In vivo efficacy of telavancin/colistin combination therapy in a Galleria mellonella model of Acinetobacter baumannii infection
In vivo efficacy of telavancin/colistin combination therapy in a Galleria mellonella model of Acinetobacter baumannii infection
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DOI：
10.1016/j.ijantimicag.2012.11.013
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发表时间：
2013-03-01
影响因子：
10.8
通讯作者：
Wareham, David W.
中科院分区：
文献类型：
--
作者：
Hornsey, Michael;Phee, Lynette;Wareham, David W.
鲍曼不动杆菌感染的治疗是具有挑战性的，由于广泛的多药耐药和缺乏新的药物。目前，人们对粘菌素和糖肽（如万古霉素和替柯planin）等非正统联合疗法的潜力非常感兴趣，因为可以在体外证明有效的协同作用。建立了一个简单的无脊椎动物模型（mellonella Galleria）来评估抗菌疗法的体内活性，并用于研究粘菌素与脂糖肽telavancin联合治疗鲍曼不动杆菌感染的疗效。将10(5)CFU/幼虫分别接种鲍曼不动杆菌ATCC 19606型菌株或耐多药临床分离株AB210。用特拉万素（10 mg/kg）、粘菌素（2.5 mg/kg）或特拉万素/粘菌素联合用药治疗受感染的毛虫。在37℃条件下孵育96 h，每天进行评分。绘制生存曲线并使用log-rank检验进行分析。特拉万素/粘菌素联合治疗两种菌株感染的幼虫均有效，但对鲍曼不动杆菌AB210的治疗效果优于粘菌素单药治疗（P < 0.001）。特拉万素联合粘菌素对鲍曼不动杆菌感染的简单无脊椎动物模型有效。这与先前的体外研究一致，并提供了初步的体内证据，表明这种组合可能在治疗上有用。(C) 2012 Elsevier B.V.与International Society of Chemotherapy。版权所有。
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 10(5) 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 degrees 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. (C) 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.