Antibacterial effect of fusidic acid combined with baicalein on Staphylococcus aureus in vitro and in vivo
Objective To investigate the antibacterial properties of fusidic acid(FA)in combination with baicalein(BE)against 13 strains of Staphylococcus aureus(SA)both in vivo and in vitro.Methods The minimum inhibitory concentration(MIC)and fractional inhibitory concentration index(FICI)were determined using the microbroth dilution method and the micro checkerboard method.The FICI was used to evaluate the comprehensive effect,while the bactericidal effect was determined using the time-killing curve method.The mutant prevention concentration(MPC)and the mutant selective window(MSW)were determined using the agar double dilution method for the comparison of the change in mutation window of drug resistance after adminstration of FA alone and in combination with BE.In vivo experiments were conducted using a mouse model of pneumonia infected with SA,and the changes in vital signs,lung organ index,colony colonization number,and serum inflammatory factors were measured following single and combined treatment with FA and BE.Results The study found that the combination of FA and BE had a synergistic effect of 53.8％,an additive effect of 30.8％,and an irrelevant effect of 15.4％.Furthermore,the researchers observed that when FA was combined with BE at specific concentrations(1 MIC and 1/2 MIC,respectively),it had a bactericidal effect on three strains of SA(SA-ATCC29213,MRSA-ATCC43300,and MRSA-210702212)after 24 hours.The MPCs of FA for these strains ranged from 128～256 μg/mL,while the MSWs ranged from 64～256 μg/mL.However,when BE was added to the mix,the MPCs of the strains decreased to 16～32 μg/mL and the MSWs were reduced by 8～16 times,indicating that BE enhanced the antimicrobial activity of FA against these strains.The combination of FA and BE had minimal impact on the vital signs of mice with SA pneumonia.The experiment showed that the combination of FA and BE had little effect on the lung organ index as well as on the colony colonization number of SA in the lungs and serum inflammatory factors.However,the therapeutic effect on mouse pneumonia was significantly better when compared to the single-drug group.Conclusion The MSW of FA was wider when applied alone,and the MSW of FA was significantly reduced after combined with BE.FA combined with BE has a synergistic bactericidal effect,which is better than a single drug group in the treatment of SA pneumonia.
Fusidic acidBaicaleinStaphylococcus aureusResistant mutation windowMouse pneumonia model
万方数据
维普
