mycology

Question 1

Candida

Answer 1

part of the flora of the GI tract

if overgrown, it can cause various storms. They can then translocate in various department such as go into catheter of the bladder
causse cadidemia, invasive candidoses etc

Question 2

Aspergillus

Answer 2

is ubiquitously present in the environment
we often inhale it which is okay except if there is damage. The spores can then germinate and grow, then invade the bloodstream.

Question 3

the big five

Answer 3

Aspergillus, Candida, Cryptococcus, Pneumocystis, and Mucormycosis infections

Question 4

pathogenesis of candidiasis

Answer 4

after colonizing the gut, peritonitis or candidaemia can occurs through surgical anastomotic leakage or translocation.

it then get in the circulation and can interfere
it can cause endopthtalmitis, infectious spleen abscess, pyelonephritis, infectious pulmonary abscess.

Question 5

pathogenesis of invasive aspergilossis

Answer 5

if lung irritation and damaged cilia, the spores can attach and cause alveolar inflammation.

from there if healthy, it can cause aspergilloma, chronic fibrosis aspergillosis. It immunocompromised status, it can lead to Subarus invasive aspergillosis and even to IP - actuate invasive pulmonary aspergillosis.
if hypersensitive system, some people develop allergic bronco pulmonary aspergillosis or allergic sinustis

After alveolar inflammation, in immunocompromised it can often leas to tissue invasion and angioinvasion and cause through dissemination invasive aspergillosis.

Question 6

Probabilité of invasive apergillosis

Answer 6

Low risk in chronic myeloproliferative disorders, myeloma, kidney transplant and Hodgkins lymphoma.

intermediate risk in acute lymphoblastic leukemia, non Hodgkins lymphoma, AIDS

high risk in acute myeloid leukemia, hear, lung, liver transplantation.

Question 7

problems of invasive fungal infection

Answer 7

have a high mortality
few symptoms - difficult to diagnose
survival depends on speed of treatment
few anti fungal available
resistance to anti fungal

Question 8

issues regarding fungal infections

Answer 8

needs to tackled

robust, rapid, simple and cheap diagnostics needed
safer and more effective anti fungal
fungal vaccines

Question 9

EORTC psk factors

Answer 9

HOST: neutropenia, allo-HSCT, corticosteroids, immunospressants,congenital immunodeficiency.

Clinical factors; modulars lesions, air-crescent signs, cavity

microbiological: culture or direct microcopy/cytology, galactomannan antigen, Beta 1,3 gluten antigen

A proven IA must have a histopathological findings but it is hard to show

a probably IA include a host characteristic and a clinical (CT evidence) and microbiological one (culture or non culture based)

Question 10

direct test

Answer 10

culture, direct microscopy and histopathology

Question 11

indirect test

Answer 11

include galactomannan, A,3 beta D gluten or PCR

Question 12

type of sample for IA

Answer 12

from the lung it can be sputum, tracheal aspirin, bronchial aspirate or bronchi alveolar lavage (most precious)

it van e blood, urine, ascites, etc.

Question 13

direct microscopy

Answer 13

is kind of rapid, more sensitive than culture and give clue for identification.

tissue histology is slower, however more sensitive, also give clues and sho the host reaction and the degree of invasion

Question 14

culture

Answer 14

they grow quickly 1 or 2 days

they can help in the identification of the genus and the species level (sequencing or malditoff)

it can help typing and test for anti fungal susceptibility ttesting

Question 15

Galactomannan

Answer 15

is a polysaccharide form the cell wall. It provide a good sensitivity in immunocompromised patients because IPA is angioinvasive

detection in serum: quite sensitive in neutropenic patients but way lower in non neutropenic. If patient is already on anti fugal treatment, super lower sensitivity.
can also get false positive due to antibiotic
this is actually an early screening in neutropenic patient
index of 0.5

this sensitivity however does depend on the OD index cutoff value. if you go for a higher threshold, you gain in specificity bu you loos in sensitivity. most appropriate is apparently 0.8 ROC curve

detection in BAL: it provides a good sensitivity in both neutropenic and non neutropenic patients. It is usually requested upon suspicion
index of 0.8-1

however you cannot use only this - you do need to use the clinical context too

more sensitive than the lateral flow device

Question 16

1,3 bea D glucan assay

Answer 16

This test is pan fungal. so it is also for aspergillum, candida etc (less specific tho) and cannot detect mucorales and cryptococcus

there is different kit available and they have only been approve for serum test only.

thye have a lower specificity on BAL. This is nonuser friendly and is based on a colorimetry assay

a lot of fast positive have been shown due to hemofiltration, blood component, surgical gauzes etc.

Question 17

PCR based diagnostisc

Answer 17

very sensitive

but less in blood samples due to the low fungal load.
it can detect contaminants due to the omnipresence of fungi in nature.

in house / commercial assays are often combined with sepsis test

PCR is expensive, does not replace the need to culture, does not check for difference between colonization or invasion

test is not 100% standardized either among practices

Question 18

Mucormycosis molcular strategies

Answer 18

its very aggressive and very hard to culture, so PCR for BAL and serum samples has been a breakthrough

for BAL fluid; PCR and qPCR has shown 100% sensitivity and 93% specificity.

in serum, 90%

Question 19

anti fungal resistance test

Answer 19

molecular test are the only non culture way of determining resistance. They give direct application to clinical samples and allows to overcome culture limitation, improve the sensitivity, give rapid results and commercial test are available. (such as Asper genius, which diagnose disease species and also give resistance makers)

Question 20

plasma cell free DNA for diagnosis

Answer 20

apparently more accurate than galactomanna for IA
non invasive

Question 21

non enhanced chest computed tomography

Answer 21

in immunocompromised patients, you can easily see without contrast the nodules, halo or air credence. However is is lacking specificity and and is not sensitive in non neutropenic patients

in non neutropenia ICU patients, you do a CT if it is feasible for the patient safety (echo - no)
only a minority of ICU patients show CT signs
CT scans can be used to exclude other pathologies or IPA??
diagnostic can be enhanced by giving contract to see clots and nodues

Question 22

DIAGNOSTIC flow chart in non ICU

Answer 22

Clinical presentation look at EORT criteria

imaging can include a CT

mycology can do serum GM, serum BDG or blood PCR

then If safe and feasible, can go on for a bronchoscopy and lung biopsy, which will help to do microscopy, culture, BAL GM and BAL PCR

the determine if IPA or just colonization (no treatment in this case)

Question 23

DIAGNOSTIC flow chart in ICU

Answer 23

first does it fit EORTC, sesvere influenza, sever covid, COPD etc

if clinical suspicion and imaging show pulmonary infiltrate, especially caveating infiltrate,

go on to do a bronchoscopy with BALF

if safe, do lung biopsy that will then be run y mycology testing - proven IPA

directly mycology IPA - probably IPA

if visible plaque and nodule - mycology testing and probable IAT8

if possible tracheobronchial biopsy - sequencing - proven IATB (Isolated invasive Aspergillus tracheobronchitis)

Question 24

IAPA

Answer 24

Influenza associated pulmonary aspergillus

Question 25

CAPA

Answer 25

covid associated pulmonary aspergillus

Question 26

treatment

Answer 26

Primary prophylaxis with antifungal- prolonged neutropenia, chemo etc; before and after manifestation

empiric fever based treatment - high risk patient with persistance fever despite antibiotic (done a lot in poor county) (they use less antigunfal and have less resistance without having inferior income)

diagnostic driven - rich country ion high risk patients, biomarkers

secondary prophylaxis - imitation/continuation AF to prevent recurrence IA

Question 27

antifungal prophylaxis

Answer 27

decrease proven and probable AFD
decrease IPA and IFD related mortality

however
compliance issues, long term safety, tolerability, drug drug interaction, resistance, impact on performance diagnostic