Activities of E1210 and Comparator Agents Tested by CLSI and EUCAST Broth Microdilution Methods against Fusarium and Scedosporium Species Identified Using Molecular Methods
Activities of E1210 and Comparator Agents Tested by CLSI and EUCAST Broth Microdilution Methods against Fusarium and Scedosporium Species Identified Using Molecular Methods
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DOI：
10.1128/aac.05414-11
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发表时间：
2012-01-01
影响因子：
4.9
通讯作者：
Pfaller, Michael A.
中科院分区：
文献类型：
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作者：
Castanheira, Mariana;Duncanson, Frederick P.;Pfaller, Michael A.
镰刀菌（n = 67）和Scedosporium（n = 63）的临床分离株进行了测试，通过两个参考肉汤微量稀释（BMD）方法对一种新的广谱（活性对酵母菌和霉菌）抗真菌剂，E1210，和比较剂。E1210抑制糖磷脂酰肌醇（GPI）生物合成中的肌醇酰化步骤，导致真菌细胞壁生物合成中的缺陷。通过分子生物学技术鉴定了5种复合镰刀菌（4个未定种）和28种尖孢赛多孢菌（Scedosporium apiospermum）、7种橙孢赛多孢菌（Scedosporium aurantiacum）和28种多产赛多孢菌（Scedosporium prolificans）。对照抗真菌药包括阿尼芬净、卡泊芬净、伊曲康唑、泊沙康唑、伏立康唑和阿替霉素B。E1210对所有测试的分离株都具有高活性，对于镰刀菌属，E1210、阿尼杜拉真菌净、卡泊芬净、伊曲康唑、泊沙康唑、伏立康唑和阿替霉素B的最小有效浓度（MEC）/MIC（90）值（μ g/ml）分别为0.12、> 16、> 16、> 8、> 8、8和4 μ g/ml。E1210对丝孢霉属（Scedosporium spp.）测试. E_（1210）MEC（90）对S. apiospermum，但对于其它测试试剂为1至> 8 μ g/ml。对于s.对于橙黄，E1210的MEC（50）为0.06 μ g/ml，而对照物为0.5至> 8 μ g/ml。对于s.对于多产者，E1210的MEC（90）仅为0.12 μ g/ml，而对于阿替西霉素B> 4 μ g/ml，对于伊曲康唑、泊沙康唑和伏立康唑> 8 μ g/ml。CLSI和EUCAST方法对于E1210和所有对照药物均高度一致。除泊沙康唑和F.尖孢菌复合体（SC）（60%）、泊沙康唑和S.枳壳（85.7%）、伏立康唑和S.枳壳（85.7%）。综上所述，E1210对唑类和黄曲霉素B类镰刀菌耐药菌株表现出非常有效和广谱的抗真菌活性。和Scedosporium spp.此外，可以使用CLSI或EUCAST BMD方法完成E1210对镰刀菌和Scedosporium分离株的体外敏感性试验，每种方法均产生非常相似的结果。
Fusarium (n = 67) and Scedosporium (n = 63) clinical isolates were tested by two reference broth microdilution (BMD) methods against a novel broad-spectrum (active against both yeasts and molds) antifungal, E1210, and comparator agents. E1210 inhibits the inositol acylation step in glycophosphatidylinositol (GPI) biosynthesis, resulting in defects in fungal cell wall biosynthesis. Five species complex organisms/species of Fusarium (4 isolates unspeciated) and 28 Scedosporium apiospermum, 7 Scedosporium aurantiacum, and 28 Scedosporium prolificans species were identified by molecular techniques. Comparator antifungal agents included anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B. E1210 was highly active against all of the tested isolates, with minimum effective concentration (MEC)/MIC(90) values (mu g/ml) for E1210, anidula-fungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B, respectively, for Fusarium of 0.12, > 16, >16, >8, >8, 8, and 4 mu g/ml. E1210 was very potent against the Scedosporium spp. tested. The E1210 MEC(90) was 0.12 mu g/ml for S. apiospermum, but 1 to >8 mu g/ml for other tested agents. Against S. aurantiacum, the MEC(50) for E1210 was 0.06 mu g/ml versus 0.5 to >8 mu g/ml for the comparators. Against S. prolificans, the MEC(90) for E1210 was only 0.12 mu g/ml, compared to >4 mu g/ml for amphotericin B and> 8 mu g/ml for itraconazole, posaconazole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparator agents. The essential agreement (EA; +/- 2 doubling dilutions) was >93% for all comparisons, with the exception of posaconazole and F. oxysporum species complex (SC) (60%), posaconazole and S. aurantiacum (85.7%), and voriconazole and S. aurantiacum (85.7%). In conclusion, E1210 exhibited very potent and broad-spectrum antifungal activity against azole- and amphotericin B-resistant strains of Fusarium spp. and Scedosporium spp. Furthermore, in vitro susceptibility testing of E1210 against isolates of Fusarium and Scedosporium may be accomplished using either of the CLSI or EUCAST BMD methods, each producing very similar results.