Microbiology: Antifungals

Question 1

What fungi is ‘ringworm?

Answer 1

Dermatophytes

Question 2

Where are Superficial mycoses?

Answer 2

Affect the skin, hair and nails

Mucosal surfaces in upper respiratory tract

Question 3

Where are Subcutaneous mycoses (Intermediate)?

Answer 3

Affect the muscle and connective tissue, below the skin

Question 4

Where are Systemic (invasive) mycoses?

Answer 4

Often relate to immune suppression or other issues
Involve the internal organs
Primary versus opportunistic

Question 5

Fungal cells are ……………..

Answer 5

Eukaryotic so unlike bacteria they have a lot more in common with the cells of the host they infect

Question 6

What do fungal cell wall contain?

Answer 6

chitin and other polysaccharides

Question 7

What is the difference in animal and fungal cell walls?

Answer 7

Animals have cholesterol as their sterols and fungi have ergosterol
Fungi also have glucans

Question 8

What antifungals work on the membrane in general?

Answer 8

Polyenes (polyene macrolides) - bind and disrupt the membranes

Question 9

What antifungals affect the membrane sterols?

Answer 9

Azoles and allylamines - interfere with ergosterol synthesis

Question 10

What antifungals affect the glucans?

Answer 10

Echinocandins - inhibit gluten synthesis

Question 11

What are the polyenes?

Answer 11

Nystatin and Amphotericin B

Question 12

How do polyenes work?

Answer 12

Form pores
Preferentially bind sterols especially ergosterol.
This binding alters membrane osmotic regulation, leakage of intracellular potassium and other small molecules

Question 13

Are azoles fungistatitic or fungicidal?

Answer 13

Azoles are only fungistatic.

Question 14

What are the groups of Azoles?

Answer 14

Two distinct groups imidazoles and triazoles

Question 15

Are azoles fast acting?

Answer 15

Slow rate of action - requires several generations to act

Question 16

How do azoles work?

Answer 16

Inhibit 14-alpha-demethylase which;
o depletes ergosterol
o causes accumulation methyl-ergostadiene-diol
o methyl-ergostadiene-diol is toxic.

Question 17

What do azoles work on?

Answer 17

Works on
o Dimorphic fungi
o Dermatophytes

Some do NOT work on:
o Aspergillus sp. (Triazoles active / azoles not)

Question 18

How do allyamines work?

Answer 18

Inhibit squalene epoxidase
Effect:
» Reduces ergosterol production
» causes accumulation of squalene which is toxic

Question 19

What are allyamines affective against?

Answer 19

Have board spectrum activity

Particular effective against dermatophytes

Question 20

How do Echinocandins work?

Answer 20

Inhibits 1,3-beta gluten synthesis by non-competitive inhibition
Glucan depletion weakens the cell wall
Fungicidal and non-toxic

Question 21

What do Echinocandins affect?

Answer 21

hyphae at their growing tips
Hyphae at branching points
In Yeasts:Buds fail to seperate from the mother cell
Also lead to osmotically sensitive fungal cells

Question 22

Is there resistance to Echinocandins?

Answer 22

There is Intrinsic resistance in some fungal genera/species where other glucans predominate.

Cryptococcus sp. are intrinsically resistant as they have mainly 1,-3-alpha and 1,6-beta glucans

Question 23

What are the nucleic acid and anti-mitotic antifungals?

Answer 23

Flucytosine and Griseofulvin

Question 24

How does Flucytosine work?

Answer 24

It is degraded in. the fungal cell to
FdUMP - Inhibits DNA synthesis
FURTP - inhibits protein synthesis

Question 25

How does Griseofulvin work?

Answer 25

Binds to (microtubules) tubulin
Interferes with microtubule function
Inhibits mitosis.

Question 26

How must you administer Griseofulvin?

Answer 26

Oral dose only it is inactive if applied topically

Teratogenic effects so contraindicated in pregnant animals

Question 27

How do you treat equine dermatophytes?

Answer 27

Azole wash: Imaverol (an azole wash) external only.

Question 28

Give an example of good equine management to avoid fungi?

Answer 28

removal of damp hay to avoid Aspergillus problems

Question 29

What are four potential mechanisms for azoles resistance?

Answer 29

• Increased efflux - leading to decreased drug concentration at target due to increased efflux.
• Altered target – so drug binds less well. This would develop slower than for equivalent effect in bacteria where growth dynamics are different.
• Up-regulation of target - hence more drug is required to inhibit.
• Development of bypass pathways / altered balance of pathways

Question 30

What is a potential mechanism for polyene resistance?

Answer 30

Fungi alter their balance of sterol types so impact of drug is less