Clostridioides Difficile

Question 1

What is the gram stain for clostridioides difficile, and how is it described?

Answer 1

It is a gram positive bacillus.
It is an anaerobic spore-forming bacteria.

Question 2

What does it mean to be an anaerobic bacteria, and how does C. Difficile combat this?

Answer 2

It means that its growth is inhibited by the presence of oxygen, limiting the conditions under which it can colonise within the body and cause disease.
To combat this, it produces spores that it can grow in.

Question 3

Where is C. Difficile found in the normal flora?

Answer 3

It makes up around 5% of the natural flora of the large bowel.

Question 4

Why are spores important when thinking about treating a patient?

Answer 4

They are resistant to high temperatures, to antibiotics and low pH.
They can survive for several months and widely present in the environment.

Question 5

How does clostridium difficile spread?

Answer 5

It is mostly a healthcare-setting acquired infection.
It spreads through spores, predominantly. This can be through the hands of healthcare workers, when treating a patient. It can also be through faeco-oral routes.

Question 6

Which bodily fluids aid in the formation of spores for the infection, and where can the infections be seen?

Answer 6

Bile acids - leads to clostridium difficile infections within the intestine.

Question 7

What is the main protective barrier against C. Difficile infections?

Answer 7

The normal flora of the intestines.
The normal flora competes for space and nutrients, preventing the overgrowth of the C. Difficile bacteria, and also produces anti-microbials that can kill the infection.

Question 8

What are the risk factors for C. Difficile infections?

Answer 8

Old age - over the age of 60.
Hospitalisation - prolonged stays with more invasive procedures are associated with increased rates.
Immunocompromised patients, inflammatory bowel disease (IBD), gastric acid suppression and severe infections.
Antibiotics - the longer a course of antibiotics, the greater the risk.

Question 9

Explain why antibiotics increase the risk of developing a clostridium difficile infection, and which antibiotics are seen to be most frequently indicated.

Answer 9

Antibiotics can kill some of the normal flora of the gut.
This means that there is less protection against C. Difficile, and so it can proliferate into the spaces left.
Cephalosporins, fluoroquinalones, amoxicillin and clindamycin.

Question 10

How does C. Difficile cause infection?

Answer 10

The proliferation of the bacteria that adheres to the epithelium, and release of A and B toxins.
It is also due to the release of enzymes such as collagenase, which damages epithelial cells, causing an inflammatory response.

Question 11

How do toxins A and B cause damage to the host?

Answer 11

Toxin A is an enterotoxin which causes an excess fluid secretion and stimulates an inflammatory response, causing damage to the cell structure.
Toxin B is a cytotoxin that damages protein synthesis and the cell structure.

Question 12

How is a clostridioides difficile infection (CDI) diagnosed, in terms of criteria?

Answer 12

The patient may have had antibiotics within the last 3 months, been hospitalised recently, and/ or have diarrhoea 48 hours or longer after hospitalisation.

Question 13

What are the asymptomatic and mild/ moderate symptoms of CDI?

Answer 13

Asymptomatic = no symptoms experienced.
Mild/ moderate infection:
- Diarrhoea (3 or more unformed stools in less than 24 hours).
- Presence of mucous or blood in the faeces.
- Fever.
- Abdominal cramping/ pain.

Question 14

What are the severe signs/ symptoms of a CDI infection?

Answer 14

Leukocytosis (>15,000 WBC/ microlitre).
Elevated serum creatinine.
Inflammation of the bowel.

Question 15

What are the signs/ symptoms of severe, complicated CDI?

Answer 15

Loss of bowel motility - ileus.
Sepsis, shock or hypotension.
Abdominal perforation.
Death.

Question 16

What tests can be used to confirm a clostridium difficile infection?

Answer 16

Enzyme immunoassay - testing for the presence of glutamate dehydrogenase, produced by C.diff.
Enzyme immunoassay for toxins A or B.
PCR for toxins A or B genes.

Question 17

What are the treatments for the different severities of CDI?

Answer 17

A mild/ moderate infection may require the cessation from taking antibiotics, allowing the normal flora to rebuild itself and protect the body from the infection.
Vancomycin orally for 10 days, for mild, moderate to severe cases.
In very severe cases, or if vancomycin does not work, fidaxomicin is used.
Life-threatening, using fidamoxicin and metronidazole.

Question 18

What kind of antibiotic is metronidazole and what kind of bacteria is it effective against? What is its mechanism for action? What is the drawback of it?

Answer 18

It is a broad-spectrum antibiotic, used to treat anaerobic bacteria.
It works by inhibiting nuclei acid synthesis.
It cannot kill the spores, meaning that the patient it more susceptible to re-infection.

Question 19

Explain how vancomycin is taken, and its mechanism?

Answer 19

It is taken orally, as it cannot cross the gastrointestinal border and so acts directly at the site of infection.
It works by inhibiting cell wall synthesis.

Question 20

Explain how fidaxomicin works against C. Difficile.

Answer 20

Fidaxomicin is a nucleic acid synthesis inhibitor (macrocyclic antibiotic).
It is taken orally but only has some absorption into the body.
It has a high activity against clostridium difficile, but a decreased activity against other gut commensals.

Question 21

What specific treatment is given to those with recurring C.diff infections? What are the risks of this?

Answer 21

Faecal microbiota transplant.
This is where the faeces of a healthy individual is donated to a patient through colonoscopy or enema to repopulate the patients normal bowel flora. This is 95% effective.
There are risks of the procedure itself in bowel perforation, but also in HIV and hepatitis transmission from the donor.

Question 22

How do you prevent the spread of clostridium difficile?

Answer 22

Patients with symptoms, offer them a test.
Isolate patients who have the infection, and those who are most at risk of becoming infected with it.
Clean the room thoroughly after a patient has left the hospital, as spores can persist on inanimate objects.
Hospital staff must clean their hands with soap and water, as alcohol hand gel does not kill the spores.
Wearing disposable gloves whilst treating patients.
Using antibiotics sparingly.

Question 23

How does a the bowel in a toxigenic CDI appear, histologically?

Answer 23

Epithelial necrosis, inflammatory exudate and ulceration of the bowel.