Centre for Infectious Diseases and Microbiology, Westmead Institute for Medical Research, Sydney, New South Wales, Australia.
Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia.
Nat Microbiol. 2020 Mar;5(3):465-472. doi: 10.1038/s41564-019-0634-z. Epub 2020 Feb 17.
In this single-arm non-comparative trial, 13 patients in an Australian hospital with severe Staphylococcus aureus infections were intravenously administered a good manufacturing practice-quality preparation of three Myoviridae bacteriophages (AB-SA01) as adjunctive therapy. AB-SA01 was intravenously administered twice daily for 14 d and the clinical, haematological and blood biochemical parameters of the recipients were monitored for 90 d. The primary outcome was the assessment of safety and tolerability (that is, pain and redness at the infusion site and systemic adverse reactions, such as fever, tachycardia, hypotension, diarrhoea or abdominal pain and the development of renal or hepatic dysfunction). No adverse reactions were reported, and our data indicate that AB-SA01 administered in this way is safe in severe S. aureus infections, including infective endocarditis and septic shock. Future controlled trials will be needed to determine the efficacy of AB-SA01 but no phage resistance evolved in vivo and the measurements of bacterial and phage kinetics in blood samples suggest that 12 h dosing of 10 plaque-forming units may be a rational basis for further studies.
在这项单臂非对照试验中，澳大利亚一家医院的 13 名严重金黄色葡萄球菌感染患者接受了静脉注射符合良好生产规范质量标准的三种肌尾噬菌体（AB-SA01）制剂作为辅助治疗。AB-SA01 每天静脉注射两次，共 14 天，监测 90 天内受者的临床、血液学和血液生化学参数。主要结局是评估安全性和耐受性（即输注部位的疼痛和发红以及全身不良反应，如发热、心动过速、低血压、腹泻或腹痛以及肾功能或肝功能障碍的发展）。未报告不良反应，我们的数据表明，以这种方式给予的 AB-SA01 在严重金黄色葡萄球菌感染中是安全的，包括感染性心内膜炎和感染性休克。未来需要进行对照试验来确定 AB-SA01 的疗效，但体内未出现噬菌体耐药性，血液样本中细菌和噬菌体动力学的测量表明，每 12 小时给予 10 个噬菌斑形成单位可能是进一步研究的合理基础。
