氟喹诺酮类药物与多西环素联用对牛源大肠杆菌的抑菌效果的应用

发布时间：2018-03-07 11:37

本文选题：牛源大肠杆菌　切入点：氟喹诺酮类药物　出处：《东北农业大学》2016年硕士论文　论文类型：学位论文

【摘要】：抗生素的发现及应用为细菌性疾病的临床治疗带来了新的进展,在现代临床治疗中抗菌药物的应用已经非常普遍,随后人们又发现抗菌药物可以促进畜禽的生长,所以畜牧从业人员开始在饲料中使用抗菌药物,使细菌的耐药性加剧,从而导致细菌性疾病的防治问题变的愈加艰巨。大肠杆菌是机体的固有菌,并且会在环境中存在,但是此类细菌会在机体免疫力下降时变成致病菌,所以人们在人类及畜牧生产中对其耐药现状都给与了极大的关注。近年来,牛大肠杆菌病给养殖户带来了巨大的经济损失,如何防治牛源大肠杆菌病已经成为各国畜牧从业人员及科研工作者共同关心的重要问题,目前,人们都是基于最小抑菌浓度制定的用于治疗牛大肠杆菌的方案。随着研究的深入,人们发现了这种用药方案的弊端,这种用药方案甚至会加剧耐药性,随后Zhao等提出了新的用药方案,即降低抗菌药物的防突变浓度或使其突变选择窗的关闭或缩小。本研究就是根据这个理论,研究氟喹诺酮类药物和多西环素联合用药对突变选择窗的关闭或缩小作用的影响。本实验是以40株牛源大肠杆菌为受试菌株通过K-B试验测定了14种抗菌药物的药物敏感性实验。结果表明受试菌株耐药情况严重,其中氟喹诺酮类药物耐药率较低在20%-32.5%之间,对头孢类药物耐药率也在50%以下,而且CAZ最为敏感,耐药率仅2.5%,对TMP的耐药率最高达到了85%,其次是对AM、AMX的耐药率也超过了60%,氟苯尼考为7.5%,多西环素为35%。之后又采用了能够定量定性的微量稀释法和联合药敏试验,将氧氟沙星、环丙沙星、多西环素对40株临床分离的牛源大肠杆菌的MIC进行了检测,对4株大肠杆菌采取了环丙沙星、氧氟沙星分别与多西环素联合的复方测量了MIC并计算FIC指数。结果显示氧氟沙星、环丙沙星分别与多西环素联用后,这四株大肠杆菌的FIC值均小于等于1,即联合应用时对此四株菌均为相加作用。并且对这四株菌株通过琼脂平板稀释法对单药及复方测定了其MPC、MSW、SI值。结果表明,氧氟沙星、环丙沙星、多西环素的MPC为12.8μg·mL-1、6.4μg·mL-1、2.56μg·mL-1、81.6μg·mL-1;16μg·mL-1、10.24μg·mL-1、16μg·mL-1、10.24μg·mL-1;102.4μg·mL-1、65.64μg·mL-1、52.43μg·mL-1、256μg·mL-1。SI为6.4/12.8/10.24/10.2;16/20.486.4/12.9;12.8/16.41、13.11/16。联合应用时其MSW分别缩小了4.6、2.4、3.4、5.4倍;8.7、4.2、2、5.4倍;5.7、2.6、2.7、3.3倍。表明了氟喹诺酮类药物与多西环素联合用药时,单药的MPC下降,并能缩小两药单用的耐药突变。通过不同药物浓度对耐药突变株恢复生长菌落数的生长曲线图可知,联合用药后菌落恢复生长平台期缩短,而且使曲线向左移动,揭示氟喹诺酮类药物与四环素类药物联合用药可以缩小两药单用的突变选择窗。
[Abstract]:The discovery and application of antibiotics have brought new progress to the clinical treatment of bacterial diseases. The use of antimicrobial agents has been very common in modern clinical treatment. Subsequently, it has been found that antimicrobial agents can promote the growth of livestock and poultry. So the livestock workers began to use antibiotics in the feed, which increased the drug resistance of the bacteria, which made the prevention and treatment of bacterial diseases more difficult. E. coli is the inherent bacteria of the body, and it will exist in the environment. But these bacteria can become pathogenic bacteria when the body's immunity drops, so people pay great attention to the current situation of drug resistance in human and livestock production. In recent years, cattle Escherichia coli disease has brought huge economic losses to farmers. How to prevent and cure colibacillosis from cattle has become an important issue of common concern to animal husbandry practitioners and scientific research workers in various countries. At present, People are based on the minimum inhibitory concentration for the treatment of bovine Escherichia coli. As research goes on, people have discovered the drawbacks of this medication, which can even increase drug resistance. Subsequently, Zhao et al proposed a new medication scheme, that is, to reduce the anti-mutation concentration of antimicrobial agents, or to close or narrow the window of mutation selection of antimicrobial agents. This study is based on this theory. To study the effect of fluoroquinolones combined with doxycycline on the closing or narrowing of mutant window, we determined 14 antimicrobial agents by K-B test with 40 strains of Escherichia coli from cattle. The results showed that the drug resistance of the tested strains was serious. The resistance rate of fluoroquinolones was between 20% and 32.5%, and the resistance rate of fluoroquinolones to cephalosporins was below 50%, and CAZ was the most sensitive. The drug resistance rate was only 2.5%, the highest drug resistance rate to TMP was 8510%, followed by the resistance rate of AMX to AMX exceeded 60%, florfenicol was 7.5% and doxycycline was 35.5%. Then the microdilution method and combined drug sensitivity test, which could be quantitatively and qualitatively, were used to test ofloxacin. Ciprofloxacin and doxycycline were used to detect MIC of 40 clinical isolates of bovine Escherichia coli and 4 strains of Escherichia coli were treated with ciprofloxacin. The combination of ofloxacin and doxycycline measured MIC and calculated the FIC index. The results showed that ofloxacin and ciprofloxacin were combined with doxycycline respectively. The FIC values of the four strains of Escherichia coli were all less than or equal to 1, that is, the four strains were all additive when combined with each other, and the MPC-MSW SI values of the four strains were determined by Agar plate dilution method. The results showed that ofloxacin, The MPC of ciprofloxacin and doxycycline was 12.8 渭 g 路mL-1hl 6.4 渭 g 路mL-1 2.56 渭 g 路mL-1l = 81.6 渭 g 路mL-1n = 16 渭 g 路mL-1n = 10.24 渭 g 路mL-1n 16 渭 g 路mL-1n = 10.24 渭 g 路mL-1102.4 渭 g 路mL-1n = 65.64 渭 g 路mL -1 = 65.64 渭 g 路mL -1 = 65.64 渭 g 路mL -1 = 65.64 渭 g 路mL -1 = 65.64 渭 g 路mL -1 = 65.43 渭 g 路mL -1 or 256 渭 g 路mL-1.SI = 6.4 / 12.810.8 渭 g 路ml -1 = 166.486.412.412.412.912.812.816.416.413.11 渭 g 路min ~ (-1) and 62.43.43.45 渭 g 路ml ~ (-1) 渭 g 路m ~ (-1) 渭 g 路m ~ (-1) 渭 g 路m ~ (-1) ~ (-1) of doxycycline were 62.43.44 渭 g 路m ~ (-1) ~ (-1) 渭 g 路m ~ (-1) 路L ~ (-1) and 256 渭 g 路m ~ (-1) 渭 g 路mL-1.SI = 6.4p 12.810.8 渭 g 路m ~ (-1) P ~ (16) 4.412.912.812.9p / 12. 816.416.413.11 / 116.@@. According to the growth curve of colony number of drug resistant mutants with different drug concentration, the period of colony recovery was shortened and the curve moved to the left after combined treatment. The results showed that the combination of fluoroquinolones and tetracyclines could reduce the mutation selection window of the two drugs.
【学位授予单位】：东北农业大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：S859.79

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