241.2 ð åèç
241.2.0.1 å¿ è â 5 Major Antifungal Classes
| Class | Drug | Mechanism |
|---|---|---|
| Polyenes | Amphotericin B | Ergosterol binding â membrane pores |
| Azoles | Fluconazole, voriconazole, posaconazole, isavuconazole | Inhibit CYP51 (lanosterol 14α-demethylase) |
| Echinocandins | Caspofungin, micafungin, anidulafungin, rezafungin | Inhibit β-1,3-glucan synthase |
| Pyrimidine | Flucytosine | DNA synthesis inhibition |
| Allylamines | Terbinafine | Inhibit squalene epoxidase |
241.2.0.2 å¿ è â Antifungal Drug of Choice
| Pathogen | First-Line |
|---|---|
| Invasive Candida | Echinocandin (caspofungin/micafungin/rezafungin) |
| C. albicans azole-sensitive | Fluconazole (step-down) |
| C. krusei (intrinsic flu R) | Echinocandin / voriconazole |
| C. glabrata (variable flu R) | Echinocandin |
| C. auris | Echinocandin (some R; need AST) |
| Aspergillus invasive | Voriconazole or isavuconazole |
| Cryptococcal meningitis | Amphotericin B + flucytosine (induction); fluconazole maintenance |
| Mucormycosis | Amphotericin B (liposomal) + isavuconazole or posaconazole |
| Histoplasmosis | Itraconazole (mild-moderate); amphotericin B (severe) |
| Pneumocystis | TMP-SMX (Ch 218) |
| Vulvovaginal Candida | Fluconazole 150 mg PO Ã 1 or topical azoles |
| Sporothrix | Itraconazole; iodide |
| Dermatophytes | Terbinafine / azoles |
241.2.0.3 å¿ è â Spectrum Gaps
- Echinocandins: NO Cryptococcus, Mucor, Fusarium
- Fluconazole: NO Mucor, weakly active Aspergillus
- Voriconazole: NO Mucor
- Posaconazole: Yes Mucor + broad mold spectrum
- Isavuconazole: Yes Mucor + broad
- Amphotericin: Broad (but not Lomentospora, Pseudallescheria)
241.2.0.4 å¿ è â TDM Drugs
- Voriconazole, posaconazole (especially suspension), itraconazole, flucytosine
- Echinocandins + fluconazole + isavuconazole â no routine TDM
241.2.0.5 å¿ è â New Drugs (2021-2024)
- Rezafungin (Rezzayo 2023): once-weekly echinocandin
- Ibrexafungerp (Brexafemme 2021): oral triterpenoid for VVC
- Olorofim (Phase 3): orotomide for resistant mold
- Fosmanogepix (Phase 3): broad-spectrum
241.2.0.6 å¿ è â Amphotericin B Toxicity
- Nephrotoxicity + electrolyte wasting (K+, Mg2+) â major
- Infusion reactions (pre-medicate)
- Liposomal less toxic than conventional