Fungal infections Flashcards
- List three examples of:
a. Yeast
b. Moulds
a. Yeast Candida Cryptococcus Histoplasma (dimorphic) b. Moulds Aspergillus Dermatophytes Agents of mucormycosis
- Describe the appearance of Candida under the microscope.
Single-celled organisms that replicated by budding
They are much bigger than bacteria
- Which systemic infections can be caused by Candida?
Septicaemia, endocarditis, meningitis
- List some patient groups that are at risk of invasive Candida infection.
VLBW infants
Immunocompromised
Patients on ITU (especially if they have lines in)
Patients receiving TPN (Toal parental nutrition)
Immunocompetent patients who have had antibiotic treatment
- List some agents that can cause candidiasis.
Candida albicans (MOST COMMON)
Candida glabrata
Candida krusei
Candida tropicalis
- Describe a screening test for candidiasis.
Candida albicans forms a germ tube
Can be identified by microscopy
- What is the acute treatment for candida?
Fluconazole – empirical for Candida albicans, topical nystatin (oral thrush) and clotrimazole (vulvovaginitis)
- Outline diagnostic tests used for candidemia.
Swabs Blood cultures Beta-D glucan assay (serology) Imaging Fundoscopy – for endopthalmitis ECHO – endocarditis
- What type of agar is needed for culturing Candida?
Sabouraud agar – impregnated with antibiotics to prevent bacteria from outcompeting the fungi
- Outline the management of candidemia.
At least 2 weeks of antifungals after the last negative culture
Echinocandins – empirical for non-albicans infections
Take out any lines and repeat blood cultures every 48 hours
- What are the serotypes of cryptococcus and who do they affect?
Serotypes A and D – immunodeficient – C neoformans
Serotypes B and C – immunocompetent – C gattii
- What types of disease does Cryptococcus tend to cause?
Pulmonary, systemic and meningitic disease
- Which group of antifungals is Cryptococcus inherently resistant to?
Echinocandins
- What is the treatment of choice for Cryptococcus infection?
Ambisome (amphotericin B)
- Which patients are particularly at risk of cryptococcosis?
Impaired T cell immunity (AIDS)
- What does Cryptococcus gatii cause?
Causes meningitis in immunocompetent individuals in tropical countries
High incidence of space-occupying lesions in the lung and brain
Increasing resistance to amphotericin B
- Describe the appearance of Cryptococcus under the microscope.
Distinct capsule around the yeast
India ink can be used to stain
NOTE: the capsule is not always present
- Outline the treatment options for Cryptococcus infection.
3 weeks amphotericin B (ambisome) +/- flucytosine
Repeat LP for pressure measurement
Secondary suppression – fluconazole
- List the diseases that can be caused by Aspergillus.
Mycotoxicosis
Allergic bronchopulmonary aspergillosis
Aspergilloma
Invasive/disseminated disease
- List the aetiological agents that can cause Aspergillus infection.
Aspergillus fumigatus Aspergillus flavus Aspergillus niger Aspergillus niduland Aspergillus terreus
- List some investigations used in the diagnosis of Aspergillus infection.
Blood test Serology (check IgE for allergic response (e.g. ABPA)) • Antigen detection (galactomannan) • Also detected in BAL PCR Histology Culture
- What is the mainstay of diagnosis of Aspergillus infection?
Microscopy – looking at fungal spores
- What is the mainstay of treatment for aspergillosis?
Amphotericin for at least 6 weeks
Other options: voriconazole, caspofungin, itraconazole
- What is used to treat pneumocystic pneumonia?
High dose Co- trimoxazole (as it lacks ergosterol in its cell wall, therefore targeting the cell membrane will not work)
- List some examples of dermatophyte infections.
Ringworm
Tinea
Nail infections
- What is tinea pedis caused by?
Tricophyton rubrum
Tricophyton interdigitale
Epidermophyton floccosum
- What is tinea cruris caused by?
Tricophyton rubrum
Epidermophyton floccosum
- What is tinea corporis caused by?
Tricophyton rubrum
Tricophyton tonsurans
- What is onychomycosis caused by?
Tricophyton spp.
Epidermophyton spp.
Microsporum spp.
- How is onychomycosis treated?
Nail lacquers
If unsuccessful, systemic treatment with terbinafine
Itraconazole is also an option
- What is pityriasis versicolor caused by?
Malassezia furfur
- What is mucormycosis?
Group of moulds that cause very severe and invasive disease
- What is the characteristic clinical manifestation of mucormycosis?
Cellulitis of the orbit and face which progresses with discharge and black pus from the palate and nose
NOTE: black eschars may be seen as the fungus destroys tissues
- What can retro-orbital extension of mucormycosis lead to?
Proptosis, ophthalmoplegia and blindness
- List three aetiological agents that can cause mucormycosis.
Rhizopum spp.
Rhizomucor spp.
Mucor spp.
- How is mucormycosis managed?
SURGICAL EMERGENCY
Refer to ENT for debridement
May need high-dose amphotericin
- What are the three targets of antifungals?
Cell membrane
DNA/RNA synthesis
Cell wall
- List antifungals that target:
a. Cell membrane
b. DNA/RNA synthesis
c. Cell wall
a. Cell membrane Polyene – amphotericin B, nystatin Azole – ketoconazole, itraconazole, fluconazole, clotrimazole b. DNA/RNA synthesis Flucytosine (pyrimidine analogue) c. Cell wall Echinocandins – caspofungin acetate
- What is the mechanism of action of azoles?
Inhibit ergosterol production by inhibiting CYP450 enzyme lanosterol 14 alpha-demethylase
This inhibition leads to the accumulation of toxic steroids in the cell membrane which cause cell death
- What are the consequences of cross-reaction of azoles with other CYP450 enzymes?
Drug interactions
Impairment of steroidogenesis
Which fungi are polyenes effective against?
all fungi except Aspergillus terreus and scedosporium
What is a side effect of polyenes
nephrotoxicity
Renovascular – decrease in renal blood flow leads to reduced GFR (azotaemia)
Tubular – distal tubular ischaemia, wasting of sodium, potassium and magnesium
- What is the mechanism of action of echinocandins?
cyclic lipopeptide antibiotic that inhibits beta-(1,3) D-glucan synthase
This enzyme is responsible for the production of beta D-glucan which is a component of the fungal cell wall
This inhibition results in osmotic fragility of the cell
- Which fungi are echinocandins active against e.g. Caspofungin?
Candida species Aspergillus species (NOT other moulds)
- What is the main polyene antifungal?
Amphotericin B
- How is amphotericin packaged in most formulations?
Put in liposomes to try and reduce toxicity and improve penetration
e.g. ambisome - amphotericin within a phospholipid bilayer
- Describe the mechanism of action of amphotericin B.
Binds to ergosterol in the fungal cell membrane and creates transmembrane channels leading to electrolyte leakage
This leads to fungal cell death
What are the sifde effect of azoles?
impaired LFT
- Describe the mechanism of action of flucytosine.
Mechanisms of resistance?
Inhibits DNA synthesis (pyrimidine analogue)
Decreased uptake (permease activity) Altered 5-FC metabolism
- Which fungi are flucytosine active against?
Candidiasis
Cryptococcosis
