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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 chron...

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Autores principales: Köhler, Thilo, Luscher, Alexandre, Falconnet, Léna, Resch, Grégory, McBride, Robert, Mai, Quynh-Anh, Simonin, Juliette L., Chanson, Marc, Maco, Bohumil, Galiotto, Raphaël, Riat, Arnaud, Civic, Natacha, Docquier, Mylène, McCallin, Shawna, Chan, Benjamin, van Delden, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10300124/
https://www.ncbi.nlm.nih.gov/pubmed/37369702
http://dx.doi.org/10.1038/s41467-023-39370-z
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author Köhler, Thilo
Luscher, Alexandre
Falconnet, Léna
Resch, Grégory
McBride, Robert
Mai, Quynh-Anh
Simonin, Juliette L.
Chanson, Marc
Maco, Bohumil
Galiotto, Raphaël
Riat, Arnaud
Civic, Natacha
Docquier, Mylène
McCallin, Shawna
Chan, Benjamin
van Delden, Christian
author_facet Köhler, Thilo
Luscher, Alexandre
Falconnet, Léna
Resch, Grégory
McBride, Robert
Mai, Quynh-Anh
Simonin, Juliette L.
Chanson, Marc
Maco, Bohumil
Galiotto, Raphaël
Riat, Arnaud
Civic, Natacha
Docquier, Mylène
McCallin, Shawna
Chan, Benjamin
van Delden, Christian
author_sort Köhler, Thilo
collection PubMed
description 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.
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spelling pubmed-103001242023-06-29 Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa Köhler, Thilo Luscher, Alexandre Falconnet, Léna Resch, Grégory McBride, Robert Mai, Quynh-Anh Simonin, Juliette L. Chanson, Marc Maco, Bohumil Galiotto, Raphaël Riat, Arnaud Civic, Natacha Docquier, Mylène McCallin, Shawna Chan, Benjamin van Delden, Christian Nat Commun Article 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. Nature Publishing Group UK 2023-06-27 /pmc/articles/PMC10300124/ /pubmed/37369702 http://dx.doi.org/10.1038/s41467-023-39370-z Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Köhler, Thilo
Luscher, Alexandre
Falconnet, Léna
Resch, Grégory
McBride, Robert
Mai, Quynh-Anh
Simonin, Juliette L.
Chanson, Marc
Maco, Bohumil
Galiotto, Raphaël
Riat, Arnaud
Civic, Natacha
Docquier, Mylène
McCallin, Shawna
Chan, Benjamin
van Delden, Christian
Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa
title Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa
title_full Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa
title_fullStr Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa
title_full_unstemmed Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa
title_short Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa
title_sort personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant pseudomonas aeruginosa
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10300124/
https://www.ncbi.nlm.nih.gov/pubmed/37369702
http://dx.doi.org/10.1038/s41467-023-39370-z
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