PDF(Pubmed)
Abstract：
Introduction: The emergence of antibiotic resistance is a significant challenge in the treatment of bacterial infections, particularly in patients in the intensive care unit (ICU). Phage-antibiotic combination therapy is now being utilized as a preferred therapeutic option for infections that are multi-drug resistant in nature. Methods: In this study, we examined the combined impact of the staph phage vB_Sau_S90 and four antibiotics on methicillin-resistant Staphylococcus aureus (MRSA). We conducted experiments on three different treatment sequences: a) administering phages before antibiotics, b) administering phages and antibiotics simultaneously, and c) administering antibiotics before phages. Results: When the media was supplemented with sub-inhibitory concentrations of 0.25 μg/mL and 1 μg/mL, the size of the plaque increased from 0.5 ± 0.1 mm (in the control group with only the phage) to 4 ± 0.2 mm, 1.6 ± 0.1 mm, and 1.6 ± 0.4 mm when fosfomycin, ciprofloxacin, and oxacillin were added, respectively. The checkerboard analysis revealed a synergistic effect between the phages and antibiotics investigated, as indicated by a FIC value of less than 0.5. The combination treatment of phages and antibiotics demonstrated universal efficacy across all treatments. Nevertheless, the optimal effectiveness was demonstrated when the antibiotics were delivered subsequent to the phages. Utilizing the Galleria mellonella model, in vivo experiments showed that the combination of phage-oxacillin effectively eliminated biofilm-infected larvae, resulting in a survival rate of up to 80% in the treated groups. Discussion: Our findings highlight the advantages of using a combination of phage and antibiotic over using phages alone in the treatment of MRSA infections.
摘要：
简介：抗生素耐药性的出现是细菌感染治疗的重大挑战，特别是在重症监护病房（ICU）的患者中。噬菌体-抗生素联合疗法现在正被用作本质上是多药耐药的感染的优选治疗选择。方法:在本研究中,我们检查了葡萄球菌噬菌体vB_Sau_S90和四种抗生素对耐甲氧西林金黄色葡萄球菌（MRSA）的联合影响。我们对三种不同的治疗顺序进行了实验：a）在抗生素之前施用噬菌体，b)同时施用噬菌体和抗生素，和c)在噬菌体之前施用抗生素。结果:当培养基补充亚抑制浓度为0.25μg/mL和1μg/mL时,斑块的大小从0.5±0.1mm（在只有噬菌体的对照组中）增加到4±0.2mm，1.6±0.1mm,和1.6±0.4毫米时，磷霉素，环丙沙星,添加了苯唑西林，分别。棋盘分析揭示了研究的噬菌体和抗生素之间的协同作用，如FIC值小于0.5所示。噬菌体和抗生素的联合治疗在所有治疗中表现出普遍的功效。然而，当抗生素在噬菌体之后递送时,证明了最佳的有效性.利用MellonellaGalleria模型，体内实验表明，噬菌体-苯唑西林的组合有效地消除了生物膜感染的幼虫，导致治疗组的存活率高达80％。讨论：我们的发现强调了在MRSA感染的治疗中，使用噬菌体和抗生素的组合比单独使用噬菌体的优势。
