Iron chelator Deferasirox (Exjade®) alone or in combination with lipid formulations of amphotericin B (AmB) is effective in treatment of murine invasive pulmonary aspergillosis

Ibrahim A.S., Ghebremariam T., French S., Edwards J.E., Spellberg B.

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Background: Increased bone marrow iron level in patients with hematologic malignancies is an independent risk factor for developing Invasive pulmonary aspergillosis (CPA) suggesting an important role for iron uptake in the pathogenesis of IPA. Therefore, chelation of host iron with an appropriate iron chelator might prove to be effective in treating IPA. We investigated the role of deferasirox (Def) mono or combination therapy with AmB in treating murine IPA. Methods: BALB/c mice with cyclophosphamide/cortisone immunosuppression were infected via inhalation with A. fumigatus, Treatment with Def (20 mg/kg/d qod, p.o.)was started at day -2 (continuous therapy) or day + 1 (delayed therapy) relative to infection and continued for a total of 5 doses. Liposomal AmB (LAmB) or AmB lipid complex (ABLC) were administered i.v. at 3 mg/kg/d for 5 days starting at 24 h post infection. Placebo control mice received vehicle control. The primary and secondary endpoints were time to survival and CFU, respectively. Results: Def-treated mice (n=24) improved median survival time compared to placebo-treated mice (6 d for placebo- vs. 9 d to Def-treated mice, P

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17th International Society for Human and Animal Mycology
    • ISHAM 17th (2009)