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

被引:38
作者
Kohler, Thilo [1 ,2 ]
Luscher, Alexandre [1 ,2 ]
Falconnet, Lena [1 ,2 ]
Resch, Gregory [3 ]
McBride, Robert [4 ]
Mai, Quynh-Anh [4 ]
Simonin, Juliette L. [5 ]
Chanson, Marc [5 ]
Maco, Bohumil [2 ]
Galiotto, Raphael [2 ]
Riat, Arnaud [6 ]
McCallin, Shawna [7 ]
Chan, Benjamin [8 ]
van Delden, Christian [1 ,2 ]
机构
[1] Geneva Univ Hosp, Serv Infect Dis, Geneva, Switzerland
[2] Univ Geneva, Dept Microbiol & Mol Med, Geneva, Switzerland
[3] Lausanne Univ Hosp CHUV, Ctr Res & Innovat Clin Pharmaceut Sci CRISP, Lausanne, Switzerland
[4] Felix Biotechnol, San Francisco, CA USA
[5] Univ Geneva, Dept Cell Physiol & Metab, Geneva, Switzerland
[6] Geneva Univ Hosp, Diagnost Bacteriol Lab, Geneva, Switzerland
[7] Balgrist Hosp, Dept Neurourol, Zurich, Switzerland
[8] Yale Univ, New Haven, CT USA
基金
瑞士国家科学基金会;
关键词
GALLERIA-MELLONELLA; EFFICACY;
D O I
10.1038/s41467-023-39370-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Kohler et al. document the treatment, and clinical improvement, of a male patient with a life-threatening chronic multi-drug resistant Pseudomonas aeruginosa infection with aerosolized personalized phage therapy, in combination with intravenous antibiotic treatment. 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.
引用
收藏
页数:10
相关论文
共 32 条
[1]  
Abedon S.T., 2015, BACTERIOPHAGE, V5
[2]   Early clinical experience of bacteriophage therapy in 3 lung transplant recipients [J].
Aslam, Saima ;
Courtwright, Andrew M. ;
Koval, Christine ;
Lehman, Susan M. ;
Morales, Sandra ;
Furr, Carrie-Lynn Langlais ;
Rosas, Francisco ;
Brownstein, Michael J. ;
Fackler, Joseph R. ;
Sisson, Brittany M. ;
Biswas, Biswajit ;
Henry, Matthew ;
Luu, Truong ;
Bivens, Brittany N. ;
Hamilton, Theron ;
Duplessis, Christopher ;
Logan, Cathy ;
Law, Nancy ;
Yung, Gordon ;
Turowski, Jason ;
Anesi, Judith ;
Strathdee, Steffanie A. ;
Schooley, Robert T. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2019, 19 (09) :2631-2639
[3]   Advances in Bacteriophage Therapy against Relevant MultiDrug-Resistant Pathogens [J].
Broncano-Lavado, Antonio ;
Santamaria-Corral, Guillermo ;
Esteban, Jaime ;
Garcia-Quintanilla, Meritxell .
ANTIBIOTICS-BASEL, 2021, 10 (06)
[4]   Deciphering β-lactamase-independent p-lactam resistance evolution trajectories in Pseudomonas aeruginosa [J].
Cabot, Gabriel ;
Florit-Mendoza, Llorenc ;
Sanchez-Diener, Irina ;
Zamorano, Laura ;
Oliver, Antonio .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2018, 73 (12) :3322-3331
[5]   Phage treatment of an aortic graft infected with ⁢Pseudomonas aeruginosa⁢ [J].
Chan, Benjamin K. ;
Turner, Paul E. ;
Kim, Samuel ;
Mojibian, Hamid R. ;
Elefteriades, John A. ;
Narayan, Deepak .
EVOLUTION MEDICINE AND PUBLIC HEALTH, 2018, (01) :60-66
[6]   Phage Therapy-History from Twort and d'Herelle Through Soviet Experience to Current Approaches [J].
Chanishvili, Nina .
ADVANCES IN VIRUS RESEARCH, VOL 83: BACTERIOPHAGES, PT B, 2012, 83 :3-40
[7]   Bacteriophage therapy for empyema caused by carbapenem-resistant Pseudomonas aeruginosa [J].
Chen, Peifen ;
Liu, Ziqiang ;
Tan, Xin ;
Wang, Haijiang ;
Liang, Yiyang ;
Kong, Yingjun ;
Sun, Wenxue ;
Sun, Liqin ;
Ma, Yingfei ;
Lu, Hongzhou .
BIOSCIENCE TRENDS, 2022, 16 (02) :158-162
[8]   Comparison of double-locus sequence typing (DLST) and multilocus sequence typing (MLST) for the investigation of Pseudomonas aeruginosa populations [J].
Cholley, Pascal ;
Stojanov, Milos ;
Hocquet, Didier ;
Thouverez, Michelle ;
Bertrand, Xavier ;
Blanc, Dominique S. .
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 2015, 82 (04) :274-277
[9]  
Coffey BM, 2014, METHODS MOL BIOL, V1149, P631, DOI 10.1007/978-1-4939-0473-0_48
[10]   Hypermutator Pseudomonas aeruginosa Exploits Multiple Genetic Pathways To Develop Multidrug Resistance during Long-Term Infections in the Airways of Cystic Fibrosis Patients [J].
Colque, C. A. ;
Orio, A. G. Albarracin ;
Feliziani, S. ;
Marvig, R. L. ;
Tobares, A. R. ;
Johansen, H. K. ;
Molin, S. ;
Smania, A. M. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2020, 64 (05)