Synergistic Antimicrobial Effect of Isopropoxy Benzene Guanidine Combined with Colistin on Klebsiella pneumoniae in vitro
This work aimed to study the antibacterial synergistic ability and the preliminary com-bined mechanism of isopropoxy benzene guanidine(IBG)combined with colistin,and to evaluate whether IBG can act as an effective colistin synergist and enhance the anti-bacterial effect of colis-tin.The findings of this study will provide a theoretical basis for the effective treatment of multi-drug resistant bacterial infections in the clinic.This study investigated the preliminary combined mechanism and synergistic effect of IBG with colistin against Klebsiella pneumoniae using the minimal inhibitory concentration,checkerboard test,time killing curves,resistance induction and fluorescent dye test.IBG has no antimicrobial activity against K.pneumoniae alone,but has a synergistic effect against K.pneumoniae in combination with colistin and an additive effect in combination with amoxicillin.Time killing curves indicate that when the two drugs are used in combination,IBG enhances the susceptibility of K.pneumoniae to colistin,with a synergistic decrease in bacterial counts of＞2 lg(CFU·mL-1)compared to the effect of colistin alone.In the long-term induced resistance test,resistance was less likely to be induced by colistin in the combination group than in the colistin monotherapy group.The results of the synergistic mecha-nism test showed that colistin and IBG,when used in combination,can destroy the permeability of the cytoplasmic membrane,affect the potential of the cell membrane,and dissipate the proton kinetic potential energy,so that it is difficult for cell membranes to perform their normal func-tions.In this study,we found that the combination of IBG and low concentration of colistin,has good synergistic antibacterial activity against K.pneumoniae and enhances the antibacterial effect of colistin.It suggests that IBG can restore the susceptibility of multidrug resistant K.pneu-moniae to colistin,and can be used as a potential therapeutic option for the treatment of K.pneumoniae infections.
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