Fungal Infections and Antifungal Therapy
Core concepts
Classify antifungals: polyenes (amphotericin B binds ergosterol; nephrotoxic, electrolyte wasting), azoles (inhibit 14-alpha-demethylase; fluconazole covers Candida and Cryptococcus, voriconazole covers Aspergillus, posaconazole covers Mucorales), echinocandins (beta-glucan synthase inhibitors; caspofungin, micafungin, anidulafungin-first-line for candidemia), and flucytosine (converted to 5-FU; used with amphotericin for cryptococcal meningitis).
Must-know syndromes
Candidemia (echinocandin first-line; remove central line; ophthalmologic exam), invasive aspergillosis (voriconazole or isavuconazole), mucormycosis (liposomal amphotericin B plus surgical debridement; posaconazole step-down), cryptococcal meningitis (amphotericin B + flucytosine induction, then fluconazole), Pneumocystis jirovecii (TMP-SMX; alternatives atovaquone, pentamidine, clindamycin-primaquine), and endemic mycoses (Histoplasma, Blastomyces, Coccidioides-itraconazole or amphotericin for severe disease).
Traps
Voriconazole causes visual disturbances, photosensitivity, and QT prolongation; levels matter. Posaconazole has variable absorption-take with food. Amphotericin B is nephrotoxic and causes hypokalemia/hypomagnesemia. Echinocandins do not cover Cryptococcus, Mucorales, or Fusarium. Fluconazole does not cover Aspergillus or Mucorales.
Worked rule of thumb
For a neutropenic patient with pulmonary nodules and halo sign, start voriconazole empirically for presumed invasive aspergillosis; if a reversed halo or sinus disease suggests Mucorales, switch to liposomal amphotericin B and call surgery.