Authors: Yang Wang Wanguo Bao Na Guo Haiying Chen Wei Cheng Kunqi Jin Fengge Shen Jiancheng Xu Qiaoli Zhang Chao Wang Yanan An Kaiyu Zhang Feng Wang Lu Yu
Publish Date: 2014/10/09
Volume: 30, Issue: 12, Pages: 3015-3025
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 baumanniiFinancial support for this work came from the National Nature Science Foundation of China Nos 31172364 31271951 31000822 Program for New Century Excellent Talents in University NCET090434 NCET130245 Fundamental Research Program of Shen Zhen JCYJ20130401172016183 JCYJ20120616142424467 and Shenzhen Promotion Plan Basic Research Laboratory in 2012 ZDSY20120616141302982
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