Combination of bacteriophages and vancomycin in a co-delivery hydrogel for localized treatment of fracture-related infections.

IF 7.8 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY npj Biofilms and Microbiomes Pub Date : 2024-08-29 DOI:10.1038/s41522-024-00552-2

Baixing Chen, Luis Ponce Benavente, Marco Chittò, Virginia Post, Caroline Constant, Stephan Zeiter, Pamela Nylund, Matteo D'Este, Mercedes González Moreno, Andrej Trampuz, Jeroen Wagemans, Rob Lavigne, Jolien Onsea, R Geoff Richards, Willem-Jan Metsemakers, T Fintan Moriarty

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Abstract

Fracture-related infections (FRIs), particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA), are challenging to treat. This study designed and evaluated a hydrogel loaded with a cocktail of bacteriophages and vancomycin (1.2 mg/mL). The co-delivery hydrogel showed 99.72% reduction in MRSA biofilm in vitro. The hydrogel released 54% of phages and 82% of vancomycin within 72 h and maintained activity for eight days, in vivo the co-delivery hydrogel with systemic antibiotic significantly reduced bacterial load by 0.99 log10 CFU compared to controls, with active phages detected in tissues at euthanasia (2 × 10³ PFU/mL). No phage resistance was detected in the phage treatment groups, and serum neutralization resulted in only a 20% reduction in phage count. In this work, we show that a phage-antibiotic co-delivery system via CMC hydrogel is a promising adjunct to systemic antibiotic therapy for MRSA-induced FRI, highlighting its potential for localized, sustained delivery and improved treatment outcomes.

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将噬菌体和万古霉素结合到共给水凝胶中，用于局部治疗骨折相关感染。

骨折相关感染（FRI），尤其是由耐甲氧西林金黄色葡萄球菌（MRSA）引起的感染，治疗难度很大。本研究设计并评估了一种装有噬菌体鸡尾酒和万古霉素（1.2 毫克/毫升）的水凝胶。在体外，这种协同给药水凝胶可减少 99.72% 的 MRSA 生物膜。水凝胶在 72 小时内释放了 54% 的噬菌体和 82% 的万古霉素，并在 8 天内保持活性。在体内，与对照组相比，联合给药水凝胶和全身抗生素可显著减少细菌负荷 0.99 log10 CFU，安乐死时可在组织中检测到活性噬菌体（2 × 103 PFU/mL）。噬菌体处理组未检测到噬菌体抗药性，血清中和只导致噬菌体数量减少 20%。在这项工作中，我们证明了通过 CMC 水凝胶的噬菌体-抗生素联合给药系统是治疗 MRSA 引起的 FRI 的一种很有前景的辅助全身抗生素疗法，突出了它在局部持续给药和改善治疗效果方面的潜力。

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来源期刊

npj Biofilms and Microbiomes Immunology and Microbiology-Microbiology

CiteScore

12.10

自引率

3.30%

发文量

审稿时长

9 weeks

期刊介绍： npj Biofilms and Microbiomes is a comprehensive platform that promotes research on biofilms and microbiomes across various scientific disciplines. The journal facilitates cross-disciplinary discussions to enhance our understanding of the biology, ecology, and communal functions of biofilms, populations, and communities. It also focuses on applications in the medical, environmental, and engineering domains. The scope of the journal encompasses all aspects of the field, ranging from cell-cell communication and single cell interactions to the microbiomes of humans, animals, plants, and natural and built environments. The journal also welcomes research on the virome, phageome, mycome, and fungome. It publishes both applied science and theoretical work. As an open access and interdisciplinary journal, its primary goal is to publish significant scientific advancements in microbial biofilms and microbiomes. The journal enables discussions that span multiple disciplines and contributes to our understanding of the social behavior of microbial biofilm populations and communities, and their impact on life, human health, and the environment.