Fungi part B Flashcards
why less antifungal drugs
fungi very similar to human cells
what mycoses are easier to treat?
• easier to treat superficial mycoses than systemic infections
ergosterol
Sterol found in fungal cell membranes;
human cells have cholesterol instead of ergosterol
where is egrosterol concentrated?
at the growing membrane ends
Polyene compounds
action
names and when used?
bind ergosterol in fungal membranes, Drugs cause altered membrane permeability,
leakage of cell constituents, and cell death
Amphotericin B: systemic disease
Nystatin: topical disease
polypenes also bind?
Polyenes also bind cholesterol in mammalian
cells, but less strongly than ergosterol
• this is basis for drug toxicity
• filipin is toxic due to binding of cholesterol
Abbreviated summary of the ergosterol biosynthetic pathway and the sites of action of ITZ
and TBF.
Allylamines action? name? mainyl effective on? formulations?
block ergosterol synthesis by inhibiting squalene epoxidase activity
terbinafine
mainly effective on the dermatophytes
topical or tablet formulations
Azoles
action?
names?
block ergosterol synthesis by inhibiting cytochrome P450-dependent 14a-lanosterol demethylation (c14 demethylase inhibiton)
ketoconazole and itraconazole
ketoconazole
First oral azole (significant number of side effect and drugs interactions)
itraconazole
active against?
improve safety?
Supplants ketoconazole
Active against many fungi and has improved safety profile.
Active against Candida species,Cryptococcus, Aspergillus, endemic (systemic) fungi, and dermatophytes.
Fungal cell wall structure diagram
Echinocandins action? selective? spectrum? why? name? mode of administration/ toxicity?
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
Caspofungin - Intravenous use and minimal toxicity
Pyrimidine inhibition
effective against what spp?
why used with other agents?
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
High risk categories for oppurtunistic mycoses
Immunocompromised individuals: blood and marrow transplant solid organ transplant major surgery AIDS neutropenia neoplastic disease (cancer patients) immunosuppressive therapy (e.g. corticosteroids) advanced age premature birth
Burn victims
Long-term IV catheter users
Broad-spectrum antibiotic therapy
Diabetes mellitus
Candidiasis related spp/ important features?
Candida albicans= predominant species colonizing humans responsible for most infections
Candida glabrata= resistant to some antifungals
Candida parapsilosis= common cause of catheter-related infections
several other species of Candida
Candidiasis
local disease vs. systemic invasive disease protections?
what prevents mucosal candidiasis?
Adequate neutrophil function protects against invasive infection, mainly local infections
Local factors and T-cell mediated defense system protects against mucosal candidiasis.
Mucosal candidiasis due to?
Due to decreased T-cell mediated immunity
Other host factors associated with protection against Candida infections:
salivary flow and constituents
blood group & secretor status
epithelial barrier
presence of normal bacterial flora
Most common opportunistic fungal pathogen
candida spp
Oral Candida
infections
acute pseudomem acute erythematous chronic plaque-like chronic erythematous angular chelitis
acute pseudomem candidasis
removable white plaques
acute erhtmatous candidasis
generalized redness/ sore tissue
Plaquelike/nodularcandidiasis
fixed white plaque at the commissures, cannot be removed
Also called chronic hyperplastic candidiasis or candidal leukoplakia
Up to 40% of lesions develop into oral cancer
Chronic erythematous candidiasis
general redness of tissue on surface fitting denture
angular chelitis
bilateral cracks at angles of the mouth, often a bacterial component
Mucosal candidiasis diagnosis
scrape and look under the microscope
culture
Invasive candidiasis diagnosis
blood culture not sensitive
biopsy of involved tissue: microscopy and culture
Staining methods to visualize fungi in clinical samples:
periodic acid-Schiff (PAS)
-surface carbohydrate
potassium hydroxide (KOH)
-tissue dissolves, fungi do not (chitin)
Grocott-Gomori methenamine silver
-surface carbohydrate
Gridleys method
-modification of PAS
Calcofluor white
-fluorescent probe for chitin
candia auris as an issue?
Drug resistant and spreads in healthcare facilities
Why Candida Aruis is such a problem
most people infect with C. Auris are?
already ill
Cryptococcus neoformans causes?
Cryptococcosis
Cryptococcus neoformans exposure where? why? when in the body begin to? purpose? crucial for infection control? melanin?
found worldwide in soil contaminated with bird excreta
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
Cryptococcus neoformans pt population
20% of patients with cryptococcosis appear to be immunocompetent
Cryptococcus neoformans primary infection symptoms
Primary pulmonary infection is usually asymptomatic
Cryptococcus neoformans trophism? significance?
C. neoformans has a striking neurotropism (basis is unknown)
minimal inflammatory response with CNS infection
Patients often present with meningitis, which worsens
Cryptococcus neoformans diagnosis
cryptococcal meningitis - examine CSF for encapsulated budding yeast
latex agglutination test for capsular polysaccharide antigen (CSF fluid and serum)
Cryptococcus neoformans treatment length
several months
sometimes lifelong therapy required
(patients with T cell defects)
Aspergillosis spp
Aspergillus fumigatus and Aspergillus flavus
Aspergillus fumigatus and Aspergillus flavus expsoure
acquired from the environment by inhalation of conidia
Aspergillosis infection
what individuals? type of growth?
Present as what kind of infection?
invasive?
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
sample contamination?
culture on Sabouraud’ s agar (grows in a few days)
caution: contamination from environment can easily occur tissue biopsy
Aspergillosis mortality/treatments
high mortality expanded-spectrum azole= voraconazole decreased exposure (filtered air)
Zygomycosis genera
septate/ hypahe?
Rhizopus and Mucor are main genera in this group
aseptate, broad hyphae
Zygomycosis invasive?
angioinvasive
Zygomycosis risk groups, additonal group? why?
in addition to standard risk groups, patients with diabetes mellitus with ketoacidosis
- acidosis reduces neutrophil chemotaxis and phagocytosis
Rhinocerebral zygomycosis
spread from nares/sinuses to palate, orbit, face then to brain
zygomycosis tx
amphotericin B and aggressive surgical debridement
Pneumocystosis spp
Pneumocystis jiroveci- never grown in vitro
Pneumocystis jiroveci infection/ disease when?
most people likely are infected early in life, but disease only occurs due to
immunosuppression (T cell deficiency most common risk factor)
Pneumocystic pneumonia
most common opportunistic infection in AIDS patients before effective antiviral therapy
Organism rarely found outside lungs
Pneumocystosis tx, what is missing from this spp?
trimethoprim-sulfamethoxazole (also used prophylactically)- target folic acid synthesis and utilization
note: P. jiroveci lacks ergosterol
