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 Management.
  • 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.