The Study On Mergence And Accumlation Of Sensitive Acterial Resistance By Time And Concentration Dependent Antibacterials In Vitro PK/PD Model

Drug resistance, also called resistance, is the relative resistance of bacteria to antimicrobial drugs. Bacterial resistance to antimicrobial drugs has become a serious problem of global public health, it has become an important issue to science researcher that how to slow down the bacterial resistance in the actual production at present.Earlier research indicated that the emergence of drug-resistant bacteria was impacted by the concentration change and spatial distribution of antibacterial drug and changes of antibacterial drug concentration also influenced the selective accumulation of drug-resistant bacteria. Different dose regimens and pharmacokinetic characteristics are the two main factors that make the changes of drug concentration in animals. So unreasonable drug regimen is an important cause of the excessive growth of resistant bacteria.In order to clarify the function of dosing regimens on the accumulation of drug-resistance bacteria. In this study, in a vitro PK/PD model, we studied the process of emergence and accumulation of drug-resistance bacteria by time dependent amoxicillin and concentration dependent enrofloxacin with different dose regimen and pharmacokinetic characteristics, Aimed to providing the basic data and ideas for dose regimen of Antibacterial drugs.The results showed that MIC99of enrofloxacin for Escherichia coli was0.015μ g/mL, MPC was O.1μg/mL. MIC99of Amoxicillin for Staphylococcus aureus was O.1μg/mL, MPC was0.35μg/mL.In vitro model, dose regimen of enrofloxacin for Escherichia coli and dose regimen of amoxicillin for Staphylococcus, Results show that if all bacteria were not killed by those drugs, the resistant bacteria would emerge earlier and the resistant strength would increase higher with higher dosing under the same dosing interval and rate of elimination, and so did it with greater rate of elimination under the same dosing interval and dosing. The accumulative level of resistant bacteria increased as time went by. The strength of resistance came stronger with the time extension. If the drugs concentration was up to a certain level, all the bacteria would be killed. And even the drug concentration increased, it would not accelerate the death of bacteria.Analysis suggests that dosing regimen and pharmacokinetic characteristics can impact the rate of bacterial resistance,and put up the regularity of scalariform enhanced.so it has some regularity for drug resistance after using of antibacterial drugs. According to the results and the analysis of existing literature, regular mutation of resistant gene leads to changes about the mergence and strength of drug resistance.The reason needs more studies and evidences.