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亚胺培南/利福平联合用药对鲍曼不动杆菌临床分离株在浮游菌和生物被膜培养状态下的抗菌活性。

Antimicrobial activity of the imipenem/rifampicin combination against clinical isolates of Acinetobacter baumannii grown in planktonic and biofilm cultures.

作者信息

Wang Yang, Bao Wanguo, Guo Na, Chen Haiying, Cheng Wei, Jin Kunqi, Shen Fengge, Xu Jiancheng, Zhang Qiaoli, Wang Chao, An Yanan, Zhang Kaiyu, Wang Feng, Yu Lu

机构信息

Department of Infectious Diseases, First Hospital of Jilin University, Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, 130062, China.

出版信息

World J Microbiol Biotechnol. 2014 Dec;30(12):3015-25. doi: 10.1007/s11274-014-1728-7. Epub 2014 Oct 9.

Abstract

To investigate the antimicrobial activity of imipenem and rifampicin alone and in combination against clinical isolates of Acinetobacter baumannii grown in planktonic and biofilm cultures. Minimum inhibitory concentrations were determined for each isolate grown in suspension and in biofilm using a microbroth dilution method. Chequerboard assays and the agar disk diffusion assay were used to determine synergistic, indifferent or antagonistic interactions between imipenem and rifampicin. We used the tissue culture plate method for A. baumannii biofilm formation to measure the percentage of biofilm inhibition and the amount of extracellular DNA after the treatment. To understand the synergistic mechanisms, we conducted hydroxyl radical formation assays. The results were verified by confocal laser scanning microscopy. Imipenem and rifampicin showed effective antimicrobial activity against suspensions and biofilm cultures of A. baumannii, respectively. Synergistic antimicrobial effects between imipenem and rifampicin were observed in 13 and 17 of the 20 clinical isolates when in suspension and in biofilms, respectively. Imipenem and rifampicin alone and in combination generated hydroxyl radicals, which are highly reactive oxygen forms and the major components of bactericidal agents. Furthermore, treatment with imipenem and rifampicin individually or in combination has obvious antibiofilm effects. The synergistic activity of imipenem and rifampicin against clinical isolates of A. baumannii (in suspension and in biofilms) was observed in vitro. Therefore, we conclude that imipenem combined with rifampicin has the potential to be used as a combinatorial therapy for the treatment of infectious diseases caused by A. baumannii.

摘要

为研究亚胺培南和利福平单独及联合使用对浮游和生物膜培养的鲍曼不动杆菌临床分离株的抗菌活性。采用微量肉汤稀释法测定每种在悬浮液和生物膜中生长的分离株的最低抑菌浓度。采用棋盘法和琼脂纸片扩散法测定亚胺培南和利福平之间的协同、无关或拮抗相互作用。我们使用组织培养板法进行鲍曼不动杆菌生物膜形成实验,以测量处理后生物膜抑制百分比和细胞外DNA量。为了解协同机制,我们进行了羟基自由基形成实验。结果通过共聚焦激光扫描显微镜进行验证。亚胺培南和利福平分别对鲍曼不动杆菌的悬浮液和生物膜培养物显示出有效的抗菌活性。在20株临床分离株中,分别有13株和17株在悬浮液和生物膜中观察到亚胺培南和利福平之间的协同抗菌作用。亚胺培南和利福平单独及联合使用均能产生羟基自由基,羟基自由基是高活性氧形式,也是杀菌剂的主要成分。此外,亚胺培南和利福平单独或联合处理均具有明显的抗生物膜作用。在体外观察到亚胺培南和利福平对鲍曼不动杆菌临床分离株(悬浮液和生物膜中)的协同活性。因此,我们得出结论,亚胺培南联合利福平有潜力作为治疗鲍曼不动杆菌引起的传染病的联合疗法。

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