院內(nèi)呼吸道MRSA的耐藥性與萬古霉素單用及聯(lián)合痰熱清的MPC研究
本文選題:萬古霉素 + 痰熱清; 參考:《河南中醫(yī)藥大學(xué)》2016年碩士論文
【摘要】:目的:耐甲氧西林金黃色葡萄球菌(methicillin-resistant staphylococcus aureus,MRSA)導(dǎo)致醫(yī)院內(nèi)的感染數(shù)量逐漸增加,目前成為了一個(gè)全球嚴(yán)重性的問題。因此檢測MRSA對(duì)藥物的敏感性,動(dòng)態(tài)觀察耐藥變遷趨勢及流行現(xiàn)狀,顯得尤為重要。本研究旨在通過測定萬古霉素(vancomycin,VAN)、及聯(lián)合痰熱清對(duì)MRSA質(zhì)控菌株ATCC43300及臨床分離菌株的最低抑菌濃度(minimum inhibitory concentration,MIC)、防耐藥突變濃度(mutant prevention concentration,MPC),以靜態(tài)方法評(píng)價(jià)VAN聯(lián)合痰熱清的抑菌效果及對(duì)防耐藥突變能力做出客觀理性的評(píng)價(jià),進(jìn)而探討中西藥聯(lián)合使用對(duì)MRSA治療的影響。方法:選取我院2014.01-2014.12年住院患者分離的MRSA菌株為研究對(duì)象,采用2014年臨床實(shí)驗(yàn)室標(biāo)準(zhǔn)化協(xié)會(huì)(clinical and laboratory standards institute,CLSI)推薦方法對(duì)分純的細(xì)菌進(jìn)行鑒定及分析,測定MIC并計(jì)算抗菌藥物的耐藥率;從呼吸道標(biāo)本分離MRSA中篩取無重復(fù)的確診MRSA肺炎的菌株30株,采用瓊脂二倍稀釋法測得痰熱清、VAN及聯(lián)合用藥對(duì)質(zhì)控MRSA菌株ATCC43300及臨床分離的MRSA菌株的MIC、MPC。計(jì)算選擇指數(shù)(selectivity index,SI)及防耐藥突變濃度窗(Mutant selection window,MSW),協(xié)同抑菌指數(shù)(fraction inhibitory concentration index,FICI),探討單用VAN及聯(lián)合痰熱清的對(duì)MRSA防止耐藥突變濃度的影響,判斷藥物聯(lián)合應(yīng)用后效果。結(jié)果:河南省人民醫(yī)院住院患者呼吸道分離的MRSA檢出率為69.53%;對(duì)抗菌藥物的耐藥性分析:分別為環(huán)丙沙星(88.8%)、妥布霉素(77.5%)、紅霉素(75.3%)、慶大霉素(70.8%)、阿奇霉素(62.5%)、阿米卡星(59.6%)、克林霉素(59.6%)、復(fù)方磺胺甲惡唑(6.7%);對(duì)VAN、替考拉寧及利奈唑胺均無耐藥;VAN單獨(dú)用藥對(duì)30株臨床分離的MIC為0.50-1.00μg/ml之間,與痰熱清聯(lián)合后VAN的MIC值0.12-0.50μg/ml之間,MIC聯(lián)用最低比MIC單用下降最高能達(dá)到4倍,較前下降的總共28株(93.33%),無變化的2株(6.66%);VAN單藥對(duì)30株臨床分離的MPC值為2.00-16.00μg/ml,與痰熱清聯(lián)合時(shí)VAN的MPC值1.00-4.00μg/ml,MPC聯(lián)用最低較MPC單用下降16倍,較前下降的總共30株(100%);VAN單藥對(duì)30株臨床分離的MSW上限為0.50~16.00μg/ml,下限為0.50~2.00μg/ml;與痰熱清聯(lián)合時(shí)VAN的MSW范圍上限為0.25~4.00μg/ml,下限為0.12~1.00μg/ml,MSW較前下降的總共30株(100%),甚至關(guān)閉MSW;VAN單藥對(duì)30株臨床分離菌株的SI為4-32,聯(lián)合用藥時(shí)VAN對(duì)30株臨床分離菌株的SI范圍為2-16之間,SI降低的22株(73.33%),無變化的7株(23.33%),增高1株(3.33%);痰熱清單用對(duì)30株臨床分離菌株MRSA的MIC為16-125μl/ml、MPC為64-500μl/ml,聯(lián)合VAN的痰熱清MIC為4-32μl/ml、MPC16-250μl/ml;VAN聯(lián)合痰熱清的FICI在0-0.5之間,協(xié)同作用總共5株(16.66%),0.5-1之間,相加作用總共23株(76.66%),1-2之間無關(guān)作用,總共2株(6.66%)。結(jié)論:1、本研究中呼吸道MRSA檢出率為69.53%,與國內(nèi)其他研究存在一定差異,未發(fā)現(xiàn)萬古霉素中介金黃色葡萄球菌(vancomycin intermediate staphylococcus aureus,VISA)、萬古霉素耐藥金黃色葡萄球菌(vancomycin resistant staphylococcus aureus,VRSA)、異質(zhì)性萬古霉素中介金黃色葡萄球菌(heterogeneous vancomycin-resistant staphylococcus aureus,h VISR)菌株、及替考拉寧、利奈唑胺耐藥的MRSA菌株;2、中成藥制劑痰熱清對(duì)體外分離的MRSA菌株有不同程度的抑制作用;痰熱清與VAN聯(lián)合應(yīng)用時(shí)降低MPC,縮窄MSW,最大幅度時(shí)能關(guān)閉MSW,提高了VAN對(duì)體外MRSA的敏感性;有望給臨床中西藥聯(lián)合治療MRSA提供實(shí)驗(yàn)依據(jù)。
[Abstract]:Objective: the number of methicillin-resistant Staphylococcus aureus (MRSA) resistant to methicillin-resistant Staphylococcus aureus (MRSA) has led to a gradual increase in the number of infections in the hospital, and it has become a global serious problem. Therefore, it is particularly important to detect the sensitivity of MRSA to the drug and to observe the trend and current status of drug resistance. The minimum inhibitory concentration (minimum inhibitory concentration, MIC) of MRSA quality control strain ATCC43300 and clinical isolates by the determination of vancomycin (vancomycin, VAN) and combined Tanreqing, and the anti drug resistance mutation concentration (mutant prevention concentration, MPC) were used to evaluate the bacteriostasis effect of combined Tanreqing and anti drug resistance by static method. The mutation ability makes an objective rational evaluation, and then discusses the effect of the combination of Chinese and Western Medicine on the treatment of MRSA. Methods: select the isolated MRSA strain of the hospitalized patients in 2014.01-2014.12 of our hospital as the research object, and use the recommended method of the 2014 clinical laboratory standardization association (clinical and Laboratory Standards Institute, CLSI) to divide and pure. The bacteria were identified and analyzed, MIC was measured and the resistance rate of antibiotics was calculated; 30 strains of MRSA pneumonia were screened from the respiratory tract specimens from MRSA, and the two times dilution method of agar was used to obtain the Tanreqing, VAN and combined use of the MIC of the MRSA strain, which were separated from the quality control MRSA strain ATCC43300 and the bed, and the MPC. calculation index (s). Electivity index, SI) and anti drug resistant mutation concentration window (Mutant selection window, MSW), synergistic bacteriostasis index (fraction inhibitory concentration index, FICI), explore the effect of single use and combined Tanreqing on the prevention of drug resistance mutation, and determine the effect after the combined application of drugs. Results: hospitalized patients' respiration in Henan Province People's Hospital The detection rate of MRSA was 69.53%, and the antibiotic resistance was analyzed: ciprofloxacin (88.8%), tobramycin (77.5%), erythromycin (75.3%), gentamicin (70.8%), azithromycin (62.5%), Amikacin (59.6%), clindamycin (59.6%), compound sulfamethoxazole (6.7%), and VAN, teicoplanin and linezolid, and VAN alone The clinical separation of 30 strains of MIC was 0.50-1.00 mu g/ml, and the MIC value of VAN with tanreone combined with 0.12-0.50 mu g/ml, and MIC combined with the lowest ratio of MIC and single use decreased to the highest level of 4 times, compared with 28 strains (93.33%) and no change of 2 strains (6.66%). The MPC value of VAN single drug for 30 clinical isolates was 2.00-16.00 mu, combined with Tanreqing. The MPC value of the time VAN was 1.00-4.00 mu g/ml, and the MPC combined with the lowest MPC single use decreased 16 times, compared with the previous decrease (100%); the MSW upper limit of the 30 clinical isolates of VAN was 0.50~16.00 micron g/ml, the lower limit was 0.50~2.00 micron, and the upper limit of the range was 0.25. A total of 30 (100%), even closed MSW; VAN single drug to 30 strains of clinical isolates of SI 4-32, VAN against 30 clinical isolates of SI range of 2-16, SI decreased 22 (73.33%), no change 7 (23.33%), increased 1 (3.33%), and Tanreqing single used for 30 strain clinical isolates MRSA MIC to be 16-125 l/ml, MPC for l/ l/ l/ Ml, the Tanreqing MIC of the combined VAN was 4-32 mu l/ml, MPC16-250 mu l/ml; VAN combined with the phlegm of the phlegm of FICI in 0-0.5, a total of 5 strains (16.66%), 0.5-1, and addition effect in total (76.66%), 1-2 independent effect, 2 strains (6.66%). Conclusion: 1. The MRSA detection rate of respiratory tract in this study is 69.53%, and there is a certain number of other studies in China. Differences were found in vancomycin mediated Staphylococcus aureus (vancomycin intermediate Staphylococcus aureus, VISA), vancomycin resistant Staphylococcus aureus (vancomycin resistant Staphylococcus aureus, VRSA), and heterogeneous vancomycin mediated Staphylococcus aureus (heterogeneous vancomycin-resistant) EUS, H VISR) strains, and teicoin and linezolid resistant MRSA strain; 2, Chinese patent medicine Tanreqing has different inhibitory effects on the isolated MRSA strain in vitro; Tanreqing and VAN combined with VAN to reduce MPC, narrow MSW, when maximum amplitude can close MSW, improve the sensitivity of VAN to in vitro MRSA; it is expected to be combined with clinical and Western medicine. The treatment of MRSA provides experimental basis.
【學(xué)位授予單位】:河南中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2016
【分類號(hào)】:R446.5
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