Infection & Immunity Nick Hadd Fungal Flashcards
What is sepsis or septic shock?
Sepsis is the physiological response of the body to a systemic infection
Septic shock occurs when the circulatory system cannot supply the demands of the body.
What does disseminated mean?
Disseminated: spread from the initial localised source of infection
What is the process of septic shock leading to multi organ failure.
Inflammatory mediators in blood make the blood vessels more leaky, thus results in decreased blood pressure
Low blood pressure leads to hypoperfusion of organs (lack of blood supply) leads to multi organ failure
What kinds are most prone to getting fungal infections?
Neutropenic patients I.e those receiving chemotherapy
Intensive care unit patients
Patients with central IV catheters
HIV and AIDs
Patients after a transplant who are on anti-rejection medication
Neutropenia is a risk for both candida and aspergillus infection.
This is the same with steroids, graft vs host disease (GVHD), mucosal colonisation and bacterial infections.
Central intra venous lines and antibacterials are a risk of candida only
Building works are a risk of aspergillus only
What are the main causative organisms of fungal infections?
Candida species
Aspergillus species
Cryptococcus species
Histoplasma capsulatum
What type of fungus is candida? Where’s it found? What’s it diagnosed by?
It’s a yeast
Part of normal gut flora
Diagnosed by culturing
What’s important to find out if a patient is found to have an infection with candida?
Any previous Azole therapy eg with fluconazole itraconazole etc
Also important to find out the species; albicans causes almost all muco-cutaneous infections
What types of candidiasis are there?
Catheter related
Acute disseminated
Chronic disseminated
Deep organ candidiasis
What type of fungus is aspergillus?
A mould
Common environmental pathogen
What type of infection does aspergillus tend to cause?
Pulmonary infections
It’s opportunistic in immuno-compromised patients
May be found after lung transplants
How can we diagnose aspergillus infections?
Imaging- fungus infections will usually show up in x-rays
Also by antibody detection
Aspergillosis can be invasive, allergic, or saprophytic. What do these mean?
Invasive:
Includes disseminated. Means that it isn’t localised, it’s spread. Typically of lung origin
Allergic:
ABPA allergic broncho pulmonary aspergillosis
Saprophytic:
Aspergilloma ( a fungal ball) growth of this ball in a pre-existing cavity, eg a patient with previous TB
What are the complications associated with invasive pulmonary aspergillosis?
Raging pneumonia
Dissemination (spread) into the CNS
Local invasion into heart/ vessels etc
Cryptococcus is a yeast, what types of infection does it usually cause?
Invasive CNS disease
Pulmonary [not usually detected]
Especially seen in HIV and AIDS patients
Histoplasmosis results from the environmental pathogen Histoplasma capsulatum. It traditionally causes _________ disease and further dissemination. Usually ______ patients more prone.
Causes pulmonary disease
Usually HIV and AIDs patients
What’s the difference between invasive and disseminated infections?
Invasive means spreading, this may be locally or to wider parts of the body because of Dissemination or seeding
Dissemination means more widely spread. NOT local spreading
What’s fungaemia?
A type of sepsis where fungi circulates the blood
What are mannan/ anti-mannan, beta D glucan, galactomannan all examples of?!
Ways we can diagnose and decide when to treat fungal infections
What’s the “proven” catergory diagnostics of fungal infections?
The exact cause of the fungus has been grown and cultured so doctors are certain what is causing it
What is the “probable” catergory of fungal infection diagnostics?
Some uncertainty of what’s causing it, usually treated empirically
To meet criteria of probable: host factor, clinical features and mycological (fungal causing) evidence must be present.
“Possible” infections meet even less criteria than this
Definition of these levels of certainty differ from one organism to the next and between different types/ sites of infection
To meet the criteria of probable fungal infection, one of the criteria is HOST factors, what’s this?
Included factors that the patient may have, eg
Neutropenia
Fever unresponsive to broad spectrum antibiotics
Use of immuno suppressants
HIV or AIDS
Recent long use of corticosteroids
One “probable” diagnostic indicator is clinical features. What are these?
Mainly relevant imaging
Eg lesions seen in respiratory tract
Meningeal enhancement / Lesions in CNS
Indirect tests such as galactomannan, and more direct tests involving microscopy, sensitivity and culture such as Sputum and NBL (squirt water into lungs, extract and then send sample to lab) samples are all part of the ________ criteria of fungal diagnostics
Mycological evidence
Fungal infections are best treated with antibiotics. True or false?
False!
Antibiotics only treat bacteria!
Could be used as a diagnostic feature though; if a patient still has fever after using broad spectrum antibiotics this may indicate fungal infection
Antifungals drugs have to be specific to target fungus and not our own cells, why is this more difficult with fungus than for bacteria?
Fungus are eukaryotic just like our own cells. So harder to target these specifically. Bacteria are prokaryotic
What class of antifungals tend to work by inhibition of egosterol biosynthesis in the cell membrane?
Azoles
Eg the triazoles:
fluconazoles
Ketaconzaole
Or imidazoles
What kind of antifungals tend to work by ergosterol disruption in the cell membrane?
Polyenes
Eg amphotericin B
Abelcet
AmBisome
Which antifungal works by inhibiting DNA / RNA synthesis in the nucleus?
Flucytosine
What is the triazoles mechanism of action INR fungus? What are their side effects
They decrease ergosterol production through inhibition of fungal cytochrome p450 enzymes. Most are static (I.e don’t kill but stops the fungi reproducing)
Orally taken
Side effects:
Hepatic effects
QT prolongation
Why do triazoles commonly interact with other medication?
They inhibit fungal CYP450 enzymes, but may also inhibit human enzymes too
What’s the best treatment for simple infections?
Fluconazole
Use where Candida albicans has been confirmed and the patient has had no previous azole therapy
What’s best to use as treatment for most ‘serious’ infections?
Lipid formulation amphoterocin
Or echinicandin
What should we consider to use for CNS infections?
Voriconazole
