Centre for Infectious Diseases and Microbiology, Westmead Millenium Institute, University of Sydney, and Westmead Hospital, Darcy Road, Westmead, NSW 2145, Australia.
Antimicrob Agents Chemother. 2010 Aug;54(8):3233-40. doi: 10.1128/AAC.00231-10. Epub 2010 Jun 7.
Ten bis(alkylpyridinium)alkane compounds were tested for antifungal activity against 19 species (26 isolates) of yeasts and molds. We then determined the MICs and minimum fungicidal concentrations (MFCs) of four of the most active compounds (compounds 1, 4, 5, and 8) against 80 Candida and 20 cryptococcal isolates, in comparison with the MICs of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and caspofungin, using Clinical Laboratory and Standards Institutes broth microdulition M27-A3 (yeasts) or M38-A2 (filamentous fungi) susceptibility protocols. The compounds were more potent against Candida and Cryptococcus spp. (MIC range, 0.74 to 27.9 microg/ml) than molds (0.74 to 59.7 microg/ml). MICs against Exophiala were 0.37 to 5.9 microg/ml and as low as 1.48 microg/ml for Scedosporium but >or=25 microg/ml for zygomycetes, Aspergillus, and Fusarium spp. Compounds 1, 4, 5, and 8 exhibited good fungicidal activity against Candida and Cryptococcus, except for Candida parapsilosis (MICs of >44 mug/ml). Geometric mean (GM) MICs were similar to those of amphotericin B and lower than or comparable to fluconazole GM MICs but 10- to 100-fold greater than those for the other azoles. GM MICs against Candida glabrata were <1 microg/ml, significantly lower than fluconazole GM MICs (P<0.001) and similar to those of itraconazole, posaconazole, and voriconazole (GM MIC range of 0.4 to 1.23 microg/ml). The GM MIC of compound 4 against Candida guilliermondii was lower than that of fluconazole (1.69 microg/ml versus 7.48 microg/ml; P=0.012). MICs against Cryptococcus neoformans and Cryptococcus gattii were similar to those of fluconazole. The GM MIC of compound 4 was significantly higher for C. neoformans (3.83 mug/ml versus 1.81 microg/ml for C. gattii; P=0.015). This study has identified clinically relevant in vitro antifungal activities of novel bisalkypyridinium alkane compounds.
研究人员测试了 10 种双（烷基吡啶）链烷化合物对 19 种酵母和霉菌（26 株分离株）的抗真菌活性，然后测定了其中 4 种活性最高的化合物（化合物 1、4、5 和 8）对 80 株念珠菌和 20 株新型隐球菌分离株的最低抑菌浓度（MIC）和最低杀菌浓度（MBC），并与两性霉素 B、氟康唑、伊曲康唑、伏立康唑、泊沙康唑和卡泊芬净的 MIC 进行了比较，采用临床实验室标准化协会肉汤微量稀释 M27-A3（酵母）或 M38-A2（丝状真菌）药敏方案。这些化合物对念珠菌和隐球菌（MIC 范围 0.74 至 27.9μg/ml）的活性比霉菌（0.74 至 59.7μg/ml）更强。对 Exophiala 的 MIC 为 0.37 至 5.9μg/ml，对 Scedosporium 的 MIC 低至 1.48μg/ml，但对接合菌、曲霉和镰刀菌的 MIC 则>25μg/ml。化合物 1、4、5 和 8 对念珠菌和隐球菌具有良好的杀菌活性，除了近平滑念珠菌（MIC>44μg/ml）。几何均数（GM）MIC 与两性霉素 B相似，低于或与氟康唑 GM MIC 相当，但比其他唑类药物高 10 至 100 倍。GM MIC 对光滑念珠菌的 MIC<1μg/ml，明显低于氟康唑 GM MIC（P<0.001），与伊曲康唑、泊沙康唑和伏立康唑相似（GM MIC 范围为 0.4 至 1.23μg/ml）。化合物 4 对热带念珠菌的 GM MIC 低于氟康唑（1.69μg/ml 与 7.48μg/ml；P=0.012）。对新型隐球菌和新型隐球菌的 MIC 与氟康唑相似。化合物 4 对新型隐球菌的 GM MIC 明显高于氟康唑（3.83μg/ml 与 1.81μg/ml 对新型隐球菌；P=0.015）。本研究发现了新型双烷基吡啶链烷化合物具有临床相关的体外抗真菌活性。
