隐球菌临床及环境分离株对卡泊芬净与特比萘芬的体外联合药敏试验

摘要

目的了解隐球菌临床及环境分离株对卡泊芬净与特比萘芬的体外联合抗菌活性.方法采用美国国家实验室标准委员会(NCCLS)M27-A方案推荐的酵母菌微量稀释法及其微量稀释棋盘法,检测78株新生隐球菌临床和环境分离株对卡泊芬净与特比萘芬的体外抗菌活性及其联合抗菌活性.结果卡泊芬净和特比萘芬对新生隐球菌最小抑菌浓度(MIC)值范围分别是0.25～32 μg/ml、2～16 μg/ml;几何均数分别是32μg/ml、8μg/ml.联合药敏试验结果显示,两者联合后对其中5%菌株有协同作用,42%菌株有累加作用及53%菌株有无关作用,任何菌株均无拮抗作用.同时卡泊芬净的MIC几何均数由26.8 μg/ml降至20.6 μg/ml(P＜0.0001),特比萘芬的MIC几何均数由7.9ug/ml降至1.3μg/ml(P＜0.0001).此外,有4株菌株对卡泊芬净药物敏感,其MIC分别是2 μg/ml、2μg/ml、0.5 μg/ml、0.25μg/ml.结论卡泊芬净与特比萘芬的体外联合药敏试验表明,两者联合应用对新生隐球菌具有较好的体外抗菌活性.%To evaluate the in vitro interactions of caspofungin and terbinafine against Cryptococcus neoformans.Methods 78 clinical and environmental isolates of Cryptococcus neoformans was tested by a modified National Committee for Clinical Laboratory Standards(NCCLS)microdilution assay,and the interactions were examined using a checkerboard design.Resuls Caspofungin MICs ranged from 0.25 μg/ml to 32 μg/ml,with a median(MIC at which 50% of the isolates are inhibited)of 32 μg/ml.Terbinafine MICs ranged from 2.0 μg/ml to 16 μg/ml,with a median of 8 μg/ml.A synergistic interaction was observed in 5%(4 of 78)of the isolates,and 42%(33 of 78)of the isolates yielded additive and 53%(41 of 78)of the isolates showed an indifferent interactions.Thus,the interaction of their combinations was synergisticto-additive for 47% isolates.Antagonism had not been observed.The geometric mean MIC of caspofungin dropped from 26.8 to 20.6 μg/ml(P＜ 0.0001),and that of terbinafine dropped from 7.9 to 1.3 μg/ml(P ＜ 0.0001)when tested in combination.While,the caspofungin MICs of the four isolates were 2 μg/ml,2 μg/ml,0.5 μg/ml and 0.25 μg/ml respectively.Conclusions In vitro synergistic drug sensitivity test indicated that the combined use of caspofungin-terbinafine resulted in better antifungal action against C.neoformans.