DataSheet1_Pharmacokinetic Assessment of Staphylococcal Phage K Following Parenteral and Intra-articular Administration in Rabbits.docx

The therapeutic value of phage as an alternative to antibiotics for the treatment of bacterial infections is being considered in the wake of mounting antibiotic resistance. In this study, the pharmacokinetic properties of Staphylococcus aureus phage K following intravenous and intra-articular administration were investigated in a rabbit model. Using a traditional plaque assay and a novel quantitative PCR assay to measure phage levels in specimens over time, it was found that intra-articularly administered phage enters the systemic circulation; that phage may be detected in synovial fluid up to 24 h following the intra-articular, but not intravenous, administration; and that qPCR-based enumeration is generally more sensitive than plaque enumeration, with fair to moderate correlation between the two methods. Findings presented should inform the design of phage therapy experiments and therapeutic drug monitoring in preclinical and human phage studies.

随着抗生素耐药性问题日益凸显，噬菌体（phage）作为抗生素替代品治疗细菌感染的治疗价值正受到广泛关注。本研究以家兔为实验模型，探究了金黄色葡萄球菌噬菌体K经静脉注射与关节腔内给药后的药代动力学特性。研究采用传统噬斑测定法（plaque assay）与新型定量聚合酶链式反应（quantitative PCR, qPCR）测定法，对样本中的噬菌体含量进行时序检测。结果显示：关节腔内给药的噬菌体可进入体循环；仅在关节腔内给药后的24小时内，可在滑液（synovial fluid）中检测到噬菌体，静脉给药则未检出；基于qPCR的噬菌体计数法整体灵敏度高于噬斑计数法，两种方法间具有中等至良好的相关性。本研究结果可为临床前及人体噬菌体治疗研究中的实验设计与治疗药物监测提供参考依据。