Comparison of azoles against aspergilli in vitro and in an experimental model of pulmonary aspergillosis.
Comparison of azoles against aspergilli in vitro and in an experimental model of pulmonary aspergillosis.
复制标题
唑类药物在体外和肺曲霉病实验模型中对抗曲霉的比较。
DOI：
10.1159/000238951
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发表时间：
1992
期刊：
影响因子：
3.3
通讯作者：
D. Armstrong
中科院分区：
文献类型：
--
作者：
H. Schmitt;F. Edwards;J. Andrade;Y. Niki;D. Armstrong
目前治疗支气管肺曲霉菌病的方法并不十分令人满意。我们测定了最近可用的唑类化合物对烟曲霉、黄曲霉和黑曲霉的体外活性。随后，在以烟曲霉菌为试验生物的支气管肺曲霉病动物模型中，对这些药物进行了评估。在体外，只有伊曲康唑有可检测到的活性(所有最低抑菌浓度，MIC，小于或等于3.2微克/毫升)。对SCH39304的MIC大于或等于12.8微克/毫升，对酮康唑和氟康唑的MIC大于或等于25.6微克/毫升。在体内，两性霉素B是被测试的最活跃的药物，SCH39304是在存活和减轻肺重量方面最活跃的唑，其次是伊曲康唑。酮康唑和氟康唑既不能提高受感染动物的存活率，也不能减轻其肺重量。我们的结论是：(1)唑类化合物的体外抗曲霉菌活性并不总是与体内活性相关；(2)在体内，SCH39304是最有效的受试唑，其次是伊曲康唑；(3)对于那些可以获得治疗人类肺曲霉菌病疗效数据的药物(两性霉素B、酮康唑、伊曲康唑)，我们的模型中的抗真菌活性与人类的活性一致，(4)SCH39304和伊曲康唑是治疗人类肺曲霉菌病临床试验的合理选择。
Current treatment modalities for bronchopulmonary aspergillosis are not very satisfying. We determined the in vitro activity of recently available azoles against Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. Subsequently, these agents were evaluated in an animal model of bronchopulmonary aspergillosis using A. fumigatus as test organism. In vitro, detectable activity was only found for itraconazole (all minimal inhibitory concentrations, MICs, less than or equal to 3.2 micrograms/ml). The MICs for SCH39304 were greater than or equal to 12.8 micrograms/ml and greater than or equal to 25.6 micrograms/ml for ketoconazole and fluconazole. In vivo, amphotericin B was the most active agent tested, and SCH39304 was the most active azole in terms of survival and reduction in lung weight, followed by itraconazole. Ketoconazole and fluconazole did not improve survival nor reduce the lung weight of infected animals. We conclude, (1) that in vitro activity of azoles against aspergilli does not always correlate with in vivo activity; (2) that in vivo, SCH39304 was the most active azole tested, followed by itraconazole; (3) that for those agents for which data about effectiveness in human pulmonary aspergillosis are available (amphotericin B, ketoconazole, itraconazole) antifungal activity in our model corresponds to activity as seen in human beings, and (4) that SCH39304 and itraconazole are rational choices for clinical trials in human pulmonary aspergillosis.