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| 土槿皮乙酸与抗真菌药联用体外抗热带念珠菌活性的研究 |
| Synergistic Effect of Pseudolaric Acid B with antifungal drugs Against C.tropicalis |
| 投稿时间：2024-12-09 修订日期：2024-12-09 |
| DOI： |
| 中文关键词: 土槿皮乙酸 热带念珠菌 体外药物敏感性实验 |
| 英文关键词: Pseudolaric Acid B Candida tropicalis In vitro drug susceptibility test |
| 基金项目: |
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| 中文摘要: |
| 目的：研究土槿皮乙酸(PAB,Pseudolaric Acid B)与四种抗真菌药物(氟康唑、伏立康唑、卡泊芬净、两性霉素B)单药及联合应用对热带念珠菌的抗真菌活性。方法：采用体外肉汤微量液基稀释法测定PAB与四种抗真菌药单独应用及联合应用于对临床分离的11株热带念珠菌的最低抑菌浓度(MIC),并通过计算最低抑菌浓度值(FICI)判断两药联合抑菌效应。进一步应用时间-杀菌曲线动态监测PAB单药不同浓度及呈协同作用的用药组合的体外抑菌效果。结果: PAB单药对本实验纳入的11株临床分离热带念珠菌均具有良好抑菌效果, MIC值范围为4~8μg/mL,MBC值为8 ug/mL。PAB与4种抗真菌药物联用对热带念珠菌的抗菌活性存在差异, 11株(100％)对伏立康唑敏感菌株均呈现PAB协同抑菌的作用,其FICI范围为0.1875 ~0.5,与单独用药相比,MIC值降低了2~8倍。PAB与VRC联合作用于热带念珠菌ATCC01463的时间-杀菌曲线在48h时,联用组(VRC+PAB)的OD值比单独使用VRC组降低了2倍以上,进一步表明VRC和与PAB联用对热带念珠菌具有协同抗菌作用；11株对氟康唑敏感菌株中,PAB与氟康唑联用对4株(36.3％)呈协同作用,余7株(63.6％)均呈无关作用,其FICI范围为0.375 ~0.75；两性霉素B与PAB联用对11株(100％)热带念珠菌的作用方式均表现为无关作用,FICI范围为1~2；8株对卡泊芬净敏感菌株中,卡泊芬净与PAB联用均表现为无关作用,3株对卡泊芬净耐药菌株中,仅有1株表现为协同作用,其FICI值为0.5,余耐药菌株均表现为无关作用。结论： PAB单药作用于热带念珠菌不仅有良好的抑菌活性,且表现出良好的杀菌作用。PAB与伏立康唑联用对热带念珠菌敏感株有较好的协同抗菌作用。 |
| 英文摘要: |
| ABSTRACT Objective: Investigate the antifungal activity of Pseudolaric Acid B (PAB) as a single agent and in combination with four antifungal drugs (fluconazole, voriconazole, caspofungin, amphotericin B) against Candida tropicalis. Method(s): The minimum inhibitory concentration (MIC) of PAB alone and in combination with the four antifungal drugs against 11 clinically isolated strains of Candida tropicalis was determined by the microbroth dilution method in vitro, and the combined inhibitory effect of the two drugs was judged by calculating the fractional inhibitory concentration index (FICI). Further, the in vitro antibacterial effects of PAB alone at different concentrations and the drug combinations with synergistic effects were dynamically monitored by the time-kill curve. Result(s): PAB exhibited good inhibitory effects on all 11 clinical isolates of Candida tropicalis included in this experiment, with the MIC values ranging from 4 to 8 μg/mL and the MBC value being 8 μg/mL. The antibacterial activities of the combination of PAB and the four antifungal drugs against Candida tropicalis were different. All 11 (100%) of the voriconazole-sensitive strains showed a synergistic inhibitory effect of PAB, with the FICI ranging from 0.1875 to 0.5. Compared with the monotherapy, the MIC values were reduced by 2-8 times. The time-kill curve of the combined action of PAB and VRC on Candida tropicalis ATCC01463 at 48h showed that the OD value of the combined group (VRC + PAB) was reduced by more than twice compared to the VRC group alone, further indicating that the combination of VRC and PAB has a synergistic antibacterial effect on Candida tropicalis. Among the 11 fluconazole-sensitive strains, the combination of PAB and fluconazole showed a synergistic effect on 4 strains (36.3%), and no effect on the remaining 7 strains (63.6%), with the FICI ranging from 0.375 to 0.75. The combination of amphotericin B and PAB showed no effect on the 11 (100%) Candida tropicalis strains, with the FICI ranging from 1 to 2. Among the 8 caspofungin-sensitive strains, the combination of caspofungin and PAB showed no effect. Among the 3 caspofungin-resistant strains, only 1 strain showed a synergistic effect with the FICI value of 0.5, and the remaining resistant strains showed no effect. Conclusion(s): The single use of PAB on Candida tropicalis not only possesses excellent inhibitory activity but also exhibits favorable bactericidal effects. The combination of PAB and voriconazole has a relatively good synergistic antibacterial effect on sensitive strains of Candida tropicalis. |
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