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选择性5-羟色胺再摄取抑制剂单独及与氟康唑联合使用时的抗真菌及抗生物被膜活性

Antifungal and Antibiofilm Activities of Selective Serotonin Reuptake Inhibitors Alone and in Combination with Fluconazole.

作者信息

Tekintaş Yamaç, Temel Aybala, Ateş Ayşegül, Eraç Bayrı, Metin Dilek Yeşim, Hilmioğlu Polat Süleyha, Hoşgör Limoncu Mine

机构信息

İzmir Katip Çelebi University Faculty of Pharmacy, Department of Pharmaceutical Microbiology, İzmir, Turkey.

Ege University Faculty of Pharmacy, Department of Pharmaceutical Microbiology, İzmir, Turkey.

出版信息

Turk J Pharm Sci. 2020 Dec 23;17(6):667-672. doi: 10.4274/tjps.galenos.2019.65481.

Abstract

OBJECTIVES

spp. are clinically important pathogens that cause difficulties for treatment by biofilm formation. Considering antifungal resistance rates and the limitations in the discovery of new antifungals, the antifungal and antibiofilm effects of various drugs used for different therapeutic purposes are becoming more important. The goal of our study was to determine the antifungal and antibiofilm effects of the selective serotonin reuptake inhibitors (SSRIs), namely sertraline (SRT), paroxetine (PRX), and fluoxetine (FLX) alone and in combination with fluconazole (FLC) against spp.

MATERIALS AND METHODS

Twenty spp. strains isolated from clinical samples from Ege University Hospital were identified by the Dalmau method and matrix-assisted laser desorption ionization time of flight mass spectrometry. The minimum inhibitory concentrations (MICs) of the SSRIs and FLC were detected by broth microdilution method. Synergistic interactions between the SSRIs and FLC were investigated by checkerboard assay. The antibiofilm effects of the SSRIs were determined by spectrophotometric microplate method.

RESULTS

Among the isolates, five different spp. (, , , , and ) were identified. The MICs of the SSRIs ranged between 16-512 μg/mL. While SRT showed the highest antifungal effect, the antibiofilm efficacy of FLX was higher than that of the other agents. Moreover, FLX and PRX showed a synergistic effect with FLC in 13 and 19 isolates, respectively. Four isolates were strong biofilm producers while nine isolates were moderate biofilm producers. strains showed higher biofilm production than the other species. At MIC/2 concentration, FLX and SRT alone inhibited mature biofilms in six and five isolates, respectively, while PRX caused increases biofilm formation in seven isolates.

CONCLUSION

This study revealed that MIC/2 concentrations of SSRIs could have antifungal and antibiofilm effects. SRT and FLX alone or in combination with antifungals may possibly have therapeutic potential for combating fungal infections.

摘要

目的

[病原菌名称]是临床上重要的病原体,可通过形成生物膜导致治疗困难。鉴于抗真菌耐药率以及新抗真菌药物发现的局限性,用于不同治疗目的的各种药物的抗真菌和抗生物膜作用变得愈发重要。我们研究的目的是确定选择性5-羟色胺再摄取抑制剂(SSRI),即舍曲林(SRT)、帕罗西汀(PRX)和氟西汀(FLX)单独及与氟康唑(FLC)联合使用对[病原菌名称]的抗真菌和抗生物膜作用。

材料与方法

通过达尔 Mau 方法和基质辅助激光解吸电离飞行时间质谱法鉴定从伊兹密尔大学医院临床样本中分离出的20株[病原菌名称]菌株。采用肉汤微量稀释法检测SSRI和FLC的最低抑菌浓度(MIC)。通过棋盘法研究SSRI和FLC之间的协同相互作用。采用分光光度微孔板法测定SSRI的抗生物膜作用。

结果

在分离株中,鉴定出5种不同的[病原菌名称]([具体名称1]、[具体名称2]、[具体名称3]、[具体名称4]和[具体名称5])。SSRI的MIC范围为16 - 512μg/mL。虽然SRT显示出最高的抗真菌作用,但FLX的抗生物膜功效高于其他药物。此外,FLX和PRX分别在13株和19株分离株中与FLC显示出协同作用。4株分离株为强生物膜产生菌,9株分离株为中度生物膜产生菌。[病原菌名称某菌株]显示出比其他菌种更高的生物膜产生能力。在MIC/2浓度下,单独的FLX和SRT分别在6株和5株分离株中抑制成熟生物膜,而PRX在7株分离株中导致生物膜形成增加。

结论

本研究表明,MIC/2浓度的SSRI可能具有抗真菌和抗生物膜作用。单独使用或与抗真菌药物联合使用的SRT和FLX可能具有对抗真菌感染的治疗潜力。

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