Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa

Bacteriophage therapy has been suggested as an alternative or complementary strategy for the treatment of multidrug resistant (MDR) bacterial infections. Here, we report the favourable clinical evolution of a 41-year-old male patient with a Kartagener syndrome complicated by a life-threatening MDR <em>Pseudomonas aeruginosa </em>infection, who was treated successfully with iterative aerosolized phage treatments specifically directed against the patient’s isolate. We followed the longitudinal evolution of both phage and bacterial loads during and after phage administration in respiratory samples. Phage titres in consecutive sputum samples showed <em>in patient</em> phage replication. Phenotypic analysis and whole genome sequencing of sequential bacterial isolates revealed a clonal, but phenotypically diverse population of hypermutator strains. The MDR phenotype in the collected isolates was multifactorial and mainly due to spontaneous chromosomal mutations. All isolates recovered after phage treatment remained phage susceptible. These results demonstrate that clinically significant improvement is achievable by personalised phage therapy even in the absence of complete eradication of <em>P. aeruginosa</em> lung colonization.噬菌体疗法被提出可作为多重耐药（MDR）细菌感染治疗的替代或辅助策略。本研究报道了一例41岁卡塔格内综合征男性患者的良好临床转归：该患者并发危及生命的多重耐药铜绿假单胞菌（Pseudomonas aeruginosa）感染，通过针对自身分离株的迭代雾化噬菌体疗法成功获得治愈。我们对呼吸样本中噬菌体与细菌载量在噬菌体给药期间及给药后的纵向动态变化进行了追踪监测。连续痰液样本中的噬菌体滴度证实存在患者体内的噬菌体增殖现象。对连续分离的细菌菌株开展表型分析与全基因组测序后发现，存在一群克隆型一致但表型多样的高突变菌株。所获分离菌株的多重耐药表型为多因素驱动，主要源于自发染色体突变。噬菌体治疗后回收的所有分离株仍对噬菌体保持敏感。本研究结果表明，即便无法完全清除铜绿假单胞菌（P. aeruginosa）肺部定植，通过个性化噬菌体疗法仍可实现具有临床意义的病情改善。