Synergistic Action of Phage and Antibiotics: Parameters to Enhance the Killing Efficacy Against Mono and Dual-Species Biofilms
Synergistic Action of Phage and Antibiotics: Parameters to Enhance the Killing Efficacy Against Mono and Dual-Species Biofilms
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DOI：
10.3390/antibiotics8030103
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发表时间：
2019-09-01
影响因子：
4.8
通讯作者：
Azeredo, Joana
中科院分区：
文献类型：
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作者：
Akturk, Ergun;Oliveira, Hugo;Azeredo, Joana
铜绿假单胞菌和金黄色葡萄球菌是条件致病菌，常见于多种微生物生物膜相关疾病，即慢性伤口。它们在生物膜中的共存有助于增加生物膜对抗生素的耐受性。噬菌体和抗生素的组合治疗已经显示出有希望的抗菌膜活性，这是由于它们的作用机制的深刻差异。在这项研究中，48小时的单和双物种的生物膜处理与新分离的铜绿假单胞菌感染噬菌体（EPA1）和7种不同的抗生素（庆大霉素，卡那霉素，四环素，氯霉素，红霉素，环丙沙星，美罗培南），单独和同时或顺序组合。测定测试的抗菌剂的治疗功效。单独的噬菌体或抗生素在减少生物膜细菌方面具有适度的效果。然而，当同时施用时，观察到杀灭效果的显著改善。此外，一个令人印象深刻的生物膜减少（低于检测限）时，观察到依次加入庆大霉素或环丙沙星后6小时的噬菌体处理。观察到的效果不取决于抗生素的类型，但受其浓度的影响。此外，在双物种生物膜中，有必要增加庆大霉素浓度以获得与单物种中发生的类似的杀灭效果。总的来说，将抗生素与抗生素组合可以协同降低生物膜中的细菌密度。然而，抗生素的浓度和抗生素的应用时间是在联合治疗中需要考虑的重要因素。
Pseudomonas aeruginosa and Staphylococcus aureus are opportunistic pathogens and are commonly found in polymicrobial biofilm-associated diseases, namely chronic wounds. Their co-existence in a biofilm contributes to an increased tolerance of the biofilm to antibiotics. Combined treatments of bacteriophages and antibiotics have shown a promising antibiofilm activity, due to the profound differences in their mechanisms of action. In this study, 48 h old mono and dual-species biofilms were treated with a newly isolated P. aeruginosa infecting phage (EPA1) and seven different antibiotics (gentamicin, kanamycin, tetracycline, chloramphenicol, erythromycin, ciprofloxacin, and meropenem), alone and in simultaneous or sequential combinations. The therapeutic efficacy of the tested antimicrobials was determined. Phage or antibiotics alone had a modest effect in reducing biofilm bacteria. However, when applied simultaneously, a profound improvement in the killing effect was observed. Moreover, an impressive biofilm reduction (below the detection limit) was observed when gentamicin or ciprofloxacin were added sequentially after 6 h of phage treatment. The effect observed does not depend on the type of antibiotic but is influenced by its concentration. Moreover, in dual-species biofilms it was necessary to increase gentamicin concentration to obtain a similar killing effect as occurs in mono-species. Overall, combining phages with antibiotics can be synergistic in reducing the bacterial density in biofilms. However, the concentration of antibiotic and the time of antibiotic application are essential factors that need to be considered in the combined treatments.