The In Vitro Activity By Coadministration Of Vancomycin And Moxifloxacin Against Methicillin-resistant Staphylococcus Aureus

Objective:1. Focus on the MRSA MIC distribution of vancomycin and predict the potential therapeutic efficacy by PK/PD parameters;2. To compare the inhibitory and prevent mutant effect by combination of vancomycin and moxifloxacin;3. Determine the bactericidal effect caused by different regimens of coadministration of vancomycin and moxiflxacin based on in vitro PK/PD model, and provide the research foundation for clinical use.Method:1. Collected the local clinical isolates and determine the vancomycin MIC, draw the discrete distribution and bacteria inhibition cumulative percentage curve, then predict the potential therapeutic efficacy and select the experimental strains.2. Determined the MRS A MIC of vancomycin and moxiflxacin single and combination by broth dilution method, calculate FIC and judge the interaction effect; Determine the MRS A MPC of vancomycin and moxiflxacin single and combination by agar dilution method, observed the combination effect on MSW.3. Established in vitro infusion PK/PD model of single and coadministraion, and simulated5regimens (vancomycin0.5g ql2h ivgtt1h, vancomycin1.0g q12h ivgtt1h, vancomycin0.5g ql2h ivgtt1h+moxiflxacin400mg q24h ivgtt1h, vancomycin1.0g q12h ivgtt1h+moxiflxacin400mg q24h ivgtt1h, moxiflxacin400mg q24h ivgtt1h) against3different clinical isolates, each regimen lasted7days, observed the dynamic time-bactericidal effect, evaluated the bactericidal caused by different regimens.Result:1. All MRSA collected were sensitive to vancomycin, no intermediate or resistant strains were found in this research,31strains (11.58%) were classified as high MIC (MIC>1μg·mL-1) and MIC90was2μg·mL-1.2. Combined sensitivity experiment showed the2isolates were defined as independent effect; The MSW were decreased to some extent.3. Moxiflocin has the ability of turning the inhibitory effect to bactericidal effect. The total bacteriacial effect was major depend on the moxiflocin sensitivity:for non-resistant strains, the coadministration was better than vancomycin single use, worse than moxiflocin single use; and for resistant strains, the coadministration was better than each single use.Conclusion:1. Although vancomycin maintains a high sensitivity to MRSA, the optimizing is very necessary for the percentage of MIC>1μg·mL-1strains is very high.2. Although the coadministration showed independent effect in the MIC experient, it showed good bacteriacidal effect. So it may use in the condition of vancomycin MIC>1μg·mL-1.