Mycology Flashcards
Structural components of fungi
- Chitin; cell wall- polymer of N-acetyl glucosamine mannans, glucans and other complex carbohydrates
- Ergosterol; cell membrane
Types of fungi
- Mold: filamentous form of fungi
- Yeast: oval-shaped, single-celled form of fungi
- Dimorphic fungi: fungi that can grow both as a mold and as a yeast
- Dematiaceous fungi: black or brown pigmented fungi
*phaeohyphomycosis- infections caused by dematiaceous fungi
Hyphae
- Filaments or tubular structures of molds
- Hyphae w/cross walls (septa) are septate; Aspergillus
- Hyphae w/o septa are coenocytic (aseptate; nonseptate; Mucormycetes
Pseudohyphae
- Hyphae-like structure formed by incomplete budding of yeast cells
- Candida albicans
Mycelium
- Mass of intertwined hyphae
Telemorph
- Fungal form producing sexual spores
Anamorph
- Fungal form producing asexual spores
Common mycoses in the US
- Superficial mycoses
*Tinea versicolor; malassezia furfur- normal skin flora
- Cutaneous mycoses
*Dermatophytes; cause ringworm, also known as tinea
*Cutaenous/ mucocutaneous candidiasis
- Subcutaneous mycoses
*Sporotrichosis- Sporothrix schenkii
Gomori’s methenamine silver
- Stain for clinical specimens of fungi
Detection of fungal infections chart
Echinocandins
- Inhibotor of fungal cell wall synthesis
- Inhibits beta-glucan synthase; cell wall beta-(1,3)-glucans are not made; forms glucan polymers in the cell wall
- Disrupts the osmotic environment of the cell, as well as cell division and growth
- Active against fungi where beta-(1,3)-glucans are a dominant component of the cell wall
*Candida
*Aspergillus
*Invasive candidiasis and invasive aspergillosis when amphotericin B is not effective
Allyamines
- Inhibitor of ergosterol synthesis
*inhibits squalene epoxidase (Squalene epox. transforms squalene into lanosterol which gets transformed through a few more reactions to Ergosterol)
- Decrease Ergosterol = Increase Squalene in the cell membrane
*squalene is toxic to the cell
- Accumulates in skin and nails
- Terbinafine
*oral form of terbinafine => nail infections
*topical forms => skin infection
- Side effects- GI upset, headache
Azoles
- Imidazoles and triazoles
- Inhibitor of ergosterol synthesis
*inhibits lanosterol 14-alpha-demethylase
+cytochrome P-450-dependent enzyme, which converts lanosterol to ergosterol
+binds to the heme moiety of cytochrome P-450
Imidazole
- Non-ketoconazole imidazoles- topical medications
*cutaneous and mucocutaneous candida infections and dermatophyte infections
- Ketoconazole
*tablets, creams and shampoos
*cutaneous infections, dimorphic mycoses and cryptococcus neoformans
*side effects- nausea, vomiting, anorexia and occasionally hepatotoxicity
*interferes w/steroid hormone synthesis and some drug metabolism
Triazoles
- Greater specificity for the fungal cytochrome P-450 enzyme than imidazoles = few side effects than ketoconazole
- Broad spectrum of activity
*candidiasis (cutaneous and invasive), dermatophytes, endemic mycoses, Cryptococcus neoformans and Aspergillus infections
Fluconazole
- Azole
- Cryptococcal meningitis
*good CNS penetration
*also mucocutaneous candidiasis; coccidioidal meningitis
*used as prophylaxis in bone marrow transplants
Itranconazole
- Azole
- Prophylaxis in neutropenic patients
- Dermatophyte infections; onychomycosis
Voriconazole
- Azole
- Invasive asperigillosis
- Also candida and dimorphic fungi
Posaconazole
- Azole
- Mucormycosis
- Also Candida and Aspergillus
Amphotericin B
- Polyene
- Antifungal that bind ergosterol producing ion channels; membrane becomes leaky; cell death
- Oxidation of drug generates toxic free radicals
- Binds cholesterol, but w/a lower affinity
- Toxicity
*renal impairment
*loss of K+ and Mg+
*infusion reaction (fever, chills, tachypnea)
*abnormal liver function tests (occasionally)
- Lipid formulations are less toxic
*higher doses can be used
- Broad spectrum antifungal; used for systemic infections
Nystatin
- Same mechanism as amphotericin B
- Not absorbed so it is not present in tissues
- Not used for systemic infections
- Used for cutaneous or mucocutaneous candidiasis
Flucytosine
- Inhibitor of intracellular processes
- Enters cells via cytosine permease
- Competes w/ uracil for RNA synthesis
- Inhibits both RNA and DNA synthesis
- Used for cryptococcal meningits, some Candida
- Not used as monotherapy b/c of the pssibility of developing resistant organisms
Candida clinical infections
- Responsible for ~95% of blood stream infections
- Hospital-acquire candidemia
- Can infect any organ system
*especially kidney, brain, liver, skin, eye
- Serious complication in compromised patient; often fatal
- AIDS patients
*oral thrush or esophagitis
*recurrent vaginal candidiasis
- Complication following:
*transplants (liver, kidney, bone marrow)
*abdominal surgery (peritonitis)
*cardiac surgery (endocarditis)
Patient population/risk factors for Candida infections
- Cellular immunodeficiency
*AIDS, chronic granulomatous disease
*neutropenic patients often given fluconazole prophylaxis
*C. glabrata seen often in ICUs b/c of widespread fluconazole use
- Immunosuppresive treatments
*bone marrow transplate patients, leukemis patients
- Patients w/indwelling catheters, intravenous lines or prosthetic devices
- Patients receiving corticosteroid treatment
- Most important risk factor for invasive candidiasis is a prolonged stay in the ICU
Candida Infection Diagnosis
- Specimens:
*tissue biopsies, sputum, CSF, blood, urine
*budding yeat cells and pseudohyphae seen microscopically
- Positive culture from normally sterile site is significant
*blood cultures are positive in only ~40-60% of cases of candidemia
*selective chromogenic medium differentiate species by color and morphology; CHROMagar
- Circulating candidal antigens are indicative of systemic infection
*antibody titers arent diagnostic
- Germ tube test is used to identify C. albicans
- Commercial test now available that looks for Beta-D-glucan
*fungitell assay- modified Limulus lysate assay
*highly sensitive, rapid diagnostic test that detects (1 => 3)- Beta-D-glucan in serum
