ANTIFUNGAL 2024

Overview of Fungi

  • Fungi are eukaryotic organisms characterized by a rigid cell wall composed of chitin and ergosterol.

  • They are resistant to antibiotics and are more frequently encountered in immunocompromised individuals.

Types of Fungi

Fungi Classification

  • Yeasts: Single-celled fungi that reproduce by budding. They are utilized in baking and alcoholic fermentation.

  • Molds: Multicellular fungi that consist of long, branching filaments called hyphae.

  • Dimorphic Fungi: Can exist as yeast or mold depending on the environment.

Common Genera

  • Candida, Aspergillus, and Histoplasma are notable fungal species, each associated with specific infections.

Infections and Symptoms

Fungal Infections

  • Fungal infections can be categorized into superficial (cutaneous, mucocutaneous, subcutaneous) and deep (systemic).

    • Superficial Infections: Often caused by Candida and dermatophytes, affecting skin and nails.

    • Deep Infections: Usually occur in immunocompromised hosts and can be life-threatening.

Specific Fungal Infections

  1. Histoplasmosis

    • Possible sites of infection: liver, spleen, lymph nodes, bone marrow.

  2. Coccidioidomycosis

  3. Blastomycosis

    • Commonly affects skin, bone, genitourinary tract, and can lead to systemic infection.

Antifungal Treatments

Categories of Antifungal Drugs

  • Polyenes (e.g., Amphotericin B, Nystatin)

  • Azoles (e.g., Fluconazole, Itraconazole, Voriconazole)

  • Echinocandins (e.g., Caspofungin)

  • Antimetabolites (e.g., Flucytosine)

  • Allylamines (e.g., Terbinafine)

Mechanism of Action

  • Amphotericin B: Binds to ergosterol in fungal cell membranes, forming pores, leading to cell death.

  • Azoles: Inhibit ergosterol synthesis by blocking cytochrome P450 enzymes, disrupting membrane structure and function.

  • Echinocandins: Inhibit 1,3-beta-D-glucan synthase, compromising the fungal cell wall integrity.

Drug Resistance

  • Resistance may occur due to reduced binding of antifungal agents, alteration in drug target sites, or reduced ergosterol content in fungal membranes.

Pharmacokinetics

  • Amphotericin B: Poor oral absorption, generally given IV; protein binding is high.

  • Azoles: Well absorbed, high oral bioavailability, metabolized in the liver.

  • Echinocandins: Given IV, eliminated via renal and fecal routes.

Adverse Effects

  • Amphotericin B: Infusion reactions, renal toxicity, electrolyte imbalances.

  • Azoles: Potential for endocrine effects, gastrointestinal disturbances, liver function abnormalities.

  • Echinocandins: Generally well tolerated but can cause fever and chills.

Clinical Applications

  • Antifungal agents are critical in treating invasive candidiasis, invasive aspergillosis, cryptococcosis, and other fungal infections, especially in immunocompromised patients.