II. Mycology study of the fungiA. Introduction

1. FORMSa. Molds-Multicellular-Filamentous (hyphae)-Can live at room temp (25 C)b. Yeasts-Unicellular-Non filamentous (except candida albicans)-Can live at body temp (37 C)

2. CHARACTERISTICSa. Plant like organisms-Also have a cell wall (chitin)

b. Saprophytic-Eats dead/ decomposing organic matters

c. Filamentous

d. Multicellular

e. Dimorphic (same fungi)-Able to live at room temp & body temp

3. MORPHOLOGYa. Hyphae-Tubular like structure-Group of hyphae (mycelium)

b. Septae-Walls formed inside a hyphae

c. Spores & conidia-Serves as mode of reproduction-Serves as major classification of fungi

3 TYPES OF CONIDIA1. Arthroconidia2. Blastoconidia3. Chlamyconidia

4. Phylaa. Phylum Glomerulomycota, order Mucorales-Formerly known as phylum zygomycota-Sexual reproduction: zygosphores-Asexual reproduction: sporangium

Ex: rhizopus & Mucor (causes mucorcytosis)Cunninghamella

b. Ascomyota termed as SAC FUNGI-LARGEST species/phylum-Sexual reproduction: ascospores-Asexual reproduction: conidia

ex. SaccharomycesCandidacoccidioidesblastomycestrichophyta

c. Basidiomycota-Termed as club fungi-Sexual rep: basidiospores

Ex. CryptococcusMushrooms

B. Medical Mycology-Study of fungal diseases & its associated tx

1. Hypersensitivity rxns-Causative agents: respiratory allergens

2. Mycotoxicosis-Ingestion of pre formed toxin from a fungusEx: stale peanuts has aspergillus spp. w/ a toxin of Aflatoxin, that causes neoplasm, hepathocellular carcinoma.

Wheat claviceps purpurea can give ergotoxin

3. Mycetisma-Ingestion of a poisonous fungiEx: amanita phalloides

4. Fungal infections-Known to be mycoses-Fungi loves keratin

A. Superficial mycoses-Found in the epidermis-Most common-Affects: hair, nails, skina.1. Black piedra-Known as Tinea nodosa Medical term-CA: Piedraia hortae-CM: Black nodules at hair shaft

a.2. white piedra-CA: Trichosporon beigelli-CM: Beige nodules at the hair shaft

a.3. Pityriasis-Aka: Tinea versicolor-CA: Malassezia furfur-CM: Patches of hyper/hypopigmentation of the skin.

a.4. Tinea Nigra CA: Hortae werneckii CM: Dark pigments (brown to black) or the palms of the hands

B. Cutaneous mycosis Caused by dermatophytes

PART OF THE BODYTINEADERMATOPHYTES

1. FeetTinea pedis (athletes foot)Trichophyton rubrumE. flocosuumT. metagrophytes

2. Groin areaTinea cruris (jockitch/hadhad)Trichophyton rubrumE. flocosuumT. metagrophytes

3. Hands / nailsTinea manuum (hands)Tinea unguium (nails)(onchomysis)Trichophyton rubrumE. flocosuumT. metagrophytes

4. TrunkTinea corporisT. rubrumE. flocossum

5. Beard areaTinea barbaeT. mentagraphytes

6. ScalpTinea capitisT. mentagraphytesM. canis

B.1. Epidermophyton-Affects the skin &nails B.2.Microsporum-Affects the skin &hair B.3. Trichophyton-Affects the skin, hair & nails

-CM: Tinea (aka: ring worm)

C. Subcutaneous Mycoses

C.1. Chromoblastomycosis CA: Phialophora Verruscosa Fonsacaea Pedrosoi Fonasacaea Compacta Cladophialophora Carrionii Rhinocladiella Aquaspersa

CM: Verrucous or warty like lesions along the draining of Lyphatics.

C.2. Mycetoma CA: A. Bacterial (More infectious): Actinomyces

B. Fungal: Pseudallescheria Boydii Madurella Mycetomatis Madurella Grisea Exophilia Jeanselmei Acremonium Falciforme

Associated with: BAREFOOTED INDIVIDUALS CM: Suppuration / Abcesses formation Granulomata Formation Formation of draining sinuses cont. granules

C.3. Sporotrichosis Occupational disease of gardeners MOT: Trauma / wound Source: ROSE THORNS, soil, free bark CA: Sporothrix SHenkii CM: Nodules and lesions are found along the draining of the lyphatics Tx: KI Soln (DOC)

C.4. Phaeohyphomycosis Caused by Dermateceous Fungi Dermeteceous Melanin Pigments CA: Exophilia Jeanselmei Phialophora Richardsiae Bifolera Specifera Wangella Dermatitidis Alternatta Spp. Cervucaleria Spp. Exhorhilum Rostratum CM: Solitary encapsulated cyst Sinusitis Brain abcess formation

D. Endemic / Systemic Mycoses

CA: Thermally Dimorphic Fungi Primary Site of infection: LUNGS TX: ITROCONAZOLE Mild to Moderate AMPHOTERICIN B Moderate to Severe

D.1. Coccidioidomycosis

a. Coccidioides Immitisb. Coccodioides Posadasi AKA: DESSERT RHEUMATISM / Valley Fever 1st outbreak: San Joaquin Valley, CA Dx: Spores inside the spherules

D.2. Histoplasmosis Most common fungal respiratory infection CA: Histoplasma Capsulatum Non Capsulated MOT: Inhalation of Bat Droppings CM: SPELUNKERS DISEASE SSxs: Mimics SSxs of PTB Dx: Ovoid cells in Macrophage

D.3. South American Blastomycosis CA: Paracoccidiodes Brasiliensis CM: Respiratory lung lesions (Granulomas) Oral Ulcers Ulcers in the Pharyngeal Mucosa Dx: Multiple Budding Yeast

D.4. North American Blastomycosis CA: Blastomyces Dermatitidis CM: Respiratory infiltrates lesions in the bone, genitalia, and the brain Dx: Thick walled single budding yeast

E. Opportunistic Mycoses

E.1. Candidiasis Most common opportunistic fungal infection. CA: Candida Albicans Candida Lusitaei* Candida Crusei* * Fluconazole Resistant CM: Cutaneous and MucocutaneousA. Intertrigenous Infections Assoc. with obese patientsB. Oral Thrush Pseudomembrane Formation White Cottage cheese like depositsC. Onchomycosis Nail InfectionsD. Vaginosis

E.2. Cryptococcosis One of the Biomarkers of AIDS CA: Cryptococcus Neoformans (capsulated) MOT: Inhalation of PIDGEON DROPPINGS CM: Cryptococcal Meningitis Dx: INDIA INK Tx: Fluconazole (DOC) Standard tx : Amphotericin B + Flucytosine E.3. Pneumocystis Jiroveci Pneumonia One of the biomarkers of AIDS Former: Pneoumonitis Carinii (Rodents) Tx: Cotrimoxazole (DOC) Pentamidine

E.4. Aspergillosis CA: Aspergillus Fumigatus (Common) Aspergillus Flavus CM: Pulmonary AspergillomaAKA: Fungal Bail Invasive Aspergillosis Allergy Bronchopulmonary Aspergillosis Tx: Voriconazole (DOC)

E.5. Mucormycosis / Zygomycosis CM: Acute inflammation of soft tissues Fungal invasion, Inflammation of blood vessels Severe Form: RHINOCEREBELLAR INFECTION Tx: Posaconazole (DOC)

C. Antifungals

1. Treatment for superficial mycoses:a. Griseofulvin Fungistatic MOA: Binds to KERATIN and it protects the new skin from fungal infection. PK: Higher absorption if given with HIGH LIPID / FATTY MEAL. Tx: Tinea / Dermatophytic Infection

b. Nystatin Chemical Polyene Antifungal MOA: Binding to ERGOSTEROL Limited use: Topical Tx: Candida Infection

c. Terbinafine Fungicidal MOA: INH. Of SQUALENE EPOXIDASE Squalene Epoxidase Responsible for synthesis of ergosterol

SQUALENE EPOXIDASE Accumulation of SQUALINE ERGOSTEROL( Toxic to Fungi)

d. Azoles MOA: INH. Of CYP450 Chem:1. Imidazoles Less selective in inhibiting CYP450 Ex: Ketoconazole (Nizoral) : Withdrawn2. Topical azoles EX: 2.1. Clotrimazole (Canesten) 2.2. Triconazole (Trosyd) 2.3. Miconazole(Daktarin)

3. Triazoles Ex: 3.1. Itraconazole 3.2. Fluconazole 3.3. Voriconazole 3.4. Posaconazole - A/E: 1. Inhibition of Mammalian CYP450 2. Antiandrogenic Effect - Man boobs (Gynecomastia) - Women (Galactorrhea)

e. Miscellaneous Agents E.1. AP-AP solution AI: Salicylic Acid E.2. Whitfields Ointment Benzoic Acid + Salicylic Acid E.3. Sekun Blue AI: Selenium Sulfide Use: Anti Seborrhic E.4.Potassium Iodide Soln DOC for sporotrichosis

2. Treatment of less serious Mycoses A. Ketoconazole First to be introduced clinically High propensity for mammalian CYP450 Inhibition Withdrawn in the U.S. MarketB. Fluconazole PK: Higher H2O Solubility Higher ability to cross BBB Use: Mucocutaneous Candidiasis (Non-Resistant) Azole of choice for Tx and Prophylaxis of: Cryptococcal Meningitis 2nd line for less serious MycosesC. Itraconazole 2nd line and alternative for AMPHOTERICIN B for the Tx of infections caused by: Thermally Dimorphic Fungi

3. Treatment of systemic MycosesA. Amphotericin B Grandfather of Antifungal MOA: 1. Binds to ERGOSTEROL2. Creates Holes / Pores3. Cytoplasmic Leakage Use: DOC Life threatening Mycoses Initially given to reduce fungal burden Route: IV (common), PO A/E: 1. Infusion Related Mx: Slow Infusion + AH1

2. Renal Toxicity Renal tubular acidosis with K+ and Mg+ wasting.B. Itroconazole Substitute for AMPHOTERICIN BC. Voriconazole Use: Fluconazole resistant Candida DOC for AspergillosisD. Eichinocandins MOA: INH. Of Beta 1,3-D Glucan Synthesis Ex:1. Caspofungin2. Micafungin3. Anidulafungin

E. Flucytosine Combined with AMPHOTERICIN B Pyrimidine Analog which comes from: Derivative of: 5 Fluorouracil Prodrug 5FU MOA:1. FC is taken inside by: CYTOSINE PERMEASE2. FC is converted into: 5-FU3. 5-FU is converted into 2 active metabolite which is antifungal:3.1. FdUMD Fluoro deoxy uridine mono phosphate3.2. FUTP Fluorouridine Tri Phosphate

Rationale of Combination: To prevent secondary resistance with: FLUCYTOSINE To facilitate entry of FC to the fungal cell Tx: Yeast Infection

F. Posaconazole DOC for Mucomycosis / Zygomycosis Effective Tx of: ASPERGILLOSIS, CANDIDA