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

Article Article scientifique Rapport de cas Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa eng 2023-06-27 2023-06-27 author Kohler Thilo 0000-0003-4889-9492 23327 Département de médecine (DEMED) author Luscher Alexandre 660541 Département de médecine (DEMED) author Falconnet Léna 898001 author Resch Grégory author McBride Robert author Mai Quynh-Anh author Simonin Juliette Lynn 892917 author Chanson Marc 0000-0001-8104-2090 32865 Département de physiologie cellulaire et métabolisme (PHYME) author Maco Bohumil 0000-0001-8444-313X 863802 Services communs de la faculté de médecine (SCMU) author Galiotto Raphaël Andrea 0009-0001-8621-2260 906589 author Riat Arnaud 134645 author Civic Natacha 47183 plan stratégique sciences vie médecine (PSVIM) author Docquier Mylene 513819 Génétique programme prioritaire (GENPP) author McCallin Shawna author Chan Benjamin author Van Delden Christian 24088 Département de médecine (DEMED) 3629 10.1038/s41467-023-39370-z 37369702 2041-1723 PMC10300124 https://www.nature.com/articles/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. Dewey 612 Dewey 616 Dewey 590 Swiss National Science Foundation Pseudomonas aeruginosa in lung-transplant recipients: exploiting adaptation and microbial interactions to fight bacterial infections 179289 CH Projects 56 Département de médecine 221 54 Département de microbiologie et médecine moléculaire 21B 134 Département de physiologie cellulaire et métabolisme 21C 23 Institut de génétique et de génomique 0DH false 1255 Virus émergents 993 400 Groupe Laurent Kaiser (virologie clinique) 668 526 Résistance aux antibiotiques 866 235 Perception du Quorum et gènes de virulence 301 338 Génomique et microbiote 604 180 Mucoviscidose et jonctions communicantes 229 https://zenodo.org/records/8005315 https://www.ncbi.nlm.nih.gov/nuccore/OQ921398 https://www.ncbi.nlm.nih.gov/bioproject/PRJNA980116 Nature communications 14 1 721a5fc9-e98f-4c9b-aa2b-23677c5b8061 Article (Published version) Public Article-scientifique-from-crossref.pdf 1552902 application/pdf CC BY-4.0 7d21c9375ca281df1bc0efb1a9546d119239ccf433fef171bf77ffd26cee6568 d6a9c18d-2aa0-45b3-b2de-f6a88406e410 Supplemental data Public 41467_2023_39370_MOESM1_ESM.pdf 1097472 application/pdf 32deb3f0a49952bf64b987d3db74f40e60b30811e88882a1e1a700598c752f60 5fa056dd-6944-4ca3-9e71-76aa99d50f2f Supplemental data Public 41467_2023_39370_MOESM2_ESM.pdf 3589926 application/pdf 156f5784d1a929001a9ed522c2203d9793ed62a0100663bf586f792b1ee79f5a 571e75e3-de88-4bd7-bd72-b64b48a64ca4 Supplemental data Public 41467_2023_39370_MOESM3_ESM.pdf 88734 application/pdf fba56dffabd4f8e3a4175df8b8ecdace981867277fce4ccb1bab33e641728749 82522380-ef12-456f-a90d-726efb515957 Supplemental data Public 41467_2023_39370_MOESM4_ESM(1).xlsx 4963747 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet af94eccb962ef06dd0fad151a406fdcbfad7ab63ee170a590b4184f391fa9d0a 884f54c7-84a1-40f2-8515-cd061df8cf7e Supplemental data Public 41467_2023_39370_MOESM5_ESM.xlsx 572938 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 0189c03fbe75102ee9a2d84de9e4f2c6905a571a27baa8efa1a41b5e758f4d89 c3adc73e-2acd-478a-a447-0fbb5759b543 Supplemental data Public 41467_2023_39370_MOESM7_ESM.xlsx 7379384 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 10a843bf458efba4967b1d4abdfa4b2702822501479862dfc40a3bcd9695136c 8bc19456-3e25-4572-b019-d429203e9b3e Erratum Public s41467-023-40202-3.pdf 257265 application/pdf CC BY-4.0 bca32afb2497e5708e8d08b783588843d50bd990f1a6ebf3d67f70ea260b2005 Published erratum : Köhler T, Luscher A, Falconnet L, Resch G, McBride R, Mai QA, Simonin JL, Chanson M, Maco B, Galiotto R, Riat A, Civic N, Docquier M, McCallin S, Chan B, van Delden C. Author Correction: Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa. Nat Commun. 2023 Jul 24;14(1):4443. 10.1038/s41467-023-40202-3 37488101 openAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Centres et instituts / Institut de génétique et de génomique

Title	Published in	Year	Views	Downloads

Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa	Nature communications	2023	216	119
Combined bacteriophage and antibiotic treatment prevents pseudomonas aeruginosa infection of wild type and cftr- epithelial cells	Frontiers in Microbiology	2020	522	174

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