Infection & Immunity Nick Hadd Fungal

Question 0

What is sepsis or septic shock?

Answer 0

Sepsis is the physiological response of the body to a systemic infection
Septic shock occurs when the circulatory system cannot supply the demands of the body.

Question 1

What does disseminated mean?

Answer 1

Disseminated: spread from the initial localised source of infection

Question 2

What is the process of septic shock leading to multi organ failure.

Answer 2

Inflammatory mediators in blood make the blood vessels more leaky, thus results in decreased blood pressure
Low blood pressure leads to hypoperfusion of organs (lack of blood supply) leads to multi organ failure

Question 3

What kinds are most prone to getting fungal infections?

Answer 3

Neutropenic patients I.e those receiving chemotherapy
Intensive care unit patients
Patients with central IV catheters
HIV and AIDs
Patients after a transplant who are on anti-rejection medication

Question 4

Neutropenia is a risk for both candida and aspergillus infection.
This is the same with steroids, graft vs host disease (GVHD), mucosal colonisation and bacterial infections.

Answer 4

Central intra venous lines and antibacterials are a risk of candida only
Building works are a risk of aspergillus only

Question 5

What are the main causative organisms of fungal infections?

Answer 5

Candida species
Aspergillus species
Cryptococcus species
Histoplasma capsulatum

Question 6

What type of fungus is candida? Where’s it found? What’s it diagnosed by?

Answer 6

It’s a yeast
Part of normal gut flora
Diagnosed by culturing

Question 7

What’s important to find out if a patient is found to have an infection with candida?

Answer 7

Any previous Azole therapy eg with fluconazole itraconazole etc
Also important to find out the species; albicans causes almost all muco-cutaneous infections

Question 8

What types of candidiasis are there?

Answer 8

Catheter related
Acute disseminated
Chronic disseminated
Deep organ candidiasis

Question 9

What type of fungus is aspergillus?

Answer 9

A mould

Common environmental pathogen

Question 10

What type of infection does aspergillus tend to cause?

Answer 10

Pulmonary infections
It’s opportunistic in immuno-compromised patients
May be found after lung transplants

Question 11

How can we diagnose aspergillus infections?

Answer 11

Imaging- fungus infections will usually show up in x-rays

Also by antibody detection

Question 12

Aspergillosis can be invasive, allergic, or saprophytic. What do these mean?

Answer 12

Invasive:
Includes disseminated. Means that it isn’t localised, it’s spread. Typically of lung origin
Allergic:
ABPA allergic broncho pulmonary aspergillosis
Saprophytic:
Aspergilloma ( a fungal ball) growth of this ball in a pre-existing cavity, eg a patient with previous TB

Question 13

What are the complications associated with invasive pulmonary aspergillosis?

Answer 13

Raging pneumonia
Dissemination (spread) into the CNS
Local invasion into heart/ vessels etc

Question 14

Cryptococcus is a yeast, what types of infection does it usually cause?

Answer 14

Invasive CNS disease

Pulmonary [not usually detected]

Especially seen in HIV and AIDS patients

Question 15

Histoplasmosis results from the environmental pathogen Histoplasma capsulatum. It traditionally causes _________ disease and further dissemination. Usually ______ patients more prone.

Answer 15

Causes pulmonary disease

Usually HIV and AIDs patients

Question 16

What’s the difference between invasive and disseminated infections?

Answer 16

Invasive means spreading, this may be locally or to wider parts of the body because of Dissemination or seeding
Dissemination means more widely spread. NOT local spreading

Question 17

What’s fungaemia?

Answer 17

A type of sepsis where fungi circulates the blood

Question 18

What are mannan/ anti-mannan, beta D glucan, galactomannan all examples of?!

Answer 18

Ways we can diagnose and decide when to treat fungal infections

Question 19

What’s the “proven” catergory diagnostics of fungal infections?

Answer 19

The exact cause of the fungus has been grown and cultured so doctors are certain what is causing it

Question 20

What is the “probable” catergory of fungal infection diagnostics?

Answer 20

Some uncertainty of what’s causing it, usually treated empirically

To meet criteria of probable: host factor, clinical features and mycological (fungal causing) evidence must be present.
“Possible” infections meet even less criteria than this

Definition of these levels of certainty differ from one organism to the next and between different types/ sites of infection

Question 21

To meet the criteria of probable fungal infection, one of the criteria is HOST factors, what’s this?

Answer 21

Included factors that the patient may have, eg
Neutropenia
Fever unresponsive to broad spectrum antibiotics
Use of immuno suppressants
HIV or AIDS
Recent long use of corticosteroids

Question 22

One “probable” diagnostic indicator is clinical features. What are these?

Answer 22

Mainly relevant imaging
Eg lesions seen in respiratory tract
Meningeal enhancement / Lesions in CNS

Question 23

Indirect tests such as galactomannan, and more direct tests involving microscopy, sensitivity and culture such as Sputum and NBL (squirt water into lungs, extract and then send sample to lab) samples are all part of the ________ criteria of fungal diagnostics

Answer 23

Mycological evidence

Question 24

Fungal infections are best treated with antibiotics. True or false?

Answer 24

False!
Antibiotics only treat bacteria!
Could be used as a diagnostic feature though; if a patient still has fever after using broad spectrum antibiotics this may indicate fungal infection

Question 25

Antifungals drugs have to be specific to target fungus and not our own cells, why is this more difficult with fungus than for bacteria?

Answer 25

Fungus are eukaryotic just like our own cells. So harder to target these specifically. Bacteria are prokaryotic

Question 26

What class of antifungals tend to work by inhibition of egosterol biosynthesis in the cell membrane?

Answer 26

Azoles
Eg the triazoles:
fluconazoles
Ketaconzaole

Or imidazoles

Question 27

What kind of antifungals tend to work by ergosterol disruption in the cell membrane?

Answer 27

Polyenes
Eg amphotericin B
Abelcet
AmBisome

Question 28

Which antifungal works by inhibiting DNA / RNA synthesis in the nucleus?

Answer 28

Flucytosine

Question 29

What is the triazoles mechanism of action INR fungus? What are their side effects

Answer 29

They decrease ergosterol production through inhibition of fungal cytochrome p450 enzymes. Most are static (I.e don’t kill but stops the fungi reproducing)

Orally taken
Side effects:
Hepatic effects
QT prolongation

Question 30

Why do triazoles commonly interact with other medication?

Answer 30

They inhibit fungal CYP450 enzymes, but may also inhibit human enzymes too

Question 31

What’s the best treatment for simple infections?

Answer 31

Fluconazole

Use where Candida albicans has been confirmed and the patient has had no previous azole therapy

Question 32

What’s best to use as treatment for most ‘serious’ infections?

Answer 32

Lipid formulation amphoterocin

Or echinicandin

Question 33

What should we consider to use for CNS infections?

Answer 33

Voriconazole