Introduction to fungal pathogens II

Question 1

conidia

Answer 1

asexual spores

a. macroconidium – large and multinucleated
b. microconidium – small and unicellular (birds on a wire)

Question 2

sporangia

Answer 2

spores are enclosed in a membranous sac

Question 3

Chlamydospores:

Answer 3

thick walled, round spores highly resistant to adverse environmental coditions

Question 4

arthrospores

Answer 4

Develop along hyphae, more numerous and elongated than chlamydospores, “barrel-like”

Question 5

spherules

Answer 5

arge, asexual spores that develop during the yeast phase of some organisms growth

Question 6

Blastoconidia

Answer 6

Yeast that bud asymmetrically

Question 7

empirical fungal dx

Answer 7

xii. Some fungal infections auto-fluoresce under black light (365 nm Wood’s lamp). This was a common method for detecting fungal infections in the early part of the 20th century.
xiii. “Athlete’s foot” or tinea pedis commonly diagnosed without any testing simply because it is so prevalent in the United States

Question 8

direct examination (microscope) fungal dx

Answer 8

Take a scraping of the epithelium from the affected area and add a drop of KOH or surfactant DMSO to denature the human material leaving the chitinous walls of fungi more visible

Question 9

culture fungal dx

Answer 9

The chief advantage of culture is that it allows for speciation of the infecting organism. However, in many clinical situations it is much less sensitive than microscopic examination or histologic examination.

Question 10

histology fungal dx

Answer 10

• sensitive and specific, rapid (2-3 days), but higher cost and more invasive
• stains make it easier

Question 11

other methods for fungal dx

Answer 11

i. Serological: Blood tests are useful in some fungal infections. Patients with disseminated cryptococcosis have a positive serological test for cryptococcal antigen in 75% of cases.
ii. PCR: not yet reached wide commercial availability. Useful for speciation of some types of fungal infections

Question 12

Polyenes:

Answer 12

MOA – Bind ergosterol in fungal cell membrane, lesser extent animal sterols –Polyenes punch holes in fungal membranes – Fungicidal
Example: Amphotericin B – creates pore in fungal membrane –ions leak out
1. “shake and bake treatment” b/c of fever, seizures induced

Question 13

Imidazoles/Triazoles:

Answer 13

MOA – inhibit 14α-demethylase the enzyme that converts lanosterol to ergosterol – fungistatic
—block steroid synth in humans, but to lesser extent
—triazoles are for the most part better tolerated than imidazoles
—most common over the counter anti-fungal drugs are imidazoles
Ex. Ketoconazole (oral Imid) and Fluconazole (oral Tri)

Question 14

Allylamines/Benzylamines:

Answer 14

MOA – inhibit the enzyme squalene epoxidase, an enzyme required for ergosterol synthesis – leads to build up of squalene within fungal cell that is directly toxic to the cell – FUNGICIDAL

ex. terbinafine- allylamine reported to unmask lupus like conditions
ex. butenafine - benzylamine

Question 15

Echinocandins:

Answer 15

MOA – inhibit the synthesis of glucan in the cell walls of fungi most likely via inhibition of 1,3 – β glucan synthase

• –fungicidal against Candida, fungistatic against Aspergillus
• –favorable kinetics that allow once daily dosing
  ex. capsofungin is the flagship drug

Question 16

Unique:

Answer 16

• –Griseofulvin: Think grease – inhibits cell mitosis by disrupting mitotic spindle formation. Used in children with tinea capitis due to long safety record – FUNGISTATIC
  
  1. should be taken with fatty foods like French fries
• –Flucytosine: interrupts DNA synthesis after being transported into a fungal cell by cytosine permease. FUNGISTATIC.
• –Ciclopirox olamine: does not effect ergosterol metabolism – instead acts by chelating polyvalent metal cations such as Fe3+ thereby inhibiting several fungal enzymes
  xiii. FUNGICDAL and/or FUNGISTATIC