Fungal and anti-fungals Flashcards
Name the molds and shape?
hyphae: Aspergillosis, mucormycoses, and fuariosis
Name the yeasts and shape?
round budding cells. malassezia, cryptococosis, candidiasis
Basic characteristics of endemic mycoses?
- grows in certain environments as a mold and infects human who inhales spores.
- All are dimphoric fungi
give examples of endemic fungus (5)
- USA: histoplasmosis, coccidiomycosis, blastomycosis
- Overseas: talaromycosis marneffei (penicillosis marneffei), paracoccidiomycosis (south american blastomycosis)
what is a dimorphic fungus?
- mold in nature and in room temperature culture
- rounded form in infected tissue
Describe the acute pneumonia from pulmonary histoplasmosis?
- 2 week after exposure to dust from rich earth, or bat guano (caving)
- difficult to culture from sputum
- lung nodule may persist
what species cause “valley fever”
Coccidioomycosis immitis and Coccidiomycosis posadasil
how does valley fever pneumonia present?
2 weeks after inhalation with acute pneumonia with possible arthralgias and erythema nodosum
residual nodule or thin walled cavity may persist
What are the symptoms of disseminated coccidiomycosis?
bone, skin, chronic meningitis
what is the treatment of cocidiomycosis?
fluconazole. If nonmeningeal can use itraconazole.
how would you diagnose coccidiomycosis?
seurm and CSF serology. Eosinophilia in CSF
what are the species associated with blastomycoses?
B.dermatitidis and B.Gilchristi
Where is blastomycoses found?
moist earth near river, beaver dams
where does blastomycoses disseminate and tx?
- skin, bone, male GU tract.
- Itraconazole
thick walled budding cells; Blasto
cocci spherule big no budding. coccidiomyocisis microscope?
Talarmycosis basics?
think blasto in thailand with bamboo rats
Illness script for aspergillus pneumonia?
sudden onset of a dense, well-circumscribed lesion in a neutropenic patient.
- halo sign early, crescent late
- galactomannan
what can create false positives in the galactomanna test?
some beta lactams and fusarium
give examples of mucormycosis?
- Mucor
- Apophysomyces
- Rhizopus, Rhizomucor
- cunninghamella
- saksenaea
what are risk factors for mucormycosis?
DM2, neutropenia, steroids, desferoxamine
how does mucormycosis transmit? treatment?
- infection acquired by inhaling spores into lung or paranasalsinus
- hyphae invavde blood vessels, causes infarction and necrosis.
- may form cavity if PMNs return
- ampho B, posaconazole
illness script for fusariosis? treatment?
- red tender skin nodules, mycetoma, or pneumonia. see in immunocompromised, transplant, aplastic anemia and burn patients.
- Tx with either ampho or voriconazole
what do you see in Scedsporiosis apiospermum?
hyphae and a clinical disease resembling aspergillus
Near drowning patient
Ampho resistant, tx with voriconazole
What do you see in Scedsporiosis prolificans?
also known as lomentospora prolificans.
similar to aspergillus
resistant to all antifungals
key point for malessezia furfur
needs oil in culture to grow
3 key points in candidemia?
- remove IV catheter if possible
- dilated fundoscopic exam in first week
- intravitreal drug if vitiritis or macular lesion
what is more likely to be seen in C.gatti compared to C.neoformans?
C.gatti more likely to be seen in lung, non-HIV patient, S.California, Vancouver island, overseas
what is the typical presentation of Cryptococcosis IRIS?
- weeks or months after ARV/antifungal rx for meningitis
- Fever, headache, seizures, new MRI lesions
- All cultures negative
- dry cough, substernal pain
- swollen nodes in mediastinum, hilum
- Treat with NSAIDs or prednisone
what mycoses DO NOT test positive for beta-d-glucan test?
cryptococcosis or mucormycosis
ddx for eosinophilic meningitis?
- Hodgkins lymphoma
- parasites: angiostronglyus, gnathostoma and baylisacaris
- Coccidiomycosis
when should you consider blastomycosis?
a previously healthy adult with indolent, ulcerative crusted skin lesions with asymptomatic pulmonary infiltrate
Fusarium - you think?
skin nodules, blood culture with mold
ecthyma gangrenosa - you think?
aspergillosis, mucor, bacteria
Histo, you think?
TNF alpha blockers, miliary infiltrates
aspergillosis think?
halo sign, crescent sign
mucormyocisis think?
mimic cavernous sinus thrombosis, aseptate, ampho
cocci think?
solitary lung cavity, eosinophilic meningitis
blasto think?
indolent skin + lung lesion
candida think?
liver, spleen lesion in neutropenic
Name the echinocandins?
caspofungin, micafungin, anidulafungin
what is the MOA of the echinocandins?
inhibit glucan synthase, block synthesis of 1-3 beta glucans in the fungal cell wall
what is the MOA of azoles?
inhibit sterol C-14 demethylase, block synthesis of sterol
what is the MOA of ampho?
damages fungal cytoplasmic membranes
what is the MOA of flucytosine?
flucytosine is converted to 5FU, inhibits DNA synthesis
what are the mechanisms of antifungal resistance in Azoles?
- Mutations in CYP51AS (code for C14 demethylase) gene in candida and aspergillus
- mutations in CYPT51A promoter region in aspergillus
- increased drug efflux in candida glabrata
what are the mechanisms of antifungal resistance in Echinocandins?
mutations in FKS1 and FKS2 (code for glucan synthase)
which species are resistant to amphotericin?
- Scedosporium apiospermum (Pseudallescheria boydii)
- Lomentospora (Sc) prolificans
- Aspergillus terreus
- variable in candida lusitaniae
- Variable in candida auris
which species are resistant to fluconazole?
- All molds
- candida krusei
- candida auris
- candida haemluonii
- some candida glabrata
which species are resistant to voriconazole?
- mucormycosis
- fusarium solani
- rarer aspergillus species (lentulus, ustus, calidoustus)
which species are resistant to posaconazole?
- mucormycosis (variable)
- fusarium solani
- rarer aspergillus species (lentulus, ustus, calidoustus)
which species are resistant to echinocandins?
- Cryptococcus
- Trichosporon
- Molds other than aspergillus
Basics of voriconazole?
- Good CSF levels, none in urine
- Use oral formulation in azotemia
- Drug interactions: photosensitivity, hallucinations, hepatitis, visual changes, peripheral neuropathy
- Long term use need to worry about skin cancer, periostitis (bone pain, alk phos, plasma fluoride high)
what combination therapy can you use for invasive pulmonary aspergillosis?
- voriconazole + echinocandin
- Isavuconazonium/isavuconazole (Cresemba)
basics of cresemba?
- no drug in CSF or urine
- teratogenic
- approved for mucor
- noninfrior to vori in invasive aspergillosis
- no dose change for renal or liver failure
basics of posaconazole?
- approved for prophylaxis in GVHD or prolonged neutropenia
- can use in mucor once responded to ampho
- CYP3A4 inhibitor
- well tolerated, check trough levels
basics on echinocandins?
cryptococcus, trichosporon resistant
no drug in urine
poor penetration into CSF and vitreous humor of eye
all candida species susceptible
active against mold aspergillus
basics on ambisome?
- deoxycholate formulation: conventional ampho b
- liposomal formulation: ambisome
- low urine concentrations
- penetrates CSF and vitreous humor poorly
- can cause acute chest pain or back pain with the first infusion
- potassium wasting in urine
basics of flucytosine?
- 100% bioavailability
- good levels in CSF and urine
- drug resistance arises during monotherapy
- Used with ampho in cryptococcal meningitis
- Accumulates in azotemia: bone marrow depression, hepatitis, colitis
- leukopenia, thrombocytopeenia, diarrhea, hepatitis
what can you use to treat a Scedosporium apiospermum lung abscess?
- oral voriconazole, no dose adjustment in azotemia
- Itraconazole relatively contraindicated in HF
- ampho has little efficacy
- Echinocandins not active
primary treatment for mucor?
ampho
Azole interacts with what drugs? (increase/decrease)?
Increase drug levels: cyclosporine, tacrolimus, steroids, imantinib
phenytoin, rifmapin decrease azole levels
when organisms can you not use ampho?
Not Scedosporium, candida lusitaniae, asperillus terreus
what do you need to watch out for while on ambisome?
renal failure, hypokalemia, hypomagnesemia, pancytopenia, hepatitis
