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In Vitro Interactions Between Antifungals and Methotrexate Against Aspergillus spp.

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Abstract

Methotrexate has been widely used in the treatment of osterosarcoma, intracranial lymphomas and leukemia. However, patients are also at high risk of opportunist pathogens such as Aspergillus spp. infection for their deeply depressed immunity. The optimal choice of antifungal agents during the infection of Aspergillus for these patients is necessary to be explored. In this study, we investigated the interactions between antifungals and methotrexate against Aspergillus in vitro. A total of 23 clinical isolates of Aspergillus spp. were studied. Microdilution checkerboard technique was performed to evaluate the interaction of methotrexate with voriconazole, itraconazole, terbinafine and amphotericin B. The highest rate of synergy was obtained for the combination of terbinafine and methotrexate, which exhibited synergy against 60.9% (14/23) of strains. No interaction was detected for the combinations of methotrexate plus itraconazole or amphotericin B against 95.7% (22/23) or 100% of strains, respectively. Although voriconazole exhibited indifferent against 87% (20/23) of strains when combined with methotrexate, antagonism effect was found against 13% (3/23) of strains. The positive interactions of terbinafine and methotrexate were also certified by disk diffusion assay. In addition, we observed the morphological changes for the interaction of methotrexate with terbinafine against Aspergillus. Further inhibition and distortion of growth were found after the combination of terbinafine and methotrexate compared with the drugs treated alone. Clinical studies are warranted to further elucidate optimal treatments for the immucompromised patients with Aspergillus infection.

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Authors and Affiliations

  1. Department of Dermatology, Research Center of Medical Mycology, Peking University First Hospital, Peking University, No. 8 Xishiku St., West District, 100034, Beijing, China

    Jianxun Yang, Zhe Wan, Xiaohong Wang, Wei Liu & Ruoyu Li

  2. Department of Dermatology, The Second Hospital of Harbin Medical University, 150086, Harbin, China

    Jianxun Yang

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  1. Jianxun Yang
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  2. Zhe Wan
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  3. Xiaohong Wang
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  4. Wei Liu
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  5. Ruoyu Li
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Correspondence to Ruoyu Li.

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Yang, J., Wan, Z., Wang, X. et al. In Vitro Interactions Between Antifungals and Methotrexate Against Aspergillus spp.. Mycopathologia 168, 237–242 (2009). https://doi.org/10.1007/s11046-009-9218-4

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  • DOI: https://doi.org/10.1007/s11046-009-9218-4

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