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替加环素/黏菌素联合治疗在棘白菌素类耐药鲍曼不动杆菌感染的家蚕模型中的体内疗效。

In vivo efficacy of telavancin/colistin combination therapy in a Galleria mellonella model of Acinetobacter baumannii infection.

机构信息

Antimicrobial Research Group, Centre for Immunology and Infectious Disease, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.

出版信息

Int J Antimicrob Agents. 2013 Mar;41(3):285-7. doi: 10.1016/j.ijantimicag.2012.11.013. Epub 2013 Jan 9.

DOI:10.1016/j.ijantimicag.2012.11.013
PMID:23312607
Abstract

Treatment of Acinetobacter baumannii infections is challenging owing to widespread multidrug resistance and the lack of novel agents. There is now considerable interest in the potential of unorthodox combination therapies such as colistin and glycopeptides (e.g. vancomycin and teicoplanin), since potent synergy can be demonstrated in vitro. A simple invertebrate model (Galleria mellonella) has been developed to assess the in vivo activity of antimicrobial therapies and was used to investigate the efficacy of colistin combined with the lipoglycopeptide telavancin in the treatment of A. baumannii infection. Galleria mellonella larvae were inoculated with 10⁵ CFU/larvae of A. baumannii type strain ATCC 19606 or the multidrug-resistant clinical isolate AB210. Infected caterpillars were treated with either telavancin (10 mg/kg), colistin (2.5 mg/kg) or a telavancin/colistin combination. Larvae were incubated at 37 °C for up to 96 h and were scored daily. Survival curves were plotted and analysed using the log-rank test. The telavancin/colistin combination was effective in the treatment of larvae infected with both strains but was superior to colistin monotherapy in the treatment of A. baumannii AB210 (P<0.001). The combination of telavancin and colistin was effective in a simple invertebrate model of A. baumannii infection. This is in agreement with a previous in vitro study and provides preliminary in vivo evidence that such a combination might be useful therapeutically.

摘要

由于广泛的多药耐药性和缺乏新的药物,治疗鲍曼不动杆菌感染具有挑战性。现在人们对非常规联合治疗方法(如多粘菌素和糖肽(如万古霉素和替考拉宁))的潜力产生了浓厚的兴趣,因为在体外可以证明有效的协同作用。已经开发出一种简单的无脊椎动物模型(家蚕)来评估抗菌治疗的体内活性,并用于研究多粘菌素与脂糖肽替拉万星联合治疗鲍曼不动杆菌感染的疗效。将 10⁵CFU/幼虫的鲍曼不动杆菌标准株 ATCC 19606 或多药耐药临床分离株 AB210 接种到家蚕幼虫。用替拉万星(10mg/kg)、多粘菌素(2.5mg/kg)或替拉万星/多粘菌素联合治疗感染的毛毛虫。将幼虫在 37°C 下孵育长达 96 小时,并每天评分。使用对数秩检验绘制和分析生存曲线。替拉万星/多粘菌素联合治疗对两种菌株感染的幼虫均有效,但在治疗 AB210 时优于多粘菌素单药治疗(P<0.001)。替拉万星和多粘菌素的联合在鲍曼不动杆菌感染的简单无脊椎动物模型中是有效的。这与之前的体外研究一致,并提供了初步的体内证据表明,这种联合可能具有治疗价值。

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