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抗真菌药物、溶菌酶和人抗菌肽 LL-37 对高生物膜生成临床分离株的影响。

Effect of antifungal agents, lysozyme and human antimicrobial peptide LL-37 on clinical isolates with high biofilm production.

机构信息

Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao Sung District, Kaohsiung 833, Taiwan, ROC.

Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao Sung District, Kaohsiung 833, Taiwan, ROC.

出版信息

J Med Microbiol. 2021 Feb;70(2). doi: 10.1099/jmm.0.001283.

Abstract

species can form biofilms on tissues and medical devices, making them less susceptible to antifungal agents. Antifungal combination may be an effective strategy to fight against biofilm. In this study, we investigated the activity of fluconazole, caspofungin and amphotericin B, alone and in combination, against 17 clinical and 6 isolates with high biofilm formation. We also tested LL-37 and lysozyme for anti-biofilm activity against a selected isolate. biofilms were prepared using the 96-well plate-based method. The minimum biofilm eradication concentrations were determined for single and combined antifungal drugs. The activity of LL-37 and lysozyme was determined by visual reading for planktonic cells and using the XTT assay for biofilms. Under biofilm conditions, fluconazole plus caspofungin showed synergistic effects against 60.9% (14 of 23) of the tested isolates, including 70.6% of [fractional inhibitory concentration index (FICI), 0.26-1.03] and 33.3% of (FICI, 0.04-2.03) isolates. Using this combination, no antagonism was observed. Amphotericin B plus caspofungin showed no effects against 78.3% (18 of 23) of the tested isolates. Amphotericin B plus fluconazole showed no effects against 65.2% (15 of 23) of the tested isolates and may have led to antagonism against 2 . and 2 isolates. LL-37 and lysozyme had no effect on biofilms of the selected isolate. We found that fluconazole plus caspofungin led to a synergistic effect against and biofilms. The efficacy of the antifungal combination therapies of the proposed schemes against biofilm-associated infections requires careful and constant evaluation.

摘要

物种可以在组织和医疗器械上形成生物膜,从而使它们对抗真菌药物的敏感性降低。抗真菌药物联合治疗可能是对抗生物膜的有效策略。在这项研究中,我们研究了氟康唑、卡泊芬净和两性霉素 B 单独和联合使用对 17 株临床分离株和 6 株高生物膜形成株的活性。我们还测试了 LL-37 和溶菌酶对选定分离株的抗生物膜活性。生物膜是通过 96 孔板法制备的。确定了单药和联合抗真菌药物的最低生物膜清除浓度。通过对浮游细胞进行目测和 XTT 测定生物膜来测定 LL-37 和溶菌酶的活性。在生物膜条件下,氟康唑加卡泊芬净对 60.9%(23 株中的 14 株)的受试分离株表现出协同作用,包括 70.6%(FICI,0.26-1.03)和 33.3%(FICI,0.04-2.03)分离株。使用这种组合没有观察到拮抗作用。两性霉素 B 加卡泊芬净对 78.3%(23 株中的 18 株)的受试分离株没有效果。两性霉素 B 加氟康唑对 65.2%(23 株中的 15 株)的受试分离株没有效果,可能导致对 2 株和 2 株的拮抗作用。LL-37 和溶菌酶对所选 株的生物膜没有影响。我们发现氟康唑加卡泊芬净对 和 生物膜有协同作用。这些方案的抗真菌联合治疗对生物膜相关感染的疗效需要仔细和持续的评估。

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