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
- particularly the ‘4 C’s’
- 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.
- treat with oral metronidazole 400mg TDS for 10 days (if oral unavailable, IV 500mg TDS)
- 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.