LECTURE OVERVIEW.
• Define gastrointestinal infection
• Clostridium difficile Associated Disease (CDAD)
- Epidemiology; risk factors for CDAD
- Pathogenesis / C. difficile ribotype 027
- Clinical manifestations of CDAD
- Laboratory diagnosis (culture / non-culture)
- Treatment and prevention
CHARACTERISATION OF GI INFECTION.
(A) Food-associated (borne) infection
• ‘Food’ acts as a vehicle for transmission
• Food-handlers contaminate ‘food’
• Consume the pathogen
Eg. Salmonella sp. Campylobacter sp. E. coli O157, Norovirus
(B) Food-poisoning
• Toxin present in food; consume toxin
Eg. Staphylococcus aureus
(C) Antibiotic-associated diarrhoea (AAD)
• BS antibiotics disrupt normal gut flora
• Over-growth of pathogenic microorganism
Eg. Clostridium difficile (Clostridioides difficile)
GI infections are mostly food borne or food associated.
They require ingestion of contaminated material, as the vehicle for transmission.
The contamination can come from the food itself, for example, undercooked chicken that
can give you an infection with campylobacter.
Or food handlers can contaminate the food themselves.
So if you have a food handler that is asymptomatically shedding norovirus, and they are
making thousands of sandwiches a day with their badly washed hands, this will be a massive
containment issue with this.
Someone has to consume the pathogen, they consume salmonella or campylobacter or
E.coli 0157, or norovirus.
These are very well documented outbreaks around food borne gastrointestinal infections.
You can also pick up GI infections from food poisoning that can be from a toxin that is
present within the food, rather than an infection of the bacterium itself.
For example, if you cook some frozen fish, you do not know if that frozen fish has been
thawed and then re-frozen through their journey to getting to you and you do not know
about that.
There can be toxins present within the food that your eating, although you cook it and you
kill the bacteria that are present, the bacterial load is such that the toxins that remain in the
food, can make you ill.
, This is food poisoining, you are getting poisoned by the toxins that are present in the food.
Even though the organism is not colonizing your gut.
Antibiotic-associated diarrhoea (ADD), this is where broad-spectrum antibiotics disrupt the
normal gut flora and you get an overgrowth of a particular pathogenic microorganism.
You expose the patient to the risk of gastrointestinal infection, by de-colonizing their gut
flora.
We are all exposed to pathogens all the time, but we do not get sick all the time. This is
because we have an immune system.
In terms of ingested pathogens, our gut microbiota, helps to maintain a healthy
environment in the gastrointestinal tract.
If you strip that out, organisms that you ingest have a much greater chance of colonization.
This is what happens a lot in clostridium difficle infections. It tends to be a major issue in
people on broad spectrum antibiotcs.
People that are on broad spectrum antibiotics are most commonly found in hospitals and
therefore this a major hospital acquired pathogen.
CLOSTRIDIUM DIFFICLE BACKGROUND.
• Discovered in 1935:
Bacillus difficilis: normal component of faecal flora of 70% newborn babies and 2-3%
healthy adults
• Clostridium difficile: Characteristics
-Gram positive rod
-Strictly anaerobic
-Spore forming microorganism (ubiquitous)
-Toxin producing
- >100 different genetic types (Ribotypes)
-Ribotypes 001, 106, 027 common in UK
• 1978: Making its mark in the NHS:
Association with antibiotic associated diarrhoea (AAD) and pseudomembranous
colitis (PMC) (>65 year-olds)
• 21st Century: C. difficile is one of the leading Healthcare Associated Infection (HAI) in
the UK; AAD, PMC, death.
Spores are the VECTOR for transmission of CDAD
First it was called bacillus difficilus because it was difficult to grow. – it is difficult to grow
because it is an obligate anaerobe.
So although we can see it by microscopy from a fecal sample, from a diahorreal sample,
from patients that had been colonized with it. We couldn’t culture it to be able to do
sensitivity testing on it, until we worked out that it only grows under anaerobic conditions.
There is not a lot of oxygen in your gut, therefore this is a really good microenvironment for
this organism to survive in and colonize.
It is a normal component in fecal flora in 70% of newborn babies, so babies tend to have
clostridium difficle in their gut, until they get recolonized with flora from the mother's body,
through breast feeding, colonization of the gastrointestinal tract with bacteria and
commensals from the mother.
In 2-10% of healthy adults you also find clostridium difficle in the gut, this has been acquired
from somewhere, and it is likely that these individuals have spent some time in the hospital
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