Chapter 46-50 Fungi 2 Flashcards
why are there fewer effective agents for antifungal drugs
because of similarity of fungal cells and human cells
easier to treat superficial mycoses than ____
systemic infections
where is ergosterol found
in fungal cell membranes
what do human cells have instead of ergosterol
cholesterol
what do polyene compounds do
-bind ergosterol in fungal membranes
- leakage of cell constituents and cell death
- bind cholesterol in mammalian cells but less strongly than ergosterol
what are the polyene compounds and what are they used for
-amphotericin B: systemic disease
- nystatin: topical disease
what is the basis for polyene toxicity
polyenes bind cholesterol in mammalian cells but less strongly than ergosterol
why is filipin toxic
binding of cholesterol
what does terbinafine target
squalene epoxidase
what does itraconzole target
C14 demethylase
what do allylamines do
block ergosterol synthesis by inhibiting squalene epoxidase activity
- mainly effective on the dermatophytes
- topical or tablet
what do azoles do
block ergosterol synthesis by inhibitins cytochrome P450 dependent 14alpha lanosterol demethylation
what does azoles supplant
ketoconazole
what are azoles active against
-candida
- crytococcus
- aspergillus
- endemic fungi
- dermatophytes
what do echinocandins do
-inhibit synthesis of Beta 1-3 D glucan - an essential component of fungal cell walls
what are echinocandins active against
aspergillus and candida
describe caspofungin and what category it falls under
- echinocandins
- intravenous use
- minimal toxicity
what does pyrimidine inhibition do
interferes with fungal protein and DNA synthesis
what are pyrimidine inhibitors active against
candida species and crytpococcus neoformans
why are pyrimidine inhibitors always used in combination with another antifungal
resistance develops quickly if used alone
what are the opportunistic mycoses
-candiasis: candida albicans
- aspergillosis: aspergillus funigatus
- crytococcosis: cryptococcus neoformans
- zygomycosis: zygomycetes
- pneumocystits pneumonia: pneumocystis jiroveci
what are the high risk categories for opportunistic mycoses
- immunocompromised individuals
- blood and marrow transplant
- organ transplant
- major surgery
- AIDS
- neutropenia
- neoplastic disease
- immunosuppressive therapy
- advanced age
- premature birth
- burn victims
- long term IV catheter users
- broad spectrum antibiotic therapy
- DM
what are the candidiasis organisms
- candida albicans
- candida glabrata
- candida parapsilosis
what is the common cause of catheter related infections
candida parapsilosis
what protects against mucosal candidiasis
local factors and T cell mediated defense system
what protects against candidiasis invasive infection
adequate neutrophil function
what are other host factors associated with protection against candida infections
- salivary flow and constituents
- blood group and secretor status
- epithelial barrier
-presence of normal bacterial flora
what are the virulence factors of candida
- adherence capability proportional to virulence rnaking of species - candida cell surface glycosylation affects adherence
- secreted enzymes
- phenotype switching: yeast to psuedohypha transformation, cell wall glycoprotein expression, proteolytic enzyme secretion
what is the clinical presentation of chronic pseudomembranous candidiasis
multiple removable white plaques
what is the clinical presentation of candida associated angular chelitis
bilateral cracks, angles of mouth
what is the clinical presentation of median rhomboid glossitis
fixed red/white lesion, dorsum of tongue
what is pseudomembranous candidiasis on palate also called
thrush
what is plaquelike/nodular candidiasis also called
chronic hyperplastic candidiasis or candidal leukoplakia
what percentage of lesions of plquelike/nodular candidiasis turn into cancer
40%
what other component often accompanies angular chelitis
bacteria
how do you diagnose mucosal candidiasis
scrape and look under the microscope culture
how do you diagnose invasive candidiasis
-blood culture not sensitive
- biopsy of involved tissue
- microscopy
- culture
what are the staining methods to visualize fungi in clinical samples
- periodic acid schiff (PAS): surface carbohydrate
- potassium hydroxide (KOH): tissue dissolves, fungi do not
- grocott-gomori methenamine silver: surface carbohydrate
- Gridley’s method: modificaion of PAS
- Calcofluor white: fluorescent probe for chitin
what drug is used to treat pseudomembranous candidiasis
amphotericin B lozenges
what drug is used to treat erythematous candidiasis
amphotericin B lozenges
what drug is used to treat plaquelike/nodular candidiasis
amphotericin B lozenges
what drug is used to treat denture associated candia lesions
miconazole oral gel
what drug is used to treat angular chelitis
miconazole oral gel
what drug is used to treat median rhomboid glossitis
amphotericin B lozenges
why is candida auris a problem
- causes serious infections
- resistant to medicines
- its becoming more common
- difficult to identify
- can spread in hospitals and nursing homes
where is cryptococcus neoformans found
in soil contaminated with bird excreta
what percentage of patients with cryptococcosis appear to be immunocompetent
20%
how does cryptococcus neoformans infect in the body
- yeast cells are inhaled in the alveoli and begin to produce a polysaccharide capsule
- capsule inhibits phagocytosis and intracellular killing
- T cell immunity crucial to infection control
- melanin production in cell wall enhances virulence
- resists free radicals and enzyme degradation
describe how patients with cryptococcus neoformans present
- usually asymptomatic
- has a striking neurotropism
- minimal inflammatory response with CNS infection
- patient often presents with meningitis which worsens
how is C. neoformans diagnosed
cryptococcal meningtis- examine CSF for encapsulated budding yeast
- latex agglutination test for capsular polysaccharide antigen
what is the treatment for C. neoformans
- cryptococcal meningitis
- drug therapy for several months
- lifelong therapy required for patients with T cell defects
how is aspergillosis acquired and how does it grow
- acquired from environment by inhalation of conidia
- grow as hyphae in immunosuppressed individuals usually as pulmonary or sinus infection
- angioinvasive: growth through blood vessel walls, cause tissue infarction, hemorrhage, necrosis
how is aspergillosis diagnosed
culture on Sabouraud’s agar
how is aspergillosis treated
- high mortality
- expanded spectrum azole voraconazole
- decreased exposure- filtered air
what are the main genera in zygomycosis
rhizopus and mucor
describe zygomycosis and risk groups
-aseptate, broad hyphae
- angioinvasive
- risk groups include DM with ketoacidosis
what is rhinocerebral zygomycosis
spread from nares/ sinuses to palate, orbit, face and to the brain
what is the treatment for zygomycosis
amphotericin B and aggressive surgical debridement
when are people infected with pneumocystis jiroveci
early in life in immunosuppressed patients
what is the most common opportunistic infection in AIDS patients
pneumocystic pneumonia
what is the treatment for pneumocystis jiroveci and what does it target
trimethoprim-sulfamethoxazole
- targets folic acid synthesis and utilization
P. Jiroveci lacks ____
ergosterol
