Fungi 2 Flashcards
- fewer effective agents because of similarity of fungal cells and human cells
- easier to treat superficial mycoses than systemic infections
Antifungal Drugs
Sterol found in fungal cell membranes; human cells have cholesterol instead of ergosterol
Ergosterol
-bind ergosterol in fungal membranes
Drugs cause altered membrane permeability,leakage of cell constituents, and cell death
bind cholesterol in mammalian cells, but less strongly than ergosterol
•this is basis for drug toxicity
•filipin is toxic due to binding of cholesterol
Polyene compounds
______ is a polyene compound used for systemic disease
Amphotericin B
______ is a polyene compound used for topical disease
Nystatin
- block ergosterol synthesis by inhibiting squalene epoxidase activity
- terbinafine
- mainly effective on the dermatophytes topical or tablet formulations
Allylamines
______ block ergosterol synthesis by inhibiting cytochrome P450-dependent 14a-lanosterol demethylation
Azoles
First oral azole (significant number of side effect and drugs interactions).
Ketoconazole
Supplants ketoconazole
Active against many fungi and has improved safety profile.
Active against Candida species, Cryptococcus, Aspergillus, endemic (systemic) fungi, and dermatophytes.
Itraconazole
_______:
inhibit synthesis of b-(1,3)-D-glucan, an essential component of fungal cell walls.
More selective than agents that target cell membrane components.
Narrow spectrum: active against Aspergillus and Candida species; these fungi have larger amounts of b-(1,3)-D-glucan
Echinocandins
______ is an Echinocandins
- Intravenous use
- minimal toxicity
Caspofungin
-interferes with fungal protein and DNA synthesis
Active against Candida species and Cryptococcus neoformans
Always used in combination with another antifungal because resistance develops quickly if used alone
Pyrimidine inhibition
_____: (candida species)predominant species colonizing humans responsible for most infections
Candida albicans
_____: (candida species) resistant to some antifungals
Candida glabrata
_____: (candida species) common cause of catheter-related infections
Candida parapsilosis
In candida, Adequate _______ function protects against invasive infection
neutrophil
______ and ________ protect against mucosal candidiasis.
Local factors and T-cell mediated defense system
Other host factors associated with protection against ______ infections:
salivary flow and constituents
blood group & secretor status
epithelial barrier,presence of normal bacterial flora
Candida
Which antifungal acts on the ergosterol biosynthesis pathway and opposes squalene epoxidase?
Terbinafine
Which antifungal acts on the ergosterol biosynthesis pathway and opposes C14-demethylase?
Itraconazole
_____ candida is characterized by multiple removable white plaques
Acute pseudomembranous candida
_____ candida is characterized by generalized redness of tissue
Acute Erythematous
_____ candida is characterized by fixed white plaques on commissures
Chronic plaque-like/nodular candida
_____ candida is characterized by generalized redness of tissue on fitting surface up upper denture
Chronic erythematous candida
_____ candida is characterized by bilateral cracks on angles of mouth
Candida-assocaited angular chelitis
_____ candidiasis
Thrush
lesions on palate that are easily wiped off
(a) Pseudomembranous candidiasis
_____ candidiasis at the commissure of the upper and lower lips (mucosal surfaces) (cannot be removed by scraping)
•Also called chronic hyperplastic candidiasis or candidal leukoplakia
•Up to 40% of lesions develop into oral cancer
c) Plaquelike/nodular candidiasis
_____ candidiasis on the palatal mucosa of an edentulous, full-denture wearing patient
b) Chronic erythematous candidiasis
_____ candidiasis: at commissures of the mouth, involving skin
Frequently has bacterial component involved
Angular cheilitis
Diagnosis of ______ candidiasis: scrape and look under the microscope culture
Mucosal candidiasis
Diagnosis of ______ candidiasis: blood culture not sensitive
biopsy of involved tissue
microscopy culture
Invasive candidiasis
_____ methods to visualize fungi in clinical samples:
periodic acid-Schiff (PAS) -surface carbohydratepotassium hydroxide (KOH)-tissue dissolves, fungi do not (chitin)Grocott-Gomori methenamine silver-surface carbohydrateGridleys method-modification of PASCalcofluor white-fluorescent probe for chitin
Staining
_______: is often resistant to medicines
- causes serious infections
- becoming more common
- Difficult to ID
- spreads in hospitals and nursing homes
- people that get this are usually already sick
C. auris
____ is found worldwide in soil contaminated with bird excreta.
20% of patients with cryptococcosis appear to be immunocompetent.
Yeast cells are inhaled in alveoli and begin to produce a polysaccharide capsule.capsule inhibits phagocytosis and intracellular killing (if cells phagocytosed)
T-cell immunity crucial to infection control
melanin production in cell wall enhances virulence resists free radicals and enzyme degradation
C. neoformansis
Primary pulmonary infection is usually asymptomatic
has a striking neurotropism (basis is unknown)
minimal inflammatory response with CNS infection
Patients often present with meningitis, which worsens
C. neoformansis
______ is diagnosed via cryptococcal meningitis -examine CSF for encapsulated budding yeast latex agglutination test for capsular polysaccharide antigen (CSF fluid and serum)
Treatment: cryptococcal meningitis and sometimes lifelong therapy required (patients with T cell defects)
C. neoformansis
acquired from the environment by inhalation of conidia
grow as hyphae in immunosuppressed individuals
usually a pulmonary or sinus infection
angioinvasive -growth through blood vessel walls
cause tissue infarction, hemorrhage, necrosis
Aspergillosis
Diagnosis: culture on Sabourauds agar (grows in a few days)caution: contamination from environment can easily occurtissue biopsy
Treatment: high mortality
expanded-spectrum azole voraconazole
decreased exposure (filtered air)
Aspergillosis
Rhizopus and Mucor are main genera in this group aseptate, broad hyphae
angioinvasive in addition to standard risk groups, patients with diabetes mellitus with ketoacidosis-acidosis reduces neutrophil chemotaxis and phagocytosis
Rhinocerebral -spread from nares/sinuses to palate, orbit, face then to brain Treatment amphotericin B and aggressive surgical debridement
Zygomycosis
Pneumocystis jiroveci- organism has never been grown in vitro
most people likely are infected early in life, but disease only occurs due to immunosuppression (T cell deficiency most common risk factor)
This pneumonia most common opportunistic infection in AIDS patients before effective antiviral therapy
Organism rarely found outside lungs
Treatment -trimethoprim-sulfamethoxazole (also used prophylactically)target folic acid synthesis and utilization note: P. jiroveci lacks ergosterol
Pneumocystosis
