ANTIMICROBIAL STUDIES OF B. BURGDOR FERI

B. BurGDOR FERI 的抗菌研究

• 批准号: 3161987
• 负责人: RUSSELL C JOHNSON
• 金额: $ 15.98万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3161987
• 关键词: Borrelia; Lyme disease; Spirochaetales; antibacterial agents; arthropod borne communicable disease; beta lactam antibiotic; combination chemotherapy; corticosterone; disease vectors; dosage; drug screening /evaluation; genetic strain; hamsters; histopathology; human tissue; injection /infusion; insect poison; nonhuman therapy evaluation; tetracyclines; ticks; virulence

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.

莱姆病是联合媒介传播的细菌疾病 国家，可能是世界。 这种疾病的病因学药物， Borrelia burgdorferi，由全球分布式IXODID传输 ixodes属的壁虱。 除了急性形式 疾病，可能会持续多年的慢性感染。 莱姆病的早期和晚期表现可以与 存在较少的可行螺旋体。 最有效的 抗菌，剂量，途径和治疗时间尚未 为莱姆病建立。 尽管临床研究表明 大多数患者对抗菌治疗的反应令人满意 在疾病早期开始，特别发生了例外 当患者患有神经系统参与时。 但是，评估 由于螺旋体潜伏期，对该疾病的治疗是有问题的 以及在 未经治疗感染的自然史。 用于确定体外和体内抗微生物的标准方法 挑剔的，缓慢的细菌的敏感性，例如B。 尚未建立一代时间为10-20小时的Burgdorferi。 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素 和动物模型，以研究各种治疗方案。 该提案的具体目的是：I。开发标准方法 确定B. 伯格多尔里。随着标准体外抗菌剂的发展 敏感性方案：A。确定B. burgdorferi对 新的以及一些常用的抗菌剂和 抗菌组合。 B.比较B的体外敏感性。 来自不同地理区域到代表的Burgdorferi分离 抗菌剂。 ii。开发确定体内抗菌剂的标准方法 B. burgdorferi在实验感染的仓鼠中的敏感性。 随后开发了体内抗微生物的标准方法 敏感性测定：A。确定B。 对具有良好体外活性的抗菌剂。 B 比较联合抗菌治疗与单药的疗效 治疗。 C.评估类固醇对抗菌治疗的影响。 D 比较实验中抗菌治疗在仓鼠中的功效 通过tick咬伤被注射与感染感染。 E.评估 抗菌预防对tick传输的有效性B。 伯格多菲利感染。