L16 C. difficile Flashcards
What disease does Clostridium difficile cause?
Antibiotic-associated diarrhoea
C. diff is an example of?
An opportunistic pathogen
1 in every __ adults carries C. diff without side effects
33
Features of C. diff?
- Slender, Gram positive bacillus
- Produces large, oval, subterminal spores
- Anaerobe
- Most strains are extremely sensitive to oxygen
- Very difficult to grow in the lab (how it got its name!)
What is C. diff?
A major nosocomial (hospital-acquired) pathogen that causes a spectrum of intestinal disease from uncomplicated antibiotic-associated diarrhoea to severe, possibly fatal, antibiotic-associated colitis
Many antibiotics have been associated with diarrhoea and pseudomembranous colitis, including…
ampicillin, cephalosporins, clindamycin, amoxicillin
C. diff really only occurs in a person who?
is taking antibiotics
The more serious the diarrhoea, the more…
pseudomembranes that form
Clinical symptoms of C. diff?
Vary widely from mild diarrhoea to severe abd pain with fever & severe weakness. Diarrhoea is watery & usually non-bloody, but approx 5-10% patients have bloody diarrhoea. In many cases, symptoms resolve 1-14 days after the offending antibiotic is discontinued, and antibiotic treatment is not needed.
What are antibiotics of choice to treat active C. diff infection?
Oral vancomycin (gold standard) or metronidazole - can have toxic effects, last resort
Bloody diarrhoea is associated with what?
Severe colitis
Metronidazole works particularly well in __ environments
anaerobic
often used for tooth infections, recommended not to drink while taking this antibiotic
What are pseudomembranes?
The immune response can form grey, white or yellow patches on the mucosa. These areas are called pseudomembranes (pseudomembranous colitis).
Besides C. diff, what other bacterium causes pseudomembrane formation?
Corynebacterium diphtheriae
Why is the ultimate cause of death often difficult to determine in a C. diff infected patient with pseudomembranous colitis?
Most patients show a non-specific deterioration over a period of weeks.
What kills most people? (C. diff)
Recurrent disease - negative feedback cycle of remission and recovery. Probiotics recommended to recolonise colon
What is C. diff disease caused by?
The overgrowth of the organism in the intestinal tract (primarily colon). This organism then replicates & secretes two toxins (TcdA and TcdB)
Pathogenesis of C. diff-associated diarrhoea in adults:
- Spores & vegetative cells ingested
- Spores germinate in SI upon exposure to bile acids
- Flagellae facilitate movement; a polysaccharide capsule discourages phagocytosis
- Multiplies in colon
- Gut mucosa facilitates adherence to the colonic epithelium
- Produce toxins A and B & hydrolytic enzymes
- Production of TNF-α & pro-inflammatory ILs, increased vascular permeability, neutrophil & monocyte recruitment
- Opening of epithelial cell junctions
- Epithelial cell apoptosis
- CT degradation → colitis → pseudomembrane formation & watery diarrhoea
2 C. diff toxins?
TcdA - enterotoxin, causes fluid accumulation in bowel, weak cytotoxin
TcdB - potent cytotoxin, related to TcdA, activity leads to disruption of tight junctions & apoptosis
- Both contribute to inflammation
- Together cause diarrhoea
- Glycosyltransferases
What is CDT?
A binary toxin that ADP-ribosylates actin (found in 6-12.5% of C. diff strains) - functions similarly to A-B toxin, except A and B parts are not attached by a disulphide bond
TcdA and TcdB are examples of?
Clostridial glycosylating toxins (CGTs) - both TcdA and TcdB act intracellularly as glycosyltransferases
What is the most widely recognised and modifiable risk factor for C. diff?
Disruption of normal enteric flora
Why are infants quite susceptible to bacteria?
Since they have an underdeveloped flora
What is the probiotic in Actimels?
Lactobacillus
