## Mechanism-Based Discrimination Between Amphotericin B and Fluconazole ### Amphotericin B **Key Point:** Polyene antibiotic that binds directly to ergosterol in the fungal cell membrane, creating pores and causing leakage of cellular contents — a **fungicidal** mechanism. ### Fluconazole **Key Point:** Azole antifungal that inhibits lanosterol 14α-demethylase (CYP51), a key enzyme in ergosterol synthesis, leading to membrane dysfunction — a **fungistatic** mechanism. ### Comparative Table | Feature | Amphotericin B | Fluconazole | | --- | --- | --- | | **Target** | Ergosterol (direct binding) | CYP51 enzyme (sterol synthesis) | | **Mechanism** | Fungicidal (membrane disruption) | Fungistatic (sterol depletion) | | **Spectrum** | Broad (Candida, Aspergillus, Cryptococcus, endemic fungi) | Narrower (Candida, Cryptococcus; poor Aspergillus coverage) | | **Toxicity** | High (nephrotoxicity, infusion reactions) | Low (hepatotoxicity, drug interactions) | | **CNS penetration** | Poor | Excellent (CSF levels 50–90% of serum) | **High-Yield:** The **direct ergosterol binding** of amphotericin B versus **enzyme inhibition** of fluconazole is the fundamental pharmacological distinction and the best discriminator. **Clinical Pearl:** Amphotericin B is reserved for severe, invasive infections and immunocompromised patients; fluconazole is preferred for oral candidiasis, cryptococcal meningitis (due to CNS penetration), and prophylaxis in neutropenic patients. [cite:KD Tripathi 8e Ch 51]
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