MI: Fungal Infections Flashcards
List three examples of:
- Yeast
- Moulds
Yeasts: single-celled, reproduce by budding
- Candida
- Cryptococcus
- Histoplasma (dimorphic)
Moulds: multicellular hyphae, reproduce by branching + extension
- Aspergillus
- Dermatophytes
- Agents of mucormycosis
What does ‘dimorphic’ mean with regards to fungi?
It can change between being a yeast and a mould
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
- Immunocompotent 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
How can Candida affect the eyes?
Causes endophthalmitis
What does generalised candidiasis in babies usually occur secondary to?
Seborrheic dermatitis
What is the term used to describe candidiasis of babies that afects the skin folds?
Intertrigo
How can candidiasis lead to mediastinitis?
If oesophageal candidiasis invades the tissue leading to perforation
Outline the diagnostic tests used for candidiasis.
- Swabs (smeared on KOH)
- Bloods
- Beta-D glucan blood test
- Antigen + serology (mannan, anti-mannan)
- DNA PCR
- Blood/tissue cultures
- Imaging
- Endoscopy
What type of agar is needed for culturing Candida?
Sabouraud agar - impregnated with antibiotics to prevent bacteria from outcompeteing the fungi
Outline the management of candidiasis.
- At least 2 weeks of antifungals after the last negative culture
- Echo and fundoscopy to look for endocarditis/endophthalmitis
- Echinocandins - empirical for non-albicans infections
- Fluconazole - empirical for Candida albicans
What type 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)
What is the main aetiological agent in cryptococcosis.
Cryptococcus neoformans
Which patients are particularly at risk of cryptococcosis?
- Impaired T cell immunity (AIDS)
- Solid organ transplant patients on T Cell immunosuppressants
What is Cryptococcus neoformans var. gatii?
- Causes meningitis in apparently 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.
- Distinc capsule around the yeast
- India ink can be used to stain
NOTE: the capsule is not always present
Which diagnostic test is important in the diagnosis of cryptococcosis?
Enzyme immunoassay (EIA) looking for components of the capsule
Why might a lumbar puncture be negative in cryptococcal meningitis?
Cryptococcal meningitis can cause hydrocephalus which prevents the circulation of CSF meaning that the sample taken at LP may not have been exposed to CSF within other parts of the ventricular system
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 (ingestion contaminated foods)
- Allergic bronchopulmonary aspergillosis
- Aspergilloma (colonising pre-formed cavities)
- Invasive/disseminated disease
List the aetiological agents that can cause Aspergillus infection.
- Aspergillus fumigatus
- Aspergillus flavus
- Aspergillus niger
- Aspergillus niduland
- Aspergillus terreus
What is the mainstay of diagnosis of Aspergillus infection?
Microscopy - looking at fungal spores
List some investigations used in the diagnosis of Aspergillus infection.
- Blood test
- Beta-D glucan
- Serology
- Check IgE for allergic response in ABPA
- Aspergillus IgG for invasive disease
- Antigen detection (galactomannan) - in blood and BAL
- PCR
- Blood/tissue culture
- Imaging (CXR/CT for ABPA and aspergilloma)
What is the mainstay of treatment for aspergillosis?
- ABPA - itraconazole plus steroids
- Aspergilloma - surgery plus itraconazole
- Invasive aspergillosis - variconazole (amphotericin B second line)
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
How are dermatophyte infections diagnosed?
Skin scarpings and microscopy
What is pityriasis versicolor caused by?
Malassezia furfur
What is mucormycosis?
Group of moulds that cause very severe and invasive disease
transmitted by direct inoculation or inhalation
Which groups of patients are affected by mucormycosis?
- Immunocompromised patients
- Patients with poorly controlled diabetes
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 the tissues
can also cause pulmonary/cutaneous manifestations
What can retro-orbital extension of mucormycosis lead to?
Proptosis, ophthalmoplegia and blindness
What is the term used to describe the invasion of the brain by mucormycosis?
Rhinocerebral mucormycosis
List three aetiological agents that can cause mucormyocosis.
- Rhizopus 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:
- Cell membrane
- DNA/RNA synthesis
- Cell wall
Cell membrane:
- Polyene - amphotericin B, nystatin
- Azole - ketoconazole, itraconazole, fluconazole, clotrimazole
DNA/RNA synthesis:
- Flucytosine (pyrimidine analogue)
Cell wall:
- Echinocandins - caspofungin acetate
What is the mechanism of action of azoles?
- Inhibit ergosterol production by inhibiting CYP450 enzyme lanosterol 14a-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 ith other CYP450 enzymes?
- Drug interactions
- Impairment of steroidogenesis
List examples of the following types of azoles along with their usual indications:
- Water-soluble triazoles
- Lipophilic triazoles
Water-soluble triazoles:
- Fluconazole - active against Candida and Cryptococcus
- Voriconazole - similar to fluconazole but better activity against Aspergillus
Lipophilic triazoles:
- Itraconazole - useful against dermatophytes
- Posaconazole - activity against mucor
List some examples of echinocandins.
- Caspofungin
- Micafungin
- Anidulafungin
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?
- Candida* species
- Aspergillus* species (NOT other moulds)
NOTE: it has NO coverage for Cryptococcus
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
What is ambisome?
Amphotericin within a phospholipid bilayer
How is amphotericin B produced?
Fermentation product of Streptomyces nodusus
Describe the mechanism of action of amphotericin B.
- Binds to ergosterol in the fungal cell membrane and creates transmembrane channels leading to electroyte leakage
- This leads to fungal cell death
Amphotericin B is active against must fungi except…
- Aspergillus terreus
- Scedosporium spp.
What is the main side-effect of amphotericin B? Describe the mechanism of this toxicity.
- Nephrotoxicity
- Renovascular - decrease in renal blood flow leads to reduced GFR (azotaemia)
- Tubular - distal tubular ischaemia, wasting of sodium, potassium and magnesium
Describe the mechanism of action of flucytosine.
Inhibits DNA synthesis (pyrimidine analogue)
What are some mechanisms of resistance to flucytosine?
- Decreased uptake (permease activity)
- Altered 5-FC metabolism
Which fungi are flucytosine active against?
Candidiasis
Cryptococcus
List some side-effects of flucytosine.
- D&V
- LFT changes
- Blood disorders
NOTE: blood concentrations should be monitored if used with amphotericin B
Types of superficial Candida infections?
- Oral candidiasis
- Oesophageal candidiasis
- Vulvovaginitis
- Cutaneous (local/ generalised)
What are dermatophytes?
group of fungi capable of invading dead keratin of skin, hair and nails
