PH8.8 | PH8.8 | Antifungal Drugs — SDL Guide — Summary & Reflection

KEY TAKEAWAYS

Polyenes: AmB — binds ergosterol → membrane pores → fungicidal; broadest spectrum (Candida, Aspergillus, Cryptococcus, Mucor); nephrotoxic (IV fluids reduce risk); liposomal formulation reduces nephrotoxicity. Nystatin — topical only.

Azoles: Inhibit CYP51 (14α-demethylase) → ergosterol depletion → fungistatic. Fluconazole — water-soluble, excellent CSF penetration, Candida + Cryptococcus; NOT Aspergillus (intrinsic resistance) or Candida krusei. Voriconazole — Aspergillus first-line, extended Candida spectrum; photopsia (unique ADR); CYP2C19 polymorphism (TDM needed); CYP inhibitor. Posaconazole — includes Mucor (broadest azole). All azoles: significant CYP3A4 inhibition → drug interactions.

Echinocandins (caspofungin/micafungin/anidulafungin): β-glucan synthase inhibition → fungicidal vs Candida; NOT Cryptococcus. Excellent tolerability; no CYP interactions; IV only.

Terbinafine: squalene epoxidase → fungicidal vs dermatophytes; hepatotoxic (monitor LFTs). Flucytosine (5-FC): cytosine deaminase → 5-FU → DNA/RNA inhibition; ONLY in combination with AmB (cryptococcal meningitis); myelosuppression risk. Griseofulvin: microtubule disruption; antidermatophyte only; largely superseded by terbinafine.

Key clinical rules: Aspergillus → voriconazole; Mucor → L-AmB (NOT voriconazole); Cryptococcal meningitis → AmB + 5-FC → fluconazole; Candidaemia → echinocandin first-line; invasive candidiasis (azole-resistant) → echinocandin.

REFLECT

The COVID-19 pandemic in India revealed a previously rare condition — mucormycosis — as a public health emergency, with tens of thousands of cases in 2021, driven by the combination of corticosteroid use (immune suppression), uncontrolled hyperglycaemia, and possibly contaminated oxygen humidifiers. India has since developed a National Action Plan for Mucormycosis. As a future clinician, what pharmacological principle explains why mucormycosis became so common in corticosteroid-treated diabetics? And what monitoring strategy would you implement in your ICU to detect mucormycosis early?