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.