In vitro and in vivo Antibacterial Effect of Isopropoxy Benzene Guanidine Combined with Colistin Against Pasteurella multocida
[Objective]This study was aimed to investigate the antibacterial effect of isopropoxy benzene guanidine(IBG)with colistin against Pasteurella multocida(P.multocida)in vivo and in vitro,in order to provide data support for the development of effective new colistin synergists and clinical prevention and treatment of P.multocida.[Method]The minimum inhibitory concentration of IBG and colistin was determined by broth microdilution.The in vitro antibacterial activity against P.multocida was evaluated by checkerboard assays and time-kill curves,and the in vivo antibacterial effect was further evaluated by establishing a mouse lung infection model.[Result]The drug sensitivity test results showed that IBG had no antibacterial effect on P.multocida(MIC＞256 μg/mL),the MIC range of colistin on the tested P.multocida strains was 1-8 μg/mL.When IBG was combined with colistin,it could enhance the antibacterial activity of colistin(FIC was 0.094-0.313),demonstrating an excellent synergistic antibacterial effect.The time-kill curves further indicated that the combination group could significantly reduce the number of bacteria.The bactericidal effect could be achieved when colistin with sub inhibitory concentration(0.5 μg/mL)was combined with IBG.In the mouse lung infection model,the combination group could significantly or extremely significantly reduce the bacterial burden of P.multocida in lungs compared to the colistin or IBG alone group(P＜0.05 or P＜0.01).The pathological tissue sections of mouse lungs showed that the alveolar structure was normal and the alveolar cavities were clean in the combined group,which was better than IBG and colistin alone.[Conclusion]The combination of IBG and colistin could enhance the antibacterial effect of colistin against P.multocida in vivo and in vitro,and was expected to be further developed as a new antibacterial synergist.
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