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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Paradoxical Effect of Caspofungin: Reduced Activity against Candida albicans at High Drug Concentrations.
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Paradoxical Effect of Caspofungin: Reduced Activity against Candida albicans at High Drug Concentrations.

机译：卡泊芬净的悖论作用：在高药物浓度下，针对白色念珠菌的活性降低。

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摘要

Resistance problems with caspofungin, an echinocandin inhibitor of fungal cell wall glucan synthesis, have been rare. We noted paradoxical turbid growth of Candida albicans isolates in broth in some high (supra-MIC) concentrations. Among isolates submitted for susceptibility testing and screened at drug concentrations up to 12.5 microg/ml, the frequency was 16%. Analysis of the turbid growth indicated slowing of growth in the presence of drug but with numbers of CFU up to 72% those of drug-free controls. Clearing of growth again by the highest drug concentrations produced a quadriphasic pattern in a tube dilution series. Cells growing at high drug concentrations were not resistant on retesting but showed the paradoxical effect of the parent. Among a selected series of isolates tested at concentrations up to 50 microg/ml, an additional 53% showed a mini-paradoxical effect concentrations (supra-minimum fungicidal concentration). These effects were reproducible; medium dependent in extent; noted in macro-and microdilution, in the presence or absence of serum, and on agar containing drug (but not when drug concentrations were not constant, as in agar diffusion); not seen with other echinocandins and less commonly in other Candida species; and not due to destruction of drug in tubes showing the effect. Cooperative enhancement of inhibition by a second drug could eradicate the effect. We postulate that high drug concentrations derepress or activate resistance mechanisms. The abilities of subpopulations to survive at high drug concentrations could have in vivo consequences.
机译：卡泊芬净（一种真菌细胞壁葡聚糖合成的棘皮菌素抑制剂）的耐药性问题很少见。我们注意到肉汤中高浓度（超MIC）的白色念珠菌分离株呈反常浑浊生长。在提交给药敏试验并以最高12.5 microg / ml的药物浓度进行筛选的分离株中，检出频率为16％。对混浊生长的分析表明在存在药物的情况下生长减慢，但是CFU的数量高达无药物对照的72％。最高药物浓度再次清除生长，在试管稀释系列中产生了四相模式。在高药物浓度下生长的细胞不耐复测，但表现出亲本的反常效应。在所选浓度最高为50微克/毫升的分离株系列中，另有53％的分离株显示出最小的反常效应浓度（超最小杀菌浓度）。这些效果是可重现的。中等程度在大量和微量稀释中，在有或没有血清的情况下以及在含有琼脂的药物上注明（但在琼脂扩散中药物浓度不是恒定的情况下则不是）;在其他棘球and苷中未见，在其他念珠菌属物种中不常见;而不是因为药物破坏了显示效果的试管。协同增强第二种药物的抑制作用可以消除这种作用。我们推测高药物浓度会抑制或激活耐药机制。亚群在高药物浓度下生存的能力可能在体内产生后果。

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