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联合使用两种抗真菌药物并不能提高感染马杜拉放线菌的大蜡螟幼虫的存活率。

Combining two antifungal agents does not enhance survival of Galleria mellonella larvae infected with Madurella mycetomatis.

作者信息

Eadie Kimberly, Parel Florianne, Helvert-van Poppel Marilyn, Fahal Ahmed, van de Sande Wendy

机构信息

Department of Medical Microbiology and Infectious Diseases, ErasmusMC, Rotterdam, The Netherlands.

Department of Clinical Pathology, St Elisabeth Ziekenhuis, Tilburg, The Netherlands.

出版信息

Trop Med Int Health. 2017 Jun;22(6):696-702. doi: 10.1111/tmi.12871. Epub 2017 May 2.

DOI:10.1111/tmi.12871
PMID:28342219
Abstract

OBJECTIVE

To determine whether combination therapy would improve therapeutic outcome in eumycetoma caused by Madurella mycetomatis.

METHODS

Survival, colony-forming units (CFU), melanisation and histopathology in M. mycetomatis-infected Galleria mellonella larvae treated with amphotericin B, itraconazole, terbinafine or combinations thereof were determined.

RESULTS

Compared to larvae treated with 5% glucose, enhanced survival was obtained when M. mycetomatis-infected larvae were treated with amphotericin B, but not when they were treated with itraconazole or terbinafine. Combination therapy did not increase survival compared to 5% glucose-treated larvae, itraconazole-treated larvae or terbinafine-treated larvae. Compared to amphotericin B monotreatment, a significant decrease in survival was noted when this therapy was combined with either itraconazole or terbinafine. CFU, melanisation and histopathology did not differ between monotherapy, combination therapy or 5% glucose-treated larvae.

CONCLUSIONS

Combining different classes of antifungal agents did not enhance the survival of M. mycetomatis-infected G. mellonella larvae. Instead of improving the therapeutic outcome, combining either itraconazole or terbinafine with amphotericin B resulted in significantly lower survival rates of infected larvae than amphotericin B monotherapy. This experimental study does not provide support for the use of combined amphotericin B and itraconazole, combined itraconazole and terbinafine or combined terbinafine and amphotericin B and should be confirmed in other animal models.

摘要

目的

确定联合治疗是否能改善由马杜拉放线菌引起的足菌肿的治疗效果。

方法

测定用两性霉素B、伊曲康唑、特比萘芬或其组合处理的感染马杜拉放线菌的大蜡螟幼虫的存活率、菌落形成单位(CFU)、黑色素沉着和组织病理学。

结果

与用5%葡萄糖处理的幼虫相比,用两性霉素B处理感染马杜拉放线菌的幼虫可提高存活率,但用伊曲康唑或特比萘芬处理则不能。与用5%葡萄糖处理的幼虫、伊曲康唑处理的幼虫或特比萘芬处理的幼虫相比,联合治疗并未提高存活率。与两性霉素B单药治疗相比,当该疗法与伊曲康唑或特比萘芬联合使用时,存活率显著降低。单药治疗、联合治疗或5%葡萄糖处理的幼虫之间的CFU、黑色素沉着和组织病理学没有差异。

结论

联合不同类别的抗真菌药物并不能提高感染马杜拉放线菌的大蜡螟幼虫的存活率。与两性霉素B单药治疗相比,将伊曲康唑或特比萘芬与两性霉素B联合使用非但改善治疗效果,反而导致感染幼虫的存活率显著降低。本实验研究不支持使用两性霉素B与伊曲康唑联合、伊曲康唑与特比萘芬联合或特比萘芬与两性霉素B联合,这一点应在其他动物模型中得到证实。

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