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新型三唑类药物SCH56592与棘白菌素类药物MK-0991(L-743,872)和LY303366对机会性丝状真菌、双相真菌和酵母的体外活性比较。

Comparison of In vitro activities of the new triazole SCH56592 and the echinocandins MK-0991 (L-743,872) and LY303366 against opportunistic filamentous and dimorphic fungi and yeasts.

作者信息

Espinel-Ingroff A

机构信息

Division of Infectious Diseases, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0049, USA.

出版信息

J Clin Microbiol. 1998 Oct;36(10):2950-6. doi: 10.1128/JCM.36.10.2950-2956.1998.

Abstract

The in vitro antifungal activities of SCH56592, MK-0991, and LY303366 against 83 isolates of Acremonium strictum, Aspergillus flavus, Aspergillus fumigatus, Aspergillus terreus, Bipolaris spp., Blastomyces dermatitidis, Cladophialophora bantiana, Fusarium oxysporum, Fusarium solani, Histoplasma capsulatum, Phialophora spp., Pseudallescheria boydii, Rhizopus arrhizus, Scedosporium prolificans, and Sporothrix schenckii were compared. The in vitro activities of these agents against 104 isolates of yeast pathogens of Candida spp., Cryptococcus neoformans, and Trichosporon beigelii were also compared. MICs were determined by following a procedure under evaluation by the National Committee for Clinical Laboratory Standards (NCCLS) for broth microdilution testing of the filamentous fungi (visual MICs) and the NCCLS M27-A broth microdilution method for yeasts (both visual and turbidimetric MICs). The in vitro fungicidal activity of SCH56592 was superior (minimum fungicidal concentrations [MFCs], 0.25 to 4 microgram/ml for 7 of 18 species tested) to those of MK-0991 and LY303366 (MFCs, 8 to >16 microgram/ml for all species tested) for the molds tested, but the echinocandins had a broader spectrum of fungicidal activity (MFCs at which 90% of strains are inhibited [MFC90s], 0.5 to 4 microgram/ml for 6 of 9 species tested) than SCH56592 (MFC90s, 0.25 to 8 microgram/ml for 4 of 9 species tested) against most of the yeasts tested. Neither echinocandin had in vitro activity (MICs, >16 microgram/ml) against C. neoformans and T. beigelii, while the SCH56592 MICs ranged from 0.12 to 1.0 microgram/ml for these two species. The MICs of the three agents for the other species ranged from <0.03 to 4 microgram/ml. These results suggest that these new agents have broad-spectrum activities in vitro; their effectiveness in the treatment of human mycoses is to be determined.

摘要

比较了SCH56592、MK - 0991和LY303366对83株曲霉属真菌、黄曲霉、烟曲霉、土曲霉、双极霉属、皮炎芽生菌、班替枝孢霉、尖孢镰刀菌、茄病镰刀菌、荚膜组织胞浆菌、瓶霉属、波氏假阿利什霉、少根根霉、多育赛多孢霉和申克孢子丝菌的体外抗真菌活性。还比较了这些药物对104株念珠菌属、新型隐球菌和白吉利毛孢子菌等酵母病原体的体外活性。通过遵循美国国家临床实验室标准委员会(NCCLS)正在评估的丝状真菌肉汤微量稀释试验程序(目测最小抑菌浓度)以及酵母的NCCLS M27 - A肉汤微量稀释法(目测和比浊法最小抑菌浓度)来测定最小抑菌浓度(MIC)。对于所测试的霉菌,SCH56592的体外杀真菌活性(对于18种测试菌种中的7种,最小杀菌浓度[MFC]为0.25至4微克/毫升)优于MK - 0991和LY303366(对于所有测试菌种,MFC为8至>16微克/毫升),但棘白菌素类药物具有更广泛的杀真菌活性谱(对于9种测试菌种中的6种,90%菌株被抑制时的MFC[MFC90]为0.5至4微克/毫升),相比之下,SCH56592(对于9种测试菌种中的4种,MFC90为0.25至8微克/毫升)对大多数测试酵母的活性。两种棘白菌素类药物对新型隐球菌和白吉利毛孢子菌均无体外活性(MIC>16微克/毫升),而SCH56592对这两种菌种的MIC范围为0.12至1.0微克/毫升。这三种药物对其他菌种的MIC范围为<0.03至4微克/毫升。这些结果表明,这些新药在体外具有广谱活性;它们在治疗人类真菌病方面的有效性有待确定。

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