Iron Chelation In Fungal Infection
ironjustice
efficacy in treating murine invasive pulmonary aspergillosis.
Ibrahim AS, Gebremariam T, French SW, Edwards JE Jr, Spellberg B.
J Antimicrob Chemother. 2009 Nov 26.
Los Angeles Biomedical Research Institute
Harbor-University of California Los Angeles (UCLA) Medical Center,
Torrance, CA, USA.
Objectives
Increased bone marrow iron levels in patients with haematological
malignancies is an independent risk factor for developing invasive
pulmonary aspergillosis (IPA), suggesting an important role for
iron uptake in the pathogenesis of IPA.
We sought to determine the potential for combination therapy with the
iron chelator deferasirox + liposomal amphotericin B (LAmB) to
improve
the outcome of murine IPA compared with LAmB monotherapy.
Methods
In vitro MIC and minimum fungicidal concentration (MFC) values of the
iron
chelator, deferasirox, for Aspergillus fumigatus were determined
by microdilution assay.
In addition, we studied the efficacy of deferasirox alone or combined
with
LAmB in treating immunocompromised mice infected with A. fumigatus
via
inhalation.
Results
Deferasirox was cidal in vitro against A. fumigatus, with an MIC and
MFC
of 25 and 50 mg/L, respectively.
Deferasirox monotherapy modestly prolonged survival of mice with IPA.
Combination deferasirox + LAmB therapy synergistically improved
survival
and reduced lung fungal burden compared with either monotherapy
alone.
Conclusions
Iron chelation therapy with deferasirox alone or in combination with
LAmB is
effective in treating experimental IPA.
Further study of deferasirox is warranted as adjunctive therapy for
IPA infections.
PMID: 19942619
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