万古霉素联合莫西沙星对耐甲氧西林金黄色葡萄球菌的体外抗菌活性研究

发布时间：2018-02-16 02:18

本文关键词： 万古霉素莫西沙星耐甲氧西林金黄色葡萄球菌体外PK/PD模型　出处：《中南大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的：1.研究万古霉素对MRSA MIC分布情况,根据已有的PK/PD参数预测本地区治疗有效性；2.研究万古霉素联合莫西沙星对MRSA抑菌效应及防耐药突变的作用；3.通过PK/PD模型研究万古霉素联合莫西沙星对MRSA杀菌效应的影响,为临床合理用药提供研究基础。方法：1.收集临床分离株并测定万古霉素MIC,绘制离散型分布图及累计抑菌百分曲线,评估临床有效性,并筛选出试验用菌株。2.肉汤稀释法测定万古霉素和莫西沙星单药和联合用药对MRSA的MIC,计算FIC指数判断其相互作用；琼脂稀释法测定万古霉素和莫西沙星单药和联合用药对MRSA的MPC,观察联合用药对MSW的影响。3.建立单药和联合用药的体外静脉滴注PK/PD模型,并使用该模型模拟5种不同给药方案(万古霉素0.5g q12h静脉滴注111、万古霉素1.0g q12h静脉滴注1h、万古霉素0.5g q12h静脉滴注111联合莫西沙星400mg q24h静脉滴注1h、万古霉素1.0g q12h静脉滴注111联合莫西沙星400mg q24h静脉滴注1h、莫西沙星400mg q24h静脉滴注1h)连续给药7天对2种不同临床分离株的动态时间杀菌效应,评价各方案杀菌能力。结果：1.万古霉素对临床分离268株MRSA均保持100%的敏感性,并未发现中介及耐药菌株,高MIC值即大于1μg·mL-1的菌株共计31株(11.58%),MIC90高达2μg·mL-1。2.静态实验表明万古霉素联合莫西沙星对2株实验菌株表现为无关作用；能够在一定程度上缩小实验菌株的MSW。3.莫西沙星可逆转万古霉素的后期抑菌作用,使之转变为杀菌作用。而总体杀菌效应的强弱则取决于莫西沙星的敏感度：对于非耐药菌,其作用优于万古霉素单用,劣于莫西沙星单用；对于耐药菌,其作用优于两药单用。结论：1.万古霉素对MRSA仍保有较高的敏感性,但介于MIC1μg·mL-1的菌株比例较大,给药方案的优化仍然是必要的。2.虽然万古霉素与莫西沙星在静态抑菌实验中表现为无关作用,但其在动态杀菌实验中有较好的效果,因此当万古霉素MIC1μg·mL-1时,可考虑与莫西沙星联合应用。
[Abstract]:Objective: 1. To study the distribution of vancomycin on MRSA MIC, Prediction of efficacy of vancomycin combined with moxifloxacin on MRSA and antimicrobial resistance according to the available PK/PD parameters 2.The effects of vancomycin combined with moxifloxacin on the bactericidal effect of MRSA were studied by using PK/PD model, and the effect of vancomycin combined with moxifloxacin on the bactericidal effect of MRSA was studied. To provide the basis for clinical rational use of drugs. Methods: 1. Clinical isolates were collected, vancomycin MICs were determined, discrete distribution maps and cumulative inhibitory percent curves were drawn to evaluate the clinical effectiveness. The strain of vancomycin and moxifloxacin against MRSA was determined by broth dilution method, and the interaction between vancomycin and moxifloxacin was evaluated by FIC index. MPCs of vancomycin and moxifloxacin on MRSA were determined by Agar dilution method, and the effects of combined drug on MSW were observed. The model was used to simulate five different administration schemes: vancomycin 0.5g q12h, vancomycin 1.0g q12h, vancomycin 0.5g q12h, vancomycin 0.5g q12h 111, moxifloxacin 400mg q24h, vancomycin 1.0g q12h, vancomycin 1.0g q12h. The dynamic time bactericidal effects of intravenous infusion of 111 and moxifloxacin 400mg / q24h and moxifloxacin 400mg / q24h respectively for 7 days on two different clinical isolates were observed. To evaluate the germicidal capacity of each program. Results the sensitivity of vancomycin to clinical isolates of MRSA was 100%, and no intermediate or resistant strains were found. A total of 31 strains with a MIC value of more than 1 渭 g 路mL-1 were found to be as high as 2 渭 g 路mL ~ (-1) 路m ~ (-1). The static test showed that vancomycin combined with moxifloxacin had no effect on the two experimental strains. MSW.3. moxifloxacin can reverse the late bacteriostatic effect of vancomycin and turn it into bactericidal effect. The overall bactericidal effect depends on the sensitivity of moxifloxacin: for non-drug-resistant bacteria, Its effect was better than that of vancomycin alone and better than that of moxifloxacin alone. Conclusion: (1) vancomycin still has a high sensitivity to MRSA, but the proportion of MIC1 渭 g 路mL-1 strain is large, and the optimization of drug administration is still necessary. Although vancomycin and moxifloxacin have no effect on static bacteriostatic test, But it has a good effect in the dynamic bactericidal test, so when vancomycin MIC1 渭 g 路mL-1, it can be combined with moxifloxacin.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R969.3

【参考文献】