Antifungal Drugs & Fungi B- Exam IV Flashcards
Why are there fewer effective antifungal agents?
because of the similarity of human cells and fungal cells
It is easier to treat ___ fungal infections than ____ fungal infections
superficial mycoses; systemic infections
Sterol found in fungal cell membranes; human cells have cholesterol instead of tis:
ergosterol
Where is ergosterol found?
in fungal cell membranes
Antifungal treatment that binds ergosterol in fungal membranes:
polyene compounds
Give an example of a polyene compound that is used to treat systemic disease:
amphotericin B
Given an example of a polyene compound that is used to treat topical disease:
nystatin
Polyene compounds cause ___, leading to:
altered membrane permeability; leakage of cell constituents & cell death
Polyenes bind ____ in mammalian cells but this is less strongly than they bind ___
cholesterol; ergosterol
What is the basis for drug toxicity with the polyene compounds?
their ability to bind cholesterol in mammalian cells
Why is fillipin a potent but toxic anti-fungal agent?
due to the binding of cholesterol
Terbinafine (TBF) acts on the Ergosterol biosynthetic pathway at the ____ step.
squalene epoxidase
Itraconazole (ITZ) acts on the Ergosterol biosynthetic pathway at the ____ step.
C-14 demethylase
Function to block ergosterol synthesis by inhibiting squalene epoxidase activity:
Allylamines
Give an example of an Allylamine that functions to block ergosterol synthesis:
Terbinafine (TBF)
Allylamines are mainly effective on the:
dermatophytes
What form of allylamines are most effective on dermatophytes?
topical or tablet formulations
Function to block ergosterol synthesis by inhibiting cytochrome P450-dependent 14(alpha)-lanosterol demtheylation:
azoles
What was the first oral azole?
Ketoconazole
What are some downfalls to ketoconazole? (the first oral azole)
significant numbers of side effects and drug interactions
What was created to supersede/replace ketoconazole?
Itraconazole
Itraconazole is preferred over ketoconazole because:
active against many fungi and has improved safety profile
What fungal species is itraconazole effective against?
- candida species
- cryptococcus
- aspergillus
- endemic (systemic) fungi
- dermaphytes
antifungal agent that inhibits the synthesis of beta-(1,3)-D-glucan, an essential component of fungal cells walls
Echinochandins
What is the significant of Echinocandins inhibiting the synthesis of beta-(1,3)-D-glucan:
This is an essential component of fungal cell walls
Echinocandins are ___ compared to agents that target cell membrane components
more selective
Echinocandins can be considered ___ against aspergillus and candida species
narrow spectrum
Why are echinocandins considered “narrow spectrum” against aspergillus and candida species?
because these fungi have larger amounts of beta-(1,3)-D-glucans
A type of echinocandin that is administered intravenously and has minimal toxicity:
Caspofungin
Antifungal drug mechanism that interferes with fungal protein and DNA synthesis:
Pyrimidine inhibition
Pyrimidine inhibition interferes with:
fungal protein and DNA synthesis
antifungal drug mechanism “pyrimidine inhibition” is active against what species?
candida species and cryptococcus neoformans
Why must drugs using the mechanism “pyrimidine inhibition” be used in combination with another antifungal drug?
because resistance develops quickly if used alone
High risk categories for opportunistic mycoses:
- immunocompromised individuals
- burn victims
- long-term IV catheter users
- broad-spectrum antibiotic therapy
- DM
Candidiasis is caused by the fungal species: (3)
- candida albicans
- candida glabrata
- candida parapsilosis
Predominant species of candida colonizing humans and responsible for most candidiasis infections:
candida albicans
responsible for some candidiasis infections and often resistant to some anti-fungals:
candida glabrata
responsible for some candidiasis infections and common cause of catheter-related infections:
candida parapsilosis
What are two categories of diseases caused by candidiasis?
local disease vs. systemic invasive disease
Adequate ____ protects against invasive infection with candidiasis
neutrophil
___ & ___ protects against mucosal candidiasis
local factors & T-cell mediated defense system
What are some other host factors associated with protection against candida infections:
- salivary flow and constituents
- blood group & secretor status
- epithelial barrier
- presence of normal bacterial flora
adequate neutrophil function protects against ____ while local factors & T-cell mediated defense system protects against ___.
invasive infection; mucosal candidiasis
What are four oral candida infections?
- acute pseudomembraneous (acute erythematous)
- chronic palquelike/nodular
- chronic erythematous
- candida-associated angular chelitis
Oral candida infection characterized by multiple removable white plaques:
acute pseudomembranous
Oral candida infection characterized by generalized redness of tissue (antibiotic sore mouth):
acute erythematous
Oral candida infection characterized by fixed white plaques on commissures:
chronic plaquelike/nodular
Oral candida infection characterized by generalized redness of tissue on fitting surface of upper denture:
chronic erythmatous
Oral candida infection characterized by bilateral cracks on angles of mouth:
candida-associated angular chelitis
pseudomembranous candidiasis lesions on the palate, easily wiped off:
thrush
form of candidiasis, cannot be easily removed:
chronic plaquelike/nodular candida infection
Plaquelike/nodular candidiasis is also called (2):
- chronic hyperplastic candidiasis
- candida leukoplakia
What is significant about plaquelike/nodular candidiasis:
up to 40% of lesions develop into oral cancer
With angular chelitis, there is frequently a ___ component
bacterial component
How is mucosal candidiasis diagnosed?
Scrape and look under microscope
How is invasive candidiasis diagnosed?
biopsy of involved tissue (blood culture not sensitive)
Staining methods to visualize fungi in clinical samples include:
- PAS
- KOH
- Grocott-Gomori methenamine silver
- Gridley’s method
- Calcofluor white
Staining methods to visualize fungi in clinical samples that stains surface carbohydrate:
Periodic acid-schiff (PAS) & Grocott-Gomori methenamine silver
Staining methods to visualize fungi in clinical samples that dissolves tissue but not the fungi due to chitin:
potassium hydroxide (KOH)
Staining methods to visualize fungi in clinical samples that is a modification of PAS:
Gridley’s method
Staining methods to visualize fungi in clinical samples that is a fluorescent probe for chitin:
calcofluor white
a drug resistant germ that is spread in healthcare facilities:
candida auris
Why is candida auris a problem?
- It causes serious infections
- Drug resistance
- Becoming more common
- Difficult to identify
- Spreads in healthcare settings
Fungal species found worldwide in soil contaminated with bird excretions:
Cryptococcus neoformans
C. neoformans is found worldwide in ___ contaminated with ___
soil; bird extreta
___% of patients with cyptococcosis appear to be ___.
20%; immunocompetent
Discuss the events that lead to cryptococcosis:
yeast cells are inhaled in alveoli and begin to produce a polysaccharide capsule
The polysaccharide capsule produced in cryptococcosis inhibits ___ and ___
phagocytosis and intracellular killing
What is crucial to control of infection with C. neoformans?
T-cell immunity
What enhances virulence of C. neoformans?
Melanin production in cell wall
C. neoformans resist ___ & ___
free radicals and enzyme degredation
The primary pulmonary infection of C. neoformans is usually described as:
asymptomatic
C. neoformans has a striking ____ with an unknown basis
neurotropism
Describe what occurs with a CNS infection caused by cryptococcus neoformans:
minimal inflammatory response
What might the clinical presentation of a patient with C. neoformans be?
worsening meningitis
What is the diagnosis for cryptococcal meningitis?
- Examine CSF for encapsulated budding yeast
- latex agglutination test for capsular polysaccharide antigen (CSF and serum)
What is the treatment of cryptococcal meningitis?
several months/lifelong therapy
What fungal agents are responsible for causing aspergillosis?
- aspergillus fumigatus
- aspergillus favus
Aspergillus species are acquired from:
the environment by inhalation of conidia
Aspergillus species grow as ___ in immunosuppressed individuals
hyphae
Aspergillus species grow as hyphae in:
immunosuppressed individuals
What are the symptoms of aspergillosis?
Usually a pulmonary or sinus infection
The growth of aspergillus through blood vessel walls causing tissue infarction, hemorrhage & necrosis:
angioinvasive growth
Describe the diagnosis of aspergillosis:
culture on sabouraud’s agar (grows in a few days)
Treatment of aspergillosis includes:
high mortality however expanded spectrum azole voraconazole may be effective
Rhizopus and Nucor are the main genres of:
zygomycosis
Describe Rhizopus and Mucor:
angioinvasive, aspettate, and broad hyphae
In addition to standard risk groups, patients with ___ are at risk of zygomycosis
DM with ketoacidosis
Why are patients with DM with ketoacidosis at an increased risk for zygomycosis?
because acidosis reduces neutrophil chemotaxis and phagocytosis
The spread from nares/sinuses to palate, orbit, face, then to brain:
rhinocerebral zygomycosis
Treatment of zygomycosis includes:
amphotericin B and aggressive surgical debridement
Pneumocystosis is caused by the fungal species:
pneumocystis jiroveci
Penuocystis jiroveci is an organism that has never:
been grown in vitro
most people infected with pneumocystosis are infected:
early in life but disease only occurs due to immunosupression
What is the biggest risk factor for disease symptoms associated with pneumocystosis?
T-cell deficiency (immunosupression)
Most common opportunistic infection in AIDS patients before antiviral therapy:
pneumocystis pneumonia
Pneumocystis jiroveci is and organism rarely found:
outside lungs
Treatment of pneumocystosis includes:
Trimethoprim-sulfamethoxazole (used prophylactically)
What is the target for treatment with Trimethoprim-sulfamethoxazole for pneumocystosis?
target folic acid synthesis and utilization
P. Jiroveci lacks ergosterol
