Fungi part B Flashcards

1
Q

why less antifungal drugs

A

fungi very similar to human cells

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2
Q

what mycoses are easier to treat?

A

• easier to treat superficial mycoses than systemic infections

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3
Q

ergosterol

A

Sterol found in fungal cell membranes;

human cells have cholesterol instead of ergosterol

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4
Q

where is egrosterol concentrated?

A

at the growing membrane ends

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5
Q

Polyene compounds
action
names and when used?

A

bind ergosterol in fungal membranes, Drugs cause altered membrane permeability,
leakage of cell constituents, and cell death

Amphotericin B: systemic disease
Nystatin: topical disease

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6
Q

polypenes also bind?

A

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

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7
Q

Abbreviated summary of the ergosterol biosynthetic pathway and the sites of action of ITZ
and TBF.

A
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8
Q
Allylamines
action?
name? 
mainyl effective on? 
formulations?
A

block ergosterol synthesis by inhibiting squalene epoxidase activity

terbinafine

mainly effective on the dermatophytes

topical or tablet formulations

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9
Q

Azoles
action?
names?

A

block ergosterol synthesis by inhibiting cytochrome P450-dependent 14a-lanosterol demethylation (c14 demethylase inhibiton)

ketoconazole and itraconazole

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10
Q

ketoconazole

A

First oral azole (significant number of side effect and drugs interactions)

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11
Q

itraconazole
active against?
improve safety?

A

Supplants ketoconazole

Active against many fungi and has improved safety profile.

Active against Candida species,Cryptococcus, Aspergillus, endemic (systemic) fungi, and dermatophytes.

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12
Q

Fungal cell wall structure diagram

A
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13
Q
Echinocandins 
action?
selective? 
spectrum? why?
name? 
mode of administration/ toxicity?
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.

Narrow spectrum: active against Aspergillus and Candida species; these fungi have larger amounts of b-(1,3)-D-glucan

Caspofungin - Intravenous use and minimal toxicity

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14
Q

Pyrimidine inhibition
effective against what spp?
why used with other agents?

A

interferes with fungal protein and DNA synthesis

Active against Candida species and Cryptococcus neoformans

Always used in combination with another antifungal because resistance develops quickly if used alone

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15
Q

High risk categories for oppurtunistic mycoses

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

Burn victims

Long-term IV catheter users

Broad-spectrum antibiotic therapy

Diabetes mellitus

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16
Q

Candidiasis related spp/ important features?

A

Candida albicans= predominant species colonizing humans responsible for most infections

Candida glabrata= resistant to some antifungals

Candida parapsilosis= common cause of catheter-related infections

several other species of Candida

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17
Q

Candidiasis

local disease vs. systemic invasive disease protections?
what prevents mucosal candidiasis?

A

Adequate neutrophil function protects against invasive infection, mainly local infections

Local factors and T-cell mediated defense system protects against mucosal candidiasis.

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18
Q

Mucosal candidiasis due to?

A

Due to decreased T-cell mediated immunity

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19
Q

Other host factors associated with protection against Candida infections:

A

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

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20
Q

Most common opportunistic fungal pathogen

A

candida spp

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21
Q

Oral Candida

infections

A
acute pseudomem
acute erythematous 
chronic plaque-like
chronic erythematous 
angular chelitis
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22
Q

acute pseudomem candidasis

A

removable white plaques

23
Q

acute erhtmatous candidasis

A

generalized redness/ sore tissue

24
Q

Plaquelike/nodularcandidiasis

A

fixed white plaque at the commissures, cannot be removed
Also called chronic hyperplastic candidiasis or candidal leukoplakia
Up to 40% of lesions develop into oral cancer

25
Q

Chronic erythematous candidiasis

A

general redness of tissue on surface fitting denture

26
Q

angular chelitis

A

bilateral cracks at angles of the mouth, often a bacterial component

27
Q

Mucosal candidiasis diagnosis

A

scrape and look under the microscope

culture

28
Q

Invasive candidiasis diagnosis

A

blood culture not sensitive

biopsy of involved tissue: microscopy and culture

29
Q

Staining methods to visualize fungi in clinical samples:

A

periodic acid-Schiff (PAS)
-surface carbohydrate

potassium hydroxide (KOH)
     -tissue dissolves, fungi do not (chitin)

Grocott-Gomori methenamine silver
-surface carbohydrate

Gridleys method
-modification of PAS

Calcofluor white
-fluorescent probe for chitin

30
Q

candia auris as an issue?

A

Drug resistant and spreads in healthcare facilities

31
Q

Why Candida Aruis is such a problem

A
32
Q

most people infect with C. Auris are?

A

already ill

33
Q

Cryptococcus neoformans causes?

A

Cryptococcosis

34
Q
Cryptococcus neoformans exposure
where? why? 
when in the body begin to? purpose? 
crucial for infection control? 
melanin?
A

found worldwide in soil contaminated with bird excreta

Yeast cells are inhaled in alveoli and begin to produce a polysaccharide capsule.
capsule inhibits phagocytosis and intracellular killing (if cells phagocytosed)

T-cell immunity crucial to infection control

melanin production in cell wall enhances virulence- resists free radicals and enzyme degradation

35
Q

Cryptococcus neoformans pt population

A

20% of patients with cryptococcosis appear to be immunocompetent

36
Q

Cryptococcus neoformans primary infection symptoms

A

Primary pulmonary infection is usually asymptomatic

37
Q

Cryptococcus neoformans trophism? significance?

A

C. neoformans has a striking neurotropism (basis is unknown)
minimal inflammatory response with CNS infection
Patients often present with meningitis, which worsens

38
Q

Cryptococcus neoformans diagnosis

A

cryptococcal meningitis - examine CSF for encapsulated budding yeast

latex agglutination test for capsular polysaccharide antigen (CSF fluid and serum)

39
Q

Cryptococcus neoformans treatment length

A

several months
sometimes lifelong therapy required
(patients with T cell defects)

40
Q

Aspergillosis spp

A

Aspergillus fumigatus and Aspergillus flavus

41
Q

Aspergillus fumigatus and Aspergillus flavus expsoure

A

acquired from the environment by inhalation of conidia

42
Q

Aspergillosis infection
what individuals? type of growth?
Present as what kind of infection?
invasive?

A

grow as hyphae in immunosuppressed individuals- usually a pulmonary or sinus infection

angioinvasive - growth through blood vessel walls cause tissue infarction, hemorrhage, necrosis

43
Q

Aspergillosis Diagnosis

sample contamination?

A

culture on Sabouraud’ s agar (grows in a few days)

caution: contamination from environment can easily occur tissue biopsy

44
Q

Aspergillosis mortality/treatments

A
high mortality
expanded-spectrum azole= voraconazole
decreased exposure (filtered air)
45
Q

Zygomycosis genera

septate/ hypahe?

A

Rhizopus and Mucor are main genera in this group

aseptate, broad hyphae

46
Q

Zygomycosis invasive?

A

angioinvasive

47
Q

Zygomycosis risk groups, additonal group? why?

A

in addition to standard risk groups, patients with diabetes mellitus with ketoacidosis
- acidosis reduces neutrophil chemotaxis and phagocytosis

48
Q

Rhinocerebral zygomycosis

A

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

49
Q

zygomycosis tx

A

amphotericin B and aggressive surgical debridement

50
Q

Pneumocystosis spp

A

Pneumocystis jiroveci- never grown in vitro

51
Q

Pneumocystis jiroveci infection/ disease when?

A

most people likely are infected early in life, but disease only occurs due to
immunosuppression (T cell deficiency most common risk factor)

52
Q

Pneumocystic pneumonia

A

most common opportunistic infection in AIDS patients before effective antiviral therapy
Organism rarely found outside lungs

53
Q

Pneumocystosis tx, what is missing from this spp?

A

trimethoprim-sulfamethoxazole (also used prophylactically)- target folic acid synthesis and utilization

note: P. jiroveci lacks ergosterol