lecture title: diversity of fungi and fungal infections · includes most fungi amphotericin b,...
TRANSCRIPT
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Lecturer name:
Dr. Ahmed M. Albarrag
Lecture Date: Oct-2019
Lecture Title:Diversity of Fungi and Fungal Infections
(Foundation Block, Microbiology)
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1. To provide students with an overview of the common medically important yeasts and mold fungi.
2. To provide students with an overview of the major fungal diseases that threatens human health.
3. To give a fundamental knowledge about the antifungal agents, their mechanisms of action, and spectrum.
Lecture Objectives..
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Hypersensitivity (Allergy)
Mycotoxicoses
Infections
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How the infection is acquired? Endogenous, Colonization (overgrowth of normal flora)
Inhalation (Airborne)
Contact
Trauma
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Healthy host?
OR
Immunocompromised host?
(When, which type of infection)
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Superficial mycoses
Cutaneous mycosis
Subcutaneous mycoses
Systemic mycoses
Opportunistic mycoses
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Healthy Host
• Superficial mycoses
• Cutaneous mycosis
• Subcutaneous mycoses
• Systemic mycoses
Immunocompromised Host
Superficial mycoses
Cutaneous mycosis
Subcutaneous mycoses
Systemic mycoses
Opportunistic mycoses
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Superficial Mycoses Affect the outer layer of the skin or hair shaft
No immune response
Cutaneous Mycoses
Dermatophytosis
Infection of the skin, hair or nails caused by a group of keratinophilic fungi, called dermatophytes
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Subcutaneous Mycoses
Fungal infections involving the dermis, subcutaneous tissues, muscle and may extend to bone.
Usually they are initiated by trauma.
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17
Primary Systemic Mycoses
•Caused by primary pathogens•Contracted by inhalation, Start as respiratory disease •Geographically restricted (endemic), north and south America
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Opportunistic fungal infections
•Diseases in immunocompromised host
•Risk factorsHIV/AIDSHematopoietic stem cell transplant (HSCT)Solid organs transplantationMalignanciesNeutropeniaDiabetes
Many others
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A) Opportunistic FungiNormal flora
Candida spp.Other yeast
Other fungi
•
The Fungi
B) Primary Pathogens Dermatophytes Endemic geographically
restricted- Histoplasma spp.- Blastomyces spp.-Coccidioides spp.-Paracoccidioides spp
Ubiquitous in our environmentAspergillus spp.Zygomycetes spp.Cryptococcus spp.
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Clinical features (history, risk factors, etc)
Imaging
Good value in diagnosis and therapy monitoring
Lab Investigations
Histopathology
Microbiology
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Antifungal agents
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Cell membrane• Polyene• Azole
Cell wall
• Echinocandins
– Caspofungin
– Micafungin
– Anidulafungin
DNA/RNA synthesis
• Pyrimidine analogues- Flucytosine
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• Amphotericin B, lipid formulations
• Nystatin
Mechanism of Action Amphotericin B (MOA): Binds to ergosterol within the fungal cell membrane resulting in formation of
pores which permit leakage of intracellular contents, and lead to death .
Amphotericin B has an broad antifungal spectrum which includes most fungi that cause human disease
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• Fluconazole
• Ketoconazole
• Itraconazole
• Voriconazole
• Posaconazole• Miconazole, clotrimazole
• Mechanism of Action
Inhibits synthesis of ergosterol, the major sterol of fungal cellmembrane.
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Fluconazole Itraconazole Voriconazole Posaconazole
Yeast +++ + +++ +++
Mold ,e.g Aspergillus
-- ++ +++ +++
Zygomycetes - - - ++
Azoles—Spectrum of Activity
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• Mechanism of Action
Fungal RNA miscoding
Interfering with DNA synthesis
• Spectrum of Activity (Restricted spectrum of activity)Active against
Candida species
Cryptococcus neoformans
Monotherapy : now limited (Resistance)
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mannoproteins
b1,6
glucans
b1,3
chitin
ergosterol
b1,3 glucansynthase
Cell membrane
The Fungal Cell Wall
Introduction to Medical Mycology. Merck and Co. 2001
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– Caspofungin
– Micafungin
– Anidulafungin
• Mechanism of Action
Inhibits B-1,3 –D glucan synthase, the enzyme complex that forms glucan polymers in the fungal cell wall.
Glucan polymers are responsible for providing rigidity to the cell wall.
• Good activity againstCandida spp
Aspergillus spp
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CommentsSpectrum of activityAntifungal AgentsMechanism of
action
GroupTarget
Serious toxic side effects
(nephrotoxicity)
Broad antifungal spectrum which
includes most fungi
Amphotericin B,
Nystatin
Binds to ergosterol
within cell
membrane,
formation of pores
which lead to cell
death
PolyenesCell
membrane
Not effective against
zygomycosis (except
posaconazole)
Adverse Effects
Drug Interactions
Fluconazole has a limited or no
activity against mould fungi
Voriconazol is the drug of choice
for Aspergillosis
Posaconazole has broader
spectrum of activity than other
azoles
Ketoconazole
Itraconazole
Fluconazole
Voriconazole
Posaconazole
Miconazole
clotrimazole
Inhibit the
synthesis of
ergosterol
Azoles
Less toxicity and side effects
compared to amphotericin B
and azoles
Good activity against
Candida spp ,Aspergillus spp
Limited or no activity against
other fungi
Caspofungin
Micafungin
Anidulafungin
Inhibits glucansynthesis, (glucan polymers in the fungal cell wall)
EchinocandinsCell wall
Monotherapy now limited
(Resistance)
Restricted spectrum of activity
Candida species
Cryptococcus neoformans
FlucytosineFungal RNA
miscoding
Interfering with
DNA synthesis
Pyrimidine
analogues
DNA/RNA
synthesis
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Dr. Ahmed M. Albarrag
Oct-2019
(Foundation Block, Microbiology)
Thank You