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

Thilo Köhler (), Alexandre Luscher, Léna Falconnet, Grégory Resch, Robert McBride, Quynh-Anh Mai, Juliette L. Simonin, Marc Chanson, Bohumil Maco, Raphaël Galiotto, Arnaud Riat, Natacha Civic, Mylène Docquier, Shawna McCallin, Benjamin Chan and Christian Delden
Additional contact information
Thilo Köhler: Geneva University Hospitals
Alexandre Luscher: Geneva University Hospitals
Léna Falconnet: Geneva University Hospitals
Grégory Resch: Lausanne University Hospital (CHUV)
Robert McBride: Felix Biotechnology
Quynh-Anh Mai: Felix Biotechnology
Juliette L. Simonin: University of Geneva
Marc Chanson: University of Geneva
Bohumil Maco: University of Geneva
Raphaël Galiotto: University of Geneva
Arnaud Riat: Geneva University Hospitals
Natacha Civic: University of Geneva
Mylène Docquier: University of Geneva
Shawna McCallin: Department of Neuro-Urology Balgrist Hospital
Benjamin Chan: Yale University
Christian Delden: Geneva University Hospitals

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-39370-z

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