Department of Microbiology, Institut Pasteur, Molecular Biology of the Gene in Extremophiles Unit, Paris, France; Cellule Pasteur UPMC, Université Pierre et Marie Curie, Paris, France.
Clin Microbiol Infect. 2014 Dec;20(12):O983-90. doi: 10.1111/1469-0691.12712. Epub 2014 Jul 26.
Bacteriophages have been shown to be effective for treating acute infections of the respiratory tract caused by antibiotic-resistant bacteria in animal models, but no evidence has yet been presented of their activity against pathogens in complex biological samples from chronically infected patients. We assessed the efficacy of a cocktail of ten bacteriophages infecting Pseudomonas aeruginosa following its addition to 58 sputum samples from cystic fibrosis (CF) patients collected at three different hospitals. Ten samples that did not contain P. aeruginosa were not analysed further. In the remaining 48 samples, the addition of bacteriophages led to a significant decrease in the levels of P. aeruginosa strains, as shown by comparison with controls, taking two variables (time and bacteriophages) into account (p = 0.024). In 45.8% of these samples, this decrease was accompanied by an increase in the number of bacteriophages. We also tested each of the ten bacteriophages individually against 20 colonies from each of these 48 samples and detected bacteriophage-susceptible bacteria in 64.6% of the samples. An analysis of the clinical data revealed no correlation between patient age, sex, duration of P. aeruginosa colonization, antibiotic treatment, FEV1 (forced expiratory volume in the first second) and the efficacy of bacteriophages. The demonstration that bacteriophages infect their bacterial hosts in the sputum environment, regardless of the clinical characteristics of the patients, represents a major step towards the development of bacteriophage therapy to treat chronic lung infections.
噬菌体已被证明在动物模型中对抗生素耐药菌引起的呼吸道急性感染有效，但尚未有证据表明它们对慢性感染患者复杂生物样本中的病原体具有活性。我们评估了在添加到来自三家不同医院的 58 份囊性纤维化 (CF) 患者的痰样本后，感染铜绿假单胞菌的十种噬菌体混合物的疗效。没有包含铜绿假单胞菌的 10 个样本没有进一步分析。在其余的 48 个样本中，考虑到两个变量（时间和噬菌体），与对照相比，添加噬菌体导致铜绿假单胞菌菌株的水平显著下降（p = 0.024）。在这些样本中的 45.8%中，这种减少伴随着噬菌体数量的增加。我们还单独测试了这十种噬菌体中的每一种对来自这 48 个样本中的每个样本的 20 个菌落的反应，并在 64.6%的样本中检测到噬菌体易感细菌。对临床数据的分析表明，患者年龄、性别、铜绿假单胞菌定植时间、抗生素治疗、FEV1（第一秒用力呼气量）与噬菌体疗效之间没有相关性。噬菌体在痰环境中感染其细菌宿主的证明，无论患者的临床特征如何，都代表着朝着开发噬菌体疗法治疗慢性肺部感染迈出的重要一步。
