May1 M1,2-Medical Mycology Flashcards
(important) SE of voriconazole (an azole) that is important to know
visual hallucinations
(important) important pathogenic superficial and invasive yeast
candida albicans
(important) where candida is in the environment
lives in our intestines normally, are normal commensals of humans
(important) step that is required for candida albicans to become virulent
morphological switching
(important) resistance pattern (fluconazole, echinocandin) of candida albicans
- fluconazole sensitive
- echinocandin sensitive
(important) resistance pattern (fluconazole, echinocandin) of candida glabrata
- fluconazole resistant
- echnicandin sensitive
- echinocandin = tx*
(important) resistance pattern (fluconazole, echinocandin) of candida parapsilosis
- fluconazole sensitive
- echinocandin sensitivie/intermediate
(important) resistance pattern (fluconazole, echinocandin) resistance of candida krusei
- fluconazole resistant
- echinocandin sensitive
- tx=echinocandin*
(important) resistance pattern (azole, echinocandin and amphotericin B) of candida auris
- fluconazole resistant
- echinocandin R or S
- amphotericin B resistant
(important) resistance pattern (fluconazole, echinocandin) main resistances to remember with candida
- glabrata and krusei resistant to fluconazole
- auris resistant to fluconazole and amphotericin B
(important) treatment of choice for all candida infections
- echinocandins IV
- for po, switch to fluco if it’s NOT glabrata or krusei (if it’s glabrata or krusei, switch to something else)
(important) necessary steps to increase the survival of patients with CANDIDEMIA (candidal blood infection) in the ICU
BOTH
- anti-fungal in <24 hours
- source control in <24 hrs (remove central vein catheter, surgical or radiological procedures to drain abscesses or fluid collections)
(important) other step of candidemia management after did anti-fungals + source control <24 hrs
assess for secondary sites of infection such a endophthalmitis, endocarditis, osteomyelitis
(important) cryptococcus spp (pathogenic yeast) 2 species
- cryptococcus neoformans (from trees and poop)
- cryptococcus gatti (from eucalyptus trees)
(important) cryptococcus spp infection: most important thing to do in your patients
manage their ICP (intracranial pressure) because of the possible, underlying fungal meningitis
(important) in patients with a significant hematologic disease (like having received a HSCT, having AML, an acute leukemia, etc.), what’s the most important cause of death
invasive aspergillosis (invasive infection by aspergillus fumigatus), an invasive mold
(important) 3 levels of diagnosis for invasive aspergillosis
- proven aspergillosis
- probable aspergillosis
- possible aspergillosis
(important) meaning of possible aspergillosis (dx)
- the patient is immunosuppressed
- one of these host factor criteria happened: neutropenia, persistant fever despite high-risk Abx, GVHD, prolonged CS use
- you suspect aspergillosis
(important) meaning of probable aspergillosis (dx)
-1+ of the 4 host factor criteria + clinical feature + galactomannan evidence
OR
-culture from sputum or BAL in immunocompromised pts with clinical signs
(important) meaning of proven aspergillosis (dx)
Proven on either of
- histopathology
- growh in culture from tissue bx or sterile site aspirate
charact of fungal cell wall (which is on top of cell membrane)
beta-glucan and other polysaccharides
what’s a hyphae
multicellular form of fungi appearing as threadlike filaments (mycelium = group of hyphae, also means hyphae)
molecule used in fungal cell membrane instead of cholesterol (which is only in animals)
ergosterol
3 types of anti-fungals acting on the cell membrane
- azoles (inhibit ergosterol synthesis)
- allyamines (inhibits early step in ergosterol pathway)
- polyenes (bind ergosterol and form MAC-like pores)
problem of polyenes
bind cholesterol too if no ergosterol around and this can be toxic
3 polyenes and their charact
- nystatin (only topical, very toxic)
- amphotericin B desoxycholate (binds cholesterol less)
- lipid-based formulations of amphotericin (added lipid carrier to reduce toxicity)
azoles and their charact
- fluconazole (most used): yeast only
- itraconazole
- voriconazole, isavuconazole, posaconazole = new and very good for mold (aspergillus included)
important SE of azoles
hallucinations (voriconazole)
allylamine used for what and why
- usually superficial (dermato) fungal infections and used topically
- because lipophilic and partition better to cells and keratin than blood
anti-fungal acting on DNA synthesis and action and used when
5-Flucytosine (5-FC)
- inhibits DNA chain synthesis (chemo-like)
- suppresses your BM and your microbiota
- only used in combination therapy for cryptococcus
anti-fungal acting on the cell wall, mode of action, acts on what fungi and route of administration
echinocandins (end with fungin)
- inhibits beta 1,3 glucan synthase
- active on fungi with beta glucan so: yes = candida and ascomycetes no = cryptococcus, histoplasma, zygomycetes
- IV only bc big molecule
hypersensitivity reactions to fungi (not anti-fungals): why happens and its charact + typical organism causing it
- sensitized bc fungi pump out enzymes to eat us + we think they’re parasites (IgE, eosinophils, etc.)
- mast cell degranulation, histamine release (asthma, rhinitis, pneumonitis, sinusitis)
- aspergillus spp*
how fungal disease is classified
- superficial by a. yeast or b. mold
2. invasive by a. yeast b. mold c. dismorphic
types of diseases that yeast (unicellular fungi) cause
syndromes like bacterias cause: meningitis, fever, infection
types of diseases that molds cause
focal local infections (lung or skin) and eat everything in their path leaving no cells alive. Then metastasize to seed elsewhere like a cancer
(important) 2 pathogenic yeast
- candida spp
- cryptococcus spp
symptoms of superficial candidiasis
- OPC (oropharyngial candidiasis = thrush) (T cell prob)
- eosphageal candidiasis (T cell prob)
- vaginitis (Abx impaired vaginal microbiome)
- skin and nail infections
invasive candidiasis symptoms
sepsis (after breaches in mucosal surfaces, chemo, IV catheters, intestinal surgery)
(important) most common candida spp for deep infections
candida albicans
antifungal used in candidemia (candida in the blood) treatment
caspofungin (an echinocandin. cell wall synthesis inhibition. works for candida but not cryptococcus)
steps of infection and symptoms in a cryptococcus infection
- pulmonary infection (asymptomatic)
- then disseminates*
- PRESENT AS MENINGITIS
cryptococcus neoformans infections happen in who and present how
- in T cell deficiency states (SOT, T cell modifying therapy, untreated HIV)
- present as chronic meningitis
cryptococcus gattii infections happen in who and present how
- in immunosuppressed
- present as meningitis
Vancouver cryptococcus outbreak was caused by what, symptoms and affects who
- cause = combination of gattii from Australian eucalyptus and native BC gattii
- immunocompetent patients
- pneumonia and meningitis
how to diagnose fungal (cryptococcus meningitis): best method, used now
Antigen testing
- cryptococcal capsule sheds in serum and CSF
- latex agglutination to check for them
treatment of cryptococcus meningitis
- liposomal (lipid) amphotericin (a polyene, ergosterol binding drug)
- after weeks, downgrade to fluconazole (an azole, inhibits ergosterol synthesis)
(important) 2 dimorphic fungi (invasive)
- histoplasma casulatum
- blastomyces dermatidis
difference between patients that have yeast infections (candida or cryptococcus spp) and dimorphic fungi infections
yeast = immunosuppressed patients
dimorphic fungi = healthy patients
endemic mycoses stands for what
dimorphic fungi infections have specific endemic zones
- histoplasma casulatum = histoplasmosis
- blastomyces dermatiditis = blastomycosis
2 forms of dimorphic fungi (endemic mycoses)
- yeast form (in tissues) at 37C
- mycelial (saprophytic) form at 25C
what infection do you get in bat caves
histoplasmosis
reservoirs of histoplasma casulatum
nitrogen rich soils. includes
- river valleys
- bats and bat caves (because is in bat guano)
- bird poop also
tunnel construction associated with what infection in nearby communities and why
histoplasmosis (histoplasma casulatum). because stirring up the soil is the best way to infect people
histoplasmosis symptoms and stages
- inhale, stays in lungs and is latent or symptomatic with possible dissemination. calcified granulomas on CXR
- latent can reactivate when T cell depleted (immunosuppressed)
reservoir of blastomyces dermatiditis
- trees
- rotten hard woods
blastomycosis symptoms and stages
- inhale, stays in lungs and is latent or symptomatic with possible dissemination.
- latent can reactivate when T cell depleted (immunosuppressed) + can also disseminate (ON THE SKIN) when reactivated
where blastomycosis relapses and typical specific location
- on the skin. verrucous cryptic ulcer lesions
- usually testicles and male genitalia bc prefers cold places
how to dx endemic mycoses (dimorphic fungi infections)
- pulmonary syndrome = culture, bronchoalveolar lavage
- disseminated disease = blood culture
- Ag testing on urine is possible
treatment of endemic mycoses
- pulmonary syndrome = azole (itraconazole, voriconazole)
- disseminated or severe = amphotericin B (a polyene)
- no echinocandins, not much cell wall*
superficial mold infections: think of what type of fungi usually
dermatophytes (molds)
dermatophytes def + 3 genera
molds that only grow superficially on skin and eat keratin only
some dermatophytes causing infections in humans
- T rubrum
- T mentagrophytes
- E. floccosum
tinea pedis (athletes foot) def + 2 types
- dermatophyte infection (T rubrum, T mentagrophytes or E floccosum)
- interdigital type or mocasin (plantar) type
treatment of tinea pedis
topical azoles or allylamines
tinea corporis (ringworm) def and tx
- dermatophyte infection (T rubrum or T mentagrophytes) of the SKIN. round plaque
- tx = topical azoles or topical terbinafine (an allylamine)
tinea unguium (onychomycosis) def and tx
- infection of the nail plate, common in elderly. nail looks yellow
- tx = topical azole or terbinafine (an allylamine) for a year (to grow a whole nail bc Abx doesn’t reach penetrate the nail)
diagnosis of dermatophytes (tinea pedis, corporis and tinea unguium)
scrape dead flakes of skin, calcofluor dye, look for hyphae
who gets invasive mold infections (aspergillus and other molds)
immunosuppressed patients (chemo, BMT, organ transplant, high dose CS) OR LOCALLY immunocompromised
invasive molds infect what regions of the body (typical syndromes)
pulmonary or sinonasal infection
dissemination follows
aspergillosis on CXR
crescent sign (dead piece of lung)
why aspergillosis dx is hard and has a specific diagnostic division (proven, probable, possible)
- you can’t dx molds with blood cultures bc do local dissemination
- 30% sensitivity BAL
non culture diagnostic test for aspergillosis (only allows probable diagnostic (not proven) if positive)
- galactomannan assay (a part of fungal cell wall)
- check for a certain level of it in serum or BAL fluid (bc it sheds normally)
- 75% sensitivity serum. 90% sensitivity BAL
4 steps of management of IFI (invasive fungal infections)
- prophylactic (asymptomatic high-risk)
- empiric (high risk Abx + fever)
- preemptive (high risk + novel dx with markers)
- therapy (full blown disease). evidence of infection
good and bad things with different steps of IFI management
- early tx = better tx but tx more patient (prophylactic. asymptomatic high risk)
- late tx = tx someone infected for sure and preserving the drugs but less successful in saving lives
(important) treatment of invasive aspergillosis
voriconazole
2 classical subcutaneous mycoses caused by local immune suppression and local inoculation due to trauma or wtv
- chromoblastomycosis (multiple fungi, like dermatiaceous molds)
- eumycotic mycetoma (caused by fungi and is not actinomycotic mycetoma caused by the bacteria actinomyces)
treatment of chromoblastomycosis and eumycotic mycetoma
amphotericin B (polyene) and mold active azoles
what’s sick building syndrome
- chronic fatigue, resp illness and general malaise
- caused by mycotoxins from fungi present in buildings and degrading their environment, making complex molecules
- we inhale mycotoxins
something that mycotoxins are 100% certainly associated with
allergies, asthma, rhinitis
not sick building syndrome
