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卡泊芬净对念珠菌属固着细胞的矛盾性生长效应不仅在高药物浓度下存在。

Paradoxical growth effect of caspofungin on Candida spp. sessile cells not only at high drug concentrations.

机构信息

Department of Microbiology, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, 9 Maria Curie-Skłodowska Street, 85-094, Bydgoszcz, Poland.

出版信息

J Antibiot (Tokyo). 2019 Feb;72(2):86-92. doi: 10.1038/s41429-018-0123-2. Epub 2018 Nov 19.

DOI:10.1038/s41429-018-0123-2
PMID:30449892
Abstract

According to the available literature, echinocandins display high anti-Candida spp. activity. Paradoxical growth (PG) of Candida spp. planktonic cells promoted by echinocandins is widely reported. Here we report on the ability of Candida spp. sessile cells to display PG when they are exposed to caspofungin in vitro, even at relatively low drug concentrations. Clinical significance of PG during echinocandin therapy of candidiasis remains uncertain. We assessed in vitro susceptibilities of Candida spp. sessile cells to caspofungin and analyzed the frequency of PG. The minimum inhibitory concentrations of caspofungin for sessile cells (SMICs) were determined for 70 clinical Candida spp. isolates (29 Candida albicans, 26 Candida parapsilosis, and 15 Candida glabrata isolates) and were defined as the lowest drug concentrations that resulted in at least 50% reduction in metabolic activity. PG was defined as a resurgence of growth (>50% of that in the drug-free growth control well) at drug concentrations above the MIC. The caspofungin SMICs ranged from ≤0.015 to >256 µg ml. We observed PG in 26.9-93.1% of isolates tested, depending on the Candida species and age of sessile cells. Antibiofilm activity of caspofungin is species-specific, and strongly strain-depending among C. albicans and C. parapsilosis isolates. Interestingly, PG was present also at relatively low caspofungin concentrations.

摘要

根据现有文献,棘白菌素类对念珠菌属具有很高的抗真菌活性。广泛报道了棘白菌素类促进念珠菌浮游细胞的反常生长(PG)。在这里,我们报告了念珠菌属固着细胞在体外接触卡泊芬净时显示 PG 的能力,即使在相对较低的药物浓度下也是如此。棘白菌素类治疗念珠菌病时 PG 的临床意义仍不确定。我们评估了念珠菌属固着细胞对卡泊芬净的体外药敏性,并分析了 PG 的频率。我们确定了 70 株临床分离的念珠菌属(29 株白色念珠菌、26 株近平滑念珠菌和 15 株光滑念珠菌)固着细胞对卡泊芬净的最小抑菌浓度(SMIC),定义为导致代谢活性至少降低 50%的最低药物浓度。PG 定义为药物浓度高于 MIC 时生长的恢复(药物无生长对照孔中生长的>50%)。卡泊芬净的 SMIC 范围为≤0.015 至>256μg/ml。我们观察到 26.9-93.1%的受试分离株出现 PG,这取决于念珠菌属和固着细胞的年龄。卡泊芬净的抗生物膜活性具有种属特异性,并且在白色念珠菌和近平滑念珠菌分离株中强烈依赖于菌株。有趣的是,PG 也存在于相对较低的卡泊芬净浓度下。

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