HAI - Clostridium difficile

Question 1

What is clostridium difficile?

Answer 1

A typically commensal bacteria found in the guts of children, and in low amounts in some adults (asymptomatic carriage)

Question 2

What are the main toxins that Clostridium difficile produce?

Answer 2

ToxA (308 kDa enterotoxin)
ToxB (270 kDa cytotoxin)

Question 3

What are the steps in toxin mechanism?

Answer 3

Attachment
Endocytosis
Acidification of vacuole
Release of enzymatic domain
Action on GTPases

Question 4

Summarise toxin attachment and endocytosis

Answer 4

Toxins bind to specific receptors on host intestinal epithelial cells. Toxins are internalised into the host cell via endocytosis, forming an endocytic vesicle

Question 5

Summarise acidification of vacuole and release of enzymatic domain

Answer 5

Endocytic vesicle undergoes acidification, which is necessary to allow translocation of their enzymatic domain into host cell cytoplasm

Question 6

Summarise action of toxins on GTPases

Answer 6

The enzymatic domains of the toxins glucoslyate small GTPases such as Rac and Rho, resulting in their inactivation. This disrupts various cellular processes, including actin cytoskeleton organisation

Question 7

What is the result of the disruption of actin cytoskeleton organisation?

Answer 7

Damages the absorptive surface of the interstinal epithelium. This impairs nutrient absorption, and contributes to diarrhea

Question 8

What can occur as a result of the toxins in severe cases?

Answer 8

Pseudomembraneous colitis: - Plaques of nectrotic tissue slough from colon - Can be fatal

Question 9

In what environments does C. difficile thrive?

Answer 9

Less diverse microbiota. Therefore use of antibiotics allows it to thrive.

Question 10

What often happens when antibiotics are used to treat C. difficile?

Answer 10

Antibiotics kill them, however the spores produced by C. difficile remain, so when antibiotic treatment ceases, the spores can germinate again, causing another infection

Question 11

What is ribotype 027?

Answer 11

A fluroquinolone resistant type of C. difficile

Question 12

What are 3 ways to reduce C. difficile rates of infection?

Answer 12

• Identification of new antibiotics e.g. fidaxomicin
• Faecal transplants
• Research into sporalisation - interference with production of spores can potentially prevent transmission and reinfection

Question 13

What is fidaxomicin?

Answer 13

An antibiotic that has a lesser impact on the microbiome, reducing the incidence of HAIs.

The problem is that it is expensive

Question 14

What is the impact of faecal transplants?

Answer 14

• Increases microbiome diversity
• Reduces disease by about 90%

Question 15

What are the 3 prerequisites for hospital acquired infections?

Answer 15

• Acquired by a patient for a reason other than that infection
• Occurring in a patient that was not present at the time of admission
• Includes infections acquired in hospital that appear within 48 hours of discharge