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用于治疗炭疽的替代预批准和新型疗法。

Alternative pre-approved and novel therapies for the treatment of anthrax.

作者信息

Head Breanne M, Rubinstein Ethan, Meyers Adrienne F A

机构信息

Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada.

National Laboratory for HIV Immunology, JC Wilt Infectious Disease Research Centre, Public Health Agency of Canada, Winnipeg, Canada.

出版信息

BMC Infect Dis. 2016 Nov 3;16(1):621. doi: 10.1186/s12879-016-1951-y.

Abstract

BACKGROUND

Bacillus anthracis, the causative agent of anthrax, is a spore forming and toxin producing rod-shaped bacterium that is classified as a category A bioterror agent. This pathogenic microbe can be transmitted to both animals and humans. Clinical presentation depends on the route of entry (direct contact, ingestion, injection or aerosolization) with symptoms ranging from isolated skin infections to more severe manifestations such as cardiac or pulmonary shock, meningitis, and death. To date, anthrax is treatable if antibiotics are administered promptly and continued for 60 days. However, if treatment is delayed or administered improperly, the patient's chances of survival are decreased drastically. In addition, antibiotics are ineffective against the harmful anthrax toxins and spores. Therefore, alternative therapeutics are essential. In this review article, we explore and discuss advances that have been made in anthrax therapy with a primary focus on alternative pre-approved and novel antibiotics as well as anti-toxin therapies.

METHODS

A literature search was conducted using the University of Manitoba search engine. Using this search engine allowed access to a greater variety of journals/articles that would have otherwise been restricted for general use. In order to be considered for discussion for this review, all articles must have been published later than 2009.

RESULTS

The alternative pre-approved antibiotics demonstrated high efficacy against B. anthracis both in vitro and in vivo. In addition, the safety profile and clinical pharmacology of these drugs were already known. Compounds that targeted underexploited bacterial processes (DNA replication, RNA synthesis, and cell division) were also very effective in combatting B. anthracis. In addition, these novel compounds prevented bacterial resistance. Targeting B. anthracis virulence, more specifically the anthrax toxins, increased the length of which treatment could be administered.

CONCLUSIONS

Several novel and pre-existing antibiotics, as well as toxin inhibitors, have shown increasing promise. A combination treatment that targets both bacterial growth and toxin production would be ideal and probably necessary for effectively combatting this armed bacterium.

摘要

背景

炭疽芽孢杆菌是炭疽病的病原体,是一种形成芽孢并产生毒素的杆状细菌,被列为A类生物恐怖剂。这种致病微生物可传播给动物和人类。临床表现取决于感染途径(直接接触、摄入、注射或气溶胶传播),症状从孤立的皮肤感染到更严重的表现,如心脏或肺部休克、脑膜炎和死亡。迄今为止,如果及时使用抗生素并持续60天,炭疽病是可治疗的。然而,如果治疗延迟或使用不当,患者的存活几率将大幅降低。此外,抗生素对有害的炭疽毒素和芽孢无效。因此,替代疗法至关重要。在这篇综述文章中,我们探讨并讨论了炭疽病治疗方面取得的进展,主要关注替代的已获批和新型抗生素以及抗毒素疗法。

方法

使用曼尼托巴大学搜索引擎进行文献检索。使用该搜索引擎可以获取更多种类的期刊/文章,否则这些期刊/文章通常会受到使用限制。为了被纳入本综述进行讨论,所有文章必须在2009年之后发表。

结果

替代的已获批抗生素在体外和体内均对炭疽芽孢杆菌显示出高效。此外,这些药物的安全性和临床药理学已经明确。针对未充分利用的细菌过程(DNA复制、RNA合成和细胞分裂)的化合物在对抗炭疽芽孢杆菌方面也非常有效。此外,这些新型化合物可防止细菌耐药。针对炭疽芽孢杆菌的毒力,更具体地说是炭疽毒素,延长了可进行治疗的时间。

结论

几种新型和现有的抗生素以及毒素抑制剂已显示出越来越大的前景。针对细菌生长和毒素产生的联合治疗将是理想的,并且可能是有效对抗这种带菌病原体所必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95c6/5094018/5bb3cc7b1c90/12879_2016_1951_Fig1_HTML.jpg

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