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目的:建立体外药效学模型,研究盐酸莫西沙星抑制金黄色葡萄球菌耐药突变体选择的体外PK/PD参数。方法:用琼脂平皿二倍稀释法测定金黄色葡萄球菌102526及105006的MIC、MPC,建立微生物法并测定莫西沙星药物浓度,建立体外药效学模型,用梯形法计算AUC0-t:MIC及AUC0-t:MPC。结果:微生物方法学的精密度RSD<10%,相对回收率范围为95%~105%。敏感菌102526对莫西沙星的MIC及MPC分别为0.064,0.25 mg·L-1,其主要PK/PD参数AUC0-24/MIC和AUC0-24/MPC分别为307,76.75 mg·h·L-1;Cmax/MIC及Cmax/MPC分别为63.75及15.94。中介耐药菌105006对莫西沙星的MIC和MPC分别为1,8 mg·L-1,其24 hAUC/MIC均远小于125 mg·h·L-1,Cmax/MIC亦小于10。结论:本研究成功建立了体外药效学模型,用其研究莫西沙星对金黄色葡萄球菌的体外抗菌活性,研究中测定了莫西沙星的PK/PD参数和细菌恢复生长曲线,验证了药物浓度处于耐药突变选择窗内时可选择性富集中介耐药菌的耐药突变窗理论。
OBJECTIVE: To establish an in vitro pharmacodynamic model to study the in vitro PK / PD parameters of moxifloxacin hydrochloride against Staphylococcus aureus drug-resistant mutants. Methods: MIC and MPC of Staphylococcus aureus 102526 and 105006 were determined by two-fold agar dilution. The microbiological method was established and the concentration of moxifloxacin was determined. The in vitro pharmacodynamic model was established. The AUC0-t: MIC and AUC0-t: MPC. Results: The precision of microbial method was less than 10% RSD, and the relative recovery ranged from 95% to 105%. The MIC and MPC of the susceptible strain 102526 to moxifloxacin were 0.064 and 0.25 mg · L -1, respectively. The main PK / PD parameters AUC0-24 / MIC and AUC0-24 / MPC were 307 and 76.75 mg · h · L- 1; Cmax / MIC and Cmax / MPC were 63.75 and 15.94, respectively. Median drug-resistant bacteria 105006 against moxifloxacin MIC and MPC were 1,8 mg · L-1, 24 h AUC / MIC were far less than 125 mg · h · L -1, Cmax / MIC also less than 10. Conclusion: The in vitro pharmacodynamic model was successfully established in this study to study the in vitro antibacterial activity of moxifloxacin against Staphylococcus aureus. The PK / PD parameters and the growth recovery curve of moxifloxacin were determined in the study. Concentration in the drug-resistant mutation window can be selectively enriched drug-resistant mutant mutants window theory.