Fungal infections Flashcards

1
Q

What are fungi?

A

Eukaryotic organisms with continuous cell walls and ergosterol containing plasma membranes

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2
Q

Yeasts vs moulds differences

A

Yeasts - single celled, reproduce by budding

Moulds - multicellular hyphae, grow by branching and extension

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3
Q

Examples of yeasts

A

Candida
Cryptococcus
Histoplasma

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4
Q

Examples of moulds

A

Aspergillus
Dermatophytes
Agents if mucormycoses

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5
Q

Commonest cause of fungal infections in humans

A

Candida

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6
Q

Clinical manifestations of candida

A

Acute, subacute, chronic, episodic

Superficial or systemic/invasive

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7
Q

Superficial candidiasis infections

A

Oral thrush
Candida oesophagitis
Vulvovaginitis
Cutaneous (localised or generalised)

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8
Q

Tx of superficial candidiasis

A

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

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9
Q

Candidaemia RFs

A

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

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10
Q

Management of candidaemia

A

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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11
Q

Invasive candida Tx

A

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

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12
Q

Cyptococcus - seroypes/species, transmission and disease

A

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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13
Q

Cryptococcus RFs

A

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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14
Q

WHat type of ink to identify cryptococcus on stain

A

India ink

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15
Q

Dx of cryptococcus memingitis

A
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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16
Q

Management of cryptoccocal meningitis

A

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

17
Q

What is aspergillosis and examples of common disease types

A

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

18
Q

Diagnosis of aspergillus

A

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

Biopsy - histology and MC&S

19
Q

Management of aspergillus

A

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

20
Q

Pneumocystis jiroveci - structure, acquision, disease caused

A

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

21
Q

RFs for pneumocystis jiroveci

A

Immunosuppressed
Debilitated infants
Severe protein malnutrition

22
Q

Sx, x-ray findings and Ix of penumocystis jiroveci

A

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

23
Q

Management of pneumocystis jiroveci

A

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

24
Q

Mucormycoses

A

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

25
Q

Manifestations of mucormycoses

A

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

26
Q

Management of mucormycoses

A

Ambisome/posaconazole
Surgery
guided by response

27
Q

Dermatophytes

A

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

28
Q

Diagnosis and management of dermatophyte infection

A

Diagnosis - Skin scrapings, nail specimens and plucked hairs - MC&S

Management
Topical e.g. clotrimazole, ketoxonazole
Oral e.g. griseofulvin, terbinafine, itraconazole

29
Q

Antifungals and side effects

A

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

30
Q

Azoles

A

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)

31
Q

Polyenes - Amphotericin B

A

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

32
Q

Echinocandins - caspofungin acetate

A

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

33
Q

Pyrimidine analogues - Flucytosine

A

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