Morphology: Dimorphic fungus — mold (mycelial) at ambient temperatures, intracellular yeast (2–4 μm, narrow-neck budding) at 37°C. Found within macrophages.
Typical drugs
- #1Itraconazole— Mild–moderate disease and step-down; check trough levels (target ≥1 mg/L).
- #2Amphotericin B (liposomal)— Severe / disseminated / CNS — induction × 1–2 wk then step down to itraconazole × ≥12 mo.
- #3Voriconazole— Salvage if itraconazole intolerance / interaction.
- #4Posaconazole— Salvage option.
Empiric therapy when resistant
Severe / immunocompromised: liposomal amphotericin B induction × 1–2 weeks, then itraconazole consolidation. Chronic suppression in HIV until CD4 >150 × 6 mo on ART.
Resistance notes
True azole resistance rare. Itraconazole TDM essential — variable absorption (need acidic gastric pH; oral solution > capsules).
Pearls
Most common endemic mycosis in US. Spectrum: asymptomatic / acute pulmonary / chronic cavitary / disseminated (HIV, transplant, anti-TNF) / mediastinal granuloma & fibrosis. Anti-TNF therapy (infliximab, adalimumab) reactivates latent infection. Disseminated histo with CD4 <100 = AIDS-defining. Pancytopenia + hepatosplenomegaly + adrenal involvement classic for disseminated.