ANTIMICROBIAL STUDIES OF B. BURGDOR FERI

莱姆病是美国主要的媒介传播的细菌性疾病， 国家，甚至全世界。 这种疾病的病原体， 伯氏疏螺旋体，是由全球分布的硬蜱传播 硬蜱属的蜱。 除了急性形式的 疾病，慢性感染可能会发展，可以持续多年。 莱姆病的早期和晚期表现可能与 存在少量的活螺旋体。 最有效的 抗菌剂，剂量，途径和治疗时间尚未被 为莱姆病而设。 尽管临床研究表明， 大多数患者对抗菌治疗反应满意， 在疾病的早期开始，这种情况的例外发生，特别是 当病人有神经系统受累时。 然而，评价 由于螺旋体的潜伏期， 和间歇性的加重和缓解模式， 未经治疗的感染的自然史。 测定体外和体内抗菌剂的标准方法 难养、生长缓慢的细菌如B的易感性。 世代时间为10-20小时的burgdorferi尚未建立。 重要的是要有这些方法来识别 可能有效治疗莱姆病的抗菌剂 和动物模型来研究各种治疗方案。 本建议的具体目标是：制定标准方法， B的体外抗菌药物敏感性测定。 burgdorferi。标准体外抗菌剂的开发 敏感性方案：A.测定B的灵敏度。布格多费里岛 新的以及一些常用的抗菌剂， 抗微生物组合。 B。比较B的体外敏感性。 从不同地理区域分离到代表性 抗菌剂。 二.建立体内抗菌药物测定标准方法 B敏感性。实验感染仓鼠的伯氏螺旋体。 体内抗菌剂标准方法的开发 敏感性测定：A.测定B的体内敏感性。 Burgdorferi的抗微生物剂具有良好的体外活性。 B。 抗菌药物联合治疗与单药治疗的疗效比较 疗法 C.评价类固醇对抗菌治疗的影响。D. 金黄地鼠抗菌药物治疗效果的实验比较 注射感染和蜱虫叮咬感染。 E. 评价 蜱传B类疾病预防性应用 伯氏感染

Lyme disease is the leading vector-borne bacterial disease in the United States and probably the world. The etiologic agent of this disease, Borrelia burgdorferi, is transmitted by the globally distributed ixodid ticks of the genus Ixodes. In addition to the acute form of the illness, a chronic infection may develop that can persist for years. The early and late manifestation of Lyme disease can be correlated with the presence of low numbers of viable spirochetes. The most effective antimicrobial, dosage, route and length of treatment have not been established for Lyme disease. Although clinical studies suggest that most patients respond satisfactorily to antimicrobial therapy if initiated early in the disease, exceptions to this occur particularly when patients have neurologic involvement. However, evaluation of the treatment of this disease is problematic due to the spirochetes latency and the intermittent pattern of exacerbations and remissions in the natural history of untreated infections. Standard methods for detemining the in vitro and in vivo antimicrobials susceptibility of fastidious, slow-growing bacteria, such as B. burgdorferi with a generation time of 10-20 hr have not been establdhed. It is important to have these methods available to identify antimicrobials that could be effective for the treatment of Lyme disease and an animal model to investigate various treatment protocols. The specific aims of this proposal are: I. Develop standard method for determination of in vitro antimicrobial susceptibility of B. burgdorferi. Following development of standard in vitro antimicrobial susceptibility protocol: A. Determine sensitivity of B. burgdorferi to new as well as some of the commonly used antimicrobials and antimicrobial combinations. B. Compare in vitro susceptibility of B. burgdorferi isolates from diverse geographical areas to representative antimicrobial agents. II. Develop standard method for determination of in vivo antimicrobial susceptibility of B. burgdorferi in experimentally infected hamsters. Following development of standard method for the in vivo antimicrobial susceptibility assay: A. Determine in vivo susceptibility of B. burgdorferi to antimicrobials that possess good in vitro activity. B. Compare efficacy of combined antimicrobial therapy with single agent therapy. C. Evaluate effect of steroids on antimicrobial therapy. D. Compare efficacy of antimicrobial therapy in hamsters experimentally infected by injection versus infection via tick bite. E. Evaluate effectiveness of antimicrobial prophylaxis for tick transmitted B. burgdorferi infection.