在大鼠假关节感染模型中评估噬菌体关节内给药后的药代动力学参数

IF 3.8 3区 医学 Q2 VIROLOGY
Viruses-Basel Pub Date : 2024-11-20 DOI:10.3390/v16111800
Jason Young, Mohammad Javad Shariyate, Prateek Misra, Shubham Laiwala, Ara Nazarian, Edward Kenneth Rodriguez
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引用次数: 0

摘要

人工关节感染(PJI)是骨科手术的一种严重并发症。噬菌体疗法作为一种辅助治疗方法前景广阔,但还需要进一步研究,尤其是在药代动力学方面。因此,我们使用表皮葡萄球菌Kirschner钢丝假体大鼠模型对噬菌体疗法治疗PJI进行了药代动力学评估。我们将 52 只雄性 Sprague-Dawley 大鼠分为四组:阴性对照组(无噬菌体、无菌植入物)、PJI 对照组(细菌、无噬菌体)、无菌噬菌体组(给予噬菌体、无菌植入物)和 PJI 组(细菌、给予噬菌体)。PJI 组接种了约 106 CFU 的表皮葡萄球菌。接受噬菌体的组在植入后五天在关节内注射约 108 PFU 的 vB_SepM_Alex。大鼠在注射后 30 分钟至 48 小时之间被安乐死。所测得的 PJI 大鼠与无菌对照组大鼠关节周围组织中的噬菌体浓度没有显著差异。在非室药代动力学分析中,噬菌体的估计半衰期低于 6 小时(综合:3.73 [IQR, 1.45, 10.07])。给药后 2 小时内达到最大噬菌体浓度(合计:0.75 [0.50,1.75])。估计噬菌体的平均停留时间约为 3 小时(综合:3.04 [1.44, 4.19])。我们的研究提供了一组初步的药代动力学参数,可为今后的噬菌体剂量研究和噬菌体治疗 PJI 的动物模型提供参考。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Assessment of Bacteriophage Pharmacokinetic Parameters After Intra-Articular Delivery in a Rat Prosthetic Joint Infection Model.

Prosthetic joint infections (PJIs) are a serious complication of orthopedic surgery. Bacteriophage (phage) therapy shows promise as an adjunctive treatment but requires further study, particularly in its pharmacokinetics. Consequently, we performed a pharmacokinetic assessment of phage therapy for PJIs using a Staphylococcus epidermidis Kirschner wire-based prosthesis rat model. We used 52 male Sprague-Dawley rats in four groups: negative controls (no phage, sterile implant), PJI controls (bacteria, no phage), sterile phage (phages given, sterile implant), and PJI (bacteria, phages given). The PJI groups were inoculated with ~106 CFU of S. epidermidis. The groups receiving phage were intra-articularly injected with ~108 PFU of vB_SepM_Alex five days post-implantation. The rats were euthanized between 30 min and 48 h post-injection. The measured phage concentrations between the PJI rats and the sterile controls in periarticular tissues were not significantly different. In a noncompartmental pharmacokinetic analysis, the estimated phage half-lives were under 6 h (combined: 3.73 [IQR, 1.45, 10.07]). The maximum phage concentrations were reached within 2 h after administration (combined: 0.75 [0.50, 1.75]). The estimated phage mean residence time was approximately three hours (combined: 3.04 [1.44, 4.19]). Our study provides a preliminary set of pharmacokinetic parameters that can inform future phage dosing studies and animal models of phage therapy for PJIs.

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来源期刊
Viruses-Basel
Viruses-Basel VIROLOGY-
CiteScore
7.30
自引率
12.80%
发文量
2445
审稿时长
1 months
期刊介绍: Viruses (ISSN 1999-4915) is an open access journal which provides an advanced forum for studies of viruses. It publishes reviews, regular research papers, communications, conference reports and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. We also encourage the publication of timely reviews and commentaries on topics of interest to the virology community and feature highlights from the virology literature in the ''News and Views'' section. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.
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