Toxin-mediated colitis after antibiotic disruption of gut microbiota; ranges from diarrhea to toxic megacolon.
Also known as: C. difficile, Clostridioides difficile, C diff, pseudomembranous colitis, CDI
Overview
Colitis caused by toxin-producing Clostridioides difficile (formerly Clostridium difficile), an anaerobic Gram-positive spore-forming bacillus. Spectrum from mild diarrhea to fulminant pseudomembranous colitis with toxic megacolon, perforation, and death.
Epidemiology
Most common healthcare-associated infection in the US; ~500,000 infections and ~30,000 deaths annually. Community-acquired CDI rising. Recurrence after first episode 15-25%; after second, 40-60%.
🔒 Free preview limit reached
Keep reading — start your free trial
You've read your 2 free diagnosis previews. Create your free account to unlock the full Clostridioides difficile Colitis outline — plus all 514 diagnoses, 3,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
Toxigenic strain BI/NAP1/027 — hypervirulent, associated with severe disease and outbreaks
Pathophysiology
Antibiotic-induced disruption of normal colonic microbiota allows C. difficile spores ingested fecal-orally to germinate. Vegetative cells produce toxins A (enterotoxin) and B (cytotoxin), and binary toxin (CDT) in some strains, which disrupt the cytoskeleton, induce inflammation, and damage colonic epithelium → pseudomembranes (fibrin, mucus, leukocytes, sloughed cells).
Clinical presentation
Symptoms
Watery diarrhea (≥3 unformed stools per 24 h) — hallmark
Lower abdominal cramping
Low-grade fever
Anorexia, nausea
Blood is unusual (consider IBD, ischemia, infection if present)
Severe disease: high fever, marked leukocytosis, severe abdominal pain, distension
Fulminant disease: shock, ileus, toxic megacolon (loss of diarrhea due to ileus)
Signs / physical exam
Abdominal tenderness
Distension (severe disease)
Fever, tachycardia
Hypotension if severe
Peritonitis suggests perforation
Diminished bowel sounds in ileus / toxic megacolon
Often normal exam in mild disease
Classic findings
Watery diarrhea, low-grade fever, leukocytosis, and abdominal pain following recent antibiotic exposure and/or hospitalization.
Differential diagnosis
Antibiotic-associated diarrhea (non-CDI) — Mild, no fever or leukocytosis, no toxin, no pseudomembranes; resolves with antibiotic cessation
CMV colitis — Immunocompromised; biopsy with inclusion bodies
Functional / IBS — Chronic, no infection, normal labs
Diagnostic workup
Diagnostic criteria
Clinical (≥3 unformed stools/24 h not otherwise explained) + positive stool test (NAAT for toxin gene, or toxin EIA, or both with multi-step algorithm). IDSA 2018 severity: Non-severe (WBC ≤15,000 AND Cr <1.5 mg/dL); Severe (WBC >15,000 OR Cr ≥1.5); Fulminant (hypotension, shock, ileus, megacolon).
Labs
Stool C. difficile testing — multi-step algorithm preferred: NAAT (PCR) alone or NAAT + toxin enzyme immunoassay
GDH antigen + toxin EIA; if discordant, reflex to NAAT
TEST ONLY in patients with clinically significant diarrhea (≥3 unformed stools/24h); do NOT test asymptomatic patients (colonization is common and not infection)
CBC — leukocytosis (WBC >15,000 = severe disease); leukemoid reaction (WBC >30,000) is poor prognostic
BMP — AKI (Cr >1.5× baseline = severe disease)
Lactate (severe disease)
Albumin (low in severe disease)
Stool studies for other pathogens if epidemiologically appropriate
Imaging
CT abdomen/pelvis — for severe or complicated disease; colonic wall thickening (mural thickening, 'accordion sign' from contrast trapped between thickened folds), pericolonic stranding, megacolon, ascites, perforation
Flexible sigmoidoscopy/colonoscopy — visualization of pseudomembranes (yellow-white plaques) is diagnostic but rarely needed and contraindicated in severe disease (perforation risk)
Diagnostic algorithm
IDSA Severity
Criteria
Preferred Therapy
Non-severe
WBC ≤15,000 AND Cr <1.5 mg/dL
Fidaxomicin 200 mg PO BID × 10 days (preferred) or oral vancomycin 125 mg QID × 10 days
Severe
WBC >15,000 OR Cr ≥1.5 mg/dL
Fidaxomicin (preferred) or oral vancomycin 125 mg QID × 10 days
Fulminant
Hypotension/shock, ileus, or megacolon
IV metronidazole 500 mg q8h + oral vancomycin 500 mg q6h (+ rectal vancomycin if ileus); early surgical consult
First recurrence
After initial cure
Fidaxomicin BID × 10 d, or tapered/pulsed vancomycin, ± bezlotoxumab
Multiply recurrent (≥2)
After multiple recurrences
Fecal microbiota transplantation (FMT) or oral microbiome therapeutics
IDSA 2018/2021 severity classification and treatment of C. difficile infection.
Treatment
First-line
DISCONTINUE inciting antibiotic if possible
Initial episode, non-severe: fidaxomicin 200 mg PO BID × 10 days (PREFERRED — lower recurrence) OR oral vancomycin 125 mg PO QID × 10 days
Initial episode, severe: fidaxomicin (preferred) or oral vancomycin 125 mg PO QID × 10 days
Fulminant disease (hypotension, shock, ileus, megacolon): IV metronidazole 500 mg q8h + oral vancomycin 500 mg q6h (and rectal vancomycin if ileus) ± early surgical consultation
Avoid antimotility agents (loperamide) in active disease — risk of toxic megacolon
Infection control: contact precautions, soap and water (alcohol does NOT kill spores), dedicated equipment
First recurrence
Fidaxomicin 200 mg BID × 10 days (preferred — lower recurrence than vancomycin)
Tapered/pulsed oral vancomycin: 125 mg QID × 10-14 d, then BID × 7 d, then daily × 7 d, then q2-3 days × 2-8 wk
Bezlotoxumab — anti-toxin B monoclonal antibody (single IV infusion adjunct to standard therapy for patients at high recurrence risk)
Multiply recurrent CDI (≥2 recurrences)
Fecal microbiota transplantation (FMT) — highly effective (~85-90% cure); via colonoscopy, enema, NG tube, capsules, or FDA-approved oral formulations (SER-109 — Vowst; RBX2660 — Rebyota)
Tapered/pulsed vancomycin or extended fidaxomicin
Add bezlotoxumab
Fulminant CDI
Combination IV metronidazole + oral high-dose vancomycin (+ rectal vancomycin if ileus)
Early surgical consultation
Surgical options: subtotal colectomy with end ileostomy (traditional), or loop ileostomy with antegrade colonic vancomycin lavage (Neal procedure — colon-sparing alternative)
Complications
Recurrence (15-25% after first episode; 40-60% after second)
Severe colitis: dehydration, electrolyte imbalance, hypotension, AKI
Toxic megacolon — colonic dilation >6 cm with systemic toxicity
Perforation
Sepsis, septic shock
Death (~5% overall; up to 80% with fulminant disease and shock)
Bowel obstruction from inflammatory stricture (rare)
Reactive arthritis (rare)
PANCE pearls
TEST ONLY symptomatic patients — colonization is common (3-15% of hospitalized adults) and testing asymptomatic patients leads to over-diagnosis.
DO NOT use IV vancomycin for CDI — does not reach colonic lumen. Oral vancomycin is essential for colonic delivery.
Fidaxomicin is now PREFERRED over vancomycin for initial CDI (IDSA 2021 update) due to lower recurrence — cost-prohibitive in some settings.
Oral metronidazole is NO LONGER first-line for initial CDI (IDSA 2017/2018) due to inferior efficacy — reserved for IV use in fulminant disease combined with oral vancomycin.
Avoid antimotility agents (loperamide, diphenoxylate) in active CDI — risk of toxic megacolon.
Alcohol-based hand sanitizer does NOT kill C. difficile spores — wash hands with soap and water.
Fecal microbiota transplantation (FMT) for recurrent CDI is highly effective (~90% cure) — FDA-approved oral formulations now available (Vowst, Rebyota).
Bezlotoxumab is a monoclonal antibody against toxin B — adjunct for patients at high risk of recurrence (age >65, prior CDI, severe disease, immunocompromised).
Toxic megacolon: colonic dilation >6 cm on imaging + systemic toxicity — STOP antimotility/opioids/anticholinergics; aggressive medical management; early surgical consultation.
Surgical options for fulminant CDI: subtotal colectomy or diverting loop ileostomy with antegrade colonic vancomycin lavage (colon-sparing).
IBD patients with CDI: continue IBD therapy; CDI worsens IBD outcomes and recurs more often.
References
IDSA/SHEA 2017 — McDonald LC et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the IDSA and SHEA. Clin Infect Dis 2018;66:e1-e48
IDSA/SHEA 2021 Focused Update — Johnson S et al. Clinical Practice Guideline by the IDSA and SHEA: 2021 Focused Update on Management of CDI in Adults. Clin Infect Dis 2021;73:e1029-e1044
ACG 2021 — Kelly CR et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol 2021;116:1124-1147
MODIFY I/II Bezlotoxumab — Wilcox MH et al. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. NEJM 2017;376:305-317
Practice Gastrointestinal questions on FirstPassPA
Turn this outline into retention. 3,500+ board-style questions with an AI tutor that explains every answer — free to start, no card required.
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants.