A 42-year-old man with acute leukemia undergoing chemotherapy develops fever and is found to have disseminated candidiasis with positive blood cultures and hepatosplenic involvement on imaging. He is haemodynamically unstable. What is the drug of choice for his condition?

Explanation

## Drug of Choice for Invasive Candidiasis with Haemodynamic Instability **Key Point:** Liposomal amphotericin B is the preferred first-line agent for invasive/disseminated candidiasis in critically ill, haemodynamically unstable patients with multi-organ involvement. ### Rationale for Liposomal Amphotericin B 1. **Mechanism & Spectrum** - Polyene antifungal that binds ergosterol in fungal cell membrane - Broadest spectrum coverage: active against *Candida* species (including fluconazole-resistant strains), *Aspergillus*, *Cryptococcus*, and other moulds - Fungicidal (not fungistatic) 2. **Clinical Advantages in Severe Disease** - Rapid onset of action (critical in septic patients) - Achieves high concentrations in blood and tissues - Effective in hepatosplenic candidiasis (excellent hepatic penetration) - Liposomal formulation reduces nephrotoxicity vs. conventional amphotericin B deoxycholate 3. **Dosing** - 3–5 mg/kg/day IV for invasive candidiasis - Can be escalated to 10 mg/kg/day in severe disease ### Comparison of Antifungals in Invasive Candidiasis | Agent | Route | Spectrum | Use in Severe/Invasive Disease | Limitation | |-------|-------|----------|--------------------------------|------------| | **Liposomal Amphotericin B** | IV | Broad (*Candida*, *Aspergillus*, moulds) | **First-line for invasive, haemodynamically unstable** | Nephrotoxicity (less with liposomal form), infusion reactions | | Fluconazole | Oral/IV | *Candida* (not C. auris, some non-albicans) | Not recommended for severe invasive disease | Inadequate for haemodynamically unstable patients; slower onset | | Caspofungin | IV | *Candida*, *Aspergillus* | Alternative if amphotericin B intolerant | Echinocandin; slower onset than amphotericin B | | Voriconazole | Oral/IV | *Candida*, *Aspergillus*, moulds | Alternative for *Aspergillus*; not preferred for acute candidiasis | Slower onset; visual disturbances; drug interactions | **High-Yield:** In invasive candidiasis with sepsis/haemodynamic instability, liposomal amphotericin B is the standard of care. Echinocandins (caspofungin, micafungin, anidulafungin) are alternatives in amphotericin B-intolerant patients. Fluconazole is inadequate for severe disease due to slower onset and risk of resistance. **Clinical Pearl:** Hepatosplenic candidiasis is a hallmark of disseminated candidiasis in neutropenic hosts (e.g., post-chemotherapy). Imaging shows multiple nodules; prolonged antifungal therapy (weeks to months) is required. Blood cultures may be negative despite disseminated disease. **Warning:** Do not use fluconazole monotherapy in haemodynamically unstable invasive candidiasis — inadequate and potentially dangerous. Conventional amphotericin B deoxycholate is avoided due to severe nephrotoxicity; liposomal formulation is preferred. [cite:Harrison 21e Ch 197]