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ALL / Gastroenterology

<i>Clostridioides difficile</i>

Clostridioides difficile

Clostridioides difficile is a Gram positive rod often encountered in hospital practice. It produces an exotoxin which causes intestinal damage leading to a syndrome called pseudomembranous colitis. C. difficile develops when the normal gut flora are suppressed by broad-spectrum antibiotics. Clindamycin is historically associated with causing C. difficile but the aetiology has evolved significantly over the past 10 years. Second and third-generation cephalosporins are now the leading cause of C. difficile.

Other than antibiotics, risk factors include:
  • proton pump inhibitors

Pathophysiology
  • anaerobic gram-positive, spore-forming, toxin-producing bacillus
  • transmission: via the faecal-oral route by ingestion of spores
  • releases two exotoxins (toxin A and toxin B) that act on intestinal epithelial cells and inflammatory cells resulting in colitis

Features
  • diarrhoea
  • abdominal pain
  • a raised white blood cell count (WCC) is characteristic
  • if severe toxic megacolon may develop

The Public Health England severity scale is often used as this may determine treatment:

MildModerateSevereLife-threatening
Normal WCC↑ WCC ( < 15 x 109/L)
Typically 3-5 loose stools per day		↑ WCC ( > 15 x 109/L)
or an acutely ↑ creatinine (> 50% above baseline)
or a temperature > 38.5°C
or evidence of severe colitis(abdominal or radiological signs)		Hypotension
Partial or complete ileus
Toxic megacolon, or CT evidence of severe disease

Diagnosis
  • is made by detecting C. difficile toxin (CDT) in the stool
  • C. difficile antigen positivity only shows exposure to the bacteria, rather than current infection

Management

Current antibiotic therapy should be reviewed and antibiotics stopped if possible.

First episode of C. difficile infection
  • first-line therapy is oral vancomycin for 10 days
  • second-line therapy: oral fidaxomicin
  • third-line therapy: oral vancomycin +/- IV metronidazole

Recurrent episode
  • recurrent infection occurs in around 20% of patients, increasing to 50% after their second episode
  • within 12 weeks of symptom resolution: oral fidaxomicin
  • after 12 weeks of symptom resolution: oral vancomycin OR fidaxomicin

Life-threatening C. difficile infection
  • oral vancomycin AND IV metronidazole
  • specialist advice - surgery may be considered



Other therapies
  • bezlotoxumab is a monoclonal antibody which targets C. difficile toxin B
    • NICE do not currently support its use to prevent recurrences as it is not cost-effective
  • faecal microbiota transplant
    • may be considered for patients who've had 2 or more previous episodes

Preventing the spread of C. difficile infection
  • isolation in side room: the patient should remain isolated until there has been no diarrhoea (types 5-7
on the Bristol Stool Chart) for at least 48 hours
  • all staff should wear disposable gloves and an apron during any contact with patients known to have C. difficile
  • hand washing is also essential - alcohol gel does not kill the spores of C. difficile

Elderly lady with infectious colitis secondary to C. difficile. On the abdominal film note the loss of bowel wall architecture and thumb-printing consistent with colitis. The CT from the same patient is enhanced by oral contrast. There is moderate free fluid in pelvis and peritoneum. The colon is oedematous throughout with enhancing walls, but of normal calibre. The sigmoid colon is smooth and featureless. Small bowel, liver, spleen, kidneys, adrenals and pancreas are normal.
+PassMedicine Notes

Clostridioides difficile is a Gram positive rod often encountered in hospital practice. It produces an exotoxin which causes intestinal damage leading to a syndrome called pseudomembranous colitis. C. difficile develops when the normal gut flora are suppressed by broad-spectrum antibiotics. Clindamycin is historically associated with causing C. difficile but the aetiology has evolved significantly over the past 10 years. Second and third-generation cephalosporins are now the leading cause of C. difficile.

Other than antibiotics, risk factors include:
  • proton pump inhibitors
Pathophysiology
  • anaerobic gram-positive, spore-forming, toxin-producing bacillus
  • transmission: via the faecal-oral route by ingestion of spores
  • releases two exotoxins (toxin A and toxin B) that act on intestinal epithelial cells and inflammatory cells resulting in colitis
Features
  • diarrhoea
  • abdominal pain
  • a raised white blood cell count (WCC) is characteristic
  • if severe toxic megacolon may develop

The Public Health England severity scale is often used as this may determine treatment:

Mild _ Moderate_ Severe _Life-threatening| Normal WCC _ ↑ WCC ( < 15 x 109/L) Typically 3-5 loose stools per day _ ↑ WCC ( > 15 x 109/L) or an acutely ↑ creatinine (> 50% above baseline) or a temperature > 38.5°C or evidence of severe colitis(abdominal or radiological signs) _ Hypotension Partial or complete ileus Toxic megacolon, or CT evidence of severe disease| Diagnosis
  • is made by detecting C. difficile toxin (CDT) in the stool
  • C. difficile antigen positivity only shows exposure to the bacteria, rather than current infection

Management

Current antibiotic therapy should be reviewed and antibiotics stopped if possible.

First episode of C. difficile infection
  • first-line therapy is oral vancomycin for 10 days
  • second-line therapy: oral fidaxomicin
  • third-line therapy: oral vancomycin +/- IV metronidazole
Recurrent episode
  • recurrent infection occurs in around 20% of patients, increasing to 50% after their second episode
  • within 12 weeks of symptom resolution: oral fidaxomicin
  • after 12 weeks of symptom resolution: oral vancomycin OR fidaxomicin
Life-threatening C. difficile infection
  • oral vancomycin AND IV metronidazole
  • specialist advice - surgery may be considered

Treatment pathway for Clostridioides difficile infection

Other therapies
  • bezlotoxumab is a monoclonal antibody which targets C. difficile toxin B
    • NICE do not currently support its use to prevent recurrences as it is not cost-effective
  • faecal microbiota transplant
    • may be considered for patients who've had 2 or more previous episodes
Preventing the spread of C. difficile infection
  • isolation in side room: the patient should remain isolated until there has been no diarrhoea (types 5-7
on the Bristol Stool Chart) for at least 48 hours
  • all staff should wear disposable gloves and an apron during any contact with patients known to have C. difficile
  • hand washing is also essential - alcohol gel does not kill the spores of C. difficile


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