L16 C. difficile

Question 1

What disease does Clostridium difficile cause?

Answer 1

Antibiotic-associated diarrhoea

Question 2

C. diff is an example of?

Answer 2

An opportunistic pathogen

Question 3

1 in every __ adults carries C. diff without side effects

Answer 3

33

Question 4

Features of C. diff?

Answer 4

• 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!)

Question 5

What is C. diff?

Answer 5

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

Question 6

Many antibiotics have been associated with diarrhoea and pseudomembranous colitis, including…

Answer 6

ampicillin, cephalosporins, clindamycin, amoxicillin

Question 7

C. diff really only occurs in a person who?

Answer 7

is taking antibiotics

Question 8

The more serious the diarrhoea, the more…

Answer 8

pseudomembranes that form

Question 9

Clinical symptoms of C. diff?

Answer 9

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.

Question 10

What are antibiotics of choice to treat active C. diff infection?

Answer 10

Oral vancomycin (gold standard) or metronidazole - can have toxic effects, last resort

Question 11

Bloody diarrhoea is associated with what?

Answer 11

Severe colitis

Question 12

Metronidazole works particularly well in __ environments

Answer 12

anaerobic

often used for tooth infections, recommended not to drink while taking this antibiotic

Question 13

What are pseudomembranes?

Answer 13

The immune response can form grey, white or yellow patches on the mucosa. These areas are called pseudomembranes (pseudomembranous colitis).

Question 14

Besides C. diff, what other bacterium causes pseudomembrane formation?

Answer 14

Corynebacterium diphtheriae

Question 15

Why is the ultimate cause of death often difficult to determine in a C. diff infected patient with pseudomembranous colitis?

Answer 15

Most patients show a non-specific deterioration over a period of weeks.

Question 16

What kills most people? (C. diff)

Answer 16

Recurrent disease - negative feedback cycle of remission and recovery. Probiotics recommended to recolonise colon

Question 17

What is C. diff disease caused by?

Answer 17

The overgrowth of the organism in the intestinal tract (primarily colon). This organism then replicates & secretes two toxins (TcdA and TcdB)

Question 18

Pathogenesis of C. diff-associated diarrhoea in adults:

Answer 18

1. Spores & vegetative cells ingested
2. Spores germinate in SI upon exposure to bile acids
3. Flagellae facilitate movement; a polysaccharide capsule discourages phagocytosis
4. Multiplies in colon
5. Gut mucosa facilitates adherence to the colonic epithelium
6. Produce toxins A and B & hydrolytic enzymes
7. Production of TNF-α & pro-inflammatory ILs, increased vascular permeability, neutrophil & monocyte recruitment
8. Opening of epithelial cell junctions
9. Epithelial cell apoptosis
10. CT degradation → colitis → pseudomembrane formation & watery diarrhoea

Question 19

2 C. diff toxins?

Answer 19

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

Question 20

What is CDT?

Answer 20

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

Question 21

TcdA and TcdB are examples of?

Answer 21

Clostridial glycosylating toxins (CGTs) - both TcdA and TcdB act intracellularly as glycosyltransferases

Question 22

What is the most widely recognised and modifiable risk factor for C. diff?

Answer 22

Disruption of normal enteric flora

Question 23

Why are infants quite susceptible to bacteria?

Answer 23

Since they have an underdeveloped flora

Question 24

What is the probiotic in Actimels?

Answer 24

Lactobacillus

Question 25

C. diff is treatable using…

Answer 25

Faecal Microbiota Transplantation

Question 26

What patients would be eligible for FMT?

Answer 26

Patients with recurrent C. diff and poor outcome

Question 27

What is faecal filtrate transplantation?

Answer 27

Left with metabolites, bacteriophages etc.

New concept, has treated cases of necrotising enterocolitis (very severe)