Evaluation of bacteriophage as an adjunct therapy for treatment of peri-prosthetic joint infection caused by Staphylococcus aureus
Evaluation of bacteriophage as an adjunct therapy for treatment of peri-prosthetic joint infection caused by Staphylococcus aureus
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DOI：
10.1371/journal.pone.0226574
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发表时间：
2019-12-26
期刊：
影响因子：
3.7
通讯作者：
McEwen, Peter
中科院分区：
文献类型：
--
作者：
Morris, Jodie L.;Letson, Hayley L.;McEwen, Peter
噬菌体治疗为治疗假体周围关节感染（PJI）提供了一种潜在的替代策略，特别是在有效抗生素有限的情况下。我们进行了临床前试验，以研究噬菌体鸡尾酒的治疗效果，单独和与万古霉素联合使用，以减少感染关节内的细菌数量，使用临床相关的金黄色葡萄球菌诱导的PJI模型。将感染的动物随机分配至4个治疗组，在手术后21天开始治疗：单独噬菌体、单独万古霉素、噬菌体和万古霉素以及假手术。在术后第28天，对动物实施安乐死，以进行植入关节的微生物和免疫学评估。与假处理的动物相比，单独用噬菌体或单独用万古霉素处理分别导致植入物周围组织内的细菌负荷减少5倍和6.2倍。与假处理的动物相比，S.在给予噬菌体与万古霉素组合的动物的关节组织中观察到金黄色葡萄球菌负荷，这对应于植入的膝关节中肿胀的减少。与假处理动物相比，给予噬菌体与万古霉素组合的动物关节内炎症减少的证据支持微生物学数据。我们的研究结果为噬菌体疗法作为PJI的可耐受和有效的辅助治疗提供了进一步的支持。
Phage therapy offers a potential alternate strategy for the treatment of peri-prosthetic joint infection (PJI), particularly where limited effective antibiotics are available. We undertook preclinical trials to investigate the therapeutic efficacy of a phage cocktail, alone and in combination with vancomycin, to reduce bacterial numbers within the infected joint using a clinically-relevant model of Staphylococcus aureus-induced PJI. Infected animals were randomised to 4 treatment groups, with treatment commencing 21-days post-surgery: bacteriophage alone, vancomycin alone, bacteriophage and vancomycin, and sham. At day 28 post-surgery, animals were euthanised for microbiological and immunological assessment of implanted joints. Treatment with phage alone or vancomycin alone, led to 5-fold and 6.2-fold reductions, respectively in bacterial load within peri-implant tissue compared to sham-treated animals. Compared to sham-treated animals, a 22.5-fold reduction in S. aureus burden was observed within joint tissue of animals that were administered phage in combination with vancomycin, corresponding with decreased swelling in the implanted knee. Microbiological data were supported by evidence of decreased inflammation within the joints of animals administered phage in combination with vancomycin, compared to sham-treated animals. Our findings provide further support for phage therapy as a tolerable and effective adjunct treatment for PJI.