葡萄糖酸亚铁及其与抗真菌药物联用对白念珠菌耐药性的影响研究

Abstract

Abstract:

Objective To investigate the effects of ferrous gluconate, both alone and in combination with conventional antifungal agents, on Candida albicans (C. albicans) biofilms and its drug resistance. Methods Experiments were conducted using standard strains and drug-resistant strains of C. albicans. Both the planktonic and biofilm states of the respective strains were cultured and established. C. albicans was treated with ferrous gluconate alone and in combination with antifungal drugs. The inhibitory effects were assessed using the XTT reduction assay and the checkerboard microdilution method respectively, while the time-kill curve tests were conducted to determine the kinetic effect of drugs on biofilm sterilization. The morphological changes of biofilms were observed under scanning electron microscopy (SEM). Results Ferrous gluconate exhibited inhibitory effects on both planktonic and biofilm states of standard strains and drug-resistant strains of C. albicans. The minimum drug concentration that inhibited 50% activity (SMIC₅₀) of biofilms was 50 mmol/L for both the standard and drug-resistant strains. A synergistic antifungal effect was observed when ferrous gluconate was combined with fluconazole. The time-kill curves for ferrous gluconate alone and in combination with fluconazole demonstrated that its inhibitory effect on the biofilms of both strains showed an overall trend of enhancement with the prolongation of time or the increase of dose, and the combination group exhibited a significantly stronger inhibitory effect compared to any agent used alone. Morphological observations revealed that both ferrous gluconate alone and in combination with antifungal drugs could reduce hyphal formation and biofilm-forming capacity of C. albicans. Conclusion Ferrous gluconate exerts an inhibitory effect on biofilms in both standard strains and drug-resistant strains of C. albicans and can reduce its drug resistance. The combination of ferrous gluconate and fluconazole demonstrates a synergistic antimicrobial effect.

Key words: Candida albicans, ferrous gluconate, antifungal agents, biofilm, drug resistance

CLC Number:

R781.5

XIONG Xuening, CHEN Wanjing, YUAN Weiyu, WANG Yufei, ZHU Shuxian, WANG Mutian, WEI Xin, MA Ming. Effects of ferrous gluconate alone and combined with antifungal agents on Candida albicans resistance[J]. Stomatology, 2026, 46(6): 448-454.

Figures/Tables 6

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References 24

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药物名称	标准株SMIC₅₀	耐药株SMIC₅₀
氟康唑	512.00	1 024.00
卡泊芬净	64.00	256.00
两性霉素B	0.50	2.00
特比萘芬	256.00	512.00
5-氟胞嘧啶	512.00	1 024.00

白念珠菌菌株	联用药物	FICI	结果
标准株	氟康唑	0.37	SYN
	卡泊芬净	0.75	IND
	两性霉素B	1.25	IND
	特比萘芬	1.03	IND
	5-氟胞嘧啶	0.63	IND
耐药株	氟康唑	0.42	SYN
	卡泊芬净	1.00	IND
	两性霉素B	1.25	IND
	特比萘芬	1.02	IND
	5-氟胞嘧啶	1.00	IND

白念珠菌菌株	联用药物	∑SYN	∑ANT	结果
标准株	氟康唑	242	-19	SYN(S)
	卡泊芬净	153	-173	IND
	两性霉素B	182	-43	SYN(M)
	特比萘芬	862	-13	SYN(S)
	5-氟胞嘧啶	282	-48	SYN(S)
耐药株	氟康唑	305	-181	SYN(M)
	卡泊芬净	218	-107	SYN(M)
	两性霉素B	17	-256	ANT(S)
	特比萘芬	14	-80	IND
	5-氟胞嘧啶	347	-39	SYN(S)

Effects of ferrous gluconate alone and combined with antifungal agents on Candida albicans resistance

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