Kozel: Intro to Medical Mycology Flashcards
About how many fungal species are there? What are they most commonly pathogenic for?
1.5 million fungal species; most pathogenic for plants, then insects, then humans (only 300 species - 50 common)
Why are mammals intrinsically resistant to fungal infections?
mammals have the ability to generate and regulate their body temperature, and every degree C above 30C excludes another 6% of fungal species
What is one major constituent of the plasma membrane of fungi?
ergosterol
What are the components of the fungal cell wall?
chitin
Beta-1,3-glucan
Beta-1,6-glucan
mannoproteins - mannan or galactomannan
a unicellular fungus that reproduces vegetatively by budding or fission
yeast
String of budding cells marked by constrictions rather than septa at the junctions
pseudohyphae
multicellular structures that elongate at tips by apical extension
hyphae
hollow, multinucleate hyphae that are produced by the mucorales
coenocytic hyphae
hyphae divided by partitions or cross-walls
septate hyphae
asexual reproductive elements (spores) produced by budding at the tip or side of a hypha
conidia
asexual reproductive elements produced by fragmentation of hyphae
arthroconidia
asexual spores produced within a sack-like structure (sporangium)
sporangiospores
Broad, thin-walled hyphae with multiple nuclei (coenocytic); septae are rare; sporangiospores
mucormycetes
Budding yeasts and hyphae, pseudohyphae
saccharomycetes
Budding yeasts, septate hyphae, asexual conidia on specialized structures, and arthroconicia
euascomycetes
What is the gold standard for diagnosis of fungal infections? How long does this take?
culture; takes days to weeks to get results
What can you use on scrapings to digest excess tissue and reveal yeast?
KOH
What is one benefit of using serology for fungal infection diagnosis? What is one drawback?
detects antibody to fungal antigen; may not reflect active infection (IgM vs IgG)
When is serology testing most useful?
for coccidiodomycosis and histoplasmosis
When is antigen detection very useful?
for cryptococcosis
What antigen tests would you use for Aspergillosis?
Beta glucan (detects cell wall glucan in blood) galactomannan
What is the structure of imidazoles? Triazoles?
2 nitrogens in a ring (ketoconazole, miconazole); 3 nitrogens in a ring (fluconazole, itraconazole, voriconazole)
What is the mechanism of the azoles?
inhibit lanosterol 14-alpha-demethylase and block ERGOSTEROL synthesis
What are 3 mechanisms of resistance that fungi have developed to azoles?
- target with decreased affinity for the drug **
- efflux pump
- overexpression of the target
What is ketoconazole used for?
limited use due to toxicity
What is fluconazole used for?
candidiasis, cryptococcosis
What is itraconazole used for?
broad spectrum antifungal
What is voriconazole used for?
broad spectrum, invasive aspergillosis
Describe the oral bioavailability of azoles and the distribution to organs of tissues
EXCELLENT oral bioavailability
good distribution to organs and tissues
What is one side effect of azoles?
interferes w cytoP450 action, so can create ADRs with other meds
What are two allylamines?
terbinafine
naftifine
What is the mechanism of action of the allylamines?
inhibit squalene epoxidase
What are allylamines used for clinically?
topical treatment of dermatophyte infection
systemic treatment of dermatophyte infection
Where are allylamines found in high concentration? What pregnancy category do they fall under?
fatty tissue, skin, hair, nails; Pregnancy category B
What is the structure of flucytosine? What happens to it inside of yeast cells?
5-fluorouracil ring with an amine group; inside of yeast cells, it is deaminated to its active form
**prodrug
What is the mechanism of action of flucytosine?
inhibits DNA/RNA synthesis by competing with uracil
What are 2 methods of resistance to flucytosine?
- decreased uptake
2. failure to convert to active form
When is flucytosine used clinically?
in combination with Amphotericin B to treat cryptococcal meningitis
How is flucytosine taken? What is its distribution like in the body? What is unique about its excretion in the urine?
taken orally and rapidly absorbed; wide distribution in the body and penetrates the CNS; excreted UNCHANGED in urine
What are two side effects of flucytosine?
depressed bone marrow
hepatotoxicity
What is the structure of the echinocandins, like capsofungin?
cyclic polypeptide
What is the mechanism of echinocandins like capsofungin?
inhibit glucan synthesis
What is the method of resistance to echinocandins?
altered target with decreased sensitivity
**resistance is currently rare
What are echinocandins used for?
used for fungi where 1,3 beta-glucans are the dominant cell wall glucan component – aspergillus and candida
**used for invasive candidiasis and invasive aspergillosis
How are echinocandins administered? How is their CNS penetration?
IV; limited CNS penetration
What is the pregnancy category of echinocandins?
C
What is the structure of the polyenes?
lipid formulations of amphotericin B
nystatin
What is the mechanism of action for the polyenes?
binds to ergosterol and causes direct membrane damage
What are some methods of resistance to polyenes?
Very rare!!!
reduced ergosterol content
ergosterol with reduced binding
making of ergosterol to block binding
How is amphotericin B administered? What happens to AmB once administered? What is this used for?
Given IV - not absorbed via GI; remains in plasma, largely bound to protein; BROAD SPECTRUM - used for all fungi
What is one problem with amphotericin B?
considerable nephrotoxicity - azotemia (Nitrogen compounds) in 80% of patients
**lipid formulations are less toxic
What are some endemic mycoses (found in nature - certain parts of the globe)?
blastomycosis
histoplasmosis
coccidioidomycosis
penicilliosis
What are some opportunistic mycoses (not unique to one place)?
aspergillosis candidiasis cryptococcosis mucormycosis pneumocystosis
Where are superficial mycoses found?
limited to very superficial surfaces of skin and hair
**don’t cause much damage more like a cosmetic concern
What do cutaneous mycoses infect? What is the pathology due to?
keratinized layers of skin, hair, and nails;
pathology due to host response
What do subcutaneous mycoses infect?
deep layers of skin
cornea
muscle
connective tissue
What causes these diseases?
Infection via traumatic inoculation
Abscess formation, nonhealing ulcers, draining sinus tracts
Localized; rarely disseminate
subcutaneous mycoses
Where are endemic mycoses found?
worldwide, really
List 5 dimorphic funguses
Dimorphic = two forms
blastomyces dermatitidis coccidioides immitis histoplasma capsulatum paracoccidioides brasiliensis penicillum marneffei
This is a DIMORPHIC fungus; in tissues, it is a broad-based yeast; in its saprobic phase - nondescript mycelium; found in decaying organic matter; Ohio and Mississippi River valleys
Blastomyces dermatitidis
What does Blastomyces dermatitidis cause?
pulmonary disease
skin, GU, CNS probs
This is a DIMORPHIC fungus; in tissue, it is an intracellular budding yeast; in its saprobic phase - tuberculate macroconidia; found in soil with high nitrogen content and in bird/bat droppings; Ohio and Mississippi River valleys, Mexico, Central and South America
Histoplasma capsulatum
What does Histoplasma capsulatum cause?
acute pulmonary disease
chronic pulmonary disease
This is a DIMPORHIC fungus; in tissue, endosporulating SPHERULE; saprobic phase - arthroconidia; found in soil and dust; found in Soutwestern US, Mexico, Central and South America
Coccidioides immitis/posadasii
What does coccidioides immitis/posadasii cause?
primary pulmonary disease
progressive pulmonary disease
This is a dimorphic fungus; in tissue - sausage shaped yeast; saprobic stage - pigmented mold; found in soil and bamboo rat; found in SE Asia
Penicillium marneffei
What diseases are caused by Penicillium marneffei?
disseminated infection in AIDS patients
**resembles histoplasmosis, cryptococcosis, TB
This is a dimorphic fungus; found in the tissue as a large, multiple budding yeast; in saprobic stage - nondescript mold; found in soil in S and Central America
Paracoccidioides brasiliensis
What diseases are caused by Paracoccidioides brasiliensis?
asymptomatic mostly
can cause self-limiting pulmonary disease, progressive pulmonary disease, disseminated disease
