Micro 8 - Fungal infections Flashcards
Fungal cell walls
Plasma membranes
Ribosomes
cell walls contain chitin
plasma membranes contain ergosterol (except Pneumocystis jiroveci)
ribosomes are 80s RNA
yeast vs mould
o Candida – most common yeast + commonest cause of fungal infections in humans
o Cryptococcus
o Histoplasma (dimorphic)
Dimorphic – change between yeasts and moulds
Low temperature – mould, high temperature – yeast
Yest during infection, mould in nature
• Moulds – multicellular hyphae, grow by branching and extension of hyphae
o Aspergillus
o Dermatophytes
o Agents of mucormycosis
Aspergillus buzzwords
presentation mainstay of dx how to determine type stain antigen
pneumonia in immunocompromised Aspergilloma formation (haemoptysis) in patients w PMH of TB
Microscopy - mainstay of dx
Spores - type of Aspergilllus
Stain - methamine silver
Antigen - Galactomannan
Cryptococcus buzzwords
animal
presentation
MRI
ix
birds, pigeons
AIDs defining illness
meningitis, pneumonia in HIV/ immunosuppressed
MRI - multiple cryptococcomas in the brain
india ink stain
CSF/serum cryptococcal antigen
very high opening pressures on LP
massive capsule around the yeast on microscopy which doesnt stain with india ink
Which agar, which stain and which assay can be used for candida?
Sabouraud agar
Periodic Acid Schiff stain (PAS)
Beta-D Glucan assay
Candida mx
– Oral thrush
– Vulvovaginitis
– Localised cutaneous
– Oesophagitis
Topical
– Oral thrush: nystatin
– Vulvovaginitis: cotrimazole
– Localised cutaneous: cotrimazole
Oral
– Vulvovaginitis: fluconazole
– Oesophagitis: fluconazole
Candidemia mx
2/52 antifungals from date of first -ve BC
echinocandin e.g. anidulafungin
BC every 48h until they have 2 persistently negative ones
mx of candidemia in
CNS
endocarditis
bones and joints
UTI
Mx - ambisome/ voriconazole
CNS
endocarditis
bone and joints
UTI
Fluconazole
Cryptococcus mx
o Induction – amphotericin B + flucytosine (at least 2/52)
o Consolidation – high dose fluconazole (at least 8/52)
o Maintenance – low dose fluconazole (at least 1 year)
o Repeat LP (pressure management from chance of hydrocephalus)
o Pulmonary disease – if mild, fluconazole alone
• You are the FY1 on a respiratory ward. Your consultant has referred a patient from
clinic who is experiencing heamoptysis and weight loss. PMHx includes treated
pulmonary TB.
• PMHx of TB – left a cavity – aspergillus grew in the cavity and formed an aspergilloma invades into surrounding tissues and pulmonary vessels causes massive haemoptysis
(aspergillus colonises without extension in preformed cavities and debilitated tissues – can cause aspergilloma )
Aspergillus mx
amphotericin B + voriconazole
at least 6/52
Pneumocystis jiroveci typical presentation + typical XR
Desaturation on walking
Bilateral infiltrates
Fine reticular appearance
Pneumocystis jiroveci stain
Methamine silver
Pneumocystis jiroveci mx
High-dose cotrimoxazole 2-3/52
Steroids if hypoxia
• Why might antifungals targeting cell membrane not work in PCP?
o It lacks ergosterol in its cell wall
How do mucormycoses present and which patients do they target?
target diabetic patients
Cellulitis of the orbit + face which progresses, extends into the brain
Discharge of black pus from palate and nose
Black eschars may be seen as the fungus invades and destroys the tissues
Retro-orbital extension proptosis, chemosis, ophthalmoplegias, blindness
Decreasing level of consciousness (invasion of brain = rhinocerebral mucormycosis)
Think about it when Severe orbital sinus disease esp. in diabetic patients
mucormycoses mx
Surgical ENT emergency- debridement of all dead tissue
high dose amphotericin B or posaconazole
Dx of
Candida Crypotococcus Aspergillosis PCP Mucormycoses Dermatophytes
Candida - swabs, blood cultures, beta d glucan assay, imaging
Crypotococcus - CSF stain, serum/CSF cryptococcal ag, culture, microscopy
Aspergillosis - imaging, sputum MCS + Ag testing, biopsy
PCP microscopy, pcr, beta d glucan
Mucormycoses - tissue biopsy
Dermatophytes - MCS skin scrappings/ nail specimens/ plucked hairs
Pityriasis versicolor causative agent (dermatophyte)
Pityriasis versicolor – Malassezia furfur
causative dermatophytes
tinea pedis tinea capitis tinea cruris tinea corporis Nails
o Foot (athlete’s foot) – tinea pedis – Trichophyton rubrum, Trichophyton interdigitale, Epidermophyton flocosum (less common)
o Scalp – tinea capitis – T rubrum or T Tonsurans
o Groin – tinea cruris – T rubrum or Epidermophyton floccosum
o Abdomen – tinea corporis – several causes, ringworm
o Nails – onychomycosis – Trichophyton spp, Epidermophyton spp, Microsporum spp
Dermatophytes mx
o Topical – clotrimazole, ketoconazole
o Oral – griseofluvin, terbinafine, itraconazole
• Side effects associated with antifungals
o Echinocandins
o Azoles
o Polyenes
o Pyrimidine analogues
o Echinocandins – relatively innocuous
o Azoles – abnormal LFTs
o Polyenes – Nephrotoxicity
o Pyrimidine analogues – blood disorders
How do azole antifungals work?
target cell membrane
o Lanosterol ergosterol by Lanosterol 14-a demethylase (CYP450 enzyme)
o Azole binds to lanosterol 14-a demethylase inhibiting production of ergosterol
Where are the following azoles used?
o Water-Soluble Triazoles
Fluconazole
Voriconazole
o Lipophilic Triazoles
Itraconazole
Posaconazole
o Water-Soluble Triazoles
Fluconazole (against Candida and Cryptococcus)
Voriconazole (similar to fluconazole but has improved activity against Aspergillus)
o Lipophilic Triazoles
Itraconazole (against dermatophytes)
Posaconazole (against Mucor)
Polyene antifungals
examples
MOA
Amphotericin B, Nystatin
o Binds sterols in fungal membrane
o Creates transmembrane channel and electrolyte leakage + also causes cells to lyse cell death
How do polyene antifungals cause nephrotoxicity
Vascular-decrease in renal blood flow leading to drop in GFR, azotemia
Tubular-distal tubular ischemia
Wasting of potassium, sodium, and magnesium
Where and how do echinocandins work?
- Target fungal cell wall synthesis by inhibition of β(1,3) D-glucan synthase
- Loss of cell wall glucan osmotic fragility
Candida aspergillus
Important: Cryptococcus in inherently resistant to echinocandins
Give an example of a pyrimidine analogue, its MOA and why resistance has been developed
Flucytosine
candida crptococcus
Inhibits fungal DNA synthesis
Permease activity Decreased uptake
Cytosine deaminase or UMP pyrophosphorylase activity Altered 5-FC metabolism
look at tables on p67
good summary of drugs
risk factors for fungal disease
– Immunodefficiency, immunosuppresive meds
– Inhaled steroids
– Malignancy, burns, complicated post op, long lines – invasive candida
– Diabetes – mucormycosis
– Moisture, genetics, CMI - dermatophyte
