Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan; Centraalbureau voor Schimmelcultures CBS-KNAW Fungal Biodiversity Centre, Utrecht, The Netherlands; Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, The Netherlands.
Erasmus MC, Department of Medical Microbiology and Infectious Diseases, Rotterdam, The Netherlands.
PLoS Negl Trop Dis. 2014 Jun 19;8(6):e2942. doi: 10.1371/journal.pntd.0002942. eCollection 2014 Jun.
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.
目前，酮康唑治疗外耳真菌病的效果并不令人满意，因为复发率高，这往往导致并发症和不必要的截肢，而且在流行地区其成本相对较高。因此，需要一种有效且负担得起的药物来改善治疗效果。E1224 是一种有效的、口服的、广谱三唑类药物，目前正在开发用于治疗恰加斯病。E1224 是一种前药，可迅速转化为拉夫康唑。E1224 的血浆水平较低且短暂，其治疗活性成分拉夫康唑具有治疗活性。在本研究中，评估了拉夫康唑对导致外耳真菌病的最常见病原体——分枝孢子菌的体外活性，并与酮康唑和伊曲康唑进行了比较。拉夫康唑显示出极好的活性，MIC 范围在≤0.002 至 0.031μg/ml 之间，明显低于酮康唑和伊曲康唑的 MIC 报告值。基于我们的发现，E1224 及其有效成分拉夫康唑可能成为治疗外耳真菌病的有效且负担得起的治疗选择。
