241.4 📌 章末速蚘

241.4.0.0.1 5 Major Classes
  • Polyenes (amphotericin B): ergosterol binding; broad spectrum; nephrotoxicity (less with liposomal)
  • Azoles (fluconazole, voriconazole, posaconazole, isavuconazole, itraconazole): CYP51 inhibition; varying spectrum + drug interactions
  • Echinocandins (caspofungin, micafungin, anidulafungin, rezafungin): β-1,3-glucan inhibition; first-line invasive Candida; NOT Cryptococcus, Mucor
  • Flucytosine (5-FC): DNA inhibition; combine with amphotericin B for cryptococcal meningitis
  • Terbinafine: squalene epoxidase; dermatophytes
241.4.0.0.2 Drug of Choice Quick
  • Invasive Candida: echinocandin
  • Aspergillus: voriconazole or isavuconazole
  • Cryptococcal meningitis: AmB lipo + flucytosine induction → fluconazole consolidation/maintenance
  • Mucormycosis: liposomal AmB + isavuconazole/posaconazole + surgery
  • Pneumocystis: TMP-SMX
  • Sporothrix: itraconazole
  • VVC: fluconazole 150 mg × 1
241.4.0.0.3 Newer (2021-2024)
  • Rezafungin (Rezzayo 2023): once-weekly IV echinocandin
  • Ibrexafungerp (Brexafemme 2021): oral triterpenoid for VVC
  • Olorofim, Fosmanogepix (Phase 3): emerging broad-spectrum
241.4.0.0.4 Key Toxicities
  • Amphotericin B: nephrotoxicity + electrolyte wasting (liposomal less)
  • Voriconazole: visual disturbances + hepatic + photosensitivity + periostitis (chronic) + QTc
  • Posaconazole: variable absorption (TDM)
  • Flucytosine: bone marrow suppression (TDM)
  • Terbinafine: hepatotoxicity
241.4.0.0.5 Drug Interactions
  • Azoles = CYP3A4 inhibitors → many interactions
  • Echinocandins = no significant CYP interactions (advantage)
  • Voriconazole + tacrolimus = reduce tacrolimus 1/4
241.4.0.0.7 盧醫垫 hint
  • Candidemia ICU patient: empirical echinocandin while AST pending; de-escalate to fluconazole if susceptible
  • Cryptococcal meningitis: AmB lipo + flucytosine delay ART 4-6 wk (COAT trial)
  • Mucormycosis + DM ketoacidosis: surgical emergency + AmB lipo + isavuconazole
  • Aspergillus + voriconazole: TDM essential