Vitale Roxana G, Afeltra Javier, Meis Jacques F G M, Verweij Paul E
Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Mycoses. 2007 Jul;50(4):270-6. doi: 10.1111/j.1439-0507.2007.01371.x.
The phenothiazine compounds chlorpromazine and trifluopherazine are antipsychotic agents that exhibit antimicrobial activity against bacteria, some protozoa and yeasts. Data of activity against filamentous fungi are lacking. The in vitro activity and postantifungal effect (PAFE) of chlorpromazine and trifluopherazine was determined against Aspergillus species, zygomycetes and Scedosporium species. In vitro susceptibility testing was performed with CLSI M38A and the PAFE was determined with previously established methods. Both drugs inhibited the growth of all fungi tested at concentrations of 16 to 64 microg ml(-1). For Aspergillus species the mean PAFE was 3.7 and 4.7 h; for zygomycetes, 3.1 and 3.4 h; for Scedosporium, 4.3 and 5.3 h for chlorpromazine and trifluoroperazine respectively. These are the first drugs shown to induce PAFE against Scedosporium. We show that phenothiazine compounds have in vitro antifungal activity and exhibit PAFE against a broad range of filamentous fungal pathogens. Although the exact mechanism of action is unknown, further studies are needed to explore the clinical usefulness of phenothiazine compounds.
吩噻嗪类化合物氯丙嗪和三氟拉嗪是抗精神病药物,对细菌、一些原生动物和酵母具有抗菌活性。目前缺乏针对丝状真菌的活性数据。测定了氯丙嗪和三氟拉嗪对曲霉属、接合菌和头孢霉属的体外活性及抗真菌后效应(PAFE)。采用CLSI M38A进行体外药敏试验,并用先前建立的方法测定PAFE。两种药物在浓度为16至64微克/毫升时均能抑制所有受试真菌的生长。对于曲霉属,氯丙嗪和三氟拉嗪的平均PAFE分别为3.7小时和4.7小时;对于接合菌,分别为3.1小时和3.4小时;对于头孢霉属,分别为4.3小时和5.3小时。这是首次显示能诱导针对头孢霉属的PAFE的药物。我们表明吩噻嗪类化合物具有体外抗真菌活性,并对多种丝状真菌病原体表现出PAFE。尽管确切的作用机制尚不清楚,但需要进一步研究以探索吩噻嗪类化合物的临床应用价值。