Salvage therapy for invasive aspergillosis

Abstract

Invasive aspergillosis (IA) makes a marked contribution to the mortality of immunocompromised hosts, especially those who have received cytotoxic chemotherapy for haematological malignancy or allogeneic haemopoietic stem cell transplantation. Salvage therapy, in the case of invasive fungal infection, generally refers to the treatment of infected individuals who are refractory or intolerant to initial therapy administered for at least 7 days. Although clinical trials of salvage therapy of IA have been undertaken, most were non-comparator studies or contained a non-randomized control group, and criteria for patient enrollment and the methods used to assess response were variable. Salvage therapy has produced relatively disappointing results, emphasizing the importance of early diagnosis and effective primary therapy for IA. Despite this, a number of agents have been studied in the treatment of IA and have demonstrated efficacy in a salvage setting. These include lipid-based formulations of amphotericin B, caspofungin, itraconazole, voriconazole, posaconazole and micafungin. Combinations of echinocandins with either azoles or amphotericin B have also been studied in small series. Further studies are required, ideally comparing newer agents and treatment strategies in randomized clinical trials, to clarify the optimal approach to salvage treatment of IA in this challenging group of patients.