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Infectious Disease

Clostridioides difficile infection

Antibiotic-associated, toxin-mediated colitis in which loss of gut colonisation resistance permits C. difficile to proliferate, causing diarrhoea that may progress to ileus, toxic megacolon and perforation.

In a nutshell

Antibiotics disrupt gut colonisation resistance, allowing toxin-producing C. difficile to cause colitis. Diagnose compatible unexplained diarrhoea with the UK laboratory algorithm, stop unnecessary antimicrobials, treat confirmed disease with NICE-directed oral therapy, and escalate rapidly for systemic toxicity, ileus, megacolon or perforation.

Classic presentation

New watery diarrhoea with abdominal cramping during or after antimicrobial exposure, often after hospital or care-home contact. Ask about recent antibiotics, previous CDI, medicines that worsen diarrhoea or dehydration, and assess for distension, shock and reduced urine output.

Key points

  • C. difficile disease follows loss of microbiome-mediated colonisation resistance, commonly after broad-spectrum antibiotics.
  • A positive NAAT or GDH result alone may represent carriage; diagnosis requires compatible diarrhoea, appropriate stool testing and clinical assessment.
  • Send unformed stool only in a symptomatic person and follow the UK SMI two-step testing algorithm; do not routinely repeat testing after clinical resolution.
  • Stop the precipitating antibiotic if possible, review proton pump inhibitors and laxatives, replace fluid losses and avoid loperamide.
  • NICE first-line treatment for an adult first episode is oral vancomycin; use the current BNF and local policy for exact prescribing details.
  • Relapse within 12 weeks is treated differently from a later recurrence; repeated confirmed episodes need specialist discussion and may need FMT.
  • Use soap and water, not alcohol handrub alone, and sporicidal environmental cleaning because spores persist in the environment.
  • Hypotension, ileus, toxic megacolon, perforation, acute kidney injury or rapid deterioration require urgent specialist and surgical escalation.

First-line investigation

Fresh unformed stool tested using the UK SMI algorithm: sensitive organism detection with toxin testing, interpreted with symptoms and severity.

Management

SIGHT: isolate and test

  • Suspect infective diarrhoea, isolate, use gloves and aprons, wash hands with soap and water, and send suitable unformed stool promptly.2,3

Assess severity and remove drivers

  • Assess hydration, renal function, abdominal findings and systemic physiology; stop unnecessary antimicrobials, review medicines that increase CDI or dehydration risk, give fluids and avoid loperamide.1,6,5

Treat the confirmed episode

  • Use NICE-directed oral vancomycin for an adult first episode; check the current BNF and local antimicrobial policy for dose, duration, interactions and special populations.1,7

Prevent transmission and recurrence

  • Use soap-and-water handwashing and sporicidal cleaning, document CDI and antibiotic restrictions, and give fluids, hygiene and recurrence advice before discharge.2,5,1

Escalate severe or recurrent disease

  • Escalate urgently for shock, ileus, megacolon, perforation or rapid deterioration; discuss recurrent confirmed episodes with specialists and consider FMT after 2 or more previous episodes.1,4

Reassess and safety-net

  • Review stool frequency, hydration, renal function and abdominal signs; do not use a test of cure, and give urgent return advice for worsening or recurrent symptoms.1,3,5

Exam traps

  • A positive PCR or GDH alone does not prove toxin-mediated disease; it can identify asymptomatic carriage.
  • Formed stool is usually unsuitable for testing, and a routine test of cure is not indicated.
  • Oral metronidazole is not the routine first-line treatment in current NICE guidance; oral vancomycin and fidaxomicin are the key adult options.
  • Loperamide and other antimotility agents are avoided in suspected or confirmed CDI.
  • Life-threatening colitis needs urgent multidisciplinary input and may need combined enteral vancomycin, intravenous metronidazole and surgery; oral therapy alone is not enough.
  • Alcohol handrub is not a substitute for soap-and-water handwashing against C. difficile spores.

Illustrations

Loss of colonisation resistanceDiagram of antibiotic-disrupted gut flora allowing C. difficile spore germination and overgrowth in the colon.PassFinals · original
Pseudomembranous colitisColonic mucosa studded with yellow pseudomembranes in Clostridioides difficile pseudomembranous colitis (pathological specimen).Samir, Wikimedia Commons · CC-BY-SA-4.0
Toxic megacolon on abdominal X-rayPlain abdominal radiograph showing marked colonic dilatation in toxic megacolon, a life-threatening complication of severe colitis including C. difficile infection.Hellerhoff, Wikimedia Commons · CC-BY-SA-3.0

Key sources

  1. NICE NG199: Clostridioides difficile infection: antimicrobial prescribing (UK antimicrobial prescribing recommendations for diagnosis, first episodes, relapse, recurrence, life-threatening disease, FMT, fluids, antimotility medicines and referral)Published 23 Jul 2021
  2. UKHSA and DHSC: Clostridioides difficile infection: how to deal with the problem, interim update 2026 (Current UK infection-prevention, SIGHT, isolation, hand hygiene, environmental cleaning, surveillance and antimicrobial-stewardship guidance; full replacement guidance is expected in 2027)Updated 24 Jun 2026
  3. UK SMI B 10 Issue 2: Investigation of faecal specimens for Clostridioides difficile (UKHSA Standards Unit laboratory standard for symptomatic stool selection and GDH, toxin and NAAT testing algorithms)Published 24 Mar 2025
  4. NICE HTG638: Faecal microbiota transplant for recurrent Clostridioides difficile infection (NICE health technology guidance recommending FMT for adults with 2 or more previous confirmed episodes, subject to governance, consent and audit)Published 23 Mar 2022
  5. NHS: C. difficile (Patient-facing UK advice on symptoms, treatment, fluids, recurrence, staying away from others and spore control at home)Updated 24 Jul 2025
  6. NICE NG29: Intravenous fluid therapy in adults in hospital (Assessment, prescription, monitoring and reassessment principles for intravenous fluids in adults)
  7. BNF online: antimicrobial prescribing monographs (Check current vancomycin, fidaxomicin and metronidazole monographs for dose, route, interactions, contraindications and special-population advice)

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.