氟康唑与5-氟胞嘧啶体外联合抗新生隐球菌临床分离株的实验研究

Vitro Study of Combination of Fluconazole with Flucytosine Against Clinical Isolates of Cryptococcus neoformans

目的评价新生隐球菌临床分离株对氟康唑和5-氟胞嘧啶联合用药的敏感性及判断两药物之间相互作用的方式。方法采用美国国家临床实验室标准化委员会(NCCLS)M27-A推荐的棋盘微量稀释法,检测了20株新生隐球菌临床分离株对氟康唑、5-氟胞嘧啶及两药联合的体外药物敏感性,同时对两药的作用方式进行了判定。结果联合用药时显著减少了每一药物MIC值的几何均数,在35%受试菌表现为协同作用方式,在55%的受试菌株表现为相加作用方式,在10%受试菌株表现为无关作用方式,未观察到拮抗作用出现。测定不同浓度下药物单独和组合作用的一株菌的菌落形成单位(cfu/mL),每一种联合用药组合都较5-氟胞嘧单独用药有明显减少。结论氟康唑与5-氟胞嘧啶联合比单一药物体外抗新生隐球菌的活性高。

Objective To evaluate the sensitivity of20clinical isolates of Cryptococcus neoformans to the combina-tion therapy of fluconazole with flucytosine and their in-vitro interactions.Methods A checkerboard titration broth mi-crodilution-based method that adhered to the recommendations of the National Committee for Clinical Laboratory Stan-dards was applied to study the sensitivity of20clinical isolates of Cryptococcus neoformans to the combination therapy of fluconazole with flucytosine and their in-vitro interactions.Results When fluconazole and flucytosine were given in com-bination,there were significant reductions in the geometric mean fluconazole MIC(from to)and flucytosine MIC(from to).For35%of the isolates the interactions were synergistic,for55%they were additive,and for10%they were indifferent,while antagonism was not abserved.Determination of cfu/mL was performed only with one isolate which was tested by one drug and different concentration combination of two drugs.For all combination,the reduction in cfu was significantly greater than that observed with single drugs alone.Conclusion The combination of fluconazole and fllucytosine is sig-nificant ly more active than any drug alone against Cryptococcus neoformans in vitro.