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首页> 外文学位 >The within host population dynamics of acute Escherichia coli K1 infection in mice and its treatment with antibiotics.
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The within host population dynamics of acute Escherichia coli K1 infection in mice and its treatment with antibiotics.

机译：小鼠中急性大肠杆菌K1感染的宿主内部种群动态及其抗生素治疗。

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摘要

Despite our continually improving understanding of antibiotics and their use, antibiotic treatment failure remains a problem, even in the absence of antibiotic resistance. Part of the solution is the development of more effective antibiotic treatment protocols, but this cannot be accomplished without a quantitative understanding of the effects of antibiotics on bacterial growth, death, dissemination, and persistence within immunocompetent hosts. This thesis investigates the population dynamics of acute Escherichia coli O18:K1:H7 infection in the mouse thigh infection model (MTI) in immunocompetent mice and its treatment with antibiotics. In vivo and in vitro experiments were performed to investigate the within host dynamics of lethal and nonlethal thigh infections, and three hypotheses were proposed and tested that could account for the infection dynamics observed. The pharmacokinetics and pharmacodynamics of treatment of these thigh infections with streptomycin and tetracycline was studied. The population dynamics of bacterial killing varied with inoculum density and the age of infection, and immediate treatment was always more successful than treatment given eight hours after infection. For streptomycin, survivorship of mice treated at eight hours after infection was improved by giving additional doses of the drug over a four day period, and experimental results suggest this may be due to control of dissemination of the bacteria from the thigh. Phenotypic tolerance, a phenomenon that allows the survival of genetically susceptible bacteria to antibiotic exposure, is studied in vitro and its potential clinical implications are explored with mathematical models.
机译：尽管我们对抗生素及其使用的理解不断提高，但是即使在没有抗生素耐药性的情况下，抗生素治疗失败仍然是一个问题。解决方案的一部分是开发更有效的抗生素治疗方案，但是，如果不能定量了解抗生素对细菌的生长，死亡，传播以及在具有免疫能力的宿主中的持久性的影响，就无法实现这一目标。本文研究了具有免疫能力的小鼠大腿感染模型（MTI）中急性大肠杆菌O18：K1：H7感染的种群动态及其抗生素治疗。进行了体内和体外实验，以研究致死性和非致死性大腿感染的宿主内部动态，提出并测试了三个假说，这些假说可以解释观察到的感染动态。研究了用链霉素和四环素治疗这些大腿感染的药代动力学和药效学。细菌杀灭的种群动态随接种密度和感染年龄的变化而变化，即时治疗总是比感染后八小时给予的治疗更为成功。对于链霉素，在感染后八小时治疗的小鼠的存活率通过在四天内给予额外剂量的药物而得到改善，实验结果表明，这可能是由于控制了大腿细菌的传播。在体外研究了表型耐受性，这种现象使遗传上易感的细菌得以生存并暴露于抗生素中，并通过数学模型探索了其潜在的临床意义。

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  • 作者

    Zappala, Renata M.;

  • 作者单位

    Emory University.;

  • 授予单位 Emory University.;
  • 学科 Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2004
  • 页码 163 p.
  • 总页数 163
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 微生物学;
  • 关键词

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