronidazole 500 mg tds, with vancomycin enema (500 mg in 100 mL saline PR qds) added if ileus prevents oral drug from reaching the colon; urgent surgical consultation given the risk of perforation and need for colectomy in refractory fulminant disease
• First recurrence: vancomycin taper/pulse regimen, or fidaxomicin if not used initially
• Multiple recurrences: fecal microbiota transplantation is highly effective and increasingly standard for recurrent disease refractory to antibiotic approaches; bezlotoxumab (a monoclonal antibody against toxin B) may be added to standard antibiotic treatment to reduce recurrence risk in high-risk patients
• Infection control: contact precautions, and note alcohol-based hand sanitizer is ineffective against C. difficile spores, soap and water handwashing is required

Referral: gastroenterology for recurrent disease or FMT; surgery emergently for fulminant colitis, megacolon, or perforation.