Fungal infections Flashcards
Sepsis
Circulatory system cannot meet demands of body due to:
- Infammatory mediators compromises integrity of blood vessels
- Leaky blood vessels lower bp
- Reduction of bp leads to hypoperfusion of lungs
Guidance for fungal infections
- EORTC/MSG
- IDSA
- ESCMID
- BSCH 2008
Candida spp.
Yeast
Normal gut flora
Diagnosed by cultures
Sources of infection: GItract and catheters
Important to know previous anti-fungal treatments
Types of candidiasis
Catheter related
acute disseminated
chronic disseminated
deep organ (distant metastasis)
Aspergillus spp
Mould
Common in environment and tends to cause pulmonary infections
Blood cultures are difficult to obtain so imaging and antibody detection is used instead
Aspergillosis
Invasive aspergillosis
ABPA (allergic bronchopulmonary aspergillosis)
Aspergilloma (fungal ball) in preexisting cavity (such as with patients that have had TB. It is saprophytic
Cryptococcus
Yeast
Most common is cryptococcus neoformans
Usually pulmonary infection or Invasive CNS
Especially common in HIV/AIDS?
Histoplasma
Histoplasma capsulatam
Usually pulmonary and found in HIV/AIDS patients
Diagnostic certainty
Diagnosis is often difficult so 3 classes of certainty:
Proven- fungal cause has been grown
Probable- 1 host, clinical and mycological
Possible- less criteria met than probable
These can vary dependant on species/site
Diagnostic indicators in host
Unresponsive to ABx Neutropenia (neutrophil count down) Immunosuppressed patients HIV/AIDS Prolonged use of corticosteroids
Clinical diagnostic indicators
Relevant imaging
Resp: Lesion, air crescent sign, cavities
CNS: Lesions or meningeal enhancment
Disseminated: Target lesions liver/spleen
Indirect tests:
Galactomannan antigens
beta d glucan in serum
sputum and NBL
Azoles
Imidazoles
Triazoles (flucanazole, itraconazole, posaconazole, voriconazole)
Triazoles
Inhibits fungal CYP450 decreasing ergosterol production
Mostly fungastatic
Side effects: hepatic derangment and QT prolongation
Lots of interactions due to CYP450
Fluconazole
Cheap af
Active against most candida and has CNS penetration
400-800mg daily depending on severity
CYP450 inhibition interactions
Itraconazole
Better at prophylaxis of IFI’s
Better absorbed as liquid but tastes awful
Increased risk of hepatotoxicity and heart failure and has multiple interactions with CYP enzymes
Cannot give with atorvastatin and simvastatin
Voriconazole
Excellent CNS penetration with 96% oral bioavailability
Generally used only for CNS infections
Visual disturbances due to administration
Amphotericin
Binds to ergosterol in fungal cells and increases permeability. Is fungacidal
Broad spectrum but poor oral bioavailability therefore must be given IV. Start at 1mg/10min then watch for 30mins
Side effects of renal/cardio/hepato toxicity, electrolyte disturbances and infusion reactions
Liquid formulations of amphotericin
Ambisome and abelcet
Significant reduction in renal toxicity
Tricky to prepareas low micron filters needed
Now first line over amphotericin B
Echinocandins
Caspofungin- broad license and ok for renal impairment
Anidula fungin- used only for invasive candidasis, good for hepatic/renal failure
Flucytosine
Nucleoside analogue of pyrimidine
Synergism with amphotericin but plasma levels must be done
Problems with resistance if used on its own
Conversion to 5-FU intracellularly and bone marrow suppression
Dermatophytes
Moulds
Keratinophilic- infects hair/nails/skin most often
Spreads through direct contact and spores
Symptoms: itching, burning and pain
Tinea?
Tinea corporis
Skin ringworm
Trichophyton rubrum
Tinea cruris
Groin ringworm
Trichophyton rubrum/mentagrophytes
Epidermaphyton floccosum
Tinea capitis
Scalp ringworm
Tricophyton tonsurans
Tinea corpis/cruris treatment
Topical imidazol- Clotrimazol, miconazol or terbinafine
Topical corticasteroids used if infection severe
Oral therapy if topical doesn’t work:
Terbinafine 250mg daily (2-4wks cruris, 4 wks corpis)
Itraconazole 100mg daily 15days or 200mg for 7 days
Tinea capitis treatment
Oral treatment- ketoconazole, selenium sulphide shampoo
Griseofulvin 1g daily 8-10wks + 2 weeks after symptoms improve. Effective against microsporum spp
Terbinafine 250mg daily 4wks. Effective against tricophyton
Griseofulvin
1st antifungal
Narrow therapuetic range therefore only used in dermatophyte infections
Long courses necessary as it does not persist in keratinous tissue and should be taken with fatty foods
Side effects: alcohol like
Cannot use if hepatic impaired, pregnant or lupus
Tinea pedis (athletes foot)
More common in adults, skin becomes scaled, macerated and fissuring
Caused by Trichophyton rubrum/mentagrophytes, Epidermophyton floccosum
Moccasin type athletes foot is less common
Athletes foot treatment
Imidazole cream:2-4wks, Terbinfine cream 1 week
Oral treatment:
terbinafine- 250mg daily 2-6wks
itraconazole- 100mg 1x daily 30days/200mg 2xdaily 7days
griseofulvin- 500mg daily+2weeks after symptoms resolve
Allylamine (Terbinafine)
Lipophilic so concentrated in keratinous tissue
Cannot use in pregnancy, hepato/renal impairment
Side effects: GI effects, headaches, hepatotoxicity, serious skin reactions (cease treatment), psychiatric effects
Interacts with rifapicin, OCP’s
Onychomycosis (nails)
Trichophyton rubrum/mentagrophytes,Epidermophyton floccosum, Candida (rare)
DLSO most common type
Treat with terbinafine (250mg 6wks-3mths) or itraconazole (pulse treatment 200mg bd 7days every 21days) due to long retention in nails.Topical treatment is amorolfine 1-2x weekly for 6mths
Pityriasis versicolor
Caused by malassezia furfur colonization of stratum corneum
Multiple patches on neck, trunk and shoulders appear-usually occurs around puberty
Treat with ketoconazole, selenium sulfide (topical)
Itraconazole 200mg daily for 7days
Seborrhoeic dermatitis may be extensive in immuno-compromised patients
Oropharyngeal candidia
> 18yrs-oral fluconazole first line 50mg 1-2 weeks
2-18yrs-topical nystatin or miconazole
<2yrs- topical miconazole
Genital candidiasis
One of the most common infections
Higher risk from: pregnancy, diabetes, broad spectrum antibiotics
symptoms: intense pruritis, pain upon urination/intercourse, adherent white plaques
Treat with: clotrimzole 10% 1-3days, fluconazole 500mg stat
Cutaneous candidiasis
Under folds of skin
risk increased by antibiotics, HIV, skin conditions
causes pruritis, burning and pain
Treat with: skincare advice +topical imidazole or oral fluconazole 50mg 2-4wks if serious or topical fails
