Antibiotics destroy the normal intestinal bacterial flora that normally suppresses C. difficile overgrowth. C. difficile is resistant to most of the commonly used antibiotics.
Gastric acid suppression (e.g., with proton pump inhibitors) or bypass (e.g., enteral feeding) c
C difficile spores are acid resistant, but proton pump inhibitors (PPIs) are thought to alter the colonic microbiome, which increases the risk for C difficile proliferation.
Recent hospitalization
Pathophysiology
Toxin A (enterotoxin): binding to brush border of enterocytes → disruption of actin cytoskeleton functioning → increase in epithelial permeability and apoptosis → diarrhea
Toxin B (cytotoxin): same as in toxin A, but can also cause pore formation within the endosomal membrane via insertion of the translocation domain → release of endosomal content into the cytosol → cytopathic effect
Mucosal Injury & Inflammation
Toxins bind to intestinal epithelial cell receptors
Initial/Screening: Stool toxin assay (EIA) or NAAT/PCR for C. diff toxin gene (only test symptomatic patients).
Key Labs:
WBC count (severe if WBC > 15,000/µL).
Serum creatinine (severe if Cr > 1.5 mg/dL or >1.5x baseline).
Imaging: Abdominal X-ray or CT scan if fulminant symptoms suspected; look for colonic dilation, wall thickening, or “thumbprinting”.
Endoscopy/Biopsy: Sigmoidoscopy/colonoscopy (usually not needed unless diagnosis unclear) showing pseudomembranous colitis (adherent yellow-white plaques on erythematous mucosa).
Treatment
Initial Step: Discontinue the inciting antibiotic if possible. Avoid antimotility agents (e.g., loperamide).
First-line (Non-severe & Severe initial episode):
Fidaxomicin PO 200 mg BID for 10 days (preferred). c
Vancomycin PO 125 mg QID for 10 days (acceptable alternative).
Fulminant (Hypotension, shock, ileus, megacolon):
IV Metronidazole (500 mg Q8h) PLUS high-dose oral/rectal Vancomycin (500 mg PO/PR Q6h).
First Recurrence:
If Vancomycin used for initial episode: Fidaxomicin PO or Vancomycin tapered and pulsed regimen.
If Fidaxomicin used for initial episode: Vancomycin tapered and pulsed regimen.
Subsequent Recurrences:
Vancomycin taper/pulsed regimen, or Fidaxomicin, or oral Vancomycin followed by rifaximin.
Consider fecal microbiota transplant (FMT).
Monoclonal antibody: Bezlotoxumab (binds toxin B) can be added to standard Abx to reduce recurrence.
Refractory/Toxic Megacolon: Urgent subtotal colectomy or diverting loop ileostomy.
Prevention
Hand Hygiene: Wash with soap and water (alcohol-based hand rubs do NOT kill C. diff spores).
Contact Precautions:
Place patient in a single-patient room (or cohort with another CDI patient).
Healthcare workers must wear gown and gloves prior to room entry.
Use dedicated medical equipment (e.g., stethoscope, BP cuff) for the patient.
Environmental Cleaning: Use sporicidal disinfectants (chlorine-based/bleach solution). c
Antibiotic Stewardship: Minimize unnecessary use and duration of high-risk Abx (clindamycin, fluoroquinolones, cephalosporins) and PPIs.
Secondary Prevention: Bezlotoxumab IV infusion during standard Abx treatment for patients at high risk for recurrence (e.g., age ≥65, immunocompromised, severe CDI episode).