Service of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.
Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
Nat Commun. 2023 Jun 27;14(1):3629. doi: 10.1038/s41467-023-39370-z.
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 chronic MDR Pseudomonas aeruginosa infection, who is treated successfully with iterative aerosolized phage treatments specifically directed against the patient's isolate. We follow the longitudinal evolution of both phage and bacterial loads during and after phage administration in respiratory samples. Phage titres in consecutive sputum samples indicate in patient phage replication. Phenotypic analysis and whole genome sequencing of sequential bacterial isolates reveals a clonal, but phenotypically diverse population of hypermutator strains. The MDR phenotype in the collected isolates is multifactorial and mainly due to spontaneous chromosomal mutations. All isolates recovered after phage treatment remain phage susceptible. These results demonstrate that clinically significant improvement is achievable by personalised phage therapy even in the absence of complete eradication of P. aeruginosa lung colonization.
噬菌体疗法已被提议作为治疗多重耐药（MDR）细菌感染的一种替代或补充策略。在这里，我们报告了一名 41 岁男性 Kartagener 综合征患者的有利临床转归，该患者患有危及生命的慢性 MDR 铜绿假单胞菌感染，经过针对患者分离株的迭代雾化噬菌体治疗后成功治愈。我们在呼吸道样本中观察噬菌体和细菌负荷在噬菌体给药期间和之后的纵向演变。连续痰液样本中的噬菌体滴度表明患者体内存在噬菌体复制。对连续分离株进行表型分析和全基因组测序揭示了一个克隆但表型多样的高突变体菌株群体。收集的分离株中的 MDR 表型是多因素的，主要归因于自发的染色体突变。噬菌体治疗后回收的所有分离株仍然对噬菌体敏感。这些结果表明，即使在未能完全清除铜绿假单胞菌肺部定植的情况下，个体化噬菌体治疗也能实现临床显著改善。
