Oh’s (73) - Fungal Infections Flashcards
The difference between yeasts and moulds
Yeast - unicellular
Mould -multicellular
Types of Invasive Fungal Infections
1) Primary Mycoses
Occur in immunoCOMPETENT Endemic in places where spores are abdundant Agent has innate virulence that overcomes normal host defences
2) Secondary / Opportunistic
Less innate virulence But occur in immunocompromised, cancer, burns, HIV, Abx use
Treatment options for fungal disease
Polyenes (Amphotericin B)
Azoles
Imidazoles and triazoles
(Voriconazole)
Echinocandins
Flucytosine
Mechanism of action of polyenes
Amphotericin B
Bind to Ergosterol in fungal wall
Cell death
Mechanism of action of Azoles
Inhibit ergosterol SYNTHESIS
Fungo-static
However - voriconazole can be fungicidal to aspergillus
Mechanism of Echinocandins
Inhibit b-glycol synthesis
Cell wall becomes unstable
Fungicidal to yeasts
Fungostatic to asperigiullius
Mechanism of flucytosine
Converts to 5 flurouracil
Incorporates into yeast RNA
Better with yeasts than moulds
Other therapeutic options of fungal infections
Folic acid inhibition in Pneumocystosis
Types of Priamry Mycoses
1) Blastomycosis (Gilchrist Disease) - Amphotericin for 12 months with Itraconazole step down
2) Coccidiodomycosis
3) Cryptococcous
4) Histyoplasmosis
5) Paracoccidiomnycosis
Dispositions to Opportunistic Mycoses
Use of CVP lines Cavity surgery Neutropenia Steroids HIV Disseminated malignancy ICU > 7 days TPN Malnutrition Burns Organ transplant
Types of Opportunistic Mycoses
Aspergillosis Candida Cryptococcosis Penicillinosis Pneumocystosis Zygomycoses
Examples of Aspergillosis
Aspergillus genus of moulds
Fumigatus
Flavus
Niger
Patients at risk of aspergillosis
Immunosuppresed - Chemo, HIV, steroids, transplant
ImmunoCOMPETENT - Liver disease, pancreatitis, DM
Chronic Lung disease on low dose steroids
Define pulmonary aspergillosis
Spectrum from
Localised Simple Aspergilloma (may lead to BPF or bleeding through erosion() To Allergic Broncopulmonary Aspergillosis (asthma /CF) To Progressive multi site pulmonary disease with extensive destructive cavitation
Leads to systemic infection —> brain and solid organs
Diagnosis Aspergillosis
Positive cultures/microscopy from samples
Focal lesions on CT chest/brain (halo sign)
Positive PCR - fluids (BAL), faster than MC&S, 90% sense/spec
Galactomannan
b-D-glucans in BAL or serum
Treatment options of aspergillosis
Systemic Voriconazole
Alternative:
Liposomal Amphotericin B
Isavuconazole
Do not use echinocandins
Convert to oral voriconazole
Resection of pulmonary lesions
Interferon gamma
Types of candida species causing invasive disease
Alibicans
Tropicalis
Galbrata
Krusei
Early symptoms of invasive candidiasis
Fever, chills, malaise, dsypnoea
Localised - joint pain, visual impairment, neuorological disturbacne
Diagnosis of candida
1) Positive cultures/microscopy
2) Focal lesions on CT chest, liver brain (lag behind serology testing)
3) . Positive PCR
4) Mannan Ag/Antimanna Ab
5) b-D-Glucan in BAL
6) PCR (limited)
7) ELISA for serum enolase and IgG to enolase (not widely available)
8) Uses of scoring systems - but these are better for saying who should NOT get treated.
What is cryptococcosis and its mechanism of infection
C.neoformans, yeast found in soil and bird excrement.
Inhaled
If immuncomprimised - haematogenous spread, disseminated disease, CNS affinity
C.gattii causes infections in immunocompetent
Diagnosis of cryptococcus
1) Positive serum cryptococcal antigen
2) MRI - dilated peri vascular spaces
Cryptococcomas - High signal in T2
40% of CT brains are normal
3) Tissue biopsy and microscopy - India Ink, Alcian Blue, Fontana-Masson
4) CSF sample, micro, biochem, cytology and cryptococcal antigen
5) CSF cultures 5 days on Saboraud Agar is CSF shows increased leucocytes
Tx of cryptococcus
Liposoman Amphotericin B with combination flucytosine
Fluconazole 400mg/day 1-2 years in residual non-respectable disease
Posaconazole in CNS disease (crosses BBB)
Manage ICP with shunts./drain
Some benefit with dexamethasone
Commonest pneumocystosis
PJP - Pneumocystis jirovecii
Fungus NOT a protozoan
But different from fungi as cell wall is cholesterol NOT ergosterol
Means that Amphotericin and azoles don’t work
Populations at risk of PJP
Children - commonly have asymptomatic childhood infections
Impaired host immunity - CD4<200 (HIV)
Non-HIV - immunosuppression due to haem malignancy or transplant immunsuppresion
Previous CMV also predisposes (reduces T-helper)
Symptoms of PJP
Non spec:
Malaise, dyspnoea, non-productive cough
Progress to:
Pyrexia, weight loss, exertion hypoxia
Minority get PTx
Radiology in PJP
CXR - widespread infiltration from Hila
Occasional - localised infiltrative patterns and cavitation
HRCT - ground glass opacity
Diagnosis of PJP
Based on history, risk factors, and radiology
40% pts have normal CXR
PJP DNA on PCR of a BAL +/- peripheral serum samples
OR
Immunoflurescene or silver staining of sputum
Treatment of PJP and how it works
Co-trimoxazole
Inhibits folic acid synthesis by two pathways
High dose for 3 weeks
In HIV - co-admin of steroids:
When the A-a gradient is less the 4.6kPa
Alternative treatments of PCP
Pentamidine
Clindamycine with Primaquine
Dapsone and trimethoprim
Atavaquone
Cases of Clinda + caspofungin
