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Block G -- Infection > Dr. Sheppard -- Basic Mycology and Antifungal Medications > Flashcards

Dr. Sheppard -- Basic Mycology and Antifungal Medications Flashcards

1
Q

Definition of hyphae

A

Filamentous tubular structure with or without internal septae

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2
Q

Define mycelium

A

Group of hyphae, often used interchangeably with hyphae

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3
Q

Define yeast

A

Unicellular round fungal cells that reproduce by budding

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4
Q

Define conidia

A

Asexual spores of ascomycetes (most pathogenic fungi)

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5
Q

Define conidiophore

A

Specialized hyphae that produce conidia

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6
Q

Define pilobolus

A

Zygomycete that grows in cow dung

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7
Q

Describe how pilobolus fungi spread their spores (3 steps)

A

1) Spores pass thruogh cow dung
2) Aims by bending stalk until shadow from sporangium falls on sensor at bottom of sporangiophore
3) Hydrostatic “cannon” guided by light shoots spores into unsoiled grass

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8
Q

Why is antifungal treatment more complicated than antibacterial treatment?

A

Antimicrobial agents exploit differences between microorganisms and humans, but fungi are eukaryotic and closely related to humans, so ribosomes and DNA replication enzyems are too similar for targeting

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9
Q

Describe the cell membrane of fungi

A

Principally ergosterol instead of cholesterol

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10
Q

3 types of antifungals that target fungal cell membrane

A

Azoles
Allylamines
Polyenes

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11
Q

Antifungal that can be activated selectively by fungi to arrest DNA synthesis

A

5-flucytosine (cytosine deaminase)

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12
Q

Component of outer layer of fungal cell that is lacking on mammalian cells

A

Cell wall

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13
Q

Antifungal that inhibits glucan synthase (disrupt cell wall)

A

Echinocandins

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14
Q

Mechanism of azoles

A

Inhibition of 14 alpha demethylase (key enzyme to synthesize ergosterol) –> toxic intermediates accumulate in the cell membrane

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15
Q

Mechanism of allylamines

A

Inhibit squalene epoxidase early in the ergosterol pathway

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16
Q

Mechanism of polyenes

A

Binds to ergosterol in membranes, forming pores to allow cell contents to leak out

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17
Q

3 forms of polyenes

A

Nystatin
Amphotericin B desoxycholate
Lipid-based formulations of Amphotericin

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18
Q

Highly toxic polyene and the only form it can be used in

A

Nystatin (topical only)

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19
Q

3 side effects of amphotericin B desoxycholate

A

Bind cholesterol
Renal failure
Severe infusional toxicity

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20
Q

How are lipid-based formulations of amphotericin less toxic than amphotericin B desoxycholate and nystatin?

A

Use of a lipid carrier intermediate in solubility between ergosterol and cholesterol

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21
Q

Disadvantage of lipi-based formulation of Amphotericin

A

VERY expensive

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22
Q

Azole with yeast only activity

A

Fluconazole

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23
Q

Oldest azole with yeast and mold activity

A

Itraconazole

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24
Q

2 disadvantages of itraconazole

A

Poor absorption

Erratic kinetics

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25
Q

Newest azoles (2)

A

Voriconazole

Posaconazole

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26
Q

Advantage of using voriconazole or posaconazole

A

Excellent anti-mold activity, particularly Aspergillus species

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27
Q

2 toxic effects of azoles (specify which azoles)

A 
Hepatitis (all agents) -- VORI > ITRA > POSA > FLU
Visual hallucinations (VORI)
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28
Q

Allylamine antifungal

A

Terbinafine (lamisil)

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29
Q

Primary use of terbinafine (lamisil)

A

Superficial fungal infections (commonly topical, but oral available for extensive infections or nail infections)

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30
Q

Side effect of allylamines

A

Hepatitis

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31
Q

What is 5-flucytosine (5-FC)

A

A prodrug converted by fungal cytosine deaminase into 5-fluorouracil (a type of chemotherapeutic)

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32
Q

Mechanism of 5-FC

A

Inhibition of DNA chain synthesis

NOTE: only useful in combination therapy

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33
Q

Toxicity of 5-FC

A

Bone marrow suppression

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34
Q

3 echinocandins

A

Caspofungin
Micafungin
Anidulafungin

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35
Q

Mechanism of echinocandins

A

Inhibition of synthesis of cell wall beta-glucan –> cell wall fragmentation

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36
Q

3 fungi that echinocandins are inactive against

A

Fungi with low levels of beta-glucan:

  • Cryptococcus
  • Histoplasma
  • Zygomycetes
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37
Q

Only method of administration of echinocandins

A

IV

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38
Q

Toxicity of echinocandins

A

None

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39
Q

Contents of Piptoporus betulinus

A

Powerful purgatives:
- Toxic resins
- Active compound = agaric acid
Oils toxic to metazoans

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40
Q

Effects of Piptoporus betunlinus

A

Strong, though short-lived bouts of diarrhea

Antibiotic action against mycobacteria

41
Q

5 effects of fungi

A

1) Hypersensitivity
2) Infection
3) Mycotoxocosis
4) Mycetismus
5) Sick building/toxic mold

42
Q

Define mycotoxicosis

A

Production of toxin in vivo

43
Q

Define mycetismus

A

Mushroom poisoning (pre-formed toxin)

44
Q

Type of hypersensitivity reaction precipitated by fungi

A

IgE-mediated (type I)

45
Q

4 symptoms of hypersensitivity due to fungi

A

Asthma
Rhinitis
Pneumonitis
Sinusitis

46
Q

Common example of fungal hypersensitivity

A

Aspergillus allergic disease (Farmer’s lung)

47
Q

Cause and effect of aspergillus allergic disease

A

Decomposing hay with very high content of thermophilic bacteria and fungi –> massive antigen inhalation –> acute hypersensitivity pneumonia

48
Q

Uncomplicated asthma from hypersensitivity cause

A

Sensitization to condial antigens of Asperigillus

49
Q

Pathogenesis of Allergic Bronchopulmonary Aspergillosis

A

1) Pre-existing airway disease such as CF
2) Colonization with A. fumigatus
3) High titers of IgE antibody to hyphal antigens
4) Severe reactive airway disease
5) Progressive and destructive airway disease

50
Q

2 classes of fungal disease

A

Superficial

Invasive

51
Q

2 fungal forms involved in superficial fungal disease

A

Yeast

Mold

52
Q

3 forms of fungi involced in invasive fungal disease

A

Yeast
Dimorphic
Mold

53
Q

Describe clinical picture of invasive yeast infection

A

Systemic

Pulmonary disease absent or subclinical

54
Q

Describe the clinical picture of invasive dimorphic fungi disease

A

Primary pulmonary disease with prominent dissemination

55
Q

Describe the clinical picture of invasive mold infection

A

Primary pulmonary disease with dissemination less common

56
Q

2 pathogenic yeasts

A

Candida species

Cryptococcus neoformans

57
Q

3 methods of growth for Candida albicans

A

Yeast
Hyphae
Pseudohyphae

58
Q

What is required for virulence in Candida albicans

A 
Morphological switching (usually a normal commensal of humans)
NOTE: evidence for mating during infection has been found
59
Q

4 forms of superficial candidiasis

A

OPC (thrush)
Esophageal candidiasis
Vaginitis
Skin and nail infections

60
Q

Define OPC

A

Suerficial infection of oral mucosa, usually associated with impaired cellular immunity

61
Q

Define esophageal candidiasis

A

Severe version of OPC that is a common complication of HIV/AIDS

62
Q

Define vaginitis due to candida

A

Superficial infection of the vaginal mucosa that is a common consequence of antibiotic therapy

63
Q

Define superficial candidiasis causing skin and nail infections

A

Superficial infection of keratinized squamous epithelium

64
Q

Define invasive candidiasis

A

Bloodstream infection (sepsis) with Candidia species

65
Q

Pathogenesis of invasive candidiasis (7 steps)

A

1) Colonization and/or overgrowth
2) Breach of integument (GI or catheter)
3) Coincident germination
4) Evasion of soluble factors and PMNs
5) Endothelial cell adherence and invasion
6) Entrance to bloodstream
7) Tissue invasion and evasion of host responses

66
Q

2 major populations at risk for invasive candidiasis

A

ICU and surgical patients

Hematology-oncology patients

67
Q

3 methods of breaching mucosal surfaces

A

Intestinal surgery
Chemotherapy (mucositis)
IV catheters

68
Q

3rd most frequent nosocomial bloodstream isolate

69
Q

Mortality of invasive candidiasis

70
Q

Where can C. krusei’s incidence reach 10 - 15% of disseminated candidiasis?

A

Centers where fluconazole prophylaxis is used

71
Q

Intrinsic resistance profile of C. albicans

A

Fluconazole S

Echinocandin S

72
Q

Intrinsic resistance profile of C. glabrata

A

Fluconazole R

Echinocandin S

73
Q

Intrinsic resistance profile of C. parapsilosis

A

Fluconazole S

Echinocandin S/I

74
Q

Intrinsic resistance profile of C. tropicalis

A

Fluconazole S

Echinocandin S

75
Q

Intrinsic resistance profile of C. krusei

A

Fluconazole R

Echinocandin S

76
Q

Traditional diagnosis of Candidemia

A

Blood culture

77
Q

What is β-D-glucan

A

Cell wall constituent of Candida and most fungi

78
Q

Define speciation

A

Growth of colony on solid agar (24 - 48h)

79
Q

2 situations where susceptibility testing is recommended

A

1) All isolates from sterile sites

2) Poor response to therapy

80
Q

Drug of choice for initial therapy of candidemia

A

Echinocandin

81
Q

Drug of choice for candidemia when sensitivity is known and patient is stable

A

Oral azole

82
Q

2 non-pharmacological points of management for candidemia

A

1) Source control critical (remove catheter, drain abscess)

2) Assess for secondary sites of infection (i.e. endophthalmitis and endocarditis)

83
Q

What is cryptococcus neoformans

A

Encapsulated yeast

84
Q

2 common species of cryptococcus neoformans

A

Neoformans

Gatti

85
Q

2 environments that harbor cryptococcus neoformans

A

Soil (esp. bird droppings)

Eucalyptus trees

86
Q

Method of infection of cryptococcus neoformans

A

Inhalation of yeast cells or basidiospores

87
Q

Clinical manifestation of cryptococcus neoformans infection (2)

A

1) Initial = asymptomatic pulmonary infection with dissemination
2) Chronic meningitis (80 - 90% associated with HIV)

88
Q

3 virulence factors of cryptococcus neoformans

A

Capsule
Thermotolerance
Melanin

89
Q

Thermotolerance effect as virulence factor

A

Permits growth in CSF

90
Q

Melanin effect as virulence factor

A

Anti-oxidant

Resists phagocyte killing

91
Q

3 diagnostic tools for cryptococcus neoformans infection

A

Microscopy
Culture
Antigen testing

92
Q

How to stain cryptococcus neoformans

A

Negative staining with India ink as capsule excludes the dye

93
Q

How is cryptococcus neoformans antigen detectible

A
  • Cryptococcal antigen from capsule shed during growth

- Detectible in serum and CSF by latex agglutination

94
Q

Induction antifungal for cryptococcus neoformans treatment

A

Amphotericin B

95
Q

Second antibiotic for cryptococcus neoformans treatment

A

Fluconazole

NOTE: lifelong suppressive therapy required

96
Q

Antifungal that does not work in crpytococcus neoformans infection

A

Echinocandins (not beta-glucan in cell wall)

97
Q

Critical symptom to manage in cryptococcus neoformans infection

A

Increased intracranial pressure

98
Q

2 main manifestations for cryptococcus gatti

A

Pneumonia and meningitis in immunocompetent

Block G -- Infection (23 decks)

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