氟西汀单独使用及联用氟康唑对白念珠菌的影响研究

doi:10.13591/j.cnki.kqyx.2024.05.005

摘要/Abstract

摘要：

目的探讨氟西汀单独使用及联用氟康唑对白念珠菌的抑制作用。方法采用白念珠菌标准株、白念珠菌临床分离株和白念珠菌耐药株进行实验,分别制备相应菌株的浮游状态和生物膜状态。XTT减低法检测氟西汀对白念珠菌的作用,改良时间-杀菌曲线测定氟西汀对白念珠菌生物膜的药效学性能,扫描电镜观察氟西汀处理后白念珠菌生物膜的形态变化,棋盘稀释法检测氟西汀与氟康唑联用对生物膜状态白念珠菌的影响。结果氟西汀对3种生物膜状态的白念珠菌均有抑制作用,抑制生物膜状态白念株菌标准株和氟康唑耐药株50%活性的最低药物浓度(sessile minimal inhibitory concentration 50%,SMIC₅₀)为32 μg/mL,对生物膜状态白念珠菌临床株的SMIC₅₀为64 μg/mL。改良时间-杀菌曲线显示在氟西汀浓度为1×SMIC₅₀和2×SMIC₅₀时,3种白念珠菌生物膜活性均较对照组显著下降。扫描电镜观察显示,氟西汀处理后白念珠菌生物膜较无药物处理时菌丝数量减少,形态发生皱缩。棋盘稀释法显示氟西汀与氟康唑联用时对生物膜状态的白念珠菌标准株表现出协同作用,对其余两种菌株表现出无关或拮抗作用。结论氟西汀单独使用对不同种类生物膜状态的白念珠菌均有较好的抑制作用,联用氟康唑对生物膜状态白念珠菌标准株有协同抑制作用。

关键词: 白念珠菌, 氟西汀, 氟康唑

Abstract:

Objective To evaluate the inhibitory activity of fluoxetine alone and in combination with fluconazole on Candida albicans. Methods This study used standard strains of Candida albicans, clinical isolates of Candida albicans, and drug-resistant strains of Candida albicans for experiments to prepare the planktonic and biofilm states of Candida albicans, respectively. The effect of fluoxetine on Candida albicans was detected by XTT reduction method. Pharmacodynamic properties of fluoxetine against Candida albicans biofilm were determined by improved time-kill test. The morphological changes of fluoxetine on Candida albicans biofilm were observed by scanning electron microscopy, and the synergistic effect of fluoxetine combined with fluconazole on Candida albicans biofilms was detected by the checkerboard dilution method. Results Fluoxetine had inhibitory effects on three types of Candida albicans biofilms. The minimum drug concentration that inhibited 50% activity (SMIC₅₀) of biofilms of standard strains of Candida albicans and drug-resistant strains was 32 μg/mL; the SMIC₅₀ of clinical strains of Candida albicans biofilm was 64 μg/mL. Time-kill test displayed that the biofilm activity of three types of Candida albicans significantly decreased compared to the control group at the fluoxetine concentration of 1×SMIC₅₀ and 2×SMIC₅₀. Scanning electron microscopy observation showed that compared with the control group, the number of fungal hyphae in the biofilm of Candida albicans treated with fluoxetine decreased and their morphology wrinkled. The checkerboard microdilution method showed that the combination of fluoxetine and fluconazole exhibited a synergistic effect on the standard strain of Candida albicans bioflim, while showing no or antagonistic effects on the other two strains. Conclusion Fluoxetine alone has inhibitory effects on biofilms of different types of Candida albicans and has a synergistic inhibitory effect on biofilms of standard strains of Candida albicans combined with fluconazole.

Key words: Candida albicans, fluoxetine, fluconazole

中图分类号:

R781.5

史般若, 吴翘楚, 缪昊宸, 魏昕. 氟西汀单独使用及联用氟康唑对白念珠菌的影响研究[J]. 口腔医学, 2024, 44(5): 344-348.

SHI Banruo, WU Qiaochu, MIAO Haochen, WEI Xin. Study on the effect of fluoxetine against Candida albicans, alone or combined with fluconazole[J]. Stomatology, 2024, 44(5): 344-348.

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白念珠菌菌株	氟康唑	氟西汀
标准株
浮游状态MIC₈₀	0.5	128.0
生物膜状态SMIC₅₀	512.0	32.0
临床分离株
浮游状态MIC₈₀	4.0	128.0
生物膜状态SMIC₅₀	1 024.0	64.0
氟康唑耐药株
浮游状态MIC₈₀	4.0	128.0
生物膜状态SMIC₅₀	1 024.0	32.0

菌株	FICI法				ΔE法
菌株	FICI		结果		∑SYN/%		∑ANT/%		结果
白念珠菌标准株		0.38		SYN		701		-36		SYN
临床分离株		0.75		IND		65		-218		ANT
氟康唑耐药株		1.50		IND		13		-1 078		ANT