Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
J Infect Dis. 2022 Apr 19;225(8):1452-1459. doi: 10.1093/infdis/jiab112.
The optimal method for delivering phages in the context of ventilator-associated pneumonia (VAP) is unknown. In the current study, we assessed the utility of aerosolized phages (aerophages) for experimental methicillin-resistant Staphylococcus aureus (MRSA) pneumonia.
Rats were ventilated for 4 hours before induction of pneumonia. Animals received one of the following: (1) aerophages; (2) intravenous (IV) phages; (3) a combination of IV and aerophages; (4) IV linezolid; or (5) a combination of IV linezolid and aerophages. Phages were administered at 2, 12, 24, 48, and 72 hours, and linezolid was administered at 2, 12, 24, 36, 48, 60, and 72 hours. The primary outcome was survival at 96 hours. Secondary outcomes were bacterial and phage counts in tissues and histopathological scoring of the lungs.
Aerophages and IV phages each rescued 50% of animals from severe MRSA pneumonia (P < .01 compared with placebo controls). The combination of aerophages and IV phages rescued 91% of animals, which was higher than either monotherapy (P < .05). Standard-of-care antibiotic linezolid rescued 38% of animals. However, linezolid and aerophages did not synergize in this setting (55% survival).
Aerosolized phage therapy showed potential for the treatment of MRSA pneumonia in an experimental animal model and warrants further investigation for application in humans.
在呼吸机相关性肺炎（VAP）的情况下，噬菌体的最佳传递方法尚不清楚。在目前的研究中，我们评估了雾化噬菌体（aerophages）在耐甲氧西林金黄色葡萄球菌（MRSA）肺炎实验中的应用。
在诱导肺炎前，大鼠通气 4 小时。动物接受以下治疗之一：（1）雾化噬菌体；（2）静脉（IV）噬菌体；（3）IV 和雾化噬菌体联合治疗；（4）IV 利奈唑胺；或（5）IV 利奈唑胺和雾化噬菌体联合治疗。噬菌体在 2、12、24、48 和 72 小时时给予，利奈唑胺在 2、12、24、36、48、60 和 72 小时时给予。主要终点是 96 小时时的存活率。次要终点是组织中的细菌和噬菌体计数以及肺部的组织病理学评分。
雾化噬菌体和 IV 噬菌体都能使 50%的严重 MRSA 肺炎动物存活（与安慰剂对照组相比，P<0.01）。雾化噬菌体和 IV 噬菌体联合治疗可使 91%的动物存活，高于单独治疗（P<0.05）。标准治疗抗生素利奈唑胺可使 38%的动物存活。然而，在这种情况下，利奈唑胺和噬菌体并没有协同作用（存活率为 55%）。
雾化噬菌体治疗在实验动物模型中显示出治疗 MRSA 肺炎的潜力，值得进一步研究，以应用于人类。
