5.46 Part B Flashcards

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1
Q

Antifungal Drugs
• fewer effective agents because of similarity
of
• easier to treat — mycoses than — infections

A

fungal cells and human cells

superficial, systemic

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2
Q

ergosterol

A

Sterol found in fungal cell membranes;
human cells have cholesterol instead of
ergostero

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3
Q

Antifungal treatments

Polyene compounds -

A

bind ergosterol in fungal membranes

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4
Q

Polyene compounds

examples (2)

A

Amphotericin B systemic disease

Nystatin topical disease

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5
Q
Polyene compounds - 
Drugs cause (3)
A

altered membrane
permeability,
leakage of cell constituents, and cell death

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6
Q

Polyenes also bind — in mammalian

cells, but less strongly than ergosterol

A

cholesterol

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7
Q

Polyenes also bind cholesterol in mammalian
cells, but less strongly than ergosterol
• this is basis for —
• — is toxic due to binding of cholesterol

A

drug toxicity

filipin

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8
Q

terbinafine (TFB) to

A

itraconazole (ITZ)

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9
Q

Allylamines-

A

block ergosterol synthesis by inhibiting

squalene epoxidase activity

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10
Q

Allylamines ex

A

terbinafine

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11
Q

Allylamines
mainly effective on the —
(2) formulations

A

dermatophytes

topical or tablet

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12
Q

Azoles

A

block ergosterol synthesis by inhibiting cytochrome

P450-dependent 14a-lanosterol demethylation

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13
Q

Azoles
First oral azole (significant number of
(2)).

A

side effect and drugs interactions

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14
Q

Supplants ketoconazole

A

Active against many fungi and has improved
safety profile. Active against Candida species,
Cryptococcus, Aspergillus, endemic (systemic)
fungi, and dermatophytes.

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15
Q

Echinocandins

A

inhibit synthesis of b-(1,3)-D-glucan, an
essential component of fungal cell walls.
More selective than agents that target cell
membrane components.

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16
Q

Echinocandins

Narrow spectrum:

A

active against Aspergillus and Candida species;

these fungi have larger amounts of b-(1,3)-D-glucan

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17
Q

Caspofungin (2)

A
  • Intravenous use

- minimal toxicity

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18
Q

Pyrimidine inhibition -

A

interferes with fungal protein and

DNA synthesis

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19
Q
Pyrimidine inhibition
Active against (2)
A

Candida species and Cryptococcus neoformans

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20
Q

Pyrimidine inhibition

Always used in combination with another antifungal because

A

resistance

develops quickly if used alone

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21
Q

High risk categories (5)

A
Immunocompromised individuals:
Burn victims
Long-term IV catheter users
Broad-spectrum antibiotic therapy
Diabetes mellitus
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22
Q

Immunocompromised individuals:

9

A
blood and marrow transplant
solid organ transplant
major surgery
AIDS
neutropenia
neoplastic disease (cancer patients)
immunosuppressive therapy (e.g. corticosteroids)
advanced age
premature birth
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23
Q

Candida albicans

A

predominant species colonizing humans

responsible for most infections

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24
Q

Candida glabrata

A

resistant to some antifungals

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25
Q

Candida parapsilosis

A

common cause of catheter-related infections

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26
Q

Candidiasis

local disease vs. systemic invasive disease

A

Adequate neutrophil function protects against invasive infection.
Local factors and T-cell mediated defense system protects against
mucosal candidiasis

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27
Q

Mucosal candidiasis on palate
of a patient with AIDS
Due to

A

decreased T-cell
mediated immunity (however,
no invasion of tissue here)

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28
Q

Other host factors associated with
protection against Candida infections:
(4)

A

salivary flow and constituents
blood group & secretor status
epithelial barrier
presence of normal bacterial flora

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29
Q

candida infection: acute pseudomembranous
acute erythematous
clinical presentation:

A

multiple removable white plaques

generalized redness of tissue (ab sore mouth, painful)

30
Q

candida infection: chronic plaquelike/nodular

clinical presentation:

A

fixed white plaques on commissures

31
Q

candida infection: chronic erthematous

clinical presentation:

A

generalized redness of tissue on fitting surface of upper denture

32
Q

candida infection: candidia associated angular chelities

clinical presentation:

A

bilateral cracks, angles of mouth

33
Q

Thrush

A

Pseudomembranous
candidiasis lesions on
palate

34
Q

Angular chelitis at
commissures of the mouth,
involving skin
Frequently there is a — component

A

bacterial

35
Q

Plaquelike/nodular candidiasis

• Also called (2)

A

chronic hyperplastic

candidiasis or candidal leukoplakia

36
Q

Plaquelike/nodular candidiasis
• Up to –% of lesions develop into oral
cancer

A

40

37
Q

Candidiasis- diagnosis

Mucosal candidiasis

A

scrape and look under the microscope

culture

38
Q

Candidiasis- diagnosis
Invasive candidiasis
(4)

A

blood culture not sensitive
biopsy of involved tissue
microscopy
culture

39
Q

Staining methods to visualize fungi in clinical
samples:
(5)

A
periodic acid-Schiff (PAS) 
potassium hydroxide (KOH)
Grocott-Gomori methenamine silver
Gridleys method
Calcofluor white
40
Q

periodic acid-Schiff (PAS)

A

-surface carbohydrate

41
Q

potassium hydroxide (KOH)

A

-tissue dissolves, fungi do not (chitin)

42
Q

Grocott-Gomori methenamine silver

A

-surface carbohydrate

43
Q

Gridleys method

A

-modification of PAS

44
Q

Calcofluor white

A

-fluorescent probe for chitin

45
Q

why is candida auris a problem? (5)

A
it causes serious infections
its often resistant to medicines
its becoming more common
its difficult to identity
it can spread in hospital and nursing homes
46
Q

C. neoformans is found worldwide in

A

soil contaminated with bird excreta

47
Q

–% of patients with cryptococcosis appear to be immunocompetent.

A

20

48
Q

Cryptococcus neoformans

Yeast cells are inhaled in alveoli and begin to produce a polysaccharide capsule. (3)

A

capsule inhibits phagocytosis and intracellular killing (if cells phagocytosed)
T-cell immunity crucial to infection control
melanin production in cell wall enhances virulence

49
Q

Cryptococcus neoformans
melanin production in cell wall enhances virulence
resists

A

free radicals and enzyme degradation

50
Q

Cryptococcus neoformans

Primary pulmonary infection is usually —

A

asymptomatic

51
Q

C. neoformans has a striking

A

neurotropism (basis is unknown)

minimal inflammatory response with CNS infection

52
Q

Cryptococcus neoformans

Patients often present with —, which worsens

A

meningitis

53
Q

Cryptococcus neoformans

Diagnosis (2)

A

cryptococcal meningitis - examine CSF for encapsulated budding yeast
latex agglutination test for capsular polysaccharide antigen (CSF fluid and serum)

54
Q

Cryptococcus neoformans

tx

A

cryptococcal meningitis
sometimes lifelong therapy required
(patients with T cell defects)

55
Q

Aspergillosis (2)

A

Aspergillus fumigatus and Aspergillus flavus

56
Q

Aspergillosis

acquired from the environment by

A

inhalation of conidia

57
Q

Aspergillosis

grow as — in immunosuppressed individuals

A

hyphae

usually a pulmonary or sinus infection

58
Q

angioinvasive -
growth through
cause (3)

A

blood vessel walls

tissue infarction, hemorrhage, necrosis

59
Q

Aspergillosis

Diagnosis

A

culture on Sabourauds agar (grows in a few days)

caution: contamination from environment can easily occur

60
Q

Aspergillosis

tx

A

high mortality
expanded-spectrum azole voraconazole
decreased exposure (filtered air)

61
Q

Zygomycosis

(2) are main genera in this group

A

Rhizopus and Mucor

62
Q

Zygomycosis (3)

A

aseptate, broad hyphae
angioinvasive
in addition to standard risk groups, patients with diabetes mellitus with ketoacidosis

63
Q

in addition to standard risk groups, patients with diabetes mellitus with ketoacidosis

A
  • acidosis reduces neutrophil chemotaxis and phagocytosis
64
Q

Rhinocerebral zygomycosis-

A

spread from nares/sinuses to palate, orbit, face then to brain

65
Q

Zygomycosis

tx

A

amphotericin B and

aggressive surgical debridement

66
Q

Pneumocystis jiroveci -

A

organism has never been grown in vitro

67
Q

Pneumocystosis

most people likely are infected early in life, but disease only occurs due to

A

immunosuppression (T cell deficiency most common risk factor)

68
Q

Pneumocystic pneumonia

A

most common opportunistic infection in AIDS patients

before effective antiviral therapy

69
Q

Pneumocystosis

Organism rarely found outside —

A

lungs

70
Q

Pneumocystosis

tx

A
  • trimethoprim-sulfamethoxazole (also used prophylactically)
    target folic acid synthesis and utilization
    note: P. jiroveci lacks ergosterol