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. 2009 Jun;53(6):2654-6.
doi: 10.1128/AAC.01547-08. Epub 2009 Mar 23.

Antifungal activities of natural and synthetic iron chelators alone and in combination with azole and polyene antibiotics against Aspergillus fumigatus

Kol A Zarember  1 , Anna R Cruz, Chiung-Yu Huang, John I Gallin
Affiliations

Antifungal activities of natural and synthetic iron chelators alone and in combination with azole and polyene antibiotics against Aspergillus fumigatus

Kol A Zarember et al. Antimicrob Agents Chemother. 2009 Jun.

Abstract

Antifungal effects of iron chelators (lactoferrin, deferoxamine, deferiprone, and ciclopirox) were tested alone and in combination with antifungal drugs against Aspergillus fumigatus B5233 conidia. Lactoferrin, ciclopirox, and deferiprone inhibited whereas deferoxamine enhanced fungal growth. Antifungal synergy against conidia was observed for combinations of ketoconazole with ciclopirox or deferiprone, lactoferrin with amphotericin B, and fluconazole with deferiprone. Iron chelation alone or combined with antifungal drugs may be useful for prevention and treatment of mycosis.

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Figures

FIG. 1.
FIG. 1.
Iron chelator effect on Aspergillus fumigatus conidial growth. Fungal growth inhibition was performed as described in the text, and the data are expressed as percentages of control growth in vehicle alone. Dose-response curves were estimated from multiple experiments (for deferoxamine, n = 3; for deferiprone, n = 38; for ciclopirox, n = 40; for lactoferrin, n = 43) using three-parameter logistic models and are plotted with 95% confidence intervals.
FIG. 2.
FIG. 2.
Isobolograms of combined antifungal effects. The doses of each agent alone (indicated by ZA and ZB) and in combination, indicated by (formula image, formula image), required to achieve a 50% reduction in growth compared to that of untreated controls are plotted along with the 95% confidence intervals. Under additivity, the dose pair (formula image, formula image) is expected to yield the same effect. Lines of additivity are indicated by open triangles, and measured drug combinations are indicated by filled circles. Statistical significance (P < 0.05) is indicated by an asterisk, and the P value of the global chi-square test is given in the upper right corner of each graph. Panels A to D show examples of synergistic combinations of chelators with antifungal drugs. The figures are generated from between four and eight checkerboard experiments for each combination of drugs.
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References

    1. Alexander, J., A. P. Limaye, C. W. Ko, M. P. Bronner, and K. V. Kowdley. 2006. Association of hepatic iron overload with invasive fungal infection in liver transplant recipients. Liver Transpl. 12:1799-1804. - PubMed
    1. Almyroudis, N. G., S. M. Holland, and B. H. Segal. 2005. Invasive aspergillosis in primary immunodeficiencies. Med. Mycol. 43(Suppl. 1):S247-S259. - PubMed
    1. Altes, A., A. F. Remacha, P. Sarda, F. J. Sancho, A. Sureda, R. Martino, J. Briones, S. Brunet, C. Canals, and J. Sierra. 2004. Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis. Bone Marrow Transplant. 34:505-509. - PubMed
    1. Antachopoulos, C., T. J. Walsh, and E. Roilides. 2007. Fungal infections in primary immunodeficiencies. Eur. J. Pediatr. 166:1099-1117. - PubMed
    1. Balajee, S. A., A. Imhof, J. L. Gribskov, and K. A. Marr. 2005. Determination of antifungal drug susceptibilities of Aspergillus species by a fluorescence-based microplate assay. J. Antimicrob. Chemother. 55:102-105. - PubMed

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