院内呼吸道MRSA的耐药性与万古霉素单用及联合痰热清的MPC研究

发布时间：2018-06-04 09:10

本文选题：万古霉素 + 痰热清　；参考：《河南中医药大学》2016年硕士论文

【摘要】：目的:耐甲氧西林金黄色葡萄球菌(methicillin-resistant staphylococcus aureus,MRSA)导致医院内的感染数量逐渐增加,目前成为了一个全球严重性的问题。因此检测MRSA对药物的敏感性,动态观察耐药变迁趋势及流行现状,显得尤为重要。本研究旨在通过测定万古霉素(vancomycin,VAN)、及联合痰热清对MRSA质控菌株ATCC43300及临床分离菌株的最低抑菌浓度(minimum inhibitory concentration,MIC)、防耐药突变浓度(mutant prevention concentration,MPC),以静态方法评价VAN联合痰热清的抑菌效果及对防耐药突变能力做出客观理性的评价,进而探讨中西药联合使用对MRSA治疗的影响。方法:选取我院2014.01-2014.12年住院患者分离的MRSA菌株为研究对象,采用2014年临床实验室标准化协会(clinical and laboratory standards institute,CLSI)推荐方法对分纯的细菌进行鉴定及分析,测定MIC并计算抗菌药物的耐药率;从呼吸道标本分离MRSA中筛取无重复的确诊MRSA肺炎的菌株30株,采用琼脂二倍稀释法测得痰热清、VAN及联合用药对质控MRSA菌株ATCC43300及临床分离的MRSA菌株的MIC、MPC。计算选择指数(selectivity index,SI)及防耐药突变浓度窗(Mutant selection window,MSW),协同抑菌指数(fraction inhibitory concentration index,FICI),探讨单用VAN及联合痰热清的对MRSA防止耐药突变浓度的影响,判断药物联合应用后效果。结果:河南省人民医院住院患者呼吸道分离的MRSA检出率为69.53%;对抗菌药物的耐药性分析:分别为环丙沙星(88.8%)、妥布霉素(77.5%)、红霉素(75.3%)、庆大霉素(70.8%)、阿奇霉素(62.5%)、阿米卡星(59.6%)、克林霉素(59.6%)、复方磺胺甲恶唑(6.7%);对VAN、替考拉宁及利奈唑胺均无耐药;VAN单独用药对30株临床分离的MIC为0.50-1.00μg/ml之间,与痰热清联合后VAN的MIC值0.12-0.50μg/ml之间,MIC联用最低比MIC单用下降最高能达到4倍,较前下降的总共28株(93.33%),无变化的2株(6.66%);VAN单药对30株临床分离的MPC值为2.00-16.00μg/ml,与痰热清联合时VAN的MPC值1.00-4.00μg/ml,MPC联用最低较MPC单用下降16倍,较前下降的总共30株(100%);VAN单药对30株临床分离的MSW上限为0.50~16.00μg/ml,下限为0.50~2.00μg/ml;与痰热清联合时VAN的MSW范围上限为0.25~4.00μg/ml,下限为0.12~1.00μg/ml,MSW较前下降的总共30株(100%),甚至关闭MSW;VAN单药对30株临床分离菌株的SI为4-32,联合用药时VAN对30株临床分离菌株的SI范围为2-16之间,SI降低的22株(73.33%),无变化的7株(23.33%),增高1株(3.33%);痰热清单用对30株临床分离菌株MRSA的MIC为16-125μl/ml、MPC为64-500μl/ml,联合VAN的痰热清MIC为4-32μl/ml、MPC16-250μl/ml;VAN联合痰热清的FICI在0-0.5之间,协同作用总共5株(16.66%),0.5-1之间,相加作用总共23株(76.66%),1-2之间无关作用,总共2株(6.66%)。结论:1、本研究中呼吸道MRSA检出率为69.53%,与国内其他研究存在一定差异,未发现万古霉素中介金黄色葡萄球菌(vancomycin intermediate staphylococcus aureus,VISA)、万古霉素耐药金黄色葡萄球菌(vancomycin resistant staphylococcus aureus,VRSA)、异质性万古霉素中介金黄色葡萄球菌(heterogeneous vancomycin-resistant staphylococcus aureus,h VISR)菌株、及替考拉宁、利奈唑胺耐药的MRSA菌株;2、中成药制剂痰热清对体外分离的MRSA菌株有不同程度的抑制作用;痰热清与VAN联合应用时降低MPC,缩窄MSW,最大幅度时能关闭MSW,提高了VAN对体外MRSA的敏感性;有望给临床中西药联合治疗MRSA提供实验依据。
[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.
【学位授予单位】：河南中医药大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R446.5

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