噻苯达唑联合抗真菌药物对新生隐球菌的体外抑菌效应

唐炼; 孙毅; 李娟

doi:10.7619/jcmp.20220973

噻苯达唑联合抗真菌药物对新生隐球菌的体外抑菌效应

唐炼¹,
孙毅²,
李娟^3, ,

1.
长江大学, 湖北荆州, 434100
2.
长江大学附属荆州医院皮肤病与性病科, 湖北荆州, 434100
3.
长江大学附属荆州医院全科医学科, 湖北荆州, 434100

基金项目:

湖北省卫生健康委员会科研项目 WJ2021M261

湖北省自然科学基金项目 2019CFB567

详细信息

通讯作者:
李娟, E-mail: 37016653@qq.com

中图分类号: R978.6;R978.5
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出版历程
- 收稿日期: 2022-03-25
- 网络出版日期: 2022-09-02

In vitro antifungal effects of thiabendazole in combination with antifungal agents on Cryptococcus neoformans

TANG Lian¹,
SUN Yi²,
LI Juan^3, ,

1.
Yangtze University, Jingzhou, Hubei, 434100
2.
Department of Dermatology and Venereal Disease, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei, 434100
3.
Department of General Medicine, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei, 434100

摘要

摘要:
目的
观察噻苯达唑分别联合抗真菌药物氟康唑、两性霉素B、泊沙康唑、伊曲康唑、伏立康唑对新生隐球菌的体外抑菌效果。
方法
参照美国临床实验室标准化研究所的M27-A3方案, 测定噻苯达唑和抗真菌药物氟康唑、两性霉素B、泊沙康唑、伊曲康唑、伏立康唑单独应用对20株新生隐球菌菌株的最低抑菌浓度(MIC)。采用棋盘法测定噻苯达唑分别联合氟康唑、两性霉素B、泊沙康唑、伊曲康唑、伏立康唑对20株新生隐球菌菌株的体外抑菌效果。
结果
噻苯达唑单独应用对新生隐球菌菌株的MIC为8.0~32.0 μg/mL; 两性霉素B、氟康唑、伊曲康唑、泊沙康唑、伏立康唑单独应用对新生隐球菌菌株的MIC分别为0.250 0~8.000 0、1.000 0~8.000 0、0.062 5~2.000 0、0.062 5~4.000 0、0.062 5~1.000 0 μg/mL。噻苯达唑与两性霉素B联合应用对7株新生隐球菌有协同作用，与氟康唑联合应用对8株新生隐球菌有协同作用，与伊曲康唑联合应用对4株新生隐球菌有协同作用，与泊沙康唑联合应用对5株新生隐球菌有协同作用，与伏立康唑联合应用对1株新生隐球菌有协同作用。
结论
噻苯达唑具有一定的抗新生隐球菌作用，在体外与常用抗真菌药物氟康唑、两性霉素B、泊沙康唑、伊曲康唑、伏立康唑联用时可起到协同作用，降低抗真菌药物对部分新生隐球菌菌株的MIC。
- 新生隐球菌 /
- 噻苯达唑 /
- 氟康唑 /
- 两性霉素B /
- 泊沙康唑 /
- 伊曲康唑 /
- 伏立康唑
Abstract:
Objective
To observe antifungal effects of thiabendazole combined with fluconazole, amphotericin B, posaconazole, itraconazole and voriconazole, respectively on Cryptococcus neoformans in vitro.
Methods
The minimum inhibitory concentrations (MIC) of the chemical agents against 20 strains of Cryptococcus neoformans by thiabendazole and antifungal agents including fluconazole, amphotericin B, posaconazole, itraconazole and voriconazole alone were determined according to the M27-A3 protocol proposed by the American Clinical Laboratory Standardization Committee. Microdilution checkerboard technique system was used to determine in vitro antifungal effects of thiabendazole in combination with fluconazole, amphotericin B, posaconazole, itraconazole or voriconazole, respectively for 20 strains of Cryptococcus neoformans.
Results
MIC of thiabendazole against Cryptococcus neoformans ranged from 8 to 32 μg/mL. MICs of amphotericin B, fluconazole, itraconazole, posaconazole and voriconazole against Cryptococcus neoformants were 0.250 0 to 8.000 0, 1.000 0 to 8.000 0, 0.062 5 to 2.000 0, 0.062 5 to 4.000 0 and 0.062 5 to 1.000 0 μg/mL, respectively. Synergistic inhibitory effect was found in 7 strains via thiabendazole and amphotericin B, 8 strains via thiabendazole and fluconazole, 4 strains via thiabendazole and itraconazole, 5 strains via thiabendazole and posaconazole, and 1 strain via thiabendazole and voriconazole, respectively.
Conclusion
Thiabendazole has potential anti-Cryptococcus neoformans effect and have synergy effects in combination with antifungal agents such as fluconazole, amphotericin B, posaconazole, itraconazole, voriconazole against Cryptococcus neoformans, which can decrease MIC of antifungal drugs against some strains of Cryptococcus neoformans.
- Cryptococcus neoformans /
- thiabendazole /
- fluconazole /
- amphotericin B /
- posaconazole /
- itraconazole /
- voriconazole

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表 1 TBZ和5种抗真菌药物单独应用对20株新生隐球菌的体外抑菌效果

菌株编号	MIC/(μg/mL)
菌株编号	TBZ	AMB	FLU	ITR	POS	VOR
5338	16.0	0.250 0	2.000 0	0.062 5	0.250 0	0.062 5
5781	16.0	0.500 0	4.000 0	0.062 5	0.062 5	0.062 5
7109	8.0	0.500 0	8.000 0	2.000 0	1.000 0	0.125 0
7394	8.0	1.000 0	1.000 0	0.062 5	0.062 5	0.062 5
7764	8.0	0.500 0	2.000 0	0.500 0	0.250 0	0.062 5
7789	32.0	8.000 0	1.000 0	0.062 5	0.062 5	0.062 5
7906	16.0	0.500 0	8.000 0	1.000 0	1.000 0	0.062 5
8026	8.0	0.250 0	4.000 0	0.062 5	0.062 5	0.062 5
8061	16.0	0.250 0	1.000 0	0.500 0	0.250 0	0.062 5
G4	32.0	0.500 0	8.000 0	1.000 0	2.000 0	1.000 0
G5	32.0	4.000 0	2.000 0	2.000 0	2.000 0	0.500 0
G6	8.0	4.000 0	2.000 0	0.062 5	0.062 5	0.062 5
G8	16.0	1.000 0	8.000 0	0.062 5	0.062 5	0.062 5
G9	8.0	0.500 0	2.000 0	1.000 0	1.000 0	0.125 0
G10	32.0	8.000 0	8.000 0	1.000 0	4.000 0	1.000 0
G11	16.0	8.000 0	4.000 0	0.250 0	0.500 0	0.125 0
G12	8.0	1.000 0	4.000 0	0.062 5	0.062 5	0.062 5
Z1	8.0	1.000 0	1.000 0	0.250 0	0.250 0	0.062 5
Z2	8.0	0.500 0	2.000 0	0.500 0	0.500 0	0.062 5
Z3	8.0	4.000 0	4.000 0	1.000 0	0.250 0	0.062 5
MIC: 最低抑菌浓度; TBZ: 噻苯达唑; AMB: 两性霉素B; FLU: 氟康唑; ITR: 伊曲康唑; POS: 泊沙康唑; VOR: 伏立康唑。

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表 2 TBZ分别联合5种抗真菌药物对新生隐球菌的体外抑菌效果

菌株编号	TBZ联合AMB			TBZ联合FLU			TBZ联合ITR			TBZ联合POS			TBZ联合VOR
菌株编号	TBZ MIC/(μg/mL)	AMB MIC/(μg/mL)	FICI	TBZ MIC/(μg/mL)	FLU MIC/(μg/mL)	FICI	TBZ MIC/(μg/mL)	ITR MIC/(μg/mL)	FICI	TBZ MIC/(μg/mL)	POS MIC/(μg/mL)	FICI	TBZ MIC/(μg/mL)	VOR MIC/(μg/mL)	FICI
5338	8.0	0.062 5	0.75	1.0	0.500 0	0.31	0.5	0.062 5	1.03	1.0	0.062 5	0.31	0.5	0.062 5	1.03
5781	16.0	0.062 5	1.13	1.0	0.250 0	0.13	0.5	0.062 5	1.03	2.0	0.062 5	1.13	0.5	0.062 5	1.03
7109	8.0	0.062 5	1.13	8.0	0.062 5	1.01	8.0	0.062 5	1.03	1.0	0.250 0	0.38	0.5	0.125 0	1.06
7394	8.0	0.062 5	1.06	0.5	0.250 0	0.31	0.5	0.062 5	1.06	0.5	0.062 5	1.06	0.5	0.062 5	1.06
7764	8.0	0.125 0	1.25	1.0	0.250 0	0.25	1.0	0.125 0	0.38	1.0	0.125 0	0.63	0.5	0.062 5	1.06
7789	4.0	0.062 5	0.13	0.5	0.250 0	0.27	0.5	0.062 5	1.02	0.5	0.062 5	1.02	0.5	0.062 5	1.02
7906	2.0	0.062 5	0.25	16.0	0.062 5	1.01	8.0	0.250 0	0.75	8.0	0.062 5	0.56	4.0	0.062 5	1.25
8026	2.0	0.125 0	0.75	8.0	0.062 5	1.02	0.5	0.062 5	1.06	0.5	0.062 5	1.06	0.5	0.062 5	1.06
8061	0.5	0.062 5	0.28	4.0	0.500 0	0.75	1.0	0.125 0	0.31	0.5	0.125 0	0.53	0.5	0.062 5	1.03
G4	8.0	0.062 5	0.38	0.5	8.000 0	1.02	8.0	0.500 0	0.75	2.0	0.500 0	0.31	0.5	1.000 0	1.02
G5	2.0	1.000 0	0.31	4.0	2.000 0	1.13	8.0	1.000 0	0.75	0.5	1.000 0	0.52	4.0	0.250 0	0.63
G6	0.5	0.062 5	0.08	8.0	0.125 0	1.06	0.5	0.062 5	1.06	0.5	0.062 5	1.06	0.5	0.062 5	1.06
G8	8.0	0.062 5	0.56	2.0	0.125 0	0.14	0.5	0.062 5	1.03	0.5	0.062 5	1.03	0.5	0.062 5	1.03
G9	8.0	0.062 5	1.13	8.0	0.062 5	1.03	8.0	0.062 5	1.06	2.0	0.062 5	0.31	0.5	0.062 5	0.56
G10	2.0	0.125 0	0.08	2.0	4.000 0	0.56	4.0	0.250 0	0.38	1.0	0.500 0	0.16	0.5	0.125 0	0.14
G11	8.0	0.062 5	0.51	4.0	0.125 0	0.28	8.0	0.125 0	1.00	2.0	0.062 5	0.25	0.5	0.062 5	0.53
G12	8.0	0.062 5	1.06	4.0	0.125 0	0.53	0.5	0.062 5	1.06	0.5	0.062 5	1.06	0.5	0.062 5	1.06
Z1	8.0	0.062 5	1.06	1.0	0.125 0	0.25	2.0	0.062 5	0.50	2.0	0.062 5	0.50	0.5	0.062 5	1.06
Z2	8.0	0.500 0	2.00	4.0	1.000 0	1.00	8.0	0.500 0	2.00	4.0	0.125 0	0.75	0.5	0.062 5	1.06
Z3	8.0	0.062 5	1.02	8.0	1.000 0	1.25	1.0	0.250 0	0.38	4.0	0.125 0	1.00	0.5	0.062 5	1.06
TBZ: 噻苯达唑; AMB: 两性霉素B; FLU: 氟康唑; ITR: 伊曲康唑; POS: 泊沙康唑; VOR: 伏立康唑; MIC: 最低抑菌浓度; FICI: 分数抑菌浓度指数。

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