Phagebiotics in treatment and prophylaxis of healthcare-associated infections.

Bacteriophage Pub Date : 2016-10-21 eCollection Date: 2016-01-01 DOI:10.1080/21597081.2016.1251379
A V Aleshkin, O N Ershova, N V Volozhantsev, E A Svetoch, A V Popova, E O Rubalskii, A I Borzilov, V A Aleshkin, S S Afanas'ev, A V Karaulov, K M Galimzyanov, O V Rubalsky, S S Bochkareva
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Abstract

We have developed a phagebiotic composition using 8 virulent bacteriophages (2 strains of each species) which are able to lyse Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. The unique character of the developed composition is ensured by particular properties of each bacteriophage comprising the preparation, including their range of lytic activity toward specific bacterial pathogens, morphology of their plaques, cycle of their development, restriction profile of their DNAs, specificity of their genomes (based on complete genome sequencing), and other properties. The preparation did not produce any signs of acute or chronic intoxication in the experimental animals. Therapeutic and prophylactic efficiency of the phagebiotic composition was demonstrated in the prevention and treatment of the experimental acute K. pneumoniae infection in mice. The investigations have shown that the preparation possesses a high therapeutic efficiency and is highly competitive with ciprofloxacin which is very effective against the infective strain K. pneumoniae. Our small-scale clinical trial was aimed to evaluate therapeutic effectiveness of the phagebiotic composition in an epidemiological emergency situation in an intensive care unit, caused by multi-resistant strains of Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Seventy nine per cent of the initial samples from 14 patients' endotracheal aspirate, blood and urine were contaminated. Twenty-four hours after the 3-day phage therapy (20 ml of cocktail at a titer for each phage 108 pfu/ml were introduced intragastrically through a tube once a day) contamination level dropped to 21%. Hence the obtained results enabled us to create a new phagebiotic composition that may be used as an alternative to antibiotics to treat these healthcare-associated infections.

治疗和预防医疗保健相关感染的噬菌体。
我们利用 8 种毒性噬菌体(每种 2 株)研制出了一种噬菌体组合物,它们能够溶解鲍曼不动杆菌、肺炎克雷伯氏菌、铜绿假单胞菌和金黄色葡萄球菌。制剂中的每种噬菌体都具有特定的特性,包括对特定细菌病原体的裂解活性范围、斑块形态、发育周期、DNA 的限制性图谱、基因组的特异性(基于完整的基因组测序)以及其他特性,从而确保了所开发组合物的独特性。该制剂不会对实验动物产生任何急性或慢性中毒症状。在预防和治疗小鼠急性肺炎双球菌感染的实验中,证明了噬菌体组合物的治疗和预防功效。研究表明,该制剂具有很高的治疗效率,与环丙沙星相比具有很强的竞争力,而环丙沙星对肺炎克氏菌感染菌株非常有效。我们的小规模临床试验旨在评估噬菌体组合物在重症监护室流行病学紧急情况下的治疗效果,该紧急情况由多重耐药菌株鲍曼不动杆菌、肺炎克雷伯菌和铜绿假单胞菌引起。从 14 名患者的气管内吸入物、血液和尿液中提取的初始样本有 79% 受到污染。经过 3 天的噬菌体治疗(每天一次通过导管将滴度为 108 pfu/ml 的 20 毫升鸡尾酒引入胃内)后 24 小时,污染水平降至 21%。因此,所获得的结果使我们能够创造出一种新的噬菌体成分,它可以作为抗生素的替代品来治疗这些与医疗保健相关的感染。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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