Fungal infections Flashcards
What are fungi?
Eukaryotic organisms with continuous cell walls and ergosterol containing plasma membranes
Yeasts vs moulds differences
Yeasts - single celled, reproduce by budding
Moulds - multicellular hyphae, grow by branching and extension
Examples of yeasts
Candida
Cryptococcus
Histoplasma
Examples of moulds
Aspergillus
Dermatophytes
Agents if mucormycoses
Commonest cause of fungal infections in humans
Candida
Clinical manifestations of candida
Acute, subacute, chronic, episodic
Superficial or systemic/invasive
Superficial candidiasis infections
Oral thrush
Candida oesophagitis
Vulvovaginitis
Cutaneous (localised or generalised)
Tx of superficial candidiasis
Topical:
- Oral thrush - nystatin
- Vulvovaginitis/localised cutaneous - cotrimazole
Oral:
- Vulvovaginitis/oesophagitis - fluconazole
Candidaemia RFs
Malignancies esp haematological
Burns pts
Complicated post-op features (eg Tx o GIT Sx)
Long lines
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
Invasive candida Tx
CNS/Endocarditis/Bone and joint - Ambisome/voriconazole
Urinary - Fluconazole
Intra-abdominal - Echinocandin/Fluconazole
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
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
WHat type of ink to identify cryptococcus on stain
India ink
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
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
