MICRO: Fungal infections Flashcards
What are fungi?
Eukaryotic cells - chitinous cell walls, membrane containing ergosterol, 80S ribosomes
What are the main 2 types of fungi?
- Dimorphic = change between yeasts and moulds
What is the commonest fungal infection?
Candida spp - this is a yeast
Where can candida be grown in the lab?
Where can you grow candida to distinguish between different species?
Chromogenic agar
- Aetiological agents:
- Candida albicans (MOST COMMON)
- Candida glabrata
- Candida krusei
- Candida tropicalis
- Candida auris (newly discovered and very dangerous)
What are the types of superficial candida infections?
How do you treat superficial candida infections?
Which one is yeast?
- Form individual cells (a bit like bacteria but much bigger)
- Replicate by budding
- Grow in colonies (a bit like bacteria)
- Distributed world-wide
- Periodic Acid-Schiff (PAS) stain
Stain gram positive on the gram stain.
What are the risk factors for candidaemia?
- malignancy esp haem
- burns
- complicated post-op courses
- long lines
What is the management of candidaemia?
Candida is very sticky so can stick to many different organs hence the many investigations.
What is the first line antifungal when you are told that there is a yeast infection in the blood?
Echinocandin e.g. anidulafungin
Give examples of invasive candida infections.
What are the main types of cryptococcis?
Characterised by having a large capsule
Which animal is cryptococcus associated with?
Pigeons
What is the lifecycle of cryptococcus?
What are the risk factors for cryptococcosis?
Impaired T cell immunity e.g. in reduced CD4 helper T cells <200/ml
Taking T cell immunosuppressants for organ transplant - 6% lifetime risk
What is the difference between cryptococcus neoformans and gatti?
-
Cryptococcus neoformans Immunodeficient
- Greatly increased in patients with impaired T-cell immunity (AIDS with very low CD4+ counts)
- Second most common cause of death in AIDS
- Patients taking immunosuppressants for solid organ transplant (6% lifetime risk)
-
Cryptococcus (neoformans var) gattii Immunocompetent
- Affects immunocompetent individuals in tropics (especially SE Asia and Australia)
- High incidence of SOLs in the lung and brain
- Increased resistance to amphotericin B
Which stain is used to identify cryptococcus? What other diagnostic tools are used?
- India ink stain of CSF (seen below with large capsule)
- Imaging
- Lateral flow for cryptococcal antigen
- Culture from body fluids/blood
What is the management of cryptococcosis?
What are the spectrum of diseases caused by aspergillus?
What does aspergillus look like on culture?
What is seen here?
TB has left a cavity which has then been invaded by aspergillus
How do you diagnose aspergillus?
- Imaging
- Sputum/BAL
- Aspergillus Abs (precipitans)
- Galactomannan - bronchial sample or circulating in blood
*
What is the management of aspergillosis?
- Voriconazole
- Ambisome
- Duration based on host/radiological/mycological factors - at least 6 weeks
How is pneumocystis jiroveci acquired? What is the cell wall like?
What is this infection?
Pneumocystic jirovecii
Diffuse bilateral infiltrates affecting all lobes of lung
Exertion after minimal activity
What is the diagnosis and mangement of pneumocystic jirovecii?
Which groups are affected by mucormycosis? What are the aetiological agents?
Diabetics and immunosuppressed
- Aetiological Agents
- Rhizopum spp.
- Rhizomucor spp.
- Mucor spp.
What are the clinical features of mucormycosis?
What is the management of mucormycoses?
What are the features of dermatophyte infection?
What causes pytyriasis vesicolor?
FUNGAL infection -
How are dermatophytes diagnosed?
- Diagnosis of the above organisms:
- These are diagnosed by taking skin scrapings
- The organisms are then cultured (can take up to 4 weeks to grow)
- Microscopy is used to identify the organisms
Azole SE
Most common: LFT abnormal
Echinocandins SE
Common: relatively innocuous
Pyrymydine analogues SE
Blood disorders
Polyene SE
Neohrotoxocity most common
What are the targets of antifungals?
What do echinocandins not treat?
Do not get into urine
Do not treat cryptococcus
What is the MOA of echinocandins? What are they active against?
-
Mechanism of action = cyclic lipopeptide antibiotic:
- Inhibit Beta-(1,3) D-glucan synthase
- Inhibits production of Beta-D glucan (a component of the fungal cell wall) à osmotic fragility
- Active Against:
- Candida species (including non-albicans isolates that are resistant to fluconazole)
- Aspergillus species (but NOT other moulds e.g. Fusarium, Zygomycosis)
What is the MOA of flucytosine/pyrimidine analogues? What is it indicated for? What is resistant to it? SE?
-
Mechanism of action = inhibits DNA in the fungal cells
- Monotherapy now limited
- Resistance is due to:
- Decreased uptake (permease activity)
- Altered 5-FC metabolism (cytosine deaminase or UMP pyrophosphorylase activity)
- Indications:
- Candidiasis
- Cryptococcosis (in combination with amphotericin B or fluconazole)
- Side Effects:
- Infrequent (D&V, changes in LFTs, blood disorders)
- Blood concentrations need monitoring when used in conjunction with amphotericin B
What is ambisome composed of?
Amphotericin B + phospholipid bilayer = more lipophilic so can enter CNS and less SE
NB: Amphotericin B is a fermentation product of Streptomyces nodusus
What is the MOA of polyene antifungals? What is it active against and what are the SE?
-
Mechanism of action:
- Binds ergosterol à creates transmembrane channels à electrolyte leakage à cell death
- Active against MOST FUNGI except:
- Aspergillus terreus
- Scedosporium spp.
- The original formulation of amphotericin B is amphotericin B deoxycholate (Fungizone) which had serious toxic side-effects (e.g. nephrotoxicity) à partially ameliorated with a lipid carrier:
- Liposomal amphotericin B
- Amphotericin B colloidal dispersion
- Amphotericin B lipid complex
-
Nephrotoxicity:
- Most significant delayed toxicity
What is the mechanism of the nephrotoxicity caused by polyene antifungals? How can it be prevented?
Renovascular and tubular mechanisms:
- Vascular – decrease in renal blood flow leading to a drop in GFR (azotaemia)
- Tubular – distal tubular ischaemia, wasting of sodium, potassium and magnesium
- Enhanced in patients who are volume-depleted or who are on concomitant nephrotoxic agents
Nephrotoxicity partially ameliorated with a lipid carrier:
- Liposomal amphotericin B
- Amphotericin B colloidal dispersion
- Amphotericin B lipid complex
What is the MOA of azoles? What are the types?
Mechanism of action –> inhibit ergosterol production (lanosterol –> ergosterol) –> toxic steroids + cell death
- Inhibit CYP450 enzyme lanosterol 14-a demethylase
- N.B. may inhibit other CYP450 enzymes –> drug interactions and impairment of steroidogenesis
- Hence, why ketoconazole and itraconazole are used to reduce steroidogenesis
- Types of Azoles:
- Water-Soluble Triazoles
- Fluconazole (good against Candida and Cryptococcus)
- Voriconazole (similar to fluconazole but has improved activity against Aspergillus)
- Lipophilic Triazoles
- Itraconazole (useful against dermatophytes)
- Posaconazole (has activity against Mucor)
- Water-Soluble Triazoles
Give examples of each antifungal type.
