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评价一种局部应用阿奇霉素制剂在小鼠模型中预防莱姆病的能力。

Evaluation of the preventive capacities of a topically applied azithromycin formulation against Lyme borreliosis in a murine model.

机构信息

Fraunhofer Institute for Cell Therapy and Immunology, Cell Technology/GLP, Leipzig, Germany.

出版信息

J Antimicrob Chemother. 2011 Dec;66(12):2814-22. doi: 10.1093/jac/dkr371. Epub 2011 Sep 15.

Abstract

OBJECTIVES

Systemic antibiotic treatment of Lyme borreliosis is effective during the early stages of the infection, while chronic manifestations of the disease may remain refractory and difficult to treat. This study was carried out in order to evaluate the potential of topically applied azithromycin to eliminate the spirochaetal organisms in the skin of the freshly bitten host and thereby prevent Lyme borreliosis.

METHODS

Laboratory mice were challenged with Borrelia burgdorferi sensu stricto by needle inoculation or via infected ticks as vectors. Then, an azithromycin-containing formulation was applied once daily to the sites of exposure for three consecutive days. In the case of needle inoculation, a 5% azithromycin formulation was applied starting 1 h, 3 days and 5 days after infection. In the case of tick exposure, 4%, 10% and 20% azithromycin formulations were applied, starting directly after the detachment of the engorged ticks. Subsequently, the infection status of the mice was determined.

RESULTS

Concentrations of azithromycin in murine skin were >3800-fold higher than the published minimal inhibitory concentration for B. burgdorferi as soon as 3 h after the first application. After needle inoculation, spirochaetes were not detectable in all infected mice after treatment, if the first application started 1 h or even after 3 days post-infection. Furthermore, no borrelial organisms were detected after topical treatment when ticks were used for spirochaete inoculation.

CONCLUSIONS

Our data indicate that topical treatment with a formulation containing azithromycin is a promising approach to prevent Lyme borreliosis shortly after a tick bite.

摘要

目的

在感染的早期阶段,全身性抗生素治疗莱姆病是有效的,而疾病的慢性表现可能仍然难以治疗。本研究旨在评估局部应用阿奇霉素消除新感染宿主皮肤中的螺旋体生物体的潜力,从而预防莱姆病。

方法

实验室小鼠通过针接种或受感染的蜱作为载体来挑战伯氏疏螺旋体。然后,将含有阿奇霉素的制剂每天应用于暴露部位,连续应用 3 天。在针接种的情况下,在感染后 1 小时、3 天和 5 天开始应用 5%阿奇霉素制剂。在蜱暴露的情况下,在蜱虫脱离后立即开始应用 4%、10%和 20%阿奇霉素制剂。随后,确定小鼠的感染状况。

结果

在第一次应用后 3 小时,鼠皮肤中的阿奇霉素浓度比已发表的伯氏疏螺旋体最小抑菌浓度高出>3800 倍。在针接种的情况下,如果第一次应用在感染后 1 小时或甚至 3 天后开始,所有感染的小鼠在治疗后均未检测到螺旋体。此外,在使用蜱虫进行螺旋体接种时,局部治疗后也未检测到伯氏疏螺旋体。

结论

我们的数据表明,在蜱叮咬后不久,局部应用含有阿奇霉素的制剂是预防莱姆病的一种有前途的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/270b/3215302/3446422115d1/dkr37101.jpg

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