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Comparative Study
. 2014 Jun 19;8(6):e2942.
doi: 10.1371/journal.pntd.0002942. eCollection 2014 Jun.

Madurella mycetomatis is highly susceptible to ravuconazole

Sarah Abdalla Ahmed  1 , Wendy Kloezen  2 , Frederick Duncanson  3 , Ed E Zijlstra  4 , G Sybren de Hoog  5 , Ahmed H Fahal  6 , Wendy W J van de Sande  2
Affiliations
Comparative Study

Madurella mycetomatis is highly susceptible to ravuconazole

Sarah Abdalla Ahmed et al. PLoS Negl Trop Dis. .

Abstract

The current treatment of eumycetoma utilizing ketoconazole is unsatisfactory because of high recurrence rates, which often leads to complications and unnecessary amputations, and its comparatively high cost in endemic areas. Hence, an effective and affordable drug is required to improve therapeutic outcome. E1224 is a potent orally available, broad-spectrum triazole currently being developed for the treatment of Chagas disease. E1224 is a prodrug that is rapidly converted to ravuconazole. Plasma levels of E1224 are low and transient, and its therapeutically active moiety, ravuconazole is therapeutically active. In the present study, the in vitro activity of ravuconazole against Madurella mycetomatis, the most common etiologic agent of eumycetoma, was evaluated and compared to that of ketoconazole and itraconazole. Ravuconazole showed excellent activity with MICs ranging between ≤ 0.002 and 0.031 µg/ml, which were significantly lower than the MICs reported for ketoconazole and itraconazole. On the basis of our findings, E1224 with its resultant active moiety, ravuconazole, could be an effective and affordable therapeutic option for the treatment of eumycetoma.

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Conflict of interest statement

FD is a salaried full time employee of Eisai, Inc. receiving the standard benefits package of the company but having no stock in it. NIAID is studying the compound E5564 for biothreat indications and has no bearing on E1224 or any study conducted in relationship to or with E1224. No travel grants were given, except for business related trips relevant to the company's routine way of conducting business or for presentation to company data at a scientific meeting. He has a collaborative agreement with the Drugs for Neglected Diseases Initiative to examine E1224 for the treatment of chronic indeterminate Chagas disease which has no bearing on this article. His employment with Eisai does not alter, in any way, his adherence to all of the PLOS NTDs policies on sharing data and materials. He does not consider his employment at Eisai Inc. or any facet of his participation in the research or development of the article to interfere in any way with the full and objective presentation, peer review, editorial decision making, or publication of research or non-research articles submitted to PLoS NTD or any related journals. The other authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. In vitro activities of ketoconazole (KTC), itraconazole (ITC), and ravuconazole (RVC) against 23 isolates of Madurella mycetomatis represented by MICs.
See this image and copyright information in PMC

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