Microbiology 16 - Fungal infections

Question 1

What is the main conponent of fungal cell walls?

Answer 1

Chitin

Question 2

What is the main component of fungal cell membranes?

Answer 2

Ergosterol

Question 3

What is the reproductive method of yeats?

Answer 3

Budding

Question 4

Recall 3 examples of yeasts that are clinically important

Answer 4

Candida
Cryptococcus
Histoplasma

Question 5

What are moulds?

Answer 5

Multicellular hyphae - grow by branching and extension

Question 6

Give 2 examples of moulds that are clinically important

Answer 6

Dermatophytes
Aspergillus

Question 7

Which stain is used to detect Candida?

Answer 7

Periodic Acid-Schiff (PAS) stain

Question 8

How can different strains of Candida be differentiated

Answer 8

chromogenic agar

Question 9

Recall the empiric treatment for oral, vulvovaginal and cutaneous candida infection

Answer 9

Topical:

Oral: nystatin
Vulvovaginal and localised cutaneous: co-trimazole

Oral:

Fluconazole

Question 10

Recall the principles of candidaemia management

Answer 10

1. Look for source and signs of dissemination:
   - Imaging
   - Serology for B-D-glucan
   - echo/fundoscopy
2. Antifungals for at least 2/52 from date of first negative blood culture - repeat BCs every 48 hours (until 2 neg)

Question 11

Treatment for invasive candidiasis of:

1. CNS
2. endocarditis
3. urinary tract
4. bone and joint
5. intra-abdominal

Answer 11

1. CNS - ambisome/voriconazole
2. endocarditis -ambisome/voriconazole
3. urinary tract - fluconazole
4. bone and joint - ambisome/voriconazole
5. intra-abdominal - echocandin/fluconazole

amphotericin B

Question 12

What does this show

Answer 12

pseudohyphae (germ tube) - only in Candida albicans

Question 13

What type of agar is used to grow Candida?

Answer 13

selective agar plate impregnated with antibiotics is usually used (Sabouraud agar) → grows in about 48 hours

Question 14

Waht is Beta-D Glucan assay used for?

Answer 14

look for evidence of invasive Candida infection

Question 15

Recall the different types of cryptococcus, and which of these infect immunocompetent vs immunocompromised hosts

Answer 15

Serotypes A and D = cryptococcus neoformans (immunocompromised HIV)

Serotypes B and C = cryptococcus gatti (immunocompetent)

Question 16

Presentation of cryptococcus infection

Answer 16

chronic, subacute to acute pulmonary, meningitis or systemic disease

predilection for CNS (C gatti)

Question 17

How is cruptococcus transmitted?

Answer 17

Inhalation of aerosolized organisms e.g. pigeons

grows in eucalyptus

Question 18

What ink can be used to stain for cryptococcus?

Answer 18

India Ink

stain all black except for capsule around yeast (if organism under stress, capsule not always present)

IMPORTANT: Cryptococcal meningitis can cause hydrocephalus which prevents the circulation of CSF so that the sample you take from an LP is not mixing with the CSF in the brain

Question 19

How to diagnose cryptococcus?

Answer 19

Serum/CSF cryptococcal Ag (CRAG) - used more as quicker + India Ink

Question 20

How should cryptococcus infection be managed?

Answer 20

1. Induction: 2/52 of amphotericin B + flucytosine
2. Consolidation: 8/52 of high dose fluconazole
3. Maintenance: 1 year low-dose fluconazole

repeat LP for pressure management (hydrocephalus)

pulmonary - fluconazole alone if mild

Question 21

Which type of aspergillus disease is an allergic disease?

Answer 21

ABPA

can cause spectrum from allergy -> invasive disease

Question 22

What parts of the body can be infected by aspergillus?

Answer 22

Pre-formed cavities (eg. by TB) - so treated pulmonary TB may be in the history

CXR - RUL cavity with opacity → aspergilloma (post TB)

Question 23

Aspergillosis diagnosis

Answer 23

What is a galactomannan assay used for?

Question 24

What is a galactomannan assay used for?

Answer 24

Aspergillosis diagnosis

Question 25

How does aspergillus appear under the microscope?

Answer 25

Fluffy colonies

Question 26

How to treat aspergillus?

Answer 26

voriconazole + ambisome at least 6/52 duration based on host/radiological/mycological factors surgery

Question 27

Why is pneumocystis jirovecii an unusual fungus?

Answer 27

No ergosterol wall

Question 28

What is the typical history for PCP pneumonia?

Answer 28

Desaturating on exertion RF - immunodeficiency/immunosuppression/debilitated infants/protein malnutrition

Question 29

How to diagnosis PCP?

Answer 29

methamine silver stain - flying saucer shaped cysts CXR - bilat infiltrates fine reticular appearance

Question 30

Treatment for PCP

Answer 30

high dose cotrimoxazole 2-3/52 alternative: atovaquone, clindamycin + primaquine steroids if hypoxic

Question 31

why might antifungals targeting cell membrane not work in PCP?

Answer 31

lacks ergosterol in cell wall

Question 32

How are mucormyycoses transmitted?

Answer 32

inhalation of spores or primary cutaneous inoculation

Question 33

What are the clinical features of mycormycoses?

Answer 33

**rhinocerebral → CNS** cellulitis of orbit and face → discharge black pus from palate and nose Black eschars may be seen as the fungus invades and destroys the tissues retro orbital extension → proptosis, chemosis, opthalmoplegia, blindness ↓ consciousness

Question 34

How are mycormycoses managed?

Answer 34

ambisome/posaconazole high dose surgical emergency → ENT, debridement necrotic tissue treatment guided by response

Question 35

Recall an example of a dermatophyte

Answer 35

tinea

Question 36

Where does tinea ... infect? 1. pedis 2. cruris 3. corporis 4. capitis 5. onchomycosis 6. pityriasis versicolor

Answer 36

1. pedis - foot 2. cruris - groin 3. corporis - abdo 4. capitis - scalp 5. onchomycosis - nail 6. pityriasis versicolor - M furfur (depigmentation in darker skin)

Question 37

How is tinea diagnosed?

Answer 37

Often clinically, but can be confirmed via skin scrapings for MC&S

Question 38

How to treat tinea?

Answer 38

topical - clotrimazole, ketoconazole oral - griseofulvin, terbinafine, itraconazole

Question 39

Recall 3 targets of antifungals

Answer 39

1. Cell membrane (polyene/azole/terbinafine) 2. DNA/RNA synthesis (pyrimidine analogues) 3. cell wall (echinocandin)

Question 40

Recall the side effect profile of each class of antifungal

Answer 40

Azoles - abnormal LFTs PolyeNes - Nephrotoxicity Echinocandins - relatively innocuous Pyrimidine analogues - blood disorders

Question 41

What is the mechanism of action of azoles?

Answer 41

bind lanosterol 14a-demethylase (CYP450 enzyme) → **inhibit prod ergosterol**

Question 42

What is the mechanism of action of polyenes?

Answer 42

binds sterols in fungal cell membrane → transmembrane channel → electrolyte leakage

Question 43

Give 2 examples of polyene medications

Answer 43

Amphotericin B, lipid formulations * Ambisome = Amphortericin B + phospholipid bilayer → more lipophilic so can enter CNS + less side effects Nystatin (topical)

Question 44

Give some exmaples of azole antifungals

Answer 44

* Ketoconazole * Itraconazole * Fluconazole * Voriconazole * Miconazole * Clotrimazole Water soluble (candida/cryptococcus) - fluconazole, voriconzaole lipophilic - itraconazole (dermatophytes)

Question 45

What is the mechanism of action of echinocandins?

Answer 45

* inhibit Beta-(1,3) D-glucan synthase * inhibit fungal cell wall synthesis * loss of cell wall glucan → osmotic fragility

Question 46

Which 2 types of fungus are echinocandins particularly useful for?

Answer 46

Candida Aspergillus No coverage C neoformans IMPORTANT: Cryptococcus is inherently RESISTANT to echinicandins

Question 47

What is the spectrum of action of pyrimidine analogues?

Answer 47

reduced spectrum activity now limited monotherapy acquired resistance due to decreased uptake (permease activity) altered 5-FC metabolism (cytosine deaminase or UMP pyrophosphorylase activity)

Question 48

What class of antifungal is flucytosine?

Answer 48

Pyrimidine analogue