Treatment Options in Invasive Aspergillosis

Aspergillus species are septated molds that cause a wide spectrum of clinical syndromes. Among these, invasive aspergillosis (IA) causes very high morbidity and mortality among the most severely immunosuppressed, especially those with profound qualitative or quantitative neutropenia. Empirical, pre-emptive, and targeted approaches have been attempted to blunt establishment of infection with variable success. The preferred treatment of primary IA is voriconazole, which has been found to be superior to amphotericin B. Azoles interfere with the synthesis of ergosterol found in the fungal cell membrane, whereas polyenes—such as amphotericin B—interfere with ergosterol function. An echinocandin that disrupts fungal cell wall synthesis—caspofungin—and itraconazole have been approved for salvage therapy of IA. Lipid amphotericin B formulations are used in those intolerant to amphotericin B deoxycholate. Posaconazole is used for prophylaxis in high-risk groups such as those with acute myelogenous leukemia, myelodysplastic syndrome, and stem cell transplant recipients with graft versus host disease to reduce the incidence of invasive fungal infections (IFI) such as IA. Combining mold-active azoles or a lipid amphotericin B formulation with an echinocandin may have a role in refractory IA. Immunomodulatory properties of antifungals, growth factors, cytokines, and immune cell infusions may enhance host ability to facilitate adjunctive control of infection, but an uncontrolled, exuberant inflammatory response can also cause significant pathology. Surgical resection may be a last resort when angioinvasion of critical structures places a patient at high risk for bleeding, thrombosis, or embolic phenomena, despite medical therapy. Nevertheless, immune reconstitution with myeloid lineage recovery is the key to successful outcomes.