On this Page

Clostridioides Difficile

Also known as Clostridium difficle and C. diff.

Clostridium difficile was renamed in 2016, after genetic analysis identified it should fall under the peptostreptococcaceae family, and thus be a Peptoclostridium.

To avoid excessive disruption to the status quo, some microbiological taxonomy loopholes were exploited to forge a new genus Clostridioides, and so keep the familiar C. diff abbreviation.

Infective diarrhoea caused by Clostridioides Difficile that:

Epidemiology and Risk Factors

Causes:

  • 10-25% of antibiotic-associated diarrhoea
  • Almost all cases of pseudomembranous colitis

Major risk factors include:

  • Broad-spectrum antibiotics
    • Clindamycin
    • Cephalosporins
    • Fluoroquinolones
  • Immunosuppression
    • Severity of illness
    • IBD
  • Exposure to infected patient
  • Age >65
  • SUP
    PPIs double risk.
  • Prolonged hospital stay
  • Renal impairment

Pathophysiology

Aetiology

Clostridioides Difficile is:

  • A spore-forming, Gram positive, anaerobic bacilli
  • Toxin-producing
    Most bacteria produce both, but up to 25% produce neither:
    • Toxin A
      • Enterocyte-toxic
      • Attracts neutrophils
    • Toxin B
      More potent than B.
  • An extremophile
    Resistant to:
    • Dessication
    • Most cleaning products
      Notably, not chlorine.

Clinical Features

Two clinical pictures:

  • Diarrhoea with associated fever
    • Mucoid
    • Green-ish
    • Watery
    • Presence of pseudomembranes
  • Ileus (and no diarrhoea) with leukocytosis and toxic megacolon

Assessment

History:

Exam:

Diagnostic Approach and DDx

Features suggestive of C. difficile:

  • Characteristic stools
    • Watery
    • Green-ish
    • Mucoid
    • >3/24 hours
    • 3-9 days after antibiotics
  • Previous broad spectrum antibiotics
  • Fever
  • Abdominal pain
  • Distension
  • Positive investigations
  • AKI

Investigations

Bedside:

Laboratory:

  • Blood
    • FBE
      • Leukocytosis
    • LFT
      • Hypoalbuminaemia
  • Stool
    • Antigen and toxin PCR
      Sensitive, persist after resolution of infection.
    • Culture
      • 2-3 days to grow
      • Technically demanding
      • Most useful for epidemiological purposes for strain typing

Imaging:

Thumbprinting

  • AXR
    • “Thumbprinting” of bowel
      Thickening of haustra due to oedema, leading to an appearance of thumbprints projecting into the aerated colonic lumen at regular intervals.
    • Pneumoperitoneum
  • CT
    • Inflamed bowel
    • Perforation
      • Pneumoperitoneum

Other:

Pseudomembranes

  • Proctoscopy/flexible sigmoidoscopy
    • Facilitates direct visualisation of pseudomembranes
    • Method to detect severe disease
    • Risk of perforation limits use
    • Role in severe disease and antigen and toxin tests are negative or unavailable

Management

  • Standard sepsis management
    Covered under .
  • Stop inciting antibiotics
  • Oral antibiotics
    Empirically if high pre-test probability.

Specific therapy:

  • Pharmacological
    • Cease other antibiotics
    • Oral antibiotics
      • Mild-moderate infection
        • Metronidazole 500mg PO Q8H for 10 days
          Change to fidaxomicin or vancomycin if no response in 5 days.
      • Severe infection
        • Fidaxomicin 200mg PO Q12H for 10 days
          Preferable to vancomycin, if available.
        • Vancomycin 125-500mg PO Q6H for 10 days
          • Higher dose indicated in shock
          • Can be given via enema if ileus present
            In this case the dose is 500mg in 100mL Q6H.
        • Metronidazole 400mg IV Q8H for 10 days
          In addition to fidaxomicin or vancomycin.
    • Bezlotoxumab 10mg/kg
      • Antibody against Toxin B
      • Indicated in second recurrence
      • Single dose of 10mg/kg
  • Procedural
    • Faecal microbiota transplant
      • Justified by restoring colonic microbial biodiversity that was disrupted by the antibiotic-induced genocide
      • Indicated for third recurrence
      • Risk of infection transmission
  • Physical
    • Faecal management system
    • Bowel resection
      Consider with:
      • Sepsis
      • WCC >50×103/mL
      • Lactate >5mmol/L

Supportive care:

  • D
    • Analgesia
  • F
    • Correct electrolyte disturbances

Preventative:

  • Antimicrobial stewardship
  • Appropriate infection control
    • Contract precautions
    • Soap-and-water handwashing
    • Individualise equipment

Marginal and Ineffective Therapies

  • Probiotics

Anaesthetic Considerations

Complications

  • C
    • SIRS
    • Hypovolaemia
  • F
    • Electrolyte disturbances
  • G
    • Toxic megacolon
    • Perforation
  • I
    • Abdominal sepsis

Prognosis

Poor prognostic features include:

  • Age >70
  • WCC
    • Rate of rise
    • Peak >20×103/mL
  • Albumin <25g/L
  • AKI
  • SBO
  • Ileus
  • Fever >38.0°C

Key Studies

References

  1. O’Grady NP, Barie PS, Bartlett JG, et al. Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. Critical Care Medicine. 2008;36(4):1330.
  2. Diseases TLI. C difficile—a rose by any other name…. The Lancet Infectious Diseases. 2019;19(5):449. doi:10.1016/S1473-3099(19)30177-X
  3. Johnson S, Lavergne V, Skinner AM, et al. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clinical Infectious Diseases. 2021;73(5):e1029-e1044. doi:10.1093/cid/ciab549
  4. Case courtesy of Derek Smith. Thumprinting. Radiopaedia.org, rID: 31329.