GI 2 - Clostridioides difficile Flashcards
(7 cards)
Shape, gram positive or negative, haemolytic, basic structure
Gram-positive anaerobic bacillus (rod shaped ).
Peritrichous flagella.
Haemolytic.
Spore forming (spores can survive stomach acid).
Found in the gut of 3 % of adults.
Proliferation usually kept low by the gut microbiome.
Produces two exotoxins (A and B).
No toxin = no infection!
C. difficile - Transmission
Faecal-oral route via person-to-person or objects.
Natural reservoirs: soil, faeces of domestic animals and humans, sewage, the human intestinal tract, and processed meat.
Hospitals are a major reservoir of infection.
Spores can remain viable on surfaces for months.
In hospitals, 3 – 21 % of patients are carriers of C. difficile. Most common cause of hospital acquired-diarrhoea.
Associated with the use of antibiotics.
Clostridioides difficile & antibiotics
Commensal flora – opportunistic.
Poor competitor for nutrients – often outcompeted (and controlled) by other bacteria.
Antibiotic disruption to microbiome = ↑ C. difficile.
Biofilm forming:
persistence in the gut in the presence of antibiotic therapy.
potentially re-establishing infections.
resulting in recurrent disease.
Para-cresol secretion inhibits other microbes
→ outcompete normal human gut flora
Clostridioides difficile – Mechanism of Infection
C. difficile spores germinate
Vegetative cells produce toxins A and B.
Toxins damage intestinal epithelial barrier.
Host inflammatory response.
Cytokine release results in neutrophil influx in the area.
Breakdown of neutrophils/pathogen/host cell and toxin AND severe inflammation results in pseudomembrane formation.
Infections in humans: C. difficile
Toxins damage epithelial cells in the intestines.
Symptoms:
Foul watery diarrhoea ≥3 loose/liquid stools in 24 h.
Abdominal pain/ tenderness.
Sometimes Fever and elevated white blood cell count.
Symptoms may start within days or weeks after beginning antibiotics.
May also have Loss of appetite & nausea.
Mortality: 6-30 %.
C. difficile: Enrichment and Detection.
Cycloserine-cefoxitin-fructose-agar (CCFA):
Cycloserine (G-) and cefoxitin (G+/-; antibiotics) inhibit the growth of most other bacteria.
Fructose is an important nutrient for C. difficile growth.
Neutral red is added as a pH indicator. Pink/orange to yellow if C. difficile is present.
Cell Cytotoxic Neutralization Assay (CCNA) = gold standard
Test toxins in (fresh) stool against a range of cell lines – look for characteristic ‘cell rounding’.
Detection of toxins by enzyme immunoassays (lateral flow devices).
PCR (qRT-PCR = look for genes relating to toxin production).
C. difficile: Treatment.
Stop antibiotics allowing C. difficile to proliferate.
Switch to alternative antibiotics such as vancomycin (class: glycopeptide) or fidaxomicin (class: macrolide) for at least 10 days.
