抗真菌药物联合应用对白色念珠菌生物膜的体外活性研究
In vitro activity of antifungal combinations against Candida albicans biofilms.
机构信息
Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
出版信息
J Antimicrob Chemother. 2010 Feb;65(2):271-4. doi: 10.1093/jac/dkp429. Epub 2009 Dec 8.
OBJECTIVES
The aim of the present study was to evaluate the in vitro activity and synergism of the combinations of amphotericin B/caspofungin and amphotericin B/posaconazole against Candida albicans, grown either as planktonic cells or in biofilms.
METHODS
Ten C. albicans bloodstream isolates used in this study were collected from intensive care patients admitted to the Vienna University Hospital between 2006 and 2007. Chequerboard tests were employed to determine the efficacy of the antifungal combinations amphotericin B/caspofungin and amphotericin B/posaconazole against both planktonic cells and biofilms. C. albicans biofilms were prepared using the static microtitre plate model. The activity of antifungal combination therapy was determined by visual reading for planktonic cells and using the XTT assay for biofilms.
RESULTS
For Candida biofilms the median MIC was 4 mg/L for amphotericin B and caspofungin, and >256 mg/L for posaconazole. The combination amphotericin B/posaconazole yielded synergism [fractional inhibitory concentration index (FICI) <0.26], whereas amphotericin B/caspofungin yielded indifferent interaction only (FICI 0.75-1.25) against all isolates when grown in biofilms. Under planktonic conditions, synergism was demonstrable for the combination amphotericin B/caspofungin against 4 of the 10 isolates, whereas the combination of caspofungin/posaconazole was indifferent against all tested isolates.
CONCLUSIONS
We showed that MICs for planktonic and biofilm forms of C. albicans were much lower when treated with an antifungal combination than when treated with single agents. The combination of amphotericin B/posaconazole yielded synergism against Candida biofilms, whereas amphotericin B/caspofungin yielded indifferent interaction.
目的
本研究旨在评估两性霉素 B/卡泊芬净和两性霉素 B/泊沙康唑联合治疗白念珠菌浮游细胞和生物膜的体外活性和协同作用。
方法
本研究使用的 10 株白念珠菌血流感染分离株于 2006 年至 2007 年从维也纳大学医院重症监护病房的患者中收集。棋盘试验用于确定两性霉素 B/卡泊芬净和两性霉素 B/泊沙康唑联合治疗浮游细胞和生物膜的疗效。使用静态微量滴定板模型制备白念珠菌生物膜。通过浮游细胞的目视读数和生物膜的 XTT 测定来确定抗真菌联合治疗的活性。
结果
对于白念珠菌生物膜,两性霉素 B 和卡泊芬净的中位 MIC 为 4mg/L,泊沙康唑的 MIC 为>256mg/L。联合使用两性霉素 B/泊沙康唑产生协同作用(分数抑菌浓度指数(FICI)<0.26),而当在生物膜中生长时,两性霉素 B/卡泊芬净仅产生无关的相互作用(FICI 0.75-1.25)。在浮游状态下,联合使用两性霉素 B/卡泊芬净对 10 个分离株中的 4 个显示出协同作用,而联合使用卡泊芬净/泊沙康唑对所有测试分离株均为无关作用。
结论
我们表明,与单独使用药物相比,两性霉素 B 联合治疗对白念珠菌浮游细胞和生物膜形式的 MIC 要低得多。两性霉素 B/泊沙康唑联合治疗对白念珠菌生物膜产生协同作用,而两性霉素 B/卡泊芬净联合治疗产生无关作用。