241.3 🩺 內科專科考前版

241.3.0.1 1⃣ Rezafungin Implementation

  • Once-weekly IV (vs daily for other echinocandins)
  • Approved 2023 for invasive candidiasis
  • Cost-effectiveness analyses for outpatient OPAT
  • Convenience advantage for prolonged courses
  • Same spectrum as other echinocandins

241.3.0.2 2⃣ Empirical Therapy in Neutropenic Fever

  • Persistent fever despite broad antibacterial
  • Options:
    • Echinocandin (broad-spectrum Candida + Aspergillus)
    • Voriconazole / posaconazole / isavuconazole (mold coverage)
    • Liposomal AmB (broadest)
  • Choice based on prior prophylaxis + risk factors + breakthrough resistance

241.3.0.3 3⃣ Mucormycosis — Drug of Choice

  • Liposomal Amphotericin B (preferred; high-dose 5-10 mg/kg/d)
  • Plus isavuconazole or posaconazole
    • Surgical debridement (essential)
    • Reverse predisposing factors (DM control, reduce immunosuppression)
  • Combination + duration: prolonged

241.3.0.4 4⃣ Cryptococcal Meningitis Treatment Phases

  • Induction (2 weeks): AmBisome 4 mg/kg/d + flucytosine 100 mg/kg/d
  • Consolidation (8 weeks): Fluconazole 400-800 mg/d
  • Maintenance (until immune recovery): Fluconazole 200 mg/d
  • HIV with CD4 < 100: maintenance until CD4 > 100 × 3 mo on ART
  • 2024 WHO: single-dose liposomal AmB alternative for HIV-related CM

241.3.0.5 5⃣ Aspergillus Treatment

  • Voriconazole first-line (TDM)
  • Isavuconazole alternative
  • Liposomal AmB if azole intolerance / failure
  • Echinocandin (alternative / combination in salvage)
  • Combination (voriconazole + echinocandin) for severe — controversial

241.3.0.6 6⃣ Drug Resistance Issues

  • C. auris: often pan-resistant (Ch 252)
  • Azole-resistant Aspergillus (TR34/L98H in Asia, Netherlands)
  • Cryptococcus fluconazole resistance in some settings
  • Mucor flucytosine + azole resistance (intrinsic)
  • Surveillance + AST

241.3.0.7 7⃣ Drug Interaction Examples

  • Voriconazole + tacrolimus: ↓ tacrolimus to 1/4 dose
  • Posaconazole + cyclosporine: monitor levels carefully
  • Fluconazole + warfarin: ↑ INR significantly
  • Itraconazole + statin: simvastatin/lovastatin contraindicated

241.3.0.8 8⃣ 健保 / Taiwan

  • 健保 standard antifungals covered
  • Newer agents (rezafungin, isavuconazole, posaconazole) ID-consult restricted
  • TDM available in tertiary centers
  • ID consultation for invasive fungal infections

241.3.0.9 9⃣ Empirical Therapy Choice Algorithm

  • Mild mucosal: topical / fluconazole
  • Severe candidemia: echinocandin (de-escalate based on AST)
  • Hematologic malignancy + suspected mold: voriconazole / isavuconazole / posaconazole
  • Suspected mucormycosis (DM ketoacidosis + facial pain + diabetic): high-dose liposomal AmB ± isavuconazole
  • Aspergillus pneumonia (immunocompromise): voriconazole

241.3.0.10 10. Future Antifungal Pipeline

  • Olorofim — broader mold coverage including Lomentospora + Scedosporium
  • Fosmanogepix — broad-spectrum
  • Encochleated AmB — oral cryptococcal meningitis
  • New triterpenoid (rezafungin family extensions)
  • Combination therapies for resistant infections