In vitro activity of a new triazole BAL4815, the active component of BAL8557 (the water-soluble prodrug), against Aspergillus spp.
In vitro activity of a new triazole BAL4815, the active component of BAL8557 (the water-soluble prodrug), against Aspergillus spp.
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DOI：
10.1093/jac/dki399
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发表时间：
2006-01-01
影响因子：
5.2
通讯作者：
Denning, DW
中科院分区：
文献类型：
--
作者：
Warn, PA;Sharp, A;Denning, DW
目的：BAL 4815是抗真菌三唑类药物BAL 8557（水溶性前药）的活性成分。我们比较了BAL 4815与伊曲康唑、伏立康唑、卡泊芬净和阿替霉素B对118株曲霉菌（包括4个不同菌种）的体外活性（烟曲霉属、土曲霉属、黄曲霉属和尼日尔属）;预先选择分离株以包括16个在体外证明对其它药剂具有抗性的分离株。采用NCCLS M38-A方法的微量稀释平板改良法，用MOPS缓冲至pH 7.0的RPMI 1640，测定BAL 4815、阿替霉素B、伊曲康唑和伏立康唑的敏感性;对于卡泊芬净，使用在1%O-2/5%CO2/94%N-2的气体混合物中孵育以帮助阅读，对该方法进行了改进。MFCs结果：所有菌株的几何平均（GM）MIC值和范围（mg/L）分别为：BAL 4815，0.620和0.125-2.0，伊曲康唑，0.399，0.063-> 8.0，伏立康唑，0.347，0.125- 8.0，阿曲康唑，0.347和0.063-> 8.0，阿曲康唑，0.347和0.063-> 8.0，阿曲康唑，0.347和0.125-> 8.0，阿曲康唑，0.347和0.125-> 8.0。卡泊芬净，0.341和0.125-4.0;两性霉素B，0.452和0.06-4.0。不同种属间对BAL 4815的敏感性无显著差异，与伊曲康唑相比，没有分离株显示MIC> 2.0 mg/L。对于所有分离株，GM MFC值和范围（mg/L）为：BAL 4815，1.68和0.25-> 8.0;伊曲康唑，1.78和0.06-> 8.0;伏立康唑，1.09和0.25-> 8.0;阿替霉素B，0.98和0.25-> 4.0。BAL 4815在体外对所有四种曲霉菌属表现出有希望的抗真菌活性，包括对伊曲康唑、卡泊芬净或阿替霉素B耐药的菌株。
Objectives: BAL4815 is the active component of the antifungal triazole agent BAL8557 (the water-soluble prodrug). We compared the in vitro activity of BAL4815 with that of itraconazole, voriconazole, caspofungin and amphotericin B against 118 isolates of Aspergillus comprising four different species (fumigatus, terreus, flavus and niger); the isolates were pre-selected to include 16 isolates demonstrating in vitro resistance to other agents.Methods: Susceptibilities were determined for BAL4815, amphotericin B, itraconazole and voriconazole using the microdilution plate modification of the NCCLS M38-A method with RPMI 1640 buffered to pH 7.0 with MOPS; for caspofungin the method was modified using incubation in a gas mixture of 1% O-2/5% CO2/94% N-2 to aid reading. MFCs (>= 99% kill) were also determined for all drugs other than caspofungin.Results: For all isolates, geometric mean (GM) MIC values and ranges (in mg/L) were: BAL4815, 0.620 and 0.125-2.0; itraconazole, 0.399 and 0.063-> 8.0; voriconazole, 0.347 and 0.125-8.0; caspofungin, 0.341 and 0.125-4.0; amphotericin B, 0.452 and 0.06-4.0. No significant differences in susceptibility to BAL4815 were seen between species and in contrast to itraconazole no isolates demonstrated MICs > 2.0 mg/L. For all isolates, GM MFC values and ranges (in mg/L) were: BAL4815, 1.68 and 0.25-> 8.0; itraconazole, 1.78 and 0.06-> 8.0; voriconazole, 1.09 and 0.25-> 8.0; amphotericin B, 0.98 and 0.25-> 4.0.Conclusions: BAL4815 demonstrated promising antifungal activity against all four Aspergillus species in vitro including strains resistant to itraconazole, caspofungin or amphotericin B.