Fungal infections Flashcards by Zina Patel

What are fungi?

Eukaryotic organisms with continuous cell walls and ergosterol containing plasma membranes

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Yeasts vs moulds differences

Yeasts - single celled, reproduce by budding

Moulds - multicellular hyphae, grow by branching and extension

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Examples of yeasts

Candida
Cryptococcus
Histoplasma

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Examples of moulds

Aspergillus
Dermatophytes
Agents if mucormycoses

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Commonest cause of fungal infections in humans

Candida

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Clinical manifestations of candida

Acute, subacute, chronic, episodic

Superficial or systemic/invasive

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Superficial candidiasis infections

Oral thrush
Candida oesophagitis
Vulvovaginitis
Cutaneous (localised or generalised)

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Tx of superficial candidiasis

Topical:
- Oral thrush - nystatin
- Vulvovaginitis/localised cutaneous - cotrimazole
Oral:
- Vulvovaginitis/oesophagitis - fluconazole

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Candidaemia RFs

Malignancies esp haematological
Burns pts
Complicated post-op features (eg Tx o GIT Sx)
Long lines

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Management of candidaemia

Investigate source and signs of dissemination
- Imagine, Serology for bet-D-glucan, ECHO fundoscopy
Antifungals for at least 2wks - echinocandin/anidulafungin
Blood culture every 48 hours
Remove any lines/prosthetic material

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Invasive candida Tx

CNS/Endocarditis/Bone and joint - Ambisome/voriconazole
Urinary - Fluconazole
Intra-abdominal - Echinocandin/Fluconazole

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Cyptococcus - seroypes/species, transmission and disease

Encapsulated yeast

Serotypes A&D = C neoformans (Immunodefieicnet)
Serotypes B&c = C gattii (meningitis in immunocompetent in tropically, space occupying lesions in brain and lung, resistance to amphotericin B)

Transmission by inhalation of aerosolised organisms
Associated with pigeons

Chronic, subacute to pulmonary, meningitic or systemic disease

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Cryptococcus RFs

Impaired T cell immunity (eg HIV who have reduced CD4 helper T cell numbers)
Pts taking T cell immunosuppressants for solid organ transplant

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WHat type of ink to identify cryptococcus on stain

India ink

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Dx of cryptococcus memingitis

Typeical Hx - immunosuppressed
Imaging - pulmonary, brain
India ink staining of CSF
Serum/CSF cyptococcal A (CRAG)
Can culture from blood/body fluids

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Management of cryptoccocal meningitis

Induction - amphotericin +flucytosine (at least 2 wks)
Consolidation - high dose fluconazole (at least 8 wks)
Maintainance - low dose fluconazole (at least 1 yr)

Repeat LP for pressure management

If mild pulmonary disease - fluconazole alone

What is aspergillosis and examples of common disease types

Mould

Mycotoxicosis - contaminated foods
Allergy/squelae - presence/growth in orifices
Colonisation - in cavities or debilitated tissues
Invasive. inflam, granulomatous, necrotising disease of the lungs and other organs
Systemic and fatal disseminated disease

Apergilomas and clinical fungal disease

Diagnosis of aspergillus

Imaging
Sputum/Bal - MC&S, Ag testing
Aspergillus Abs (precipians)
Galactomannan (surface Ag)

Biopsy - histology and MC&S

Management of aspergillus

Voriconazole
Ambisome
Duration based on host/radiological/mycological factors - at least 6 wks

Pneumocystis jiroveci - structure, acquision, disease caused

Lacks ergosterol in cell wall
Airbourne route
Causes pneumonia (extrapulmonary disease rare)

RFs for pneumocystis jiroveci

Immunosuppressed
Debilitated infants
Severe protein malnutrition

Sx, x-ray findings and Ix of penumocystis jiroveci

Cough, SOB
X-ray - Diffuse bilateral infiltrates affecting all lobes of the lung with fine reticular appearance
Dx - microscopy, PCR, Beta-D-glycan

Management of pneumocystis jiroveci

High dose cotrimoxazole 2-3 wks
Alternatives: atovaquone, clindamycin + primaquine
Steroids if hypoxia present

Mucormycoses

clin syndrome by number of fungal sp belonging to Mucorales (e.g. Rhizopus, Rhizomucor, Mucor)

Inhalation of spores

Favours immunosuppressed or diabetic pts

Dx - tissue biopsy

Manifestations of mucormycoses

Rhinocerebral (CNS) - cellulitis of orbit/face -> black pus from palate/nose. retroorbital extention - ophthalmoplegias and blindness. Decreasing levels of consciousness Pulmonary Cutaneous

Management of mucormycoses

Ambisome/posaconazole Surgery guided by response

Dermatophytes

Group of fungi capable of invading dead keratin of skin, hair, nails Classified by site infected e.g. tinea capitis Pedis - food - trichophyton rubrum Capitis - scalp - T rubrum or Tonsurans Cruris - groin - T rubrum or E floccosum Corporis - abdomen Onchomycosis - Trichophyton spp, Epidermophyton spp, Microsporum spp Pityriasis versicolor - malassezia furfur Spread via contract with desquamated skin scales RFs: Moisture Deficiencies in cell mediated immunity Genetic predisposition

Diagnosis and management of dermatophyte infection

Diagnosis - Skin scrapings, nail specimens and plucked hairs - MC&S Management Topical e.g. clotrimazole, ketoxonazole Oral e.g. griseofulvin, terbinafine, itraconazole

Antifungals and side effects

Azoles (target cell membrane) e.g. Amphotericin B, Nystatin- Abnormal LTFs Polyenes (target cell membrane) e.g. Ketoconazole, Fluconazole, Vorizonazole - Nephrotoxicity Echinocandins (target cell wall) - Relatively innocuous Pyrimidine analogues (DNA synthesis inhibitors) - Blood disorders

Azoles

Fungi cytochrome P450-enzyme lanosterol 14-a demethylase converts lanosterol to ergosterol Azoles inhibit enzyme and production of ergosterol Cross reactivity with human cyP450 - drug interactions, impairment of steroidneogenesis (ketoconazole, itraconazole)

Polyenes - Amphotericin B

Broad spectrum Binds sterols in fungal cell membrane, created transmembrane channel and electrolyte leakage Active against most fungi except Aspergillus terreus, Scedosporium spp Nephrotoxicity - delayed - renovascular - drop in blood flow/GFR - Distal tubular - ischaemia, wasting of K+, Na+, Mg+ Enhanced in volume depleted/concominatn nephrotoxic agent pts Are less toxic preparations

Echinocandins - caspofungin acetate

Cyclic lipopeptide that interferes with fungal cell wall synthesis by inhibition of B-(1,3) D-glucan synthase Loss of cell wall glucan results in osmotic fragility Work well for yeasts/candida, less well for moulds/aspergillus, dont work for crytococcus neoformans

Pyrimidine analogues - Flucytosine

Restricted spectrum, easy resistance Use limited to candida and cryptococcosis (+Ambisome/fluconazole) Side effects - D&V, alterations in LFTs, blood disorders Monitor blood if using with Amphotericin