Emerging pathogens & antifungal agents

Question 1

Name 3 organisms described as Emerging pathogens.

Answer 1

• Candida auris
• Fusarium sp
• Scedosporium sp: S. apiospermum

Question 2

What are dematiaceous hyphomycetes? Name 2 examples.

Answer 2

• soil (&plant) organisms, can be pathogen of plants
• besides soil & plants, can be isolated in shower curtains & toilet bowls
  e.g. Cladosporium & Bipolaris

Question 3

What targets of fungal cells have been exploited in the development of anti-fungal drugs? (4) *

Answer 3

• Ergosterol >maintain cell memb. integrity
• Enz makes Ergosterol
• interferes w/ DNA (&protein) synthesis
• Enz makes beta glucan (for cell wall)

Question 4

Name the currently available classes of antifungal agents. (PA FAME)

Answer 4

Polyenes
Azoles
Fluoropyramidines
Allylamines (topica/oral)
Morpholines (topical)
Echinocandins

Question 5

What standardised methods of antifungal susceptibility testing are available?

Answer 5

• broth dilution assay (tube MIC)
• microtitre assay
• Disc diffusion test
• E test
• colorimetric & automated approaches

Question 6

Describe a non-culture-based technique for the identification of fungi

Answer 6

• Molecular detection from fungal DNA sequences
• Rapid Ag test e.g. cryptococcus
• Serological test for Aby &/or Ag

Question 7

Name and describe 2 serological tests for the detection of fungal antigens which are used in the diagnosis of systemic fungal infections

Answer 7

• Galactomannan Ag detection kits = dx Aspergilosis
• (1,3)-beta-D-glucan assay = detect Aspergillus & Candida
  (*Rapid test w/ high sensitivity & specificity)

Question 8

Why is Candida auris a public health concern? (5)

Answer 8

• multi-drug resistant to drugs (3 major antifungals)
• survives cold innate surfaces
• cause serious infection
• spread in hospitals & nursing homes
• difficult to ID

Question 9

Why is Scedosporium sp a public health concern? (2)

Answer 9

• Resistant to antifungals
• mycetoma (sub- & cutaneous - bone) and systemic (brain)

Question 10

Why is Fusarium sp a public health concern? (3)

Answer 10

• infect humans & animals
• infect burned/necrotic skin, ulcers, onycomyosis (nail, skin)
• inc incidence pneumonia & fungemia

Question 11

Describe the site and mechanism of action of polyenes and give examples (at least 1)

Answer 11

Binds to ergosterol => inc memb. permeability = loss of ions & metabolites => cell death
E.g. Amphoterricin B & Nystatin

Question 12

Describe the site and mechanism of action of azoles and give examples (at least 1)

Answer 12

inhibits ergosterol synthesis (by inhibiting C 14-alpha demethylase) = Reduce ergosterol in membrane = lose cell content & interfere w/ function
E.g. Fluconazole & Itraconazole

Question 13

Describe the site and mechanism of action of echinocandins and give examples (at least 1)

Answer 13

Inhibit beta d-glucan synthesis in cell wall
e.g. Caspofungin, micafungin (…fungin)

Question 14

Describe the site and mechanism of action of Fluoropyrimidines and give examples (at least 1)

Answer 14

interferes w/ DNA synthesis => improper transcription of RNA
(& inhibits protein synthesis)
e.g. 5 flucytosine

Question 15

Limitations of current antifungal therapy (5-7)

Answer 15

• many fungistatic
• significant toxicity
• Resistance emerging/present in some sp
• interact w/ other medications
• cost
• few available both IV & orally
• Variable antifungal spectrum

Question 16

Describe the site and mechanism of action of Morpholines and give examples (at least 1)

Answer 16

inhibit ergosterol synthesis reductase & isomerase => plasma membrane damage
E.g. Loceryl nail paint (for dermatophyte)

Question 17

Describe the site and mechanism of action of Allylamines (& thiocarbmates) and give examples (at least 1)

Answer 17

inhibit squalene epoxidase (> squalene to lanosterol) => dec ergosterol = membrane disrupted

Question 18

When interpreting an MIC what does it mean when a yeast isolate is Intermediate or dose dependent (aside from S or R)

Answer 18

Intermediate: drug may be appropriate depending on certain conditions

Question 19

Briefly explain the 3 virulence factors of Cryptococcus sp

Answer 19

1. Polysaccharide capsule = antiphagocytic, dec complement, prevent dehydration
2. Melanin production: protects from cell damage (by oxidative stress, antifungal, T-cell resp. & Aby-mediated phagocytosis)
3. Grow at 37ºC