MICRO: Fungal infections

Question 1

What are fungi?

Answer 1

Eukaryotic cells - chitinous cell walls, membrane containing ergosterol, 80S ribosomes

Question 2

What are the main 2 types of fungi?

Answer 2

• Dimorphic = change between yeasts and moulds

Question 3

What is the commonest fungal infection?

Answer 3

Candida spp - this is a yeast

Question 4

Where can candida be grown in the lab?

Answer 4

Question 5

Where can you grow candida to distinguish between different species?

Answer 5

Chromogenic agar

• Aetiological agents:
  
  • Candida albicans (MOST COMMON)
  • Candida glabrata
  • Candida krusei
  • Candida tropicalis
  • Candida auris (newly discovered and very dangerous)

Question 6

What are the types of superficial candida infections?

Answer 6

Question 7

How do you treat superficial candida infections?

Answer 7

Question 8

Which one is yeast?

Answer 8

• 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.

Question 9

What are the risk factors for candidaemia?

Answer 9

• malignancy esp haem
• burns
• complicated post-op courses
• long lines

Question 10

What is the management of candidaemia?

Answer 10

Candida is very sticky so can stick to many different organs hence the many investigations.

Question 11

What is the first line antifungal when you are told that there is a yeast infection in the blood?

Answer 11

Echinocandin e.g. anidulafungin

Question 12

Give examples of invasive candida infections.

Answer 12

Question 13

What are the main types of cryptococcis?

Answer 13

Characterised by having a large capsule

Question 14

Which animal is cryptococcus associated with?

Answer 14

Pigeons

Question 15

What is the lifecycle of cryptococcus?

Answer 15

Question 16

What are the risk factors for cryptococcosis?

Answer 16

Impaired T cell immunity e.g. in reduced CD4 helper T cells <200/ml

Taking T cell immunosuppressants for organ transplant - 6% lifetime risk

Question 17

What is the difference between cryptococcus neoformans and gatti?

Answer 17

• 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

Question 18

Which stain is used to identify cryptococcus? What other diagnostic tools are used?

Answer 18

• India ink stain of CSF (seen below with large capsule)
• Imaging
• Lateral flow for cryptococcal antigen
• Culture from body fluids/blood

Question 19

What is the management of cryptococcosis?

Answer 19

Question 20

What are the spectrum of diseases caused by aspergillus?

Answer 20

Question 21

What does aspergillus look like on culture?

Answer 21

Question 22

What is seen here?

Answer 22

TB has left a cavity which has then been invaded by aspergillus

Question 23

How do you diagnose aspergillus?

Answer 23

• Imaging
• Sputum/BAL
• Aspergillus Abs (precipitans)
• Galactomannan - bronchial sample or circulating in blood
  *

Question 24

What is the management of aspergillosis?

Answer 24

• Voriconazole
• Ambisome
• Duration based on host/radiological/mycological factors - at least 6 weeks

Question 25

How is pneumocystis jiroveci acquired? What is the cell wall like?

Answer 25

Question 26

What is this infection?

Answer 26

Pneumocystic jirovecii Diffuse bilateral infiltrates affecting all lobes of lung Exertion after minimal activity

Question 27

What is the diagnosis and mangement of pneumocystic jirovecii?

Answer 27

Question 28

Which groups are affected by mucormycosis? What are the aetiological agents?

Answer 28

Diabetics and immunosuppressed * Aetiological Agents * Rhizopum spp. * Rhizomucor spp. * Mucor spp.

Question 29

What are the clinical features of mucormycosis?

Answer 29

Question 30

What is the management of mucormycoses?

Answer 30

Question 31

What are the features of dermatophyte infection?

Answer 31

Question 32

What causes pytyriasis vesicolor?

Answer 32

FUNGAL infection -

Question 33

How are dermatophytes diagnosed?

Answer 33

* 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

Question 34

Azole SE

Answer 34

Most common: LFT abnormal

Question 35

Echinocandins SE

Answer 35

Common: relatively innocuous

Question 36

Pyrymydine analogues SE

Answer 36

Blood disorders

Question 37

Polyene SE

Answer 37

Neohrotoxocity most common

Question 38

What are the targets of antifungals?

Answer 38

Question 39

What do echinocandins not treat?

Answer 39

Do not get into urine Do not treat cryptococcus

Question 40

What is the MOA of echinocandins? What are they active against?

Answer 40

* **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)

Question 41

What is the MOA of flucytosine/pyrimidine analogues? What is it indicated for? What is resistant to it? SE?

Answer 41

* **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

Question 42

What is ambisome composed of?

Answer 42

Amphotericin B + phospholipid bilayer = more lipophilic so can enter CNS and less SE NB: Amphotericin B is a fermentation product of *Streptomyces nodusus*

Question 43

What is the MOA of polyene antifungals? What is it active against and what are the SE?

Answer 43

* **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

Question 44

What is the mechanism of the nephrotoxicity caused by polyene antifungals? How can it be prevented?

Answer 44

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

Question 45

What is the MOA of azoles? What are the types?

Answer 45

**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_)

Question 46

Give examples of each antifungal type.

Answer 46