Clostridium difficile

Microbiology and Pathogenesis

  • C difficile is
    • Gram positive
    • Anaerobic
    • Spore forming
      • Commonly found in the environment: soils, water, GI tract
    • Motile
    • Increasingly resistant to antibiotics
  • If the GI tract’s normal flora or resistance to colonisation is impaired e.g. by the use of antibiotics, the lower gut can become susceptible to colonisation by spores
    • Spores are able to evade host defenses e.g. stomach acid etc
    • C diff can release toxins (A, B and/or Binary) which cause an inflammatory response and are cytotoxic (kills enterocytes and damages the GI tract)
  • The damage to the GI tract leads to:
    • Loss of fluid by leakage through the damaged mucosa
    • Reduced absorption across the gut wall
    • the formation of pseudomembranes (accumulation of fibrin)
      • following the ‘explosion’ of neutrophils through the damaged mucosa and opened tight junctions
    • general gut inflammation, toxic megacolon and risk of perforation

Risk factors

  • Current/recent use of antimicrobial agents
    • particularly the ‘4 C’s’
      • Co-amoxiclav
      • Clindamycin
      • Cephalosporins (all)
      • Ciprofloxacin (and actually any quinolone antibiotic)
    • Can occur after 6 days and up to 6 weeks after antibiotic treatment
  • Age
  • Prolonged hospital stay
    • Hospital associated disease is defined as onset of symptoms 48 hours after admission OR up to 4 weeks after discharge
    • True community acquired disease can be diagnosed if the patient has not in hospital for >12 weeks and if the onset of symptoms is either in the community or within 48 hours of admission
  • Serious underlying illness/diseases
  • Surgical (particularly bowel) procedures
  • Immunocomprimising conditions
  • PPIs
  • Other smaller risk factors include other GI procedures, NG tube, ICU patient

Clinical manifestations

  • Asymptomatic carriage (around 4% of the population)
  • Diarrhoea/simple colitis
    • Usually profuse, watery diarrhoea, which can be bloody
    • Abdominal cramps are usually present and can be severe
    • Fever is usually a sign of severe disease (see below)
  • Pseudomembranous colitis
  • Fulminant colitis

 

  • Severe colitis
    • fever, rigors
    • haemodynamic instability/signs of shock e.g. tachycardia, tachypnoea, hypotension
    • signs of peritonitis e.g. decreased bowel sounds, abdominal tenderness, rebound tenderness and guarding
    • signs of ileus e.g. vomiting and absent passage of stools

Investigations

  • FBC (raised WCC (neutrophilia)); U&Es (raised creatinine); raised lactate
  • Stool C diff toxin should be requested in the presence of risk factors
  • Imaging (AXR/CT)
    • Distension of the large intestine
    • Colonic wall thickening
    • Pericolonic fat stranding
    • Ascites of no other cause

Management (as per Tayside protocol)

  • If C diff toxin positive, assess severity (one or more of the following indicates severe disease; otherwise non-severe)
    • Temp >38.5°C
    • Ileus, colonic dilation >6cm on AXR/CT, toxic megacolon and/or pseudomembranous colitis
    • WCC >15×10^9/l
    • Acute rising serum creatinine >1.5x baseline
  • In severe disease (NB all patients should be managed by infectious diseases for close monitoring e.g. of fluid/food balance)
    • treat with oral vancomycin 125mg QDS for 10 days (if oral route unavailable, via NG tube)
    • If the patient is deemed to have life-threatening disease (one of admission to HDU/ICU, hypotension, ileus or significant abdominal distension, mental state changes, WBC >35 or <2, serum lactate >2.2mmol/l, any other signs of end-organ failure), consider surgical referral
      • In patients with ileus, treat with IV metronidazole 500mg TDS + NG vancomycin 500mg QDS until ileus resolves (otherwise surgery should be considered urgently)
  • In non-severe disease (If not a recurrence)
    • treat with oral metronidazole 400mg TDS for 10 days (if oral unavailable, IV 500mg TDS)
      • If no improvement after 5 days, switch to oral vancomycin 125mg for 10 days.
  • In non-severe, recurrent C diff infection
    • Contact microbiology for approval to prescribe Fidaxomicin 200mg BD for 10 days
    • If the patient has already received a course of fidaxomicin, contact microbiology/ID for advice (for further regimens, see here)

NB All cases should be reported to HPS (Health protection)

Prognosis

  • Around 20% of patients will actually relapse following an initial infection.
    • Around half will involve a different strain of C diff.
    • Others at higher risk include those infected with a hypervirulent strain of C diff (e.g. 027/NAP1/BI)
  • These patients are at higher risk of multiple relapses also

A note about C diff in the neonate

  • Neonates are usually asymptomatic carriers.  If C diff is cultured, then it can be used as a measure of cross-infection within the neonatal unit.
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