Microbiology 16 - Fungal infections Flashcards by Adya Rao

What is the main conponent of fungal cell walls?

Chitin

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What is the main component of fungal cell membranes?

Ergosterol

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What type of RNA do fungi contain?

80S

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What are yeasts? How do they reproduce?

Single celled organisms

Reproduce by budding

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Recall 3 examples of yeasts that are clinically important

Candida
Cryptococcus
PCP

CCP

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What are moulds?

Multicellular hyphae

Reproduce by branching and extension

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Which fungus is dimorphic (can change between yeast and moulds)?

histoplasma

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Give 3 examples of moulds that are clinically important

MAD

mucormyocsis

aspergillus

dermatophytes

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What is the most common cause of fungal infections in humans?

Candida

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What is candida? What patterns of infection does it cause?

Yeast

Commonest cause of fungal infections in humans

Can cause acute, subacute, chronic or episodic infection

Can be superficial or invasive

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

Oral candidasis: TOPICAL NYSTATIN

Localised cutaneous: TOPICAL CLOTRIAZMOLE

Vulvovaginal: TOPICAL CLOTRIMAZOLE or if severe - ORAL FLUCONAZOLE

Oesohpageal: TOPICAL CLOTRIMAZOLE or if severe - ORAL FLUCONAZOLE

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What are the risk factors for candidamiea?

Malignancies, esp haematological

– Burns patients

– Complicated post-op courses (eg Tx or GIT Sx)

– Long lines

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Examples of superficial candida infections

Oral candidasis

Oesophageal candidasis

Cutaneous - localised or generalised

Vulvovaginal candidasis

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Recall the principles of candidaemia management

Look for source and signs of dissemination:
- Imaging
- Serology for B-D-glucan
- echo (for endocarditis)/fundoscopy (for eye infection)
Antifungals for at least 2/52 from date of first negative blood culture - repeat BCs every 48 hours (echinocandin until sensitivities identified) 3. remove any lines/prosthetic material

cbd - candida beta glucan

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Examples of invasive candida infections and specific treatments

1. Urinary tract (vulvogaintis or catheter): fluconazole

2. CNS: ambisome (amphotericin B) or voriconazole

3. Bone and joint: ambisome (amphotericin B) or voriconazole

4. Endocarditis (abnormal or prosthetic valves): ambisome (amphotericin B) or voriconazole

5. Intra-abdominal: echinocandin or fluconazole

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How is cryptococcus spread?

Aerosolised fungus is inhaled

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Morphology of cryptococcus

Encapsulated yeast

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Life cycle of cryptococcus

C. neoformans: associated with pigeon droppings

C. gatii: associated with eucalyptus trees

–>inhalation of ubiquitous spores can disseminate in immunocompromised people, has a prediliction for the CNS

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

Serotypes A and D = cryptococcus neoformans (immunocompromised hosts)

*NB: T cell deficiency makes you particularly susceptible (eg AIDS, post transplant immunosuppression)

Serotypes B and C = cryptococcus gatti (immunocompetent hosts)

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Which type of cryptococcus can cause meningitis?

Cryptococcus gatti

In apparently immunocomptenet people

Especially in Australia and SE asia; tropical latitudes

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WHich organ system does cryptococcus have a predlicition for?

Central nervous system

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What ink can be used to stain for cryptococcus?

What is the gold standard investigation?

India Ink - stains everything black except for the capsule

*appears as an encapsulated yeast

Gold standard: enzyme immunoassay for antigens in capsule

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What is c. gatii resistant to?

Amphotericin B (ambisome)

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What is C. neoformans resistant to?

echinocandins

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How should cryptococcus infection be managed?

* *1. Induction:** 2/52 of amphotericin B +/- flucytosine * *2. Consolidation:** 8/52 of _high dose_ fluconazole * *3. Maintenance:** 1 year _low-dose_ fluconazole + LP for symptomatic relief (as patients tend to have high opening pressure) IF MILD PULMONARY INFECTION - fluoconazole alone \*\*Path guide: amphotericin B and flucytosine

Why is pneumocystis jirovecii an unusual fungus?

No ergosterol in cell membrane ^so antifungals targeting cell membrane will not work

What is the typical history for PCP pneumonia? Typical CXR feature? Diagnosis of PCP? Treatment?

Desaturating on exertion CXR: bat winging Diagnosis: usually immunofluorescence, but can also be detected on silver stain Treatment: cotrimxazole (+ steroids if hypoxia is present)

Main species of aspergillus that is clinically important How is it transmitted?

Aspergillus fumigatus Airborne transmission

Clinical spectrum of aspergillus disease?

1. Aspergilloma 2. ABPA 3. Invasive aspergillosis - mostly immunocompromised patients

How does ABPA present?

* Chronic wheeze * Allergy * Bronchiectasis * Eosinophilia

How does aspergilloma present?

Colonises pre-formed cavities eg those formed by TB \*so treated pulmonary TB may be in the history

What assay is used for asperigillus diagnosis and why?

Galactomannan assay - because aspergillus contains this in the cell wall

What is a galactomannan assay used for?

Aspergillosis diagnosis

How does aspergillus appear under the microscope?

Can see hyphae But can't identify the type based on hyphae. Need to analyse the spores produced by the fungi.

Tx of aspergillus infection

Ambisome or voriconazole Fluconazole has POOR ACTIVITY AGAINST MOULDS!!

What are dermatophytes?

Moulds They invade dead keratin Spread by contamination with desquamated skin scales

Examples of dermatophytes

trichophyton rubrum pitiriasis veriscolor

Types of tinea - and which organism causes them?

Pedis: foot (athlete's foot) Capitis: head Corposis: body (AKA RINGWORM) Cruris: groin Caused by TRYCHOPHYTON

Pityriasis versicolor: - cauasative agent - features - diagnosis - management

Caused by: Malassezia furfur - Characterised by discolouration of the skin hypopigmentation (in patients with dark skin tones) hyperpigmentation (in patients with pale skin - diagnosis: "sphaghetti with meatballs" appearance with potassium hydroxide, or orange fluorescence under wood's lamp - management: topical clotrimazole, ketoconazole

How is tinea diagnosed?

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

What are the clinical features of mucormycoses?

Orbital/facial cellulitis with discharge of black pus from nose/ palate Can also spread to brain \*can spread via inhalation of spores or primary colonisation of skin \* immunocompromised patients, poorly controlled diabetics

How are mycormycoses managed?

Surgical emergency- debridement of necrotic tissue LONG duration of ambisone (amphotericin B)

Recall 4 classes of antifungal

Azoles Polyenes Echinocandins Pyrimidine analogues

Recall the side effect profile of each class of antifungal

Azoles - abnormal LFTs PolyeNes - Nephrotoxicity Echinocandins - relatively innocuous - whci his good bc this is the one you use broad spectrum if you dno't know the organism causing candidaemia Pyrimidine analogues - blood disorders

What is the mechanism of action of azoles?

Inhibit ergosterol synthesis

What is the mechanism of action of polyenes?

Bind sterols in membranes to create leakage of electrolytes \*so targets ergosterol

Give 2 examples of polyene medications

Amphotericin B Nystatin

Which 2 types of fungus are echinocandins particularly useful for?

Candida (rmb it is used for candidaemia until cultures are back) Aspergillus \*so one yeast (candida) and one mould (aspergillus)

What class of antifungal is flucytosine?

Pyrimidine analogue

Example of echinocandin?

Capsofungin

How to diagnose superficial fungal infections?

Wood's lamp

Which fungi cause superficial infections?

**Tinea:** Dermatophyte e.g. Tricophyton rubrum: Ringworm, Athlete’s foot o **Pityriasis:** Malassezia globosa/furfur : seborrhoeic dermatitis, T. versicolor

(depigmentation in those with darker skin

Pityriasis versicolor

Which fungi cause deep seated infection?

Candida Aspiergillus Cryptococcus

Dx of candida

Culture, Mannan, Antibodies

Summary of treatment of candida infections

a) fluconzaole: canddia albicans b) amphotericin-B: invasive disease

Dx of aspergillus

ELISA, PCR, β-Glucan test, grows on Czapek dox agar

Tx of aspergillus

Voriconazole (AV)

Polyene

eg amphotericin target: cell membrane integrity indication: yeast

azole antifungals

eg fluconazole target- cell membrane syntehiss indication- yeast

terbinafine

target: cell membrane indication: mould (specifically- dermatophytes) \*\*need to order LFTs before starting

flucytosine

target: DNA synthesis

echinocandin

eg capsofungin target: cell wall indication: yeast (less toxic side effects)

WHat does coccioides cause?

systemic infection - valley fever fever, cough, lethargy etc. \*from arizona, utah etc (think valleys)

what fungus causes mucormycosis?

rhizopum species