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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Influence of human serum on antifungal pharmacodynamics with Candida albicans.
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Influence of human serum on antifungal pharmacodynamics with Candida albicans.

机译：人血清对白色念珠菌抗真菌药效的影响。

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Antifungal susceptibilities (NCCLS, approved standard M27-A, 1997) were determined for the reference strain ATCC 90028 and 21 clinical isolates of Candida albicans with varying levels of fluconazole susceptibility using RPMI 1640 (RPMI) and 80% fresh human serum-20% RPMI (serum). Sixty-four percent (14 of 22) of the isolates tested demonstrated significant decreases (> or = 4-fold) in fluconazole MICs in the presence of serum, and the remaining eight isolates exhibited no change. Itraconazole and ketoconazole, two highly protein-bound antifungal agents, had MICs in serum that were increased or unchanged for 46% (10 of 22) and 41% (9 of 22) of the isolates, respectively. All 10 isolates tested against an investigational antifungal agent, LY303366, demonstrated significant increases in the MIC required in serum, while differences in amphotericin B MICs in the two media were not observed. Four of 10 isolates tested demonstrated fourfold higher flucytosine MICs in serum than in RPMI. Postantifungal effects (PAFEs) and 24-h kill curves were determined by standard methods for selected isolates. At the MIC, fluconazole, itraconazole, ketoconazole, flucytosine, and LY303366 kill curves and PAFEs in RPMI were similar to those in serum. Isolates of fluconazole-resistant C. albicans required lower MICs in serum than in RPMI, without relative increases in fungal killing or PAFEs. Isolates tested against amphotericin B demonstrated significantly reduced killing and shorter PAFEs in serum than in RPMI without observable changes in MIC. In conclusion, antifungal pharmacodynamics in RPMI did not consistently predict antifungal activity in serum for azoles and amphotericin B. Generally speaking, antifungal agents with high protein binding exhibited some form of reduced activity (MIC, killing, or PAFE) in the presence of serum compared to those with low protein binding.
机译：使用RPMI 1640（RPMI）和80％新鲜人血清-20％RPMI测定了参考菌株ATCC 90028和21种白色念珠菌念珠菌临床药的抗真菌药敏性（NCCLS，已批准标准M27-A，1997） （血清）。测试的分离株中有64％（22个中的14个）在存在血清的情况下显示氟康唑MICs显着降低（>或= 4倍），其余8个分离株未显示变化。伊曲康唑和酮康唑是两种高度结合蛋白的抗真菌剂，血清中的MIC分别升高或保持不变，分别为46％（22/10）和41％（22/9）。针对研究性抗真菌剂LY303366测试的所有10个分离株均显示血清中所需的MIC显着增加，而未观察到两种培养基中两性霉素B MIC的差异。测试的10个分离株中有4个显示血清中的胞嘧啶MIC比RPMI高4倍。通过标准方法针对选定的分离物确定了真菌后的作用（PAFE）和24小时的杀死曲线。在MIC处，RPMI中的氟康唑，伊曲康唑，酮康唑，氟胞嘧啶和LY303366的杀灭曲线和PAFE与血清相似。耐氟康唑的白色念珠菌的分离物需要比RPMI更低的血清MIC，而不会导致真菌杀灭或PAFE的相对增加。与两性霉素B相比，针对两性霉素B的分离株的杀灭作用显着降低，而PAFEs则比RPMI显着减少，而MIC却没有明显变化。总之，RPMI中的抗真菌药效学不能始终如一地预测血清中对唑类和两性霉素B的抗真菌活性。一般而言，与高蛋白结合的抗真菌剂在存在血清的情况下表现出某种形式的活性降低（MIC，杀伤或PAFE）那些蛋白质结合力低的人

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