The Effect Of Amoxicillin MSW On The Resistance Evolution Of Staphylococcus Aureus In Rabbits

Resistance are the result of bacterial adaptive evolution,to investigate the mutant selection window(MSW)change and the enrichment of resistant strain selection,this paper uses the research organization rabbit cage infection model of amoxicillin different dosage regimen of staphylococcus aureus and enrichment of impact resistance,at the same time,we screened and sequenced the drug-resistant bacteria genome and screened the resistance genes,and initially determined the resistance mechanism of the bacteria.The results are as follows:1 In vitro,amoxicillin was 0.25 ?g/mL of MIC for staphylococcus aureus ATCC6538,MIC99 was 0.20 ?g/mL,MPCpr was 4.00 ?g/mL,and MPC was 3.00 ?g/mL.The range of MSW is between 0.20?g/mL and 3.00 ?g/mL.2 Successful organization rabbit cage infection model is set up to 5mg/kg/12h(n=5),10mg/kg/12h(n=5),20mg/kg/l 2h(n=4),30mg/kg/12h(n=4),5mg/kg/24h(n=5),10mg/kg/24h(n=5),20mg/kg/24h(n=5),30mg/kg/24h(n=4)dose group,coxal muscle note amoxicillin injection;blank control group(n=3),sterile saline injections in the same way,for 5 consecutive times.The determination of the drug concentration and the determination of bacterial content were collected at different time points.It was concluded that under different drug administration regimens,the patients with the same interval time were given the same dosage,and the higher the dosage,the earlier the emergence of drug-resistant bacteria.In the same dosage group,the longer the interval,the earlier the resistance bacteria appeared.The drug resistance level showed cumulative growth,and with the extension of time of administration,the drug resistance level was higher.When the drug concentration was greater than that of MPC,the percentage of the drug interval was greater than 52%,which could not only produce good antibacterial activity,but also inhibit the occurrence of drug resistance.3 Using Illumina sequencing technology to complete 3 strains of genome,scanning,through the analysis of the gene annotation,GO,COG,KEGG analysis methods,such as screening and drug resistance genes associated with mecA,femA,femB and femX genes,based on resistance gene function analysis,the mechanism of drug resistance is a PBP2a protein produced by mecA gene expression,fem kind of gene regulation in the cell wall peptidoglycan synthesis.The absence of base replacement,malposition and deletion of drug resistance genes indicates that drug resistance has not occurred in the gene level,which may occur at the level of transcription or protein level,and further study is needed.Based on the above results,the changes of amoxicillin MSW can have an effect on the time and the degree of enrichment of staphylococcus aureus resistance.When the drug concentration was greater than that of MPC,the percentage of the drug interval was greater than 52%,which could not only produce good antibacterial activity,but also inhibit the occurrence of drug resistance.Through the genome sequencing of drug-resistant bacteria,the genes involved in drug resistance were mecA,femA,femB and femX.