Fungal Infections Flashcards
What are two major risk factors for Aspergillus infection?
Neutropenia, chronic granulomatous disease, lung dysfunction (asthma, emphysema)
Which species of Aspergillus is most commonly pathogenic in humans?
A. fumigatus
What is the infectious agent of Aspergillus?
The spores, or conidia
Describe the three steps in the pathogenesis of Aspergillus.
(1) Germination of the spores, (2) hyphal extension, (3) mold extension into vasculature
What is the presentation and the worst course of invasive aspergillosis?
It presents with respiratory symptoms and fever like a primary pulmonary infection, but can worsen to organ dissemination and can even spread to the CNS
What sorts of patients usually develop chronic aspergillosis?
Patients with altered anatomy (e.g. emphysema patients) but intact immune systems
What is an aspergilloma and why can it develop?
It is a fungal ball and can develop when patients have lung cavities (sometimes due to past TB)
How is allergic bronchopulmonary aspergillosis treated and why is it different from the usual tx?
It is treated with anti-inflammatories because it is an allergic reaction to the mold in asthma patients, and there is minimal hyphal extension
What are two crucial antigens in blood/BAL that can indicate Aspergillus?
Galactomannan and β-D-glucan
What is the appearance of Aspergillus under the microscope?
Regular, septate hyphae with acute angle branching
What is the radiographic appearance of invasive aspergillosis?
“Air crescent” sign of lungs, which forms as dead tissue is expectorated
What is the best treatment for aspergillosis?
Due to diagnostic challenges, empiric tx for this disease is crucial; mold-active azoles (voriconazole is the best), amphotericin B, echinocandins are less effective; surgical debridement can be indicated
What are two morphological characteristics of mucorales or zygomycete fungi?
Rapidly growing hyphal molds (grow on bread), broad hyphal diameter, few septa, ribbon-like folding in tissue
What is the classic (and most deadly) presentation of mucormycosis?
Rhinocerebral infection that spreads from the sinuses into other facial structures and even into the brain
What is the critical sign of rhino cerebral mucormycosis?
Palatal eschar, a necrotic lesion on the hard palate
What are alternate (less common) presentations of mucormycosis?
Pulmonary or GI infection
What is the most effective diagnostic tool for mucor infection? What is ineffective?
Radiography is not effective because it is not specific; culture is a terrible idea because of contamination risk; histopathology is the move because you can see the ribbon-like, aseptate hyphae
What is the treatment for mucormycosis?
Surgical debridement is really the only effective therapy; antifungals are not effective; Fe modulation has been approached as a potential therapy
What is a major endemic fungus of the Southwest USA?
Coccidioides immitis/posadasii
Distinguish the primary and chronic infections in coccidiomycosis/“valley fever.”
The primary infection is a self-limiting respiratory infection, while the secondary causes chronic pneumonia, skin, or eosinophilic meningeal infections
Name the two different structures present in the tissue vs environmental forms of Coccidioides.
The tissue form contains spherules, or sacs of yeast cells while the environmental form has hyphae with many arthroconidia
What is a major endemic fungus of the Ohio/Mississippi River valleys?
Histoplasma spp.
Distinguish the primary and chronic infections in histoplasmosis.
The primary infection is a self-limiting respiratory infection, while the secondary causes chronic pneumonia, hiding in macrophages and DCs for years until it emerges, causing infections in AIDS or anti-TNF patients
What is a major endemic fungus of the Great Lakes region?
Blastomyces spp.
Distinguish the primary and chronic infections in blastomycosis.
The primary infection is a self-limiting respiratory infection, while the secondary causes chronic pneumonia, skin/bone lesions, and male GU tract issues.
What is the defining characteristic of paracoccidiomycosis?
The captain’s wheel form in culture
Describe the course of Sporothrix infection.
Primary skin inoculation followed by proximal spread via lymphatics causing “nodular lymphangitis”
What is the mechanism of amphotericin B?
It binds ergosterol and forms pores in membrane, which disrupts the structure and causes cell death
What are two major adverse effects of amphotericin B?
Renal toxicity and electrolyte changes; ototoxicity, altered vestibular function causing hearing loss and ringing in ears
Which formulation of amphotericin B minimizes adverse effects?
Lipid associated amphotericin B
What is the spectrum of amphotericin B?
Cryptococcal meningitis (induction phase); systemic mold infections (mucormycosis); serious endemic fungal infections; resistant Candida infections
What is the mechanism of triazoles?
Inhibit the Erg11 protein in the ergosterol synthesis pathway
What are two major adverse effects of triazoles?
P450 enzyme inhibition can cause liver and drug metabolism issues; QT prolongation
Which azoles are mold-active and which are yeast-active?
Fluconazole is yeast-active and voriconazole, itraconazole, and posaconazole are mold-active
What is the usage of fluconazole?
Candida, Cryptococcus neoformans maintenance-phase therapy
What is the usage of the mold-active azoles?
Systemic infections of Aspergillus fumigatus; invasive yeast infections; endemic fungal infections
What is the mechanism of echinocandins?
Inhibit β-glucan synthesis
What is the usage of echinocandins?
Serious Candida infections like candidemia; second-line therapy for Aspergillus
What is the usage of flucytosine?
C. neoformans meningitis, induction phase in combination with amphotericin B; never alone
