Dr. Sheppard -- Basic Mycology and Antifungal Medications Flashcards Preview

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

Flashcards in Dr. Sheppard -- Basic Mycology and Antifungal Medications Deck (98)
1

Definition of hyphae

Filamentous tubular structure with or without internal septae

2

Define mycelium

Group of hyphae, often used interchangeably with hyphae

3

Define yeast

Unicellular round fungal cells that reproduce by budding

4

Define conidia

Asexual spores of ascomycetes (most pathogenic fungi)

5

Define conidiophore

Specialized hyphae that produce conidia

6

Define pilobolus

Zygomycete that grows in cow dung

7

Describe how pilobolus fungi spread their spores (3 steps)

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

8

Why is antifungal treatment more complicated than antibacterial treatment?

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

9

Describe the cell membrane of fungi

Principally ergosterol instead of cholesterol

10

3 types of antifungals that target fungal cell membrane

Azoles
Allylamines
Polyenes

11

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

5-flucytosine (cytosine deaminase)

12

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

Cell wall

13

Antifungal that inhibits glucan synthase (disrupt cell wall)

Echinocandins

14

Mechanism of azoles

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

15

Mechanism of allylamines

Inhibit squalene epoxidase early in the ergosterol pathway

16

Mechanism of polyenes

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

17

3 forms of polyenes

Nystatin
Amphotericin B desoxycholate
Lipid-based formulations of Amphotericin

18

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

Nystatin (topical only)

19

3 side effects of amphotericin B desoxycholate

Bind cholesterol
Renal failure
Severe infusional toxicity

20

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

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

21

Disadvantage of lipi-based formulation of Amphotericin

VERY expensive

22

Azole with yeast only activity

Fluconazole

23

Oldest azole with yeast and mold activity

Itraconazole

24

2 disadvantages of itraconazole

Poor absorption
Erratic kinetics

25

Newest azoles (2)

Voriconazole
Posaconazole

26

Advantage of using voriconazole or posaconazole

Excellent anti-mold activity, particularly Aspergillus species

27

2 toxic effects of azoles (specify which azoles)

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

28

Allylamine antifungal

Terbinafine (lamisil)

29

Primary use of terbinafine (lamisil)

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

30

Side effect of allylamines

Hepatitis

31

What is 5-flucytosine (5-FC)

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

32

Mechanism of 5-FC

Inhibition of DNA chain synthesis
NOTE: only useful in combination therapy

33

Toxicity of 5-FC

Bone marrow suppression

34

3 echinocandins

Caspofungin
Micafungin
Anidulafungin

35

Mechanism of echinocandins

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

36

3 fungi that echinocandins are inactive against

Fungi with low levels of beta-glucan:

- Cryptococcus
- Histoplasma
- Zygomycetes

37

Only method of administration of echinocandins

IV

38

Toxicity of echinocandins

None

39

Contents of Piptoporus betulinus

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

40

Effects of Piptoporus betunlinus

Strong, though short-lived bouts of diarrhea
Antibiotic action against mycobacteria

41

5 effects of fungi

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

42

Define mycotoxicosis

Production of toxin in vivo

43

Define mycetismus

Mushroom poisoning (pre-formed toxin)

44

Type of hypersensitivity reaction precipitated by fungi

IgE-mediated (type I)

45

4 symptoms of hypersensitivity due to fungi

Asthma
Rhinitis
Pneumonitis
Sinusitis

46

Common example of fungal hypersensitivity

Aspergillus allergic disease (Farmer's lung)

47

Cause and effect of aspergillus allergic disease

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

48

Uncomplicated asthma from hypersensitivity cause

Sensitization to condial antigens of Asperigillus

49

Pathogenesis of Allergic Bronchopulmonary Aspergillosis

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

2 classes of fungal disease

Superficial
Invasive

51

2 fungal forms involved in superficial fungal disease

Yeast
Mold

52

3 forms of fungi involced in invasive fungal disease

Yeast
Dimorphic
Mold

53

Describe clinical picture of invasive yeast infection

Systemic
Pulmonary disease absent or subclinical

54

Describe the clinical picture of invasive dimorphic fungi disease

Primary pulmonary disease with prominent dissemination

55

Describe the clinical picture of invasive mold infection

Primary pulmonary disease with dissemination less common

56

2 pathogenic yeasts

Candida species
Cryptococcus neoformans

57

3 methods of growth for Candida albicans

Yeast
Hyphae
Pseudohyphae

58

What is required for virulence in Candida albicans

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

59

4 forms of superficial candidiasis

OPC (thrush)
Esophageal candidiasis
Vaginitis
Skin and nail infections

60

Define OPC

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

61

Define esophageal candidiasis

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

62

Define vaginitis due to candida

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

63

Define superficial candidiasis causing skin and nail infections

Superficial infection of keratinized squamous epithelium

64

Define invasive candidiasis

Bloodstream infection (sepsis) with Candidia species

65

Pathogenesis of invasive candidiasis (7 steps)

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

2 major populations at risk for invasive candidiasis

ICU and surgical patients
Hematology-oncology patients

67

3 methods of breaching mucosal surfaces

Intestinal surgery
Chemotherapy (mucositis)
IV catheters

68

3rd most frequent nosocomial bloodstream isolate

Candida

69

Mortality of invasive candidiasis

40 - 50%

70

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

Centers where fluconazole prophylaxis is used

71

Intrinsic resistance profile of C. albicans

Fluconazole S
Echinocandin S

72

Intrinsic resistance profile of C. glabrata

Fluconazole R
Echinocandin S

73

Intrinsic resistance profile of C. parapsilosis

Fluconazole S
Echinocandin S/I

74

Intrinsic resistance profile of C. tropicalis

Fluconazole S
Echinocandin S

75

Intrinsic resistance profile of C. krusei

Fluconazole R
Echinocandin S

76

Traditional diagnosis of Candidemia

Blood culture

77

What is β-D-glucan

Cell wall constituent of Candida and most fungi

78

Define speciation

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

79

2 situations where susceptibility testing is recommended

1) All isolates from sterile sites
2) Poor response to therapy

80

Drug of choice for initial therapy of candidemia

Echinocandin

81

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

Oral azole

82

2 non-pharmacological points of management for candidemia

1) Source control critical (remove catheter, drain abscess)
2) Assess for secondary sites of infection (i.e. endophthalmitis and endocarditis)

83

What is cryptococcus neoformans

Encapsulated yeast

84

2 common species of cryptococcus neoformans

Neoformans
Gatti

85

2 environments that harbor cryptococcus neoformans

Soil (esp. bird droppings)
Eucalyptus trees

86

Method of infection of cryptococcus neoformans

Inhalation of yeast cells or basidiospores

87

Clinical manifestation of cryptococcus neoformans infection (2)

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

88

3 virulence factors of cryptococcus neoformans

Capsule
Thermotolerance
Melanin

89

Thermotolerance effect as virulence factor

Permits growth in CSF

90

Melanin effect as virulence factor

Anti-oxidant
Resists phagocyte killing

91

3 diagnostic tools for cryptococcus neoformans infection

Microscopy
Culture
Antigen testing

92

How to stain cryptococcus neoformans

Negative staining with India ink as capsule excludes the dye

93

How is cryptococcus neoformans antigen detectible

- Cryptococcal antigen from capsule shed during growth
- Detectible in serum and CSF by latex agglutination

94

Induction antifungal for cryptococcus neoformans treatment

Amphotericin B

95

Second antibiotic for cryptococcus neoformans treatment

Fluconazole
NOTE: lifelong suppressive therapy required

96

Antifungal that does not work in crpytococcus neoformans infection

Echinocandins (not beta-glucan in cell wall)

97

Critical symptom to manage in cryptococcus neoformans infection

Increased intracranial pressure

98

2 main manifestations for cryptococcus gatti

Pneumonia and meningitis in immunocompetent