本文關(guān)鍵詞： 萬古霉素 莫西沙星 耐甲氧西林金黃色葡萄球菌 體外PK/PD模型　出處：《中南大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的：1.研究萬古霉素對MRSA MIC分布情況,根據(jù)已有的PK/PD參數(shù)預(yù)測本地區(qū)治療有效性；2.研究萬古霉素聯(lián)合莫西沙星對MRSA抑菌效應(yīng)及防耐藥突變的作用；3.通過PK/PD模型研究萬古霉素聯(lián)合莫西沙星對MRSA殺菌效應(yīng)的影響,為臨床合理用藥提供研究基礎(chǔ)。 方法：1.收集臨床分離株并測定萬古霉素MIC,繪制離散型分布圖及累計抑菌百分曲線,評估臨床有效性,并篩選出試驗用菌株。2.肉湯稀釋法測定萬古霉素和莫西沙星單藥和聯(lián)合用藥對MRSA的MIC,計算FIC指數(shù)判斷其相互作用；瓊脂稀釋法測定萬古霉素和莫西沙星單藥和聯(lián)合用藥對MRSA的MPC,觀察聯(lián)合用藥對MSW的影響。3.建立單藥和聯(lián)合用藥的體外靜脈滴注PK/PD模型,并使用該模型模擬5種不同給藥方案(萬古霉素0.5g q12h靜脈滴注111、萬古霉素1.0g q12h靜脈滴注1h、萬古霉素0.5g q12h靜脈滴注111聯(lián)合莫西沙星400mg q24h靜脈滴注1h、萬古霉素1.0g q12h靜脈滴注111聯(lián)合莫西沙星400mg q24h靜脈滴注1h、莫西沙星400mg q24h靜脈滴注1h)連續(xù)給藥7天對2種不同臨床分離株的動態(tài)時間殺菌效應(yīng),評價各方案殺菌能力。 結(jié)果：1.萬古霉素對臨床分離268株MRSA均保持100%的敏感性,并未發(fā)現(xiàn)中介及耐藥菌株,高MIC值即大于1μg·mL-1的菌株共計31株(11.58%),MIC90高達2μg·mL-1。2.靜態(tài)實驗表明萬古霉素聯(lián)合莫西沙星對2株實驗菌株表現(xiàn)為無關(guān)作用；能夠在一定程度上縮小實驗菌株的MSW。3.莫西沙星可逆轉(zhuǎn)萬古霉素的后期抑菌作用,使之轉(zhuǎn)變?yōu)闅⒕饔�。而總體殺菌效應(yīng)的強弱則取決于莫西沙星的敏感度：對于非耐藥菌,其作用優(yōu)于萬古霉素單用,劣于莫西沙星單用；對于耐藥菌,其作用優(yōu)于兩藥單用。 結(jié)論：1.萬古霉素對MRSA仍保有較高的敏感性,但介于MIC1μg·mL-1的菌株比例較大,給藥方案的優(yōu)化仍然是必要的。2.雖然萬古霉素與莫西沙星在靜態(tài)抑菌實驗中表現(xiàn)為無關(guān)作用,但其在動態(tài)殺菌實驗中有較好的效果,因此當萬古霉素MIC1μg·mL-1時,可考慮與莫西沙星聯(lián)合應(yīng)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.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R969.3

【參考文獻】

相關(guān)期刊論文 前7條

1 鄭波;呂媛;;Mohnarin 2009年度報告:革蘭陽性菌耐藥監(jiān)測[J];中國臨床藥理學(xué)雜志;2011年05期

2 徐修禮;胡曉衛(wèi);孫怡群;樊新;程曉東;;萬古霉素和左氧氟沙星對金黃色葡萄球菌的體外聯(lián)合抗菌活性研究[J];中國藥物與臨床;2007年07期

3 丁俊杰;焦正;王藝;;基于D最優(yōu)設(shè)計的最大后驗貝葉斯法估算個體藥動學(xué)參數(shù)[J];藥學(xué)學(xué)報;2011年12期

4 肖永紅;王進;趙彩云;高磊;鄭波;薛峰;李湘艷;郝鳳蘭;代表Mohnarin協(xié)作組;;2006-2007年Mohnarin細菌耐藥監(jiān)測[J];中華醫(yī)院感染學(xué)雜志;2008年08期

5 肖永紅;沈萍;魏澤慶;陳云波;孔海深;楊青;張偉麗;陳曉;李蘭娟;;Mohnarin 2010年度全國細菌耐藥監(jiān)測[J];中華醫(yī)院感染學(xué)雜志;2011年23期

6 張光艷;卓超;黎曉強;;2007—2009年金黃色葡萄球菌對萬古霉素MIC值變化的研究[J];中國抗生素雜志;2011年09期

7 喻婷;梅清;朱玉林;程君;葉英;李家斌;;萬古霉素聯(lián)合用藥降低對金黃色葡萄球菌防耐藥突變濃度的研究[J];中國抗生素雜志;2011年11期

，

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