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65 Cards in this Set

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What are the natural reservoirs of Fusarium?
plants, soil

can't bring plants in hospital rooms b/c fusarium and aspergillus
How does one obtain a Fusarium infection?
traumatic inoculation (usually)

disseminated infections usually result of immune system suppression
What are the infectious preferences of Fusarium?
cutaneous infection

spreads to heart and bones if it gets into your blood

contact lenses/corneal infections
Why are macrophages not so useful for fighting fungal infections?
NAIVE macrophages ingest but do not immediately kill fungi

fungi continue to grow --> hyphae or buds lyse macrophage
After the skin, what is the primary immune defense against fungal infections?
Neutrophils

--> neutropenia predisposes to mycoses
What do polyene drugs target?
Fungal cell membrane function

bind ergosterol and make pore in membrane
What are some problems with polyene drugs?
low solubility --> mostly topical use or IV, not good for systemics

cause kidney and liver problems
What solution has been developed for low AmB solubility?
create liposomes with AmB embedded in membrane

macrophages engulf --> become saturated with AmB --> when they eat fungi AmB works inside macrophage!
What are some examples of polyene drugs?
Nystatin

Amphotericin B (last resort b/c not much resistance)
What does 5-Flu-Cytosine target?
DNA/RNA synthesis

only fungi have enzyme to convert 5-Flu-C to 5-Flu-Uracil and incorporate it into DNA.
What are some problems with 5-Flu-Cytosine?
easy to develop resistance

cannot be used alone, must be combined with another drug.
What do azole drugs target?
Ergosterol biosynthesis at ERG11 gene
What are the two classes of azole drugs and what types of mycoses are they used for?
imidazoles (OTC, topical application)

triazoles (Rx only, for systemic infections)
What are some examples of azole drugs?
OTC: ketoconazole, clotrimazole, miconazole

Rx: FLUCONAZOLE!, voriconazole, itraconazole

New: Posaconazole
What are some other examples of ergosterol biosynthesis inhibitors?
ERG1: terbinafine (Lamisil), tolnaftate (Tinactin)

ERG24 and ERG2: aorolfine, fempropimorph
What do echinocandins target?
Inhibit cell wall synthesis --> fungi more susceptible to phagocytosis
What are some problems with echinocandins?
low solubility --> IV only

new so we don't know long term effects
What drug is being used to treat mycoses in African AIDS patients?
Fluconazole (Pfizer: Diflucan)

Leaning toward HAART now
What is HAART?
Highly Active Antiretroviral Therapy

Restore immune system function to AIDS patients (hopefully)
What are some problems with azoles?
don't kill, just inhibit growth

fungi may develop resistance
Which groups of fungi are hardest to treat with existing antifungal medication?
Zygomycetes
Fusarium spp.
Scedosporium spp.
What species are resistant to azoles?
some Candida, Cryptococcus, Aspergillus species found in AIDS, Bone Marrow Transplant, etc, patients
What is the difference between primary and secondary resistance?
primary = naturally resistant, always been that way

secondary = strain gains resistance via mutation, lateral gene transfer, etc.
Which Candida species are most likely to be drug resistant?
C. lusitaniae, C. krusei (AmB), C. glabrata (Azoles)
Which Cryptococcus species is considered a "true pathogen" and why?
C. gatii because it attacks even non-immunocompromised patients.
MIC = ?
Minimum Inhibitory Concentration

conc. of antifungal drug required to inhibit growth
Which black mold species has been implicated for "sick building syndrome," etc.?
Stachybotrys chartarum, S. atra
What humidity level is required for production of mycotoxins by Stachybotrys species?
~95%

a swamp, basically. so no mycotoxins in your house, unless you live in a swamp.
What are the goals of the California Toxic Mold Protection Act of 2001?
-establish research priorities
-provide sampling/investigation/remediation guidelines
-disclosure of mold in properties (real estate)
Describe the pseudohyphae of Candida albicans.
single cell (no septation)

elongated, bullet-shaped, un-separated buds.

sausage links
Which strains of Candida form Chlamydospores? What is their purpose?
C. albicans

occur at end of hyphae; purpose unknown
Which Candida species form septate hyphae?
only C. albicans and dubliniensis

the rest form aseptate hyphae
How does Candida appear in tissue?
EVERYTHING

budding yeasts + hyphae + pseudohyphae
Where does Candida like to grow?
plastics: dentures, catheters, implanted heart valves

everywhere in environment and world

everywhere in all humans (commensal)
What factors predispose one to vaginal yeast infections?
-tight skanky clothing
-hormone imbalances (pregnancy, oral contraceptives)
-anemia
-taking antibiotics that kill lactobacilli
What are the risk factors for oral and esophageal Candidiasis?
-immune suppression (diabetes, AIDS)
-poor oral hygiene!
-infants: immature immune system
-high sucrose diet
-antibiotics
What causes the white "bloom" on your tongue when you take antibiotics?
bloom of candida

all your oral bacteria are dead so candida party hardy
What are the three types of oral candidiasis?
pseudomembranous

erythematous

angular chelitis
What are the symptoms of pseudomembranous candidiasis?
overgrowth of white yeast patches in mouth

pain, loss of appetite
What are the symptoms of erythematous candidiasis?
appetite loss, pain, inflammation in roof of mouth due to small number of yeast cells in tissue.

subtle; most often Dx by dentists
What are the symptoms of angular chelitis?
crusty patches, lesions at corners of mouth due to infection by candida spp

pain, loss of appetite
What are the symptoms of Esophageal candidiasis?
ulcerations and white patches of yeast growth on esophagus lining

may spread to stomach, GI tract, respiratory tract, urinary tract
What is a nosocomial infection?
an infection obtained while one is staying in a hospital
What predisposes you to systemic candidiasis (blood infection)?
-immune suppression: neutropenia, chemotherapy
-catheters
-surgery
-artificial heart valves
-burns
Where does candida often spread in systemic infections?
-skin (esp heroin addicts)
-kidneys because candida in blood lodges in kidneys
What is Chronic Mucocutaneous Candidiasis?
immune dysfunction

candida grows on all mucosal surfaces --> crusting, hyperkeratosis, chronic skin infections

treat with topical antifungal drugs.
Which Candida species form germ tubes?
C. albicans
C. dubliniensis

*in vitro only diagnostic test for these species*
What genus is responsible for most mucormycoses?
Rhizopus: 60% of all cases
What is the pathology of mucormycosis?
twisting hyphae grow rapidly in tissue

invade blood vessels --> block blood flow --> necrosis from lack of blood
What are the most frequent etiologic agents of mucormycoses?
Rhizopus microsporus (var. rhisopodformis)

Cunninghamella betholletiae

Saksenaea vasiformis
What are natural reservoirs of mucoraceae?
decaying matter containing carbohydrates

soil, compost, animal poo

common lab contaminant.
Why are nosocomial mucormycoses on the rise?
We've got aspergillosis and candidiasis under control --> mucoraceae have no competition
Mucormycoses may indicate underlying disease. Examples?
-diabetic ketoacidosis
-steroid use
-leukopenia
-lymphoma
-neutropenia
How does one usually obtain mucormycoses?
traumatic inoculation (immune compromised)

takes a huge dose to infect healthy immune competent person.
What is the most damaging form of mucormycosis?
Mucormycotic sinusitis because it spreads to your BRAIN

puts you in a coma, kills you in 4 weeks
What are symptoms of pulmonary mucormycosis?
fever
rapidly progressing lung invasion
lesions in trachea and bronchial tubes
lung necrosis

death in 2-3 weeks
What is the taxonomic classification of Pneumocystis carinii?
Archiascomycete

previously thought to be a protozoan b/c similar drug susceptibility and has double membrane

no ergosterols
Why is Pneumocystis carinii so difficult to study?
unable to culture in vitro.
What are the infectious preferences of Pneumocystis carinii?
-only mammalian lungs
-very picky and species specific
-opportunistic infection of severely immune compromised only
What are the natural reservoirs of Pneumocistis carinii?
all mammalian lungs

we've all got it in our lungs commensally
What are trophozoites?
Active stage Pneumocystis carinii cells

amoeba-like with filopodia for adhesion to host lungs
What are sporozoites?
intracystic bodies of P. carinii; develop into trophozoites upon cyst maturation.
What are the symptoms of Pneumocystis carinii Pneumonia (PCP)?
pneumonia, inflammation, fever

death by asphyxia

foamy excretion from lungs containing P. carinii cells
What is the most common AIDS-defining opportunistic infection?
PCP

Pneumocystis Carinii Pneumonia
Which Aspergillus species is known to be drug-resistant?
A. terreus