NH L1 Invasive Fungal Infections Flashcards
‘Mycosis’
fungal infection
‘Invasive’
as opposed to localised
‘Disseminated’
spread from the initial localised source
‘Fungaemia’
fungus in the blood
‘Systemic’
of a system, usually the blood
‘Septic shock’
circulatory system cannot supply the demands of the body
What happens during septic shock?
Inflammatory mediators compromise the integrity of blood vessels - leakage of intravascular fluids - low BP - hypoperfusion of organs - death
Are fungi prokaryotes or eukaryotes?
eukaryotes
Where can we look for evidence about fungus?
Inasive fungal infections coooperative group,
Infectrions diseases society of america etc.
Who gets fungal infections (7)
neutropenic patients (bone marrow transplant/chemotherapy) ITU patients IV catherters HIV/AIDS Transplant (anti-rejection drugs) Impaired immune function
Main causative organisms (4)
Candida
Aspergillus
Cryptococcus
Histoplasma capsulatum
Candida is what sort of fungus?
A yeast
T/F Candida is normal flora
T
Diagnosis of candida via….
culture
Important to know when diagnosing candida: (3)
Previous azole therapy
Species
Susceptibility
Types of candida infection (4)
catheter related
acute disseminated
chronic disseminated
deep organ
Sources of candida infection (2)
GI tract
central venous catheter
Complications of candida infection (2)
- Dissemination, acute/chronic/deep organ
- Fungal endocarditis
- Endophthalmitis (eyes)
Aspergillus is what type of fungus?
A mould
Aspergillus tends to cause infections where? in whom?
In the lungs
immunocompromised or lung transplant pts
How do we detect aspergillus? (2)
Blood culture are hard to obtain
Imagin or antibody detection?
What is aspergillosis
-invasive aspergillus (typically of lung origin)
OR
-AMPA (allergic bronchopulmonary aspergillosis
What is aspergilloma
A fungal ball - growth in a pre-existing cavity e.g. TB patient
What are the complications of aspergillosis?
RAGING PNEUMONIA
dissemination to the CNS
localised invitation to heart/vessels
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?
y
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
