Why Griseofulvin is not effective against candida & malassezia?

Why Griseofulvin is not effective against candida & malassezia ?

Griseofulvin is an antifungal medication primarily effective against dermatophytes but not effective against Candida or Malassezia. Here are the reasons why:

Mechanism of Action of Griseofulvin

Griseofulvin works by:

  • Inhibiting Microtubule Function: It binds to fungal microtubules, interfering with the mitotic spindle formation, thereby inhibiting cell division and replication.
  • Accumulating in Keratinized Tissues: It becomes concentrated in keratin-containing tissues such as skin, hair, and nails, where it exerts its antifungal effects.

Reasons for Ineffectiveness against Candida and Malassezia

  1. Target Organisms:
  • Candida: Candida species are yeasts that have different cellular structures and metabolic pathways compared to dermatophytes. Griseofulvin’s mechanism of action, which disrupts microtubules, is not effective against the cellular biology of Candida.
  • Malassezia: Malassezia species are lipophilic yeasts that also differ significantly from dermatophytes in terms of cell structure and metabolism. They require lipid-rich environments, and their unique lipid-dependent physiology renders griseofulvin ineffective.
  1. Pharmacokinetics:
  • Griseofulvin accumulates in keratinized tissues, which is suitable for dermatophytes that infect these areas. Candida and Malassezia can infect mucous membranes and sebaceous areas where griseofulvin does not effectively concentrate.
  1. Different Cellular Targets:
  • Candida: Effective treatments for Candida infections often target cell membrane components (e.g., ergosterol synthesis) or cell wall synthesis. Drugs like azoles (fluconazole) and echinocandins (caspofungin) are effective against Candida.
  • Malassezia: Treatment for Malassezia often involves agents that affect lipid synthesis or use (e.g., ketoconazole, selenium sulfide), reflecting their unique growth requirements.

Effective Alternatives

  • Candida Infections: Typically treated with azoles (e.g., fluconazole), polyenes (e.g., amphotericin B), or echinocandins (e.g., caspofungin).
  • Malassezia Infections: Treated with topical or systemic azoles (e.g., ketoconazole), selenium sulfide, or other antifungals effective against lipid-dependent fungi.

Summary

Griseofulvin is ineffective against Candida and Malassezia because of differences in cellular targets, the environments they infect, and their specific physiological requirements. These fungi require treatments that target their unique structures and metabolic pathways.