Fungal Flashcards
Examples of azoles?
Fluconazole
Itraconazole
Voriconazole
Posiconazole
Mechanisim of action of azoles?
inhibit ergosterol synthesis via inhibiton of CYP 450 enzyme
Ergosterol is a vital part of the cell membrane
Indications for fluconazole?
Candida Albicans infection
- not good for non-albicans candida
Indications for Itraconazole?
Aspergillous, Candida
Indications for Voriconazole?
All candida species and aspergillous
Indications for Posiconazole
Candida (all species)
Aspergillous
Zygomycosis (mucor etc.)
Cautions in use of azoles?
CYP3a4 inhibitors
P-glycoprotein inhibitors
Lots of drug interactions
Caution in renal impairment
Example of a polyene anti-fungal?
Amphotericin B
Mechanism of action of amphotericin B
Binds to sterols in cell membrane and increases membrane permeability and pore formation
Indications for amphotericin B
Aspergillous
Cryptococcus (first line for cryptococcal meningitis)
Mucor/Fusarium
Candida - particularly C. Glabrata and C. Krusei
Side effects of amphotericin B
Renal impairment
Distal type 1 RTA
Electrolyte wasting
Infusion reaction
*Note - liposomal preparation decreases drug toxicity
Mechanism of echinocandins?
inhibits synthesis of glucan in cell wall thereby inhibiting cell wall synthesis
Example of echinocandin?
Caspofungan
Indications for echinocandins?
Candida
Aspergillous
Mechanism of action of Flucytosine?
inhibitor of fungal DNA synthesis
Indications for flucytosine?
Cryptococcus
Candida
What are some side effects of flucytosine?
Bone marrow suppression
Raised LFTs
Treatment of crytpococcal meningitis?
Amphotericin B and flucytosine for 6 weeks - crosses BBB
Followed by fluconazole maintaince
Risk factors for systemic candidiasis?
loss of gut integrity (particularly upper abdomen)
prolonged neutropenia (chemotherapy/immunosuppression)
central lines, TPN
Haemodialysis
ICU patient
Clinical manifestations of disseminated candida?
sepsis
eye lesions - white exudates on retina
skin lesions - papules or pustules with an erythematous base
abscesses in liver, spleen, kidney, lungs, brain
Treatment of disseminated candida?
Fluconazole if not C.glabrata or krusei and not severely unwell
Otherwise Voriconazole, Caspofungin, amphotericin B
What is galactomannan assay?
a component of the cell wall of aspergillous that can be measured in serum
What is the first line treatment for disseminated aspergillous?
Voriconazole
What is the treatment for aspergillioma?
surgical removal
Risk factors for mucor infection?
haematologic malignancy
poorly controlled diabetes
severe burns
iron chelating therapy (desferrioxamine)
Complications of cryptococcus meningitis?
hydrocephalus
cryptococcoma