Topical Antibiotics to Prevent Lyme Disease

描述(申请人提供)：莱姆病，由伯氏疏螺旋体引起，是美国最常见的扁虱传播感染，自2002年以来每年报告超过20,000例。在预防莱姆病的有效策略中，只有接种重组外表面蛋白A疫苗和单剂量多西环素对被肩虱叮咬的硬蜱进行抗生素化学预防，才能降低人类病例的发生率。然而，莱姆疫苗不再在市场上销售。2003年6月，美国疾病控制和预防中心的美国公共卫生服务部门建议，可以考虑将单剂强力霉素作为预防被一号肩关节扁虱叮咬后莱姆病的一种选择(Hayes EB，Piesman J.)。《英国医学杂志》2003 12：348：2424-30)。使用多西环素的一个实际限制是，该药物不能在非处方药中获得；需要抗生素处方，并且必须在驱除扁虱后72小时内获得药物，才能有效治疗。此外，多西环素只推荐给被充血的我肩虱叮咬的患者，这一评估需要技能，只有在扁虱已被保存且相对完好的情况下才能进行评估。此外，多西环素是幼儿和孕妇或哺乳期妇女的禁忌药物。各种外用抗菌药被广泛用于治疗常见疾病。这些制剂被广泛接受，而且是安全的。一项动物研究表明，应用某些局部抗菌制剂在预防被扁虱叮咬后播散性伯氏疏螺旋体感染方面非常有效，但不幸的是，这项研究没有测试获准用于人类的抗生素配方。目前这项建议的目的是在小鼠模型中调查一种适合于人类使用的局部抗生素制剂的疗效。如果成功，这些研究将具有高度相关的公共卫生影响，并将导致未来的人体试验，以测试局部抗菌治疗在有莱姆病风险的患者中的有效性和安全性。

DESCRIPTION (provided by applicant): Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common tick-borne infection in the United States with more than 20,000 cases reported annually since 2002. Of the available strategies to prevent Lyme disease, only vaccination with a recombinant outer surface protein A and antibiotic chemoprophylaxis of Ixodes scapularis tick bites with single-dose doxycycline have been shown to decrease the incidence of human cases. However, the Lyme vaccine is no longer marketed. In June 2003, authorities from the United States Public Health Services at the Centers for Disease Control and Prevention suggested that single-dose doxycycline be considered as an option for the prevention of Lyme disease after an I. scapularis tick bite (Hayes EB, Piesman J. How can we prevent Lyme disease. N Engl J Med 2003 June 12:348:2424-30). A practical limitation of using doxycycline is that the drug is not available over-the-counter; an antibiotic prescription is required and the medication must be obtained within 72 hours of tick removal for the treatment to be effective. In addition, doxycycline is only recommended for patients bitten by I. scapularis ticks that are engorged with blood, an assessment that requires skill and can only be done if the tick has been saved and is relatively intact. Further, doxycycline is contraindicated in young children and pregnant or lactating women. A variety of topical antimicrobials are in wide general usage for treatment of common conditions. These preparations are well accepted and safe. An animal study demonstrated that application of certain topical antimicrobial preparations was highly efficacious in preventing disseminated Borrelia burgdorferi infection after a tick bite, but unfortunately this study did not test antibiotic formulations approved for use on humans. The purpose of the current proposal is to investigate the efficacy of a topical antibiotic preparation suitable for use in humans in a mouse model. If successful, these studies would have highly relevant public health implications and should result in future human trials to test the efficacy and safety of topical antimicrobial therapy in patients at risk for Lyme disease after an Ixodes scapularis tick bite.