Fungal Flashcards
What patient groups get serious fungal infections? [6]
Chemo, bone marrow transplants. ITU patients. Central IV catheters. HIV/AIDS. Organ transplants. Long term corticosteroid use.
Where do we get information on how to manage invasive fungal infections?
(EORTC/MSG) (IDSA) (ESCMID) (BCSH)
European org for research and treatment of cancer/invasive fungal infections/mycoses study group.
Infectious disease society of america guidelines.
Euro society of clinical microbiology and infectious diseases.
Where do we get information on how to manage invasive fungal infections?
European org for research and treatment of cancer/invasive fungal infections/mycoses study group.
Infectious disease society of america guidelines.
Euro society of clinical microbiology and infectious diseases.
What are the main causative agents of invasive fungal infections? [4]
Candida, Aspergillus, Cryptococcus, Histoplasma.
What factors are important to know when treating candida infections? [2]
If previous azole therapy has been tried, what species is present.
What are the main types of candidiasis? [4]
Catheter related.
Acute disseminated.
Chronic disseminated.
Deep organ.
What is candidaemia?
Blood infection of candida. Can lead to dissemination of infection to acute/chronic deep organs. Endophthalmitis. fungal endocarditis.
What is aspergillus?
Type of mould. Common environmental pathogen which tends to cause pulmonary infections in immuno-compromised patients. Blood cultures are hard to obtain so must be diagnosed by using imaging, antibody detection etc.
What types of infection does aspergillus tend to cause?
Pulmonary in immuno-compromised patients (lung transplants).
How is an infection caused by aspergillus diagnosed?
Imaging, antibody detection etc. Blood cultures are hard to obtain.
What is aspergillosis?
An aspergillus infection which commonly originates in the lung and has become invasive. Can cause ABPA: allergic bronchopulmonary aspergillosis.
What is ABPA?
allergic bronchopulmonary aspergillosis can be caused by an aspergillosis infection.
What is an aspergilloma?
This is a fungal ball grown in a pre-existing cavity e.g. patient with previous TB. [Saprophytic]
What is the most common Cryptococcus?
Neoformans. Causes undetected pulmonary infections and invasive CNS disease in HIV/AIDS patients.
What types of infections are most commonly associated with Cryptococcus neoformans?
Undetected pulmonary infections and invasive CNS disease in HIV/AIDS patients.
What is Histoplasmosis?
Pulmonary disease caused by common environmental pathogen histoplasma capsulatum. Typically in AIDS/HIV patients.
How can fungal infections be diagnosed? [7]
With difficulty.
- Cultures of blood, respiratory, biopsy, material.
- Microscopy
- Imaging via X-ray or CT
- Mannan/anti-mannan
- Beta-D-glucan
- Galactomannam
- Serology for antibodies
What are the three diagnostic certainty levels?
Proven - fungal cause known.
Probable - 1x host, clinical + mycological
Possible - less criteria than probable
What diagnostic indicators are often present in the host? [5]
Neutropenia. Fever (unresponsive to broad spectrum antibiotics) Immunosuppressive therapy HIV/AIDS Recent prolonged use of corticosteroids.
What clinical diagnostics are there? [3]
Relevant imaging:
Resp: lesions, air-crescent sign or cavity.
CNS: lesions or meningeal enhancement.
Disseminated: lesions on liver or spleen.
What mycological indicators of a fungal infection are there? [3]
Galactomannan antigens
Beta-D-glucan in serum
MC&S, sputum, NBL.
What key characteristics are common across antifungals?
SPECIFICITY:
We need the drug to kill the fungi before us!
As fungi are eukaryotic we share many more similarities than with bacteria etc.
What are the main classifications of antifungals? [4]
Azoles (Imidazoles, triazoles)
Echinocandins (caspofungin, anidulafungin)
Polyenes (amphoterocin)
Nucleoside analogues (flucytosine)
How do azoles work? [3]
Inhibit fungal CYP450 enzymes causing decreased ergosterol biosynthesis.
Cause significant interactions via p450 enzymes.
Most are static and only kill actively dividing fungal cells.
What side effects do azoles cause?
They are orally active but cause hepatic and QT interval side effects. Cause significant interactions via p450 enzymes.
How is fluconazole used and at what doses?
IV/Oral.
400mg daily in severe infections, up to 800mg IV unlicensed.
Active against most candida with CNS penetration but many interactions via p450 inhibition (like all other azoles)
Why would itraconazole be used in preference to fluconazole?
Superior for prophylaxis of IFI but can cause heart failure (negative initrope) and increased hepatotoxicity.
What are the side effects of itraconazole?
Interactions with CYP3A4. Heart failure, hepatotoxicity. Tastes horrible but the oral liquid has better absorption.
Cannot be administered with statins.
Can statins and itraconazole be co-administered?
NO
Why would voriconazole be used instead of itra/fluconazole?
Superior CNS penetrations and active against both Candida and Aspergillus spp.
Good Oral and IV BA.
Use is restricted to CNS infections, or where patients cannot take other medication. Can cause dose associated visual disturbances?
Which antifungal is associated with dose related visual disturbances?
Voriconazole.