本文關(guān)鍵詞： 萬(wàn)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(wàn)古霉素對(duì)MRSA MIC分布情況,根據(jù)已有的PK/PD參數(shù)預(yù)測(cè)本地區(qū)治療有效性；2.研究萬(wàn)古霉素聯(lián)合莫西沙星對(duì)MRSA抑菌效應(yīng)及防耐藥突變的作用；3.通過(guò)PK/PD模型研究萬(wàn)古霉素聯(lián)合莫西沙星對(duì)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(cè)定萬(wàn)古霉素MIC,繪制離散型分布圖及累計(jì)抑菌百分曲線,評(píng)估臨床有效性,并篩選出試驗(yàn)用菌株。2.肉湯稀釋法測(cè)定萬(wàn)古霉素和莫西沙星單藥和聯(lián)合用藥對(duì)MRSA的MIC,計(jì)算FIC指數(shù)判斷其相互作用；瓊脂稀釋法測(cè)定萬(wàn)古霉素和莫西沙星單藥和聯(lián)合用藥對(duì)MRSA的MPC,觀察聯(lián)合用藥對(duì)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(wàn)古霉素0.5g q12h靜脈滴注111、萬(wàn)古霉素1.0g q12h靜脈滴注1h、萬(wàn)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(wàn)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(duì)2種不同臨床分離株的動(dòng)態(tài)時(shí)間殺菌效應(yīng),評(píng)價(jià)各方案殺菌能力。 結(jié)果：1.萬(wàn)古霉素對(duì)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M(jìn)IC值即大于1μg·mL-1的菌株共計(jì)31株(11.58%),MIC90高達(dá)2μg·mL-1。2.靜態(tài)實(shí)驗(yàn)表明萬(wàn)古霉素聯(lián)合莫西沙星對(duì)2株實(shí)驗(yàn)菌株表現(xiàn)為無(wú)關(guān)作用；能夠在一定程度上縮小實(shí)驗(yàn)菌株的MSW。3.莫西沙星可逆轉(zhuǎn)萬(wàn)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(qiáng)弱則取決于莫西沙星的敏感度：對(duì)于非耐藥菌,其作用優(yōu)于萬(wàn)古霉素單用,劣于莫西沙星單用；對(duì)于耐藥菌,其作用優(yōu)于兩藥單用。 結(jié)論：1.萬(wàn)古霉素對(duì)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(wàn)古霉素與莫西沙星在靜態(tài)抑菌實(shí)驗(yàn)中表現(xiàn)為無(wú)關(guān)作用,但其在動(dòng)態(tài)殺菌實(shí)驗(yàn)中有較好的效果,因此當(dāng)萬(wàn)古霉素MIC1μg·mL-1時(shí),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(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R969.3

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