Colonic inflammation resulting in an exudative plaques (‘pseudomembranes’), usually caused by Clostridium difficile (spore-forming organism, anaerobic G+)
Diagnosis = A + (B or C)
A. Clinical features suggestive of CDI (diarrhoea, ileus, toxic megacolon)
B. Microbiological evidence of toxin producing C difficile
C. Pseudomembranous colitis on colonoscopy.
Severe CDI: Episode of CDI with one or more of
Fever, rigors
Haemodynamic instability
Peritonitis/perforation
Ileus/toxic megacolon
WCC >15
High lactate
Rise in creatinine level
Albumin <25
LI distension, colonic wall thickening, fat stranding, unexplained ascites
In US C. difficile is one of the most prevalent hospital-acquired infections
1-10/1000 hospital admissions
Up to 20% of hospitalised pts taking Abs
Classification
Nonfulminant disease
Fulminant disease
Hypotension/shock/ileus/megacolon
Can also classify into
Mild
Moderate
Severe
Recurrent
Aetiology and associations
Broad-spectrum Abx, esp: Penicillins, Cephalosporins, Clindamycin → these lead to changes in normal colonic flora, with resultant overgrown of some commensals, Clostridium difficile
Proton pump inhibitors has been proposed as a risk factor
Pathophysiology
C diff is an anaerobic, gram positive, spore-forming, toxin-producing bacillius
It is a resident of the GIT in 3% of people & 10% of hospital pts
Patients who have antibiotic therapy have disruption of normal colonic microflora
Exposure to C difficile and colonisation occurs
C difficile releases endotoxin A (enterotoxin) and toxin B (cytotoxin). Both of these toxins bind to receptors on endothelial cells and cause a severe inflammatory host response characterised by inflammation and mucosal damage.
Toxins A and B inactivate regulatory pathways mediated by Rho family proteins that are involved in cytoskeleton structure and signal transduction via guanosine triphosphate.
Toxin A causes release of host response immune mediators such as substance P, TNF-alpha, IL1, IL-6, IL-8
Toxin B has 10 x the potency of toxin A and also causes inflammation and mucosal injury
Both of them inactivate members o the Rho GTPase family (molecules switches) leading to colonocyte death and destabilisation of tight junctions compromising the epithelial barrier
This leads to loss of intestinal barrier function and neutrophilic colitis
Pseudomembranes arise from inflamed erupted crypts - these are comprised of fibrin, mucus, bacteria and neutrophils
Inappropriate release of nitric oxide reduces normal contractility of the colon and can lead to ischaemia and perforation. At high concentrations, NO. disrupts the actin cytoskeleton, inhibits ATP formation, dilates cellular tight junctions, and produces a hyperpermeable state.
Oedema and extensive lamina propria neutrophil infiltration
Rectum spared in 25%
Clinical features
Symptoms
Diarrhoea (not bloody)
Abdo pain/distension, fever
Signs
Possible bacteraemia & septic shock
Toxic megacolon
Investigations
Stool specimen
GDH (Glutamate dehydrogenase measurement) (stool)
Enzyme immunoassay for toxins A and B (stool)
PCR (stool)
Sigmoidoscopy/colonoscopy: elevated, yellow pseudomembranes of necrotic mucosa with mucosal ulceration
Management
Asymptomatic carriage
Treatment not indicated in patients who are asymptomatic
Non-operative
Correction of fluid & electrolyte status
Stop ABx
Contact isolation
Cease antibiotic administration if possible
Adjuncts to normalize colonic flora: probiotics
Antibiotics
Mild-moderate: Metronidazole 400mg PO TDS for 14/7
Severe: Oral vancomycin 125 mg QID for 10/7
Oral fidaxomicin 200 mg twice daily (BD) is a treatment alternative
Other options
Cholestyramine
Vancomycin enemas
Faecal transplant
Operative
Severe/unresponsive to medical therapy/perforated bowel: Total abdominal colectomy or diverting loop ileostomy + colonic lavage
Up to 20% of patients with fulminant infections will require colectomy