Fungi B & Antifungal Treatments (EXAM IV) Flashcards
1
Q
Why are their fewer effective antifungal agents?
A
Because of the similarity of fungal cells & human cells
2
Q
It is easier to treat ______ fungal infections vs. ____ fungal infections
A
Superficial mycoses; systemic infections
3
Q
Sterol found in fungal cell membranes; human cells have cholesterol instead of this:
A
Ergosterol
4
Q
Where is ergosterol found?
A
In fungal cell memrbanes
5
Q
Antifungal treatment that binds ergosterol in fungal membranes:
A
Polyene compounds
6
Q
Give an example of a polyene compound used to treat systemic disease:
A
Amphotericin B
7
Q
Give an example of a polyene compound used to treat topical disease:
A
Nystatin
8
Q
Polyene compounds cause ______ leading to:
A
Altered membrane permeability; leading to leakage of cell constituents & cell death
9
Q
Polyenes bind ____ in mammalian cells but this is less strongly than they bind ___
A
Cholesterol; ergosterol
10
Q
What is the basis for drug toxicity with the use of polyene compounds?
A
Their ability to bind cholesterol in mammalian cells
11
Q
Why is Filipin a potent but toxic antifungal agent?
A
Due to the binding of cholesterol
12
Q
Terbinafine (TBF) acts on Ergosterol biosynthetic pathway at the _____ step
A
Squaline Epoxidase
13
Q
Itraconazole (ITZ) acts on Ergosterol biosynthetic pathway at the _____ step
A
C14-Demethylase
14
Q
Function to block ergosterol synthesis by inhibiting squalene epoxidase activity:
A
Allylamines
15
Q
Give an example of allylamine that functions to block ergosterol synthesis:
A
Terbinafine (TBF)
16
Q
Allylamines are mainly effective on the:
A
Dermatophytes
17
Q
What form of allylamines are most effective on dermatophytes?
A
Topical or tablet formulations
18
Q
Function to block ergosterol synthesis by inhibiting cytochrome P450-dependent 14-alpha-lanosterol demethylation:
A
Azoles
19
Q
What was the first oral azole?
A
Ketoconazole
20
Q
What are some downfalls to Ketoconazole (the first oral azole)?
A
Significant numbers of side effects & drug interactions
21
Q
What was created to supersede/replace Ketoconazole?
A
Itraconazole
22
Q
Itraconazole is preferred over Ketoconazole because:
A
Active against many fungi & has improved safety profile
23
Q
What fungal species is Itraconazole effective against?
A
- Candida species
- Cryptococcus
- Aspergillus
- Endemic (systemic) fungi
- Dermaphytes
24
Q
Antifungal agent that inhibits the synthesis of Beta-(1,3)-D-glucan, an essential component of fungal cell walls:
A
echinocandins
25
What is the significance of echinocandins inhibiting the synthesis of Beta-(1,3)-D-glucan?
This is an essential component of fungal cell walls
26
Echinocandins are ______ compared to agents that target cell membrane components
More selective
27
Echinocandins can be considered _____ against Aspergillus & Candida species
Narrow spectrum
28
Why are echinocandins considered narrow spectrum against Aspergillus & Candida species?
Because these fungi have larger amounts of Beta-(1,3)-D-glucans
(and this is the target of these agents)
29
Antifungal drug mechanism that interferes with fungal protein & DNA synthesis:
Pyrimidine inhibition
30
A type of echinocandin that is administered intravenously & has minimal toxicity:
Caspofungin
31
Pyrimidine inhibition interferes with:
Fungal protein & DNA synthesis
32
Antifungal drug mechanism "pyrimidine inhibition" is active against what fungal species?
Candida species & cryptococcus neoformans
33
Why must antifungal drugs using the mechanism "pyrimidine inhibition" ALWAYS be used in combination with another antifungal?
Because resistance develops quickly if used alone
34
High risk categories for opportunistic mycoses include:
1. Immunocompromised individuals
2. Burn victims
3. Long-term IV catheter users
4. Broad-spectrum antibiotic therapy
5. Diabetes mellitus
35
Candidiasis is caused by the fungal species (3):
1. Candida albicans
2. Candid glabrata
3. Candida parapsilosis
36
Predominant species of candida colonizing humans & responsible for most candidiasis infections:
Candida albicans
37
Responsible for some candidiasis infections & often resistant to some antifungals:
Candida glabrata
38
Responsible for some candidiasis infections & common cause of catheter-related infections:
Candida parapsilosis
39
What are two categories of diseases caused by candidiasis:
Local disease vs. systemic invasive disease
40
Adequate _______ protects against invasive infection of candidiasis:
Neutrophil function
41
_____ & _____ protects against mucosal candidiasis
Local factors & T-cell mediated defense system
42
What are some other host factors associated with protection against Candida infections:
1. Salivary flow & constituents
2. Blood group & secretor status
3. Epithelial barrier
4. Presence of normal bacterial flora
43
Adequate neutrophil function protects against _____ while local factors & T-cell mediated defense system protects against _____
invasive infection; mucosal candidiasis
44
What are four oral candida infections?
1. Acute pseudomembranous (acute erythematous)
2. Chronic plaquelike/nodular
3. Chronic erythematous
4. Candida-associated angular chelitis
45
Oral candida infection characterized by multiple, removable, white plaques:
Acute pseudomembranous
46
Oral candida infection characterized by generalized redness of tissue (antibiotic sore mouth):
Acute erythematous
47
Oral candida infection characterized by fixed white plaques on commissures:
Chronic plaquelike/nodular
48
Oral candida infection characterized by generalized redness of tissue on fitting surface of upper denture:
Chronic erythematous
49
Oral candida infection characterized by bilateral cracks on angles on mouth:
Candida-associated angular chelitis
50
Psuedomembranous candidiasis lesions on the palate; easily wiped off:
Thrush
51
Form of candidiasis that cannot be easily removed by scraping:
Plaquelike/nodular Candidiasis
52
Plaquelike/nodular candidiasis is called: (2)
1. Chronic hyperplastic candidiasis
2. Candidal leukoplakia
53
What is the significance of plaquelike/nodular candidiasis?
Up to 40% of lesions develop into oral cancer
54
With angular chelitis there is frequently:
A bacterial component
55
How is mucosal candidiasis diagnosed?
Scrape & look under microscope
56
How is invasive candidiasis diagnosed?
Biopsy of involved tissue
(Blood culture not sensitive)
57
Staining methods to visualize fungi in clinical samples include:
1. PAS
2. KOH
3. Grocott-Gomori methenamine silver
4. Gridley's method
5. Calofluor white
58
Staining methods to visualize fungi in clinical sample that stain surface carbohydrate:
Periodic acid-Schiff (PAS) & Grocott-Gomori mehenamine silver
59
Staining methods to visualize fungi in clinical samples that dissolves tissue but not the fungi due to chitin:
Potassium hydroxide (KOH)
60
Staining methods to visualize fungi in clinical samples that is a modification of PAS:
Gridley's method
61
Staining methods to visualize fungi in clinical samples that is a fluorescent probe for chitin:
Calcofluor white
62
A drug-resistant germ that spreads in healthcare facilities:
Candida auris
63
Why is candida auras a problem?
1. It causes serious infections
2. Drug resistance
3. Becoming more common
4. Difficult to identify
5. Spreads in healthcare settings
64
Fungal species found worldwide in soil contaminated with bird excreta:
Cryptococcus neoformans
65
C. Neoformans is found worldwide in ______ contaminated with ____
Soil; bird excreta
66
___% of patients with cryptococcosis appear to be _____
20% ; immunocompetent
67
Discuss the events that lead to cryptococcosis:
Yeast cells are inhaled in alveoli & begin to produce a polysaccharide capsule
68
The polysaccharide capsule produce in cryptococcosis inhibits ______ and _____
Phagocytosis & intracellular killing
69
What is crucial to control of infection with C. Neoformans?
T-cell immunity
70
What enhances virulence of C. Neoformans?
Melanin production in cell wall
71
C. Neoformans resists ____ & ____
Free radicals & enzyme degradation
72
The primary pulmonary infection of Cryptococcus neoformans is usually described as:
Asymptomatic
73
C. Neoformans has a striking _____ with an unknown basis
Neurotropism
74
Describe what occurs with a CNS infection caused by cryptococcus neoformans:
Minimal inflammatory response
75
What might the clinical presentation of patient of C. Neoformans be?
Worsening meningitis
76
What is the diagnosis for cryptococcal meningitis?
1. Examine CSF for encapsulated budding yeast
2. Latex agglutination test for capsular polysaccharide antigen (CSF fluid & serum)
77
What is the treatment of cryptococcal meningitis?
Several months/lifelong therapy required
78
What fungal agents are responsible for causing Aspergillosis?
1. Aspergillus fumigatus
2. Aspergillus flavus
79
Aspergillus species are acquired from:
Environment by inhalation of conidia
80
Aspergillus species grow as ____ in immunosuppressed individuals
hyphae
81
Aspergillus species grow as hyphae in:
immunocompromised individuals
82
What are the symptoms of aspergillosis?
Usually a pulmonary or sinus infection
83
The growth of aspergillus through blood vessel walls causing tissue infarction, hemorrhage & necrosis:
Angioinvasive growth
84
Describe the diagnosis of Aspergillosis:
Culture on Sabourad's agar (grows in a few days)
85
What is the treatment of Aspergillosis?
High mortality however it may be treated with expanded spectrum Azole Voraconazole
86
Rhizopus & Mucor are the main genera of:
Zygomycosis
87
Describe Rhizomes & Mucor:
Angioinasive; aseptate & brand hyphae
88
In addition to standard risk groups, patients with _____ are at increased risk of zygomycosis
Diabetes mellitus with ketoacidosis
89
Why are patients with diabetes mellitus in ketoacidosis at an increased risk for Zygomycosis?
Because acidosis reduces neutrophil chemotaxis and phagocytosis
90
The spread from nares/sinuses to palate, orbit, face then to brain may be seen in:
Rhinocerebral zygomycosis
91
Treatment of zygomycosis includes:
Amphotericin B & aggressive surgical debridement
92
Pneumocystosis is caused by the fungal species:
Pneumocystis jiroveci
93
Pneumocystis jiroveci is an organisms that has never:
Been grown in itro
94
Most people infected with pneumocystosis are infected:
early in life, but disease only occurs due to immunosuppression
95
What is the biggest risk factor for disease symptoms associated with pneumocystosis?
T cell deficiency (immunosuppression)
96
Most common opportunistic infection in AIDS patients before effective antiviral therapy:
Pneumocystic pneumonia
97
Pneumocystis jiroveci is a fungal organism rarely found:
Outside lungs
98
Treatment of pneumocystosis includes:
Trimethoprim-sulfamethoxazole (used prophylactically)
99
What is the target for treatment of pneumocystosis with Trimethoprim-sulfamethoxazol?
Target folic acid synthesis & utilization
(Jiroveci lacks ergosterol)
