Oh’s (73) - Fungal Infections Flashcards

1
Q

The difference between yeasts and moulds

A

Yeast - unicellular

Mould -multicellular

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2
Q

Types of Invasive Fungal Infections

A

1) Primary Mycoses

Occur in immunoCOMPETENT
Endemic in places where spores are abdundant
Agent has innate virulence that overcomes normal host defences

2) Secondary / Opportunistic

Less innate virulence
But occur in immunocompromised, cancer, burns, HIV, Abx use
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3
Q

Treatment options for fungal disease

A

Polyenes (Amphotericin B)

Azoles
Imidazoles and triazoles
(Voriconazole)

Echinocandins

Flucytosine

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4
Q

Mechanism of action of polyenes

A

Amphotericin B

Bind to Ergosterol in fungal wall

Cell death

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5
Q

Mechanism of action of Azoles

A

Inhibit ergosterol SYNTHESIS

Fungo-static

However - voriconazole can be fungicidal to aspergillus

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6
Q

Mechanism of Echinocandins

A

Inhibit b-glycol synthesis
Cell wall becomes unstable

Fungicidal to yeasts
Fungostatic to asperigiullius

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7
Q

Mechanism of flucytosine

A

Converts to 5 flurouracil
Incorporates into yeast RNA

Better with yeasts than moulds

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8
Q

Other therapeutic options of fungal infections

A

Folic acid inhibition in Pneumocystosis

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9
Q

Types of Priamry Mycoses

A

1) Blastomycosis (Gilchrist Disease) - Amphotericin for 12 months with Itraconazole step down
2) Coccidiodomycosis
3) Cryptococcous
4) Histyoplasmosis
5) Paracoccidiomnycosis

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10
Q

Dispositions to Opportunistic Mycoses

A
Use of CVP lines
Cavity surgery
Neutropenia
Steroids
HIV
Disseminated malignancy
ICU > 7 days
TPN
Malnutrition
Burns
Organ transplant
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11
Q

Types of Opportunistic Mycoses

A
Aspergillosis
Candida
Cryptococcosis
Penicillinosis 
Pneumocystosis
Zygomycoses
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12
Q

Examples of Aspergillosis

A

Aspergillus genus of moulds

Fumigatus
Flavus
Niger

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13
Q

Patients at risk of aspergillosis

A

Immunosuppresed - Chemo, HIV, steroids, transplant

ImmunoCOMPETENT - Liver disease, pancreatitis, DM
Chronic Lung disease on low dose steroids

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14
Q

Define pulmonary aspergillosis

A

Spectrum from

Localised Simple Aspergilloma (may lead to BPF or bleeding through erosion()

To

Allergic Broncopulmonary Aspergillosis (asthma /CF)

To

Progressive multi site pulmonary disease with extensive destructive cavitation

Leads to systemic infection —> brain and solid organs

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15
Q

Diagnosis Aspergillosis

A

Positive cultures/microscopy from samples

Focal lesions on CT chest/brain (halo sign)

Positive PCR - fluids (BAL), faster than MC&S, 90% sense/spec

Galactomannan

b-D-glucans in BAL or serum

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16
Q

Treatment options of aspergillosis

A

Systemic Voriconazole

Alternative:
Liposomal Amphotericin B
Isavuconazole

Do not use echinocandins

Convert to oral voriconazole

Resection of pulmonary lesions
Interferon gamma

17
Q

Types of candida species causing invasive disease

A

Alibicans
Tropicalis
Galbrata
Krusei

18
Q

Early symptoms of invasive candidiasis

A

Fever, chills, malaise, dsypnoea

Localised - joint pain, visual impairment, neuorological disturbacne

19
Q

Diagnosis of candida

A

1) Positive cultures/microscopy
2) Focal lesions on CT chest, liver brain (lag behind serology testing)
3) . Positive PCR
4) Mannan Ag/Antimanna Ab
5) b-D-Glucan in BAL
6) PCR (limited)
7) ELISA for serum enolase and IgG to enolase (not widely available)
8) Uses of scoring systems - but these are better for saying who should NOT get treated.

20
Q

What is cryptococcosis and its mechanism of infection

A

C.neoformans, yeast found in soil and bird excrement.

Inhaled

If immuncomprimised - haematogenous spread, disseminated disease, CNS affinity

C.gattii causes infections in immunocompetent

21
Q

Diagnosis of cryptococcus

A

1) Positive serum cryptococcal antigen

2) MRI - dilated peri vascular spaces
Cryptococcomas - High signal in T2
40% of CT brains are normal

3) Tissue biopsy and microscopy - India Ink, Alcian Blue, Fontana-Masson
4) CSF sample, micro, biochem, cytology and cryptococcal antigen
5) CSF cultures 5 days on Saboraud Agar is CSF shows increased leucocytes

22
Q

Tx of cryptococcus

A

Liposoman Amphotericin B with combination flucytosine

Fluconazole 400mg/day 1-2 years in residual non-respectable disease

Posaconazole in CNS disease (crosses BBB)

Manage ICP with shunts./drain

Some benefit with dexamethasone

23
Q

Commonest pneumocystosis

A

PJP - Pneumocystis jirovecii

Fungus NOT a protozoan

But different from fungi as cell wall is cholesterol NOT ergosterol

Means that Amphotericin and azoles don’t work

24
Q

Populations at risk of PJP

A

Children - commonly have asymptomatic childhood infections

Impaired host immunity - CD4<200 (HIV)

Non-HIV - immunosuppression due to haem malignancy or transplant immunsuppresion

Previous CMV also predisposes (reduces T-helper)

25
Q

Symptoms of PJP

A

Non spec:
Malaise, dyspnoea, non-productive cough

Progress to:
Pyrexia, weight loss, exertion hypoxia

Minority get PTx

26
Q

Radiology in PJP

A

CXR - widespread infiltration from Hila
Occasional - localised infiltrative patterns and cavitation

HRCT - ground glass opacity

27
Q

Diagnosis of PJP

A

Based on history, risk factors, and radiology

40% pts have normal CXR

PJP DNA on PCR of a BAL +/- peripheral serum samples

OR

Immunoflurescene or silver staining of sputum

28
Q

Treatment of PJP and how it works

A

Co-trimoxazole

Inhibits folic acid synthesis by two pathways

High dose for 3 weeks

In HIV - co-admin of steroids:
When the A-a gradient is less the 4.6kPa

29
Q

Alternative treatments of PCP

A

Pentamidine
Clindamycine with Primaquine
Dapsone and trimethoprim
Atavaquone

Cases of Clinda + caspofungin