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Diarrhoea - antibiotic associated

SNOMED: 301469002664 wordsUpdated 03/03/2026
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Exam Tips

  • Think CDI in any patient with new diarrhoea during or within weeks of antibiotics, especially age >65 or recent hospital exposure.
  • No symptom is pathognomonic: diagnosis depends on testing unformed stool for C. difficile in the right clinical context.
  • Severity markers to memorise: WCC >=15 x 10^9/L, creatinine rise >50%, temperature >38.5 C; hypotension/ileus/megacolon = fulminant.
  • Do not send formed stool and do not do routine test-of-cure after treatment.
  • In severe abdominal distension with little stool output, consider fulminant CDI with ileus rather than improvement.
  • Image recall point: review classic endoscopic pseudomembranes (raised yellow-white plaques) often shown in GI infection textbook figures.

Definition

Antibiotic-associated diarrhoea is diarrhoea that develops during or after antibiotic exposure due to disruption of normal gut microbiota, direct drug effects on intestinal motility, or less commonly drug hypersensitivity. A key severe subtype is Clostridioides difficile infection (CDI), in which toxigenic strains produce colonic toxins causing inflammatory colitis that can progress to fulminant, life-threatening disease.

Pathophysiology

Most cases follow antibiotic-driven loss of colonization resistance in the bowel microbiome, allowing osmotic/secretory diarrhoea or pathogen overgrowth. In CDI, spores germinate after microbiota disruption; toxins A and B injure colonic epithelial cells, trigger neutrophilic inflammation, and can form pseudomembranes (classically seen as yellow-white plaques at endoscopy). Disease severity ranges from mild diarrhoea to systemic toxicity with ileus, toxic megacolon, perforation, and septic shock.

Risk Factors

  • Age over 65 years
  • Recent or current antibiotic therapy (especially clindamycin, broad-spectrum beta-lactam combinations, cephalosporins, carbapenems, fluoroquinolones, macrolides)
  • Longer antibiotic courses, repeated courses, or multiple concurrent antibiotics
  • Previous CDI (high recurrence risk after first recurrence)
  • Current proton pump inhibitor or H2-receptor antagonist use
  • Recent hospitalization, care-home residence, or close exposure to a person with CDI
  • Comorbidity: chronic kidney disease, inflammatory bowel disease, recent abdominal surgery, immunosuppression, malignancy treatment

Clinical Features

Symptoms

  • Watery diarrhoea (may be frequent, mucoid, usually little blood)
  • Crampy abdominal pain
  • Fever
  • Nausea or vomiting (less common)
  • Abdominal bloating/distension (suggests severe disease or ileus)
  • Systemic unwellness, dizziness, reduced urine output from dehydration

Signs

  • Lower abdominal tenderness
  • Pyrexia
  • Tachycardia
  • Hypotension in fulminant disease
  • Abdominal distension with reduced bowel sounds in ileus/toxic megacolon
  • Peritonism if perforation

Investigations

Stool sample for C. difficile testing (unformed stool only; toxin assay with local NAAT/GDH algorithm):Detection of toxigenic C. difficile supports CDI in compatible clinical context
Full blood count:Leukocytosis; WCC >=15 x 10^9/L suggests severe infection
Urea, electrolytes, creatinine:Creatinine rise >50% from baseline suggests severe CDI; may show dehydration/AKI
CRP and serum albumin:Raised inflammatory markers and hypoalbuminaemia support severe systemic illness
Blood cultures (if febrile/systemically unwell):May identify bacteraemia/sepsis in complicated disease
Abdominal imaging (AXR or CT abdomen/pelvis) when severe pain, ileus, or peritonism:Colonic dilatation, mural thickening, toxic megacolon, perforation, or alternative diagnosis

Management

Lifestyle Modifications

  • Stop the precipitating antibiotic where clinically safe and review need for acid suppression (especially PPIs)
  • Oral/IV rehydration and electrolyte correction
  • Strict infection prevention: isolate patient, handwashing with soap and water, environmental sporicidal cleaning
  • Avoid antimotility agents (for example loperamide) in suspected/confirmed CDI due to risk of toxin retention and ileus

Pharmacological Treatment

First-line CDI-directed antibiotic

  • Fidaxomicin 200 mg orally twice daily for 10 days

Preferred for initial non-severe or severe CDI where available; narrow spectrum with lower recurrence risk than vancomycin.

Alternative CDI-directed antibiotic

  • Vancomycin 125 mg orally four times daily for 10 days

Use if fidaxomicin unsuitable/unavailable. Oral route is required for colonic effect; IV vancomycin does not treat CDI colitis.

Fulminant CDI regimen (specialist/inpatient)

  • Vancomycin 500 mg orally or via NG tube four times daily
  • Metronidazole 500 mg IV every 8 hours
  • Consider rectal vancomycin if ileus limits oral delivery (specialist protocol)

Urgent senior, microbiology and surgical input required. Monitor for shock, perforation, megacolon. Metronidazole monotherapy is not preferred for routine adult CDI.

Recurrence strategies (specialist-guided)

  • Fidaxomicin 200 mg orally twice daily for 10 days (or extended-pulsed regimen per local protocol)
  • Vancomycin tapered/pulsed oral regimens (for selected recurrent cases)

Do not perform test-of-cure stool testing. Re-test only if symptoms resolved then recur.

Surgical / Interventional

  • Subtotal colectomy or diverting loop ileostomy with colonic lavage for toxic megacolon, perforation, or refractory fulminant colitis

Complications

  • Pseudomembranous colitis
  • Toxic megacolon
  • Paralytic ileus (may occur with little or no diarrhoea)
  • Colonic perforation
  • Peritonitis
  • Sepsis and septic shock
  • Acute kidney injury from dehydration/sepsis
  • Death

Prognosis

Most antibiotic-associated diarrhoea is mild and resolves after supportive care and withdrawal of the triggering antibiotic. CDI has a more guarded course, with substantial recurrence (about 20% after a first episode and higher after subsequent episodes) and meaningful mortality in older, comorbid, or fulminant presentations; early recognition and severity-based treatment improve outcomes.

Sources & References

NICE Guidelines(1)

📖Textbook References(10)

  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 194)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 194)[context]
  • Emergencies in - Obstetrics and Gynaecology, Second Edition (Stergios K. Doumouchtsis, S. Arulkumaran) (Z-Library).pdf(pp. 329)[context]
  • [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 406)[context]
  • [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 273)[context]
  • [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 406)[context]
  • [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 443)[context]
  • [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 443)[context]
  • [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 1175, 1176)[context]
  • [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 1176)[context]

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