Superficial mycoses (dermatophytoses) Deep-seated Mycoses (Systemic mycoses)

 Tinea barbae (barber’s itch): lower face  Aspergillosis: extensive invasion of white matter by Aspergillus hyphae in a neutropenic host
 Tinea pedis (athlete’s foot): feet → itching, → round gray reddish lesion typically with hemorrhagic wall
burning, dry, cracked skin between the toes.  Numerous septate branching hyphae (“Y shape”) → dichotomic sprouting penetrating vessel
 tinea corporis (ringworm): Trichophyton walls illustrated in a Grocott methenamine silver stain.
mentagrophytes. 
 Cutaneous candidiasis: opportunistic infection
of skin (Candida albicans)
 Fungal infections of nail (tinea unguium):
dermatophytes / Candida spp. → nail becomes
yellow, brittle, prone to breaking.
 C. albicans growing on Sabouraud dextrose
agar.
The similarity of fungal and mammalian cells

1. Fungal cell has distinct cytoplasmic organelles including endoplasmic reticulum, Golgi apparatus, mitochondria, and storage vacuoles.
2. DNA is organized into chromosomes within the cell nucleus.
3. Fungi share similar mechanisms for DNA replication and protein synthesis.

Target of antifungals
Fungal cell membrane
 Lipid bilayers (unstable structure → cannot retain its shape & functions): Sterols lie within lipid bilayer (stiffening agents) e.g. cholesterol,
ergosterol in pathogenic fungi.
 Polyene antifungals, Azole antifungals, Allylamines

Fungal cell wall

 fungal cell wall → complex network of proteins and polycarbohydrates: protective shell & critical site for exchange + filtration of ions and
proteins.
 Disruption of this protein/carbohydrate matrix →structurally-defective cell wall, rendering the fungal cell sensitive to osmotic lysis.
 glucan synthesis inhibitors - Echinocandins

DNA/RNA synthesis
 Fungal and mammalian cells share remarkable homology in DNA replication and RNA translation.
 DNA and protein synthesis is difficult targets for the development of selectively-toxic antifungal therapy.
 antimetabolites - Flucytosine
Class MoA Prodrug Target sp Routes Adverse effects DDI

Polyene binding to ergosterol in Amphoteric  Candida Endemic Lipid formulation (IV) Inflammatory → fever, chills, Enhanced
antifungals fungal cell membrane → in B  Cryptococc Mycoses rigor, nausea, vomiting, nephrotoxicity:
formation of pores → us  Histoplasm myalgia, athralgia aminoglycosides,
electrolyte imbalance →  Aspegillus a High [con]: nephrotoxicity cyclosporine
cell death  Blastomyce
s
Poor GI absorption  Coccidioles

Nystatin Only TOPICAL: >toxic

for parenteral
Azole Inhibit 14- α- Systemic ↑↑ toxic: less Blastomycosis, oral tablet, cream &  Non-toxic ↓↓ testosterone
antifungals demethylase → interrupt Ketoconazol effective, coccidioidomyc dandruff shampoo  GI upset, clinical hepatitis (gynecomastia) +
ergosterol synthesis e does not osishistoplasmo formulations (rare) corticosterone
cross BBB sis (Nizoral™)
accumulation of Fluconazole CNS IV infusion
intermediate sterols penetration:
(toxic) → increase Cryptococcus
membrane permeability Itraconazol Aspergillus
→ inhibit fungal growth e
Topical
Clotrimazol
e
Allylamines inhibit ergosterol Terbinafine Dermatophytes: Candida,  Oral General transient & mild: GI
synthesis → inhibit Aspergillus  Topical
squalene epoxidase
Echinocandin Inhibit enzyme 1,3-β glucan synthase → Caspofung Disseminated, mucocutaneous  IV formulation
s abnormal weak cell wall (XX withstand in candida  Slow infusion (~1
osmotic stress) Empiric antifungal → febrile hour)
neutropenia
Flucotysine Transported into fungal cells → 5-  Cryptococcus  Oral
phosphorylated 5-FU → inhibit RNA, DNA flucytosine neoformans
functions  Some Candida sp
Griseofulvin  Disrupt mitotic spindle formation → inhibit fungal cell mitosis
 Replaced by newer antifungal (itraconazole)