ANTIMICROBIAL STUDIES OF B. BURGDOR FERI

B. BurGDOR FERI 的抗菌研究

• 批准号: 3161986
• 负责人: RUSSELL C JOHNSON
• 金额: $ 16.56万
• 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/3161986
• 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.

莱姆病是美国主要的媒介传播细菌性疾病 国家，可能还有世界。 这种疾病的病原体， 伯氏疏螺旋体 (Borrelia burgdorferi)，由全球分布的 ixodid 传播 硬蜱属蜱。 除了急性形式 患病后，可能会出现持续数年的慢性感染。 莱姆病的早期和晚期表现可能与 存活螺旋体数量较少。 最有效的 抗菌药物、剂量、治疗途径和时间长度尚未确定 为治疗莱姆病而建立。 尽管临床研究表明 大多数患者对抗菌药物治疗的反应令人满意，如果 在疾病早期开始，特别是出现例外情况 当患者有神经系统受累时。 然而，评价 由于螺旋体潜伏期，这种疾病的治疗存在问题 以及间歇性的恶化和缓解模式 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 对挑剔、生长缓慢的细菌（例如 B. 尚未建立世代时间为 10-20 小时的伯氏疏螺旋体。 重要的是要有这些方法来识别 可有效治疗莱姆病的抗菌药物 以及用于研究各种治疗方案的动物模型。 本提案的具体目标是： I. 制定标准方法 B.体外抗菌药物敏感性测定 博格多弗里。随着标准体外抗菌剂的开发 药敏方案： A. 确定伯氏疏螺旋体对 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。 伯氏疏螺旋体从不同的地理区域中分离出来，具有代表性 抗菌剂。 二.开发测定体内抗菌剂的标准方法 实验感染仓鼠对伯氏疏螺旋体的敏感性。 随着体内抗菌标准方法的开发 药敏试验：A.确定体内药敏B. 伯氏杆菌转化为具有良好体外活性的抗菌剂。 B. 比较联合抗菌治疗与单药治疗的疗效 治疗。 C. 评估类固醇对抗菌治疗的效果。 D . 通过实验比较仓鼠抗菌治疗的效果 注射感染与蜱虫叮咬感染。 E、评估 抗菌预防对蜱传播的有效性 B. 伯氏杆菌感染。