Week 11 - Fungal infections Flashcards
Fungi are made of ____________ cells, their cell wall contains ___________, their plasma membranes contain ____________, and their ribosomes are _____
eukaryotic cells
cell wall contains chitinous
plasma membranes contain ergosterol
80S
Fungi are divided into two classes - name them, and state their difference
Yeasts - single-celled, reproduce by BUDDING
Moulds - multicellular hyphae, grow by BRANCHING and EXTENSION
Name 2 types of yeast and 3 types of moulds
Yeast:
- candida
- cryptococcus
Moulds:
- dermatophytes
- aspergillus
- mucormycosis
What are dimorphic fungi? Name an example.
Dimorphic fungi exist as moulds at lower temperatures and as yeasts at higher temperatures
Example: histoplasma
What is the commonest cause of fungal infection in humans?
candida species
You are an FY1 on the MFE ward. The nurse is looking after F bay bleeps you saying Mr A is complaining of a painful mouth and his tongue looks strange.
What do you see?
Superficial candida infection = oral thrush
What do you see?
Superficial candida infection = cutaneous candidiasis
Which picture is the yeast?
left
same magnification
You see the yeasts are larger, they’re a bit more ovoid and much more prominent than G+ cocci bacteria
What is the treatment for:
- Oral thrush?
- Vulvovaginitis?
- Localised cutaneous?
- Oesophagitis?
- Oral thrush => nystatin (topical)
- Vulvovaginitis => cotrimazole (topical), or fluconazole (oral)
- Localised cutaneous => cotrimazole (topical)
- Oesophagitis => fluconazole (oral)
What colour do candida stain on Gram staining?
Candida will usually stain + on Gram stain due to thick polysaccharide around it
Name 4 risk factors for developing candidaemia
- Malignancies, esp haematological
- Burn patients
- Complicated post-op courses
- Long lines
Cryptococcus are most commonly associated with contact with ________
birds/pigeons
Name the steps (4) for management of candidaemia
- Look for source and signs of dissemination:
- Imaging
- Serology for beta- D-glucan
- ECHO
- Fundoscopy
* candida is sticky and could stick to heart valves and/or back of eyes (causing candida ophthalmitis)
- Antifungals for at least 2/52 (from date of 1st negative BC)
- Echinocandin e.g. anidulafungin - BC every 48 hours
- Remove any lines/prosthetic material
Name the 4 serotypes of cryptococci and the organism - which patients is each more common in?
Serotypes A & D = cryptoccous neoformans => IMMUNODEFICIENT
Serotypes B & C => cryptococcus gattii => IMMUNOCOMPETENT
You’re an FY1 on the medical take. A patient known to the HIV team who has refused ARVs has presented with fever, headache, and confusion. Your SpR has asked you to go and review the patient and clerk them in. There is an MRI already done. what do you see?
multiple cryptococcomas (CNS invasion of cryptococcus into parenchymal regions).
NOTE: cryptococcomas are a rare complication of infection by the Cryptococcus genus of invasive fungi, where a discrete, encapsulated lesion of immune infiltrates and pathogen forms.
How does cryptoccocus spread?
via inhalation of aerosolised organisms
India ink stain on CSF. What do you see?
massive capsule of organism in CSF = cryptococcus in CSF = CNS cryptococcal infection
What do you see in this culture?
Hyphae around pierphery that are branching off = aspergillus culture
You’re and FY1 on the resp ward. Consultant referred a patient from clinic who is experiencing haemoptysis and weight loss. PMHx includes treated pulmonary TB.
What is the diagnosis? Explain the haemoptysis
This is an aspergilloma – the aspergillus has found that scarred cavity from the previous infection to grow in.
If the aspergillus grows too large, it can invade into the pulmonary vasculature and cause haemoptysis
What are the risk factors (2) for cryptococcus?
- Imapired T cell immunity
- eg patients with HIV with reduced CD4 T cell counts of <200/ml
* extrapulmonary infection is an AIDS-defining illness
- Patients taking T cell immunosuppressants for solid organ transplantation (lifetime risk 6%)
C gattii:
- Does it affect immunocompetent or immunocompromised individuals?
- Changes in brain and lung?
- Geographic locations of infection?
- Immunocompetent
- causes meningitis; high incidence of SOL in brain/lungs
- Tropical altitudes (SE Asia + Australia)
Which type of dye is used for a cryptococcal stain?
India ink
You are the FY1 on the renal team. You have been asked to go and review a patient in the renal assessment unit who has a cough and SOB. The nurse tells you that the patient is desaturating when she walks. A CXR is done.
What do you see? What is the diagnosis?
Diffuse bilateral infiltrates with fine reticular interstitial changes = likely PCP
Describe management steps (3) for CNS cryptoccal infection
- Induction => Amphotericin B + Flucytosine (at least 2/52)
- Consolidation => High dose fluconazole (at least 8/52)
-
Maintenance => Low dose fluconazole (at least 1 year)
- repeat LP for pressure management
- if mild pulmonary disease; fluconazole alone.
What diagnostic investigations (5) would you order in suspected aspergillosis?
- Imaging - CXR
- Sputum/BAL - MC&S, Ag testing
- Biopsy - Histology, MC&S
- Aspergillus abs - aspergillus precipitan test
5 Galactomannan - to check for disseminated aspergillosis
How would you manage (1) aspergillosis?
Voriconazole OR amphotericine B (at least 6/52)
- duration depends on host/radiological/mycological factors
Pneumocystis jiroveci - describe it’s cell wall
lacks ergosterol
Diagnosis?
How would you treat it (2 steps)?
- Mucormycosis - will confirm with tissue biopsy
- Mx:
- ambisome/posaconazole
- debridement
Pneumocystis jiroveci - route of transmission
Airborne route therefore commonly presents as pneumonia
* extra-pulmonry disease is RARE
RFs (1) for Pneumocystis jiroveci pneumonia
Any aetiology leading to immunodeficiency (drugs, infection, genetics, enviromental)
What is the diagnosis? most common causative agents?
onchomycosis - often caused by dermatophytes
Describe the diagnostic tests (3) for pneumocystic jiroveci (PCP)?
Serum/Sputum/BAL/biopsy:
- Microscopy
- PCR
- Beta-D-glucan
What is the management (2) of PCP?
- High dose co-trimoxazole (2-3/52)
- Steroids if hypoxic
Why might antifungal targeting the cell membrane not work in PCP?
Lacks ergosterol in cell wall
therefore can’t used azoles
How does mucormycoses spread (2)?
- Inoculation via inhalationo of spores
- Primary cutaneous inoculation
Mucormycoses - high risk groups (2)?
- Immunosuppressed
- Diabetics
Describe rhinocerebral to CNS infection of mucormycoses
Cellulitis of the orbit + face => progresses with discharge of black pus from the palate and nose => Retro-orbital expansion produces proptosis, chemosis, ophthalmoplegias, blindness.
Can spread back to brain, causing decreasing levels of consciousness
What are dermatophytes? How do they spread?
A group of moulds capable of invadind DEAD keratin of skin, hair, nails
spread via contact with desquamated skin scales
RFs (3) for dermatophyte infections
- Moisture
- Deficiencies in cell-mediated immunity
- Genetic predisposition
Name the dermatophyte infection of each site
- Foot
- Scalp
- Groin
- Abdomen
- Foot = tinea pedis
- Scalp = tinea capitis
- Groin = tinea cruris
- Abdomen = tinea corporis
Treatment (2) of dermatophytic infections (nail/skin)
- Topical => clotrimazole,, ketoconazole
- Oral => itraconazole
Name the most common associated side effect of each antifungal class
- Azoles
- Polyenes
- Echinocandins
- Pyrimidine analogues
- Azoles = abnormal LFTs
- Polyenes = nephrotoxicity
- Echinocandins = relatively innocuous
- Pyrimidine analogues = blood disorders
Name 2 groups of antifungals that target cell membrane
- Azoles (ketoconazole, itraconazole, fluconazole) = inhibit ergosterol synthesis
- Polyenes (amphotericin B, nystatin) = punch holes in cell membrane
Name 1 antifungal class that acts against cell wall and its MOA
Echinocandins - inhibits B(1,3)-D-glucan synthase - loss of cell wall glucan => osmotic fragility
Which of the following are echinocandins effective against?
- Yeast
- Mould
- Cryptoccocus
Which body site can they NOT penetrate?
- Yeast = yes
- Mould = no
- Crytpo = no
Cannot get into urine
Name 1 antifungal that work by inhibiting DNA/RNA synthesis?
- Pyrimidine analogues (i.e. Flucytosine)
