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尼氯硝唑与黏菌素联合用药对黏菌素敏感和耐药的 和 的协同作用

Synergistic Activity of Niclosamide in Combination With Colistin Against Colistin-Susceptible and Colistin-Resistant and .

机构信息

Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.

Department of Medicine, University of Seville, Seville, Spain.

出版信息

Front Cell Infect Microbiol. 2018 Oct 3;8:348. doi: 10.3389/fcimb.2018.00348. eCollection 2018.

DOI:10.3389/fcimb.2018.00348
PMID:30338245
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6178895/
Abstract

Colistin is among the few antibiotics effective against multidrug-resistant and clinical isolates. However, in the last few years, colistin-resistant and strains have emerged. Therefore, combination therapies, between colistin and other old drugs, restoring the activity of colistin are required. The main objective of this study was to analyse the activity of niclosamide, an anthelmintic drug, in combination with colistin against colistin-susceptible (Col-S) and colistin-resistant (Col-R) and . The MIC were determined by microdilution assay and the time-kill curves were performed. The zeta potential of Col-S and Col-R of and in presence of niclosamide was assessed. Niclosamide in combination with colistin showed improved activity against Col-S and Col-R and . Time-killing curves showed synergic activity between niclosamide and colistin against Col-S and Col-R and , especially when niclosamide or colistin was added for second time at 4 h of the 24 h killing curve. Col-R and in presence of niclosamide exhibited a greater negative charge (-34.95 ± 0.35 mV and -38.85 ± 0.92 mV; < 0.05) than Col-R and in absence of niclosamide (-26.85 ± 3.65 mV and -35.27 ± 0.72 mV). These data suggest that niclosamide might be combined with colistin, being a potential alternative for treatment of Col-R Gram-negative bacilli infections.

摘要

黏菌素是少数几种对抗多药耐药和临床分离株有效的抗生素之一。然而,在过去的几年中,已经出现了对黏菌素耐药的菌株。因此,需要联合治疗,将黏菌素与其他旧药物结合使用,恢复黏菌素的活性。本研究的主要目的是分析驱虫药硝氯酚与黏菌素联合使用对黏菌素敏感(Col-S)和黏菌素耐药(Col-R)和 菌株的活性。通过微量稀释法测定 MIC 值,并进行时间杀伤曲线实验。评估了在硝氯酚存在下 Col-S 和 Col-R 的 和 的 ζ 电位。硝氯酚与黏菌素联合使用对 Col-S 和 Col-R 的 和 显示出改善的活性。时间杀伤曲线显示硝氯酚和黏菌素对 Col-S 和 Col-R 的 和 具有协同作用,特别是在 24 小时杀伤曲线的 4 小时时第二次加入硝氯酚或黏菌素时。与不存在硝氯酚时相比,存在硝氯酚时 Col-R 和 Col-R 的 和 表现出更大的负电荷(-34.95 ± 0.35 mV 和 -38.85 ± 0.92 mV;<0.05)。这些数据表明,硝氯酚可能与黏菌素联合使用,是治疗 Col-R 革兰氏阴性杆菌感染的潜在替代药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac1/6178895/1b0c66237043/fcimb-08-00348-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac1/6178895/c086968a513c/fcimb-08-00348-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac1/6178895/7b1f9547e5e2/fcimb-08-00348-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac1/6178895/4fadb6f44701/fcimb-08-00348-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac1/6178895/1b0c66237043/fcimb-08-00348-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac1/6178895/c086968a513c/fcimb-08-00348-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac1/6178895/7b1f9547e5e2/fcimb-08-00348-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac1/6178895/4fadb6f44701/fcimb-08-00348-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aac1/6178895/1b0c66237043/fcimb-08-00348-g0004.jpg

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