Exam 1 - Mycology P2

Question 1

Fungal Contamination

Answer 1

• most of the fungi that infect humans are considered opportunistic
◦ low/limited virulence, usually cause disease in debilitated or immunosuppressed patients
◦ typically found as saprobes in the environment

Question 2

Spectrum of Antifungal Agents

Answer 2

Range of activity of an Antifungal agent

Broad or narrow spectrum

Question 3

Fungistatic

Answer 3

Level of Antifungal activity that inhibits the growth of an organism

Question 4

Fungicidal

Answer 4

The ability of Antifungal agent to kill an organism in vitro or in vivo

Question 5

Polyenes

Primary mechanism, Toxicity, Spectrum, activity

Answer 5

• Primary mechanism - binding of antifungal to ergosterol, the principal membrane sterol of fungi
• Binding produces ion channels, which destroy the osmotic integrity of the fungal cell membrane and lead to leakage of intracellular constituents and cell death
• Toxicity - binds to cholesterol, the main membrane sterol of mammalian cells (less avidly than ergosterol) ** cross reaction **
◦ nephrotoxicity
• Broad spectrum
• Fungicidal

Question 6

Azoles

Primary mechanism, and activity

Answer 6

• Inhibit the fungal cytochrome P-450-dependent enzyme, lanosterol 14-α-demethylase
◦ Enzyme functions in the conversion of lanosterol to ergosterol
◦ inhibition disrupts cell membrane synthesis in the fungal cell
• Fungistatic (yeast)
• Fungicidal (mold)

Question 7

Echinocandins

Primary mechanism, Activity, Toxicity

Answer 7

• Inhibit the synthesis of 1,3-β-glucans (consituent of fungal cell wall)
• Fungicidal (Candida)
• Fungistatic (Aspergillus)
• Low Toxicity

Question 8

Flucytosine

* Primary Mechanism, Activity*

Answer 8

• Interferes with the synthesis of DNA, RNA and protiens in the the fungal cell wall
• enters the fungal cell wall via cytosine permease; converted by cytosine deaminase in fungal cells to fluorouracil (competes with uracil and results in RNA miscoding)
• Flurouracil is metabolized to 5 fluorodeoxyuridylic acid (inhibitor of thymidylate synthase; halts DNA synthesis)
• Fungistatic
• Limited spectrum of activity (candida, cryptococcus and selected dematiaceaous molds)
• Typically used in combination with another antifungal agent (due to resistace)

Question 9

Allyamines

* Primary mechanism, Activity*

Answer 9

• Ex Terbinafine
• Inhibit the enzyme squalene epoxidase which results in a decrease in ergosterol and an increase in squalene (toxic affect) within the fungal cell membrane
• Broad spectrum of activity (dermatophytes, yeast, mold)
• Fungicidal

Question 10

Topical vs Systemic therapy use depends on

Answer 10

◦ host status (age, immune status…)

◦ Type and extent of the infection (location)

Question 11

Antifungal resistance (mechanisms)

Answer 11

• resistance develops slowly and involves the emergence of intrinsically resistance species or gradual, stepwise alteration of cellular structures or functions
• Mechanisms
◦ Efflux pumps (reduces accumulation of drug)
◦ Target alterations (change enzyme/ point mutations)
◦ Overexpression of target ( 2x target –> not enough drug)

Question 12

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Answer 12

Blastomyces dermatitidis

Question 13

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Answer 13

Coccidioides immitis/posadasii

Question 14

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Answer 14

Histoplasma capsulatum

Question 15

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Answer 15

Talaromyces (penicillium) marneffei