NH L1 Invasive Fungal Infections Flashcards by Alethea Charlton

‘Mycosis’

fungal infection

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‘Invasive’

as opposed to localised

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‘Disseminated’

spread from the initial localised source

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‘Fungaemia’

fungus in the blood

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‘Systemic’

of a system, usually the blood

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‘Septic shock’

circulatory system cannot supply the demands of the body

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What happens during septic shock?

Inflammatory mediators compromise the integrity of blood vessels - leakage of intravascular fluids - low BP - hypoperfusion of organs - death

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Are fungi prokaryotes or eukaryotes?

eukaryotes

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Where can we look for evidence about fungus?

Inasive fungal infections coooperative group,

Infectrions diseases society of america etc.

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Who gets fungal infections (7)

neutropenic patients (bone marrow transplant/chemotherapy)
ITU patients
IV catherters
HIV/AIDS
Transplant (anti-rejection drugs)
Impaired immune function

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Main causative organisms (4)

Candida
Aspergillus
Cryptococcus
Histoplasma capsulatum

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Candida is what sort of fungus?

A yeast

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T/F Candida is normal flora

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Diagnosis of candida via….

culture

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Important to know when diagnosing candida: (3)

Previous azole therapy
Species
Susceptibility

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Types of candida infection (4)

catheter related
acute disseminated
chronic disseminated
deep organ

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Sources of candida infection (2)

GI tract

central venous catheter

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Complications of candida infection (2)

Dissemination, acute/chronic/deep organ
Fungal endocarditis
Endophthalmitis (eyes)

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Aspergillus is what type of fungus?

A mould

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Aspergillus tends to cause infections where? in whom?

In the lungs

immunocompromised or lung transplant pts

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How do we detect aspergillus? (2)

Blood culture are hard to obtain

Imagin or antibody detection?

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What is aspergillosis

-invasive aspergillus (typically of lung origin)
OR
-AMPA (allergic bronchopulmonary aspergillosis

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What is aspergilloma

A fungal ball - growth in a pre-existing cavity e.g. TB patient

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What are the complications of aspergillosis?

RAGING PNEUMONIA
dissemination to the CNS
localised invitation to heart/vessels

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Why do we surgery on people with aspergillosis?

Restriction of locally invasive legions

Cryptococcus is what sort of fungus?

Yeast

Most common species cryptococcus is....

cryptococcus neoformans

Types of infection from cryptococcus (2)

Pulmonary | Invasive CNS disease

How is particularly prone to cryptococcus infection?

HIV/AID patients

Histoplasma is what sort of ting?

An environmental pathogen

Histoplasmosis is usually where?

Pulmonary - but disseminates elsewhere

Who does histoplamsa usually affect?

HI/AIDS pattients

Types of infection (4) (catagories)

Invasive Disseminated Fungemia Distant site of infection (endocarditis)

Diagnosis is difficult but can be via..... (5)

``` Diagnosis is difficult - (systemic/neurological/respiratory symptoms?). Cultures Microscopy Imaging Other clever tools ```

Type o' culture (4)

blood respiratory biopsy material

Other clever tools includes (4)

Mannan/anti-mannan Beta-D-glucan Galactomannan Other serology (to detect antigens)

Diagnostic certainty levels

Proven - fungal cause known Probable - 1x host, clinical and mycological Possible Definitions of these levels of certainty vary from one organism to the next - between types/site of infection

Diagnostic indicators: host factors (5)

``` Neutropenia Fever unresponsive to broad spec antibiotics Use of immunosuppressants HIV/AIDs recent prolonged use of corticosteroids ```

Clinical diagnostic indicators: respiratory

lesions air crescent sign cavity

Clinical diagnostic indicators: CNS

legions, meningeal enhancement

Clinical diagnostic indicators: disseminated

target lesions liver/spleen

MYCO diagnostic indicators (4)

Galactomannan Beta-D-glucan MC&C (sputum, NBL)

Key characteristics of an antifungal

specificity i.e. drug kills fungus not us.

problems with treating fungi?

they are eukaryotic, harder to treat the differences between them and us

4 classifications of antifungals

Azoles Echinocandins Polyenes Nucleoside analogues

How do Azoles work?

Inhibition of ergosterol biosynthesis in the cell membrane

Polyenes work by....

Ergosterol disruption in the cell membrane

Echinocandins work by...

Inhibition of the beta-1.3-glucan synthesis in the cell wall

2 types of azoles

Imidazoles | Triazoles (such as fluconazole, itraconazole)

Triazoles work by

decreased ergosterol production through inhibitions of fungal CYP p450

Triazoles are static or cidal

static

triazoles are orally active?

s/e of triazoles

hepatic derangement | QT prolongation

Interactions with triazoles?

yes, many through CYP P450

Cheap and cheerful triazole?

Fluconazole

Fluconazole is active against most....

candida

Itraconazole is administered by...

liquid - needs acidic stomach and taste horrible

s/e

hepatotoxicity

itraconazole or fluconazole is better for prophylaxis of invasive fungal infections

Intraconzole

Itraconazole has interactions?

yes (via CYP)

Itraconazole is contraindicated with what class?

Statins

Voriconazole is effective against.... (2)

candida and aspergillus

Voriconazole is cool because...

it has superior CNS penetration

Voriconazole s/e

taste disturbances

Voriconazole tends to be restricted to...

CNS infections | or where patient factors dictate

Amphotericin works by

binding to ergosterol creating pores, increasing permeability

Amphotericin interacts with

most stuff, including other nephrotoxic

Amphotericin is broad or narrow spectrum

broad

Amphotericin is cidal or static

cidal

Amphotericin is administered via

IV - with a crash trolley ready | or liquid amphotericin now used first line

s.e of Amphotericin

``` renal tox electrolyte disturbances infusion reactions cardiotox hepatotox ```

Amphotericin delivered orally gives significant reduction in....

renal toxicity

Amphotericin has a tricky preparation as ....

low micron fibres

Echinocandins include (2)

Caspofungin (broad license, okay in renal impairment) | Anidulafungin (invasive endocarditis - okay in hepatic and renal failure)

Flucytosine is a nucleoside analogue, | synergistic with

amphotericin (resistance is a problem if used alone)

Flucytosine works by

converting 5-FU intracellularly, and suppressing bone marrow

What treatment to use?

``` Evidence base Empirical vs confirmed Pt group Activity (susceptibility and CNS penetration) Toxicity Interactions (chemotherapy drugs) Cost ```

For most simple infections use...

fluconazole (where no previous azole therapy)

For most serious infections use

lipid formulations of amphotericin or echinocandin

For CNS infections consider using

vorconazole