Synergistic efficacy of meropenem and rifampicin in a murine model of sepsis caused by multidrug-resistant Acinetobacter baumannii

详细信息    查看全文

• 作者：Yuan Sun¹ ; Lei Wang¹ ; Jiankang Li ; Chongbo Zhao ; Jinyi Zhao ; Meiyou Liu ; Shan Wang ; Chengtao Lu ; Gangwei Shang ; Yanyan Jia ; ^{jiayanyan-2004@hotmail.com" class="auth_mail} ; Aidong Wen ; ^{adwen-2004@hotmail.com" class="auth_mail}
• 关键词：ATCC ; The American Type Culture Collection ; CFU ; colony-forming unit ; FIC ; fractional inhibitory concentrations ; MIC ; minimum inhibitory concentration ; LPS ; lipopolysaccharide ; TNF-伪 ; tumor necrosis factor-伪 ; IL-6 ; interleukin-6
• 刊名：European Journal of Pharmacology
• 出版年：15 April, 2014
• 年：2014
• 卷：729
• 期：Complete
• 页码：116-122
• 全文大小：726 K

文摘

Multidrug-resistant Acinetobacter baumannii becomes an increasing challenge due to the overuse of antibiotics. Combination therapies are considered as effective options to overcome this matter. The present study was to investigate the synergistic activity of meropenem combined with other antibiotics in vitro and in vivo. Checkerboard assay and time-kill assay were performed to study the combination effects in vitro. For the animal model, a murine sepsis model injected with inoculums intraperitoneally was used. Susceptibility test showed that all the twelve strains in this study were resistant to most of the antibiotics except rifampicin. In combination, meropenem plus rifampicin exhibited synergistic activity against six of twelve strains. In the sepsis model, meropenem monotherapy had no therapeutic effect in this model while it can enhance the activity of rifampicin in both survival rate and bacterial clearance from blood. Moreover, combination therapy significantly reduced plasma IL-6 levels compared with rifampicin monotherapy. Pharmacokinetic analysis of rifampicin was also performed in this study. These data above showed that there was synergistic activity between meropenem and rifampicin against multidrug-resistant Acinetobacter baumannii both in vitro and for experimental model of sepsis. It suggested that combining meropenem with rifampicin may be appropriate in treating multidrug-resistant Acinetobacter baumannii infections.