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Editorial commentary: what is the role of combination therapy in management of zygomycosis?

In several oncology and transplantation centers across the United States, invasive zygomycosis has been reported with increased frequency in the form of severe, frequently lethal sinopulmonary and disseminated infection [1-4]. Zygomycetes have the propensity to cause infection in a broad range of patients in whom different patterns of infection prevail [1]. In patients with poorly controlled diabetes mellitus, sino-orbital and rhinocerebral infection are the most common patterns, and in neutropenic patients, pulmonary and disseminated cases of zygomycosis are common. Crude mortality with antifungal therapy is ~40% among patients with zygomycosis [1]. Hematological malignancy and hematopoietic stem cell transplantation have more ominous prognoses, with an associated mortality of 66%-91% [1, 2]. For nearly 50 years, the management of zygomycosis has depended on the triad of amphotericin B deoxycholate (AmB) therapy, surgical resection, and reversal of underlying host deficits. The past decade has been marked by the development of new pharmacological, immunomodulatory, and conceptual advances that may help in the treatment of this uncommon but lethal infection. Among the therapeutic developments are the lipid formulations of AmB [5, 6], posaconazole [7, 8], deferasirox [9, 10], the echinocandins to be used in combination with AmB [11, 12], and the recombinant cytokines, such as granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor [13, 14]. The role of these agents alone, in combination, or in sequential use for the treatment of zygomycosis has important implications for outcome in patients with these life-threatening infections. Laboratory and clinical studies of 2 combined antifungal agents for the treatment of infections caused by Cryptococcus neoformans [15-17], Candida species [18, 19], and Aspergillus species [20-23] demonstrated a beneficial role for some but not all combinations. Some combina-