Morphology: Septate hyaline mold, dichotomously branching hyphae at acute (45°) angles. Conidiophores with characteristic vesicle and phialides on culture.
Typical drugs
- #1Voriconazole— First-line for invasive aspergillosis (IDSA / ECIL recommendation).
- #2Isavuconazole— Equivalent efficacy, fewer drug interactions, no levels needed.
- #3Amphotericin B (liposomal)— Salvage / azole-resistant / pregnancy.
- #4Posaconazole— Salvage and prophylaxis (heme/onc, severe GVHD).
- #5Caspofungin— Salvage — limited monotherapy data; combo with voriconazole for severe disease.
Empiric therapy when resistant
Start voriconazole or isavuconazole pending speciation + susceptibilities. If azole-resistant: liposomal amphotericin B + echinocandin combo. ID consult mandatory.
Resistance mechanisms
Target alteration
Cyp51A point mutations (TR34/L98H, TR46/Y121F/T289A) reduce azole binding
Example: Environmental azole-resistant strains from agricultural azole use (Netherlands, India, UK).
Resistance notes
Environmental azole resistance rising due to agricultural triazole use. Cross-resistance among voriconazole, posaconazole, itraconazole.
Pearls
Risk factors: prolonged neutropenia, allogeneic HSCT, solid organ transplant (esp. lung), chronic steroid use, advanced HIV. Spectrum: invasive pulmonary, ABPA, aspergilloma, chronic pulmonary aspergillosis. Voriconazole TDM target trough 1–5 mg/L. Beware drug interactions (voriconazole inhibits CYP3A4).