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Block 6 Week 5 > Kozel: Intro to Medical Mycology > Flashcards

Kozel: Intro to Medical Mycology Flashcards

1
Q

About how many fungal species are there? What are they most commonly pathogenic for?

A

1.5 million fungal species; most pathogenic for plants, then insects, then humans (only 300 species - 50 common)

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2
Q

Why are mammals intrinsically resistant to fungal infections?

A

mammals have the ability to generate and regulate their body temperature, and every degree C above 30C excludes another 6% of fungal species

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3
Q

What is one major constituent of the plasma membrane of fungi?

A

ergosterol

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4
Q

What are the components of the fungal cell wall?

A

chitin
Beta-1,3-glucan
Beta-1,6-glucan
mannoproteins - mannan or galactomannan

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5
Q

a unicellular fungus that reproduces vegetatively by budding or fission

A

yeast

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6
Q

String of budding cells marked by constrictions rather than septa at the junctions

A

pseudohyphae

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7
Q

multicellular structures that elongate at tips by apical extension

A

hyphae

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8
Q

hollow, multinucleate hyphae that are produced by the mucorales

A

coenocytic hyphae

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9
Q

hyphae divided by partitions or cross-walls

A

septate hyphae

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10
Q

asexual reproductive elements (spores) produced by budding at the tip or side of a hypha

A

conidia

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11
Q

asexual reproductive elements produced by fragmentation of hyphae

A

arthroconidia

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12
Q

asexual spores produced within a sack-like structure (sporangium)

A

sporangiospores

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13
Q

Broad, thin-walled hyphae with multiple nuclei (coenocytic); septae are rare; sporangiospores

A

mucormycetes

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14
Q

Budding yeasts and hyphae, pseudohyphae

A

saccharomycetes

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15
Q

Budding yeasts, septate hyphae, asexual conidia on specialized structures, and arthroconicia

A

euascomycetes

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16
Q

What is the gold standard for diagnosis of fungal infections? How long does this take?

A

culture; takes days to weeks to get results

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17
Q

What can you use on scrapings to digest excess tissue and reveal yeast?

A

KOH

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18
Q

What is one benefit of using serology for fungal infection diagnosis? What is one drawback?

A

detects antibody to fungal antigen; may not reflect active infection (IgM vs IgG)

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19
Q

When is serology testing most useful?

A

for coccidiodomycosis and histoplasmosis

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20
Q

When is antigen detection very useful?

A

for cryptococcosis

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21
Q

What antigen tests would you use for Aspergillosis?

A 
Beta glucan (detects cell wall glucan in blood)
galactomannan
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22
Q

What is the structure of imidazoles? Triazoles?

A

2 nitrogens in a ring (ketoconazole, miconazole); 3 nitrogens in a ring (fluconazole, itraconazole, voriconazole)

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23
Q

What is the mechanism of the azoles?

A

inhibit lanosterol 14-alpha-demethylase and block ERGOSTEROL synthesis

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24
Q

What are 3 mechanisms of resistance that fungi have developed to azoles?

A
  1. target with decreased affinity for the drug **
  2. efflux pump
  3. overexpression of the target
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25
Q

What is ketoconazole used for?

A

limited use due to toxicity

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26
Q

What is fluconazole used for?

A

candidiasis, cryptococcosis

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27
Q

What is itraconazole used for?

A

broad spectrum antifungal

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28
Q

What is voriconazole used for?

A

broad spectrum, invasive aspergillosis

29
Q

Describe the oral bioavailability of azoles and the distribution to organs of tissues

A

EXCELLENT oral bioavailability

good distribution to organs and tissues

30
Q

What is one side effect of azoles?

A

interferes w cytoP450 action, so can create ADRs with other meds

31
Q

What are two allylamines?

A

terbinafine

naftifine

32
Q

What is the mechanism of action of the allylamines?

A

inhibit squalene epoxidase

33
Q

What are allylamines used for clinically?

A

topical treatment of dermatophyte infection

systemic treatment of dermatophyte infection

34
Q

Where are allylamines found in high concentration? What pregnancy category do they fall under?

A

fatty tissue, skin, hair, nails; Pregnancy category B

35
Q

What is the structure of flucytosine? What happens to it inside of yeast cells?

A

5-fluorouracil ring with an amine group; inside of yeast cells, it is deaminated to its active form

**prodrug

36
Q

What is the mechanism of action of flucytosine?

A

inhibits DNA/RNA synthesis by competing with uracil

37
Q

What are 2 methods of resistance to flucytosine?

A
  1. decreased uptake

2. failure to convert to active form

38
Q

When is flucytosine used clinically?

A

in combination with Amphotericin B to treat cryptococcal meningitis

39
Q

How is flucytosine taken? What is its distribution like in the body? What is unique about its excretion in the urine?

A

taken orally and rapidly absorbed; wide distribution in the body and penetrates the CNS; excreted UNCHANGED in urine

40
Q

What are two side effects of flucytosine?

A

depressed bone marrow

hepatotoxicity

41
Q

What is the structure of the echinocandins, like capsofungin?

A

cyclic polypeptide

42
Q

What is the mechanism of echinocandins like capsofungin?

A

inhibit glucan synthesis

43
Q

What is the method of resistance to echinocandins?

A

altered target with decreased sensitivity

**resistance is currently rare

44
Q

What are echinocandins used for?

A

used for fungi where 1,3 beta-glucans are the dominant cell wall glucan component – aspergillus and candida

**used for invasive candidiasis and invasive aspergillosis

45
Q

How are echinocandins administered? How is their CNS penetration?

A

IV; limited CNS penetration

46
Q

What is the pregnancy category of echinocandins?

A

C

47
Q

What is the structure of the polyenes?

A

lipid formulations of amphotericin B

nystatin

48
Q

What is the mechanism of action for the polyenes?

A

binds to ergosterol and causes direct membrane damage

49
Q

What are some methods of resistance to polyenes?

A

Very rare!!!

reduced ergosterol content
ergosterol with reduced binding
making of ergosterol to block binding

50
Q

How is amphotericin B administered? What happens to AmB once administered? What is this used for?

A

Given IV - not absorbed via GI; remains in plasma, largely bound to protein; BROAD SPECTRUM - used for all fungi

51
Q

What is one problem with amphotericin B?

A

considerable nephrotoxicity - azotemia (Nitrogen compounds) in 80% of patients

**lipid formulations are less toxic

52
Q

What are some endemic mycoses (found in nature - certain parts of the globe)?

A

blastomycosis
histoplasmosis
coccidioidomycosis
penicilliosis

53
Q

What are some opportunistic mycoses (not unique to one place)?

A 
aspergillosis
candidiasis
cryptococcosis
mucormycosis
pneumocystosis
54
Q

Where are superficial mycoses found?

A

limited to very superficial surfaces of skin and hair

**don’t cause much damage more like a cosmetic concern

55
Q

What do cutaneous mycoses infect? What is the pathology due to?

A

keratinized layers of skin, hair, and nails;

pathology due to host response

56
Q

What do subcutaneous mycoses infect?

A

deep layers of skin
cornea
muscle
connective tissue

57
Q

What causes these diseases?
Infection via traumatic inoculation
Abscess formation, nonhealing ulcers, draining sinus tracts
Localized; rarely disseminate

A

subcutaneous mycoses

58
Q

Where are endemic mycoses found?

A

worldwide, really

59
Q

List 5 dimorphic funguses

Dimorphic = two forms

A 
blastomyces dermatitidis
coccidioides immitis
histoplasma capsulatum
paracoccidioides brasiliensis
penicillum marneffei
60
Q

This is a DIMORPHIC fungus; in tissues, it is a broad-based yeast; in its saprobic phase - nondescript mycelium; found in decaying organic matter; Ohio and Mississippi River valleys

A

Blastomyces dermatitidis

61
Q

What does Blastomyces dermatitidis cause?

A

pulmonary disease

skin, GU, CNS probs

62
Q

This is a DIMORPHIC fungus; in tissue, it is an intracellular budding yeast; in its saprobic phase - tuberculate macroconidia; found in soil with high nitrogen content and in bird/bat droppings; Ohio and Mississippi River valleys, Mexico, Central and South America

A

Histoplasma capsulatum

63
Q

What does Histoplasma capsulatum cause?

A

acute pulmonary disease

chronic pulmonary disease

64
Q

This is a DIMPORHIC fungus; in tissue, endosporulating SPHERULE; saprobic phase - arthroconidia; found in soil and dust; found in Soutwestern US, Mexico, Central and South America

A

Coccidioides immitis/posadasii

65
Q

What does coccidioides immitis/posadasii cause?

A

primary pulmonary disease

progressive pulmonary disease

66
Q

This is a dimorphic fungus; in tissue - sausage shaped yeast; saprobic stage - pigmented mold; found in soil and bamboo rat; found in SE Asia

A

Penicillium marneffei

67
Q

What diseases are caused by Penicillium marneffei?

A

disseminated infection in AIDS patients

**resembles histoplasmosis, cryptococcosis, TB

68
Q

This is a dimorphic fungus; found in the tissue as a large, multiple budding yeast; in saprobic stage - nondescript mold; found in soil in S and Central America

A

Paracoccidioides brasiliensis

69
Q

What diseases are caused by Paracoccidioides brasiliensis?

A

asymptomatic mostly

can cause self-limiting pulmonary disease, progressive pulmonary disease, disseminated disease

Block 6 Week 5 (11 decks)

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