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针对人工关节感染患者分离噬菌体及其抗生物膜活性研究

Isolation and Antibiofilm Activity of Bacteriophages against from Patients with Periprosthetic Joint Infection.

机构信息

Department of Trauma Surgery, University Hospitals Leuven, 3000 Leuven, Belgium.

Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium.

出版信息

Viruses. 2024 Oct 10;16(10):1592. doi: 10.3390/v16101592.

Abstract

BACKGROUND

Infections following shoulder surgery, particularly periprosthetic joint infection (PJI), are challenging to treat. is the causative pathogen in 39% to 76% of these cases. This study explores the efficacy of bacteriophage therapy as an alternative to conventional antibiotics for treating such infections.

METHODS

Nine phages with lytic activity were isolated from the skin of humans using ATCC 6919 as the indicator host. These phages were tested individually or in combination to assess host range and antibiofilm activity against clinical strains of associated with PJIs. The phage cocktail was optimized for broad-spectrum activity and tested in vitro against biofilms formed on titanium discs to mimic the prosthetic environment.

RESULTS

The isolated phages displayed lytic activity against a range of clinical isolates. The phage cocktail significantly reduced the bacterial load of strains 183, 184, and GG2A, as compared with untreated controls ( < 0.05). Individual phages, particularly CaJIE7 and CaJIE3, also demonstrated significant reductions in bacterial load with respect to specific strains. Moreover, phages notably disrupted the biofilm structure and reduced biofilm biomass, confirming the potential of phage therapy in targeting biofilm-associated infections.

CONCLUSIONS

Our preclinical findings support the potential of phage therapy as a viable adjunct to traditional antibiotics for treating infections in orthopedic device-related infections. The ability of phages to disrupt biofilms may be particularly beneficial for managing infections associated with prosthetic implants.

摘要

背景

肩部手术后的感染,特别是人工关节周围感染(PJI),治疗具有挑战性。金黄色葡萄球菌是这些感染中 39%至 76%的病原体。本研究探讨了噬菌体治疗作为传统抗生素治疗这些感染的替代方法的疗效。

方法

使用 ATCC 6919 作为指示宿主,从人体皮肤中分离出 9 种具有溶菌活性的噬菌体。单独或组合测试这些噬菌体,以评估其对与 PJI 相关的金黄色葡萄球菌临床株的宿主范围和抗生物膜活性。优化噬菌体鸡尾酒以实现广谱活性,并在体外针对钛盘上形成的生物膜进行测试,以模拟假体环境。

结果

分离的噬菌体对一系列金黄色葡萄球菌临床分离株表现出溶菌活性。噬菌体鸡尾酒与未处理的对照组相比,显著降低了菌株 183、184 和 GG2A 的细菌负荷(<0.05)。个别噬菌体,特别是 CaJIE7 和 CaJIE3,对特定菌株的细菌负荷也显示出显著降低。此外,噬菌体明显破坏了生物膜结构并减少了生物膜生物量,证实了噬菌体治疗在靶向生物膜相关感染方面的潜力。

结论

我们的临床前发现支持噬菌体治疗作为传统抗生素治疗骨科器械相关感染中金黄色葡萄球菌感染的可行辅助手段的潜力。噬菌体破坏生物膜的能力可能对管理与假体植入物相关的感染特别有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/11512206/5e936af087ca/viruses-16-01592-g001.jpg

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