Betts Jonathan W, Hornsey Michael, Wareham David W, La Ragione Roberto M
Department of Pathology and Infectious Diseases, School of Veterinary Medicine, University of Surrey, Guildford, UK.
Antimicrobial Research Group, Blizard Institute, Queen Mary University of London, London, UK.
Infect Dis Ther. 2017 Sep;6(3):435-442. doi: 10.1007/s40121-017-0161-2. Epub 2017 Jun 21.
Acinetobacter baumannii is an important human nosocomial pathogen; most clinical isolates are multidrug-resistant (MDR). Infections caused by A. baumannii often lead to high morbidity and mortality, with limited treatment options. Owing to the small number of anti-Gram-negative antibiotics in the development pipeline, researchers are looking to other natural compounds. The aim of this study was to determine the in vitro kill kinetics, in vivo efficacy and toxicity of theaflavin-epicatechin combinations against MDR A. baumannii.
Kill-kinetic assays were performed in Mueller-Hinton 2 broth over 24 h. Toxicity of the compound in the insect model, Galleria mellonella was investigated. The effect of theaflavin-epicatechin combinations on mortality and morbidity were assessed in Acinetobacter baumannii-infected G. mellonella. Larvae were scored for morbidity (melanisation: scale; 0-4) and mortality over 96 h.
Kill-kinetic assays revealed that monotherapy had bacteriostatic activity over 24 h, whereas theaflavin-epicatechin combinations were bactericidal (a >3 log reduction in bacterial numbers at 24 h compared with the starting inoculum). Both polyphenols were non-toxic to G. mellonella at concentrations of up to 1000 mg/kg. In vivo treatment assays showed that the combination significantly increased (t test; p ≤ 0.05) larval survival at 96 h to 86% [±17 standard deviation percentage points (pp)] compared to monotherapy with theaflavin (52% ± 14 pp), epicatechin (44% ± 25 pp) or PBS (31% ± 13 pp). Morbidity was also lower in larvae treated with the combination, compared with monotherapy.
Polyphenol combinations produce effective antibacterial action against A. baumannii and show great potential for the treatment of infections caused by MDR A. baumannii.
鲍曼不动杆菌是一种重要的人类医院感染病原菌；大多数临床分离株具有多重耐药性（MDR）。鲍曼不动杆菌引起的感染常导致高发病率和死亡率，治疗选择有限。由于处于研发阶段的抗革兰氏阴性菌抗生素数量较少，研究人员正在寻找其他天然化合物。本研究的目的是确定茶黄素 - 表儿茶素组合对多重耐药鲍曼不动杆菌的体外杀菌动力学、体内疗效和毒性。
在穆勒 - 欣顿2肉汤中进行24小时的杀菌动力学测定。研究该化合物在昆虫模型黄粉虫中的毒性。评估茶黄素 - 表儿茶素组合对感染鲍曼不动杆菌的黄粉虫死亡率和发病率的影响。在96小时内对幼虫的发病率（黑化程度：0 - 4级）和死亡率进行评分。
杀菌动力学测定表明，单一疗法在24小时内具有抑菌活性，而茶黄素 - 表儿茶素组合具有杀菌作用（与起始接种物相比，24小时时细菌数量减少>3个对数）。两种多酚在浓度高达1000 mg/kg时对黄粉虫均无毒。体内治疗试验表明，与用茶黄素（52%±14个百分点）、表儿茶素（44%±25个百分点）或PBS（31%±13个百分点）进行单一疗法相比，该组合在96小时时显著提高（t检验；p≤0.05）幼虫存活率至86%[±17标准差百分点（pp）]。与单一疗法相比，用该组合处理的幼虫发病率也较低。
多酚组合对鲍曼不动杆菌产生有效的抗菌作用，在治疗多重耐药鲍曼不动杆菌引起的感染方面显示出巨大潜力。
