| It was a challenge to dicide a dosing regimen because of the complex relationship among bactera,host and the concentration of drug in the body of host. It made something unreasonable to decide a dosing regimen only on the basis of parameters of pharmacokinetics and pharmacodynamics.The mutation selection windows provided a new way to prevent or slow down the emergence of drug-resistance bacteria,and a new requirement to the decision of dosing regimen of antimicrobial and the new drug research and development.MSW wasn’t complete to guide the decision of a dosing regimen for the study for it was new,and there were to much gaps.So the MSWs of several frequently-used aveterinary drugs on A. hydrophila were determined by in vitro method.And how the drug-resistance bacteria emerged and accumlated in vitro model was studied,to provide information and thinking to decide a reasonable dosing regimen.The result shows that the MIC99S of kanamycin for A. hydrophila were2.000.1.200.1.200.1.200.1.600μ g/mL,MPCs were16.000.4.800,9.600.25.600.9.600μg/mL;the MIC99S of enrofloxacin for A. hydrophila were0.125.0.150.0.150.0.100.0.100μg/mL,MPCs were1.600.0.800.1.600.1.200.1.800μg/mL;the MIC99S of florfenicol for A hydrophila were8.000.19.200.9.600.9.600.9.600μ g/mL,MPCs were128μ g/mL.In the vitro model,bacteria were killed under a dosing regimen,or the drug-resistance bacteria emerged.The drug-resistance bacteria emerged earlier with higher dosing under the direction of same dosing interval and rate of elimination,and so did it with greater rate of elimination under the direction of same dosing interval and dosing, and so did it with longer dosing interval under the direction of same rate of elimination and dosing.The strength of resistance accumulative increased as time went by.The strength of resistance came stronger with the time extension. After the analysis of the correlation between pharmacokinetic parameters and AUBKCs,the T>MIC wasn’t very well correlated to AUBKC;but Cmax/MIC and AUC24/MIC were with no difference by logarithm.Analysis suggests that the emergence and accumlation of drug-resistance bacteria is affected by dosing regimen and pharmacokinetic characteristics.It may involve the evolutionary mechanism of bacteria,and how it works is still need more research to do. |
