Gastrointestinal & Hepatic · Topic 17 of 26

Clostridioides difficile Infection

Gastrointestinal · infectious colitis

Clostridioides difficile Infection

Antibiotic-associated toxin colitis. Test only true diarrhea, grade severity by WBC and creatinine, and treat by mouth — fidaxomicin first, oral vancomycin as the alternative.

Key numbers

Test only ≥ 3 unformed stools/24 h≥ 3 unformed stools/24 h

Severe if WBC ≥15,000 or Cr >1.5WBC ≥ 15k or Cr > 1.5

Fidaxomicin 200 mg twice daily200 mg BID × 10 d

Fulminant: oral vancomycin 500 mg QIDvancomycin 500 mg QID

01 · GiveFidaxomicin 200 mg twice daily

First episode (nonsevere or severe): fidaxomicin 200 mg PO twice daily for 10 days is preferred; oral vancomycin 125 mg four times daily for 10 days is an acceptable alternative.

02 · Defined bySevere if WBC ≥15,000 or Cr >1.5

Severe CDI = WBC ≥ 15,000 cells/µL or serum creatinine > 1.5 mg/dL; nonsevere disease has neither.

03 · GiveFulminant: oral vancomycin 500 mg QID

Fulminant CDI: vancomycin 500 mg PO or NG four times daily plus metronidazole 500 mg IV every 8 hours; with ileus, add rectal vancomycin 500 mg in about 100 mL saline every 6 hours.

Causes & risk factors

Why it happens

Highest-risk antibiotics: clindamycin, cephalosporins, fluoroquinolonesHighest-risk antibiotics are clindamycin, fluoroquinolones, cephalosporins (especially third-generation) and penicillins; other risks are older age, long hospital stay, nursing-home residence, severe illness, abdominal surgery and acid suppression.

Diagnosis & monitoring

Work-up

Test only ≥ 3 unformed stools/24 h must knowTest for C. difficile only with unexplained new-onset diarrhea of 3 or more unformed stools in 24 hours, and not in a patient who received a laxative within the previous 48 hours.

Fulminant CDI: shock, ileus or megacolon must knowFulminant CDI (formerly severe, complicated) is CDI with hypotension or shock, ileus, or megacolon.

Do right now

In this order

First moves

Test only ≥ 3 unformed stools/24 h≥ 3 unformed stools/24 h

→

Stop the inciting antibiotic as soon as possible

→

Fidaxomicin 200 mg twice daily200 mg BID × 10 d

→

Contact precautions; wash hands with soap

Why each step

Test only ≥ 3 unformed stools/24 hTest for C. difficile only with unexplained new-onset diarrhea of 3 or more unformed stools in 24 hours, and not in a patient who received a laxative within the previous 48 hours.

Stop the inciting antibiotic as soon as possibleDiscontinue the inciting antibiotic as soon as possible, or switch to an agent less likely to cause CDI; continued antibiotic exposure lowers cure and raises recurrence.

Fidaxomicin 200 mg twice dailyFirst episode (nonsevere or severe): fidaxomicin 200 mg PO twice daily for 10 days is preferred; oral vancomycin 125 mg four times daily for 10 days is an acceptable alternative.

Contact precautions; wash hands with soapUse contact precautions until at least 48 hours after diarrhea resolves; alcohol rubs remove spores poorly, so prefer soap-and-water hand hygiene in outbreaks and clean rooms with EPA-registered sporicidal agents.

Management

Orders

Metronidazole no longer first-lineMetronidazole is not first-line for adults; use oral metronidazole 500 mg three times daily for 10 days only for nonsevere CDI when vancomycin and fidaxomicin are unavailable.

Fulminant colitis: early surgery, subtotal colectomyConsult surgery early in fulminant CDI; the operation of choice is subtotal colectomy preserving the rectum, with diverting loop ileostomy plus colonic vancomycin lavage as an alternative.

First recurrence: fidaxomicin preferredCDI recurs in 15–20% of patients, usually within weeks. Treat a first recurrence with fidaxomicin (standard or extended-pulsed); tapered-pulsed or standard oral vancomycin is an alternative — not metronidazole.

Multiple recurrences: fecal microbiota transplantationFor multiple recurrences (at least 2 recurrences, ie, 3 episodes) after appropriate antibiotics, offer fecal microbiota transplantation; tapered-pulsed vancomycin, vancomycin then rifaximin, or fidaxomicin are antibiotic options.

Red flags & don'ts

Avoid harm

Avoid antimotility agents avoidAvoid antimotility agents such as loperamide in active CDI; toxic megacolon is more likely after their use.

The rules

Know these

No retesting within 7 days or cure testingDo not repeat testing within 7 days in the same diarrheal episode, and do not test for cure — over 60% of successfully treated patients stay positive.

Fidaxomicin or oral vancomycin?

Commonly confused

Initial-episode dose	200 mg twice daily × 10 days
IDSA/SHEA 2021	Preferred
Recurrence	Lower recurrence rate
Fulminant CDI	Not the recommended agent
First recurrence	Preferred (standard or extended-pulsed)

Commonly confused

Tell apart

GDH plus toxin; NAAT resolves discordant resultsGDH antigen is sensitive but shows only the organism; toxin assay is specific but insensitive; NAAT (PCR) detects toxigenic strains even in colonized patients. Concordant GDH and toxin decide; NAAT breaks a discordant pair.

More detail

Reference

Show 7 reference facts

A rising WBC (≥ 25,000) or lactate (≥ 5 mmol/L) marks high mortality in fulminant CDI and should prompt early colectomy before the patient becomes unsalvageable.

Oral fecal microbiota spores (live-brpk) and rectal fecal microbiota (live-jslm) are FDA-approved, given a few days after antibiotic treatment of recurrent CDI to prevent further recurrence.

Bezlotoxumab, the anti–toxin B monoclonal antibody that IDSA/SHEA 2021 suggested for recurrence within 6 months, is no longer manufactured.

Diarrhea typically starts 5–10 days after starting antibiotics but can begin on day 1 or up to 2 months later; fever and leukocytosis may be present, nausea and vomiting are rare.

Get abdominal radiographs or CT if fulminant colitis, perforation or megacolon is suspected; sigmoidoscopy (pseudomembranes) helps when ileus prevents stool testing or assays are nondiagnostic.

Start CDI therapy before confirmation only when results will be delayed (> 48 hours) or the patient presents with fulminant disease; otherwise treat after diagnosis.

Discontinue proton pump inhibitors that lack an indication, although evidence is insufficient to recommend stopping a needed PPI solely to prevent CDI.

Pearl

Three unformed stools, no laxatives, then oral drug: fidaxomicin first, vancomycin by mouth — and 500 mg four times daily plus IV metronidazole when it turns fulminant.

Sources · McDonald LC et al. IDSA/SHEA Clinical Practice Guidelines for C. difficile Infection in Adults and Children: 2017 Update (Clin Infect Dis 2018;66:e1–e48) · IDSA/SHEA 2021 Focused Update Guidelines on Management of C. difficile Infection in Adults (Johnson S et al. Clin Infect Dis 2021) · Contagion Live — Recommendations for diagnosis, disease severity and treatment of C. difficile infection: 2017 IDSA/SHEA update (severity cut-offs) · Merck Manual Professional — Clostridioides difficile Infection (Dec 2025; cites ACG 2021 and IDSA/SHEA 2021) · Kelly CR et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of C. difficile Infections. Am J Gastroenterol 2021;116:1124–1147 · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).