Adjunctive phage therapy improves antibiotic treatment of ventilator-associated-pneumonia with Pseudomonas aeruginosa
Abstract Bacterial multidrug resistance poses an urgent challenge for the treatment of critically ill patients developing ventilator-associated pneumonia (VAP). Phage therapy, a potential alternative when conventional antibiotics fail, has been unsuccessful in first clinical trials when used alone....
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59806-y |
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| author | Chantal Weissfuss Jingjing Li Ulrike Behrendt Karen Hoffmann Magdalena Bürkle Chunjiang Tan Gopinath Krishnamoorthy Imke H. E. Korf Christine Rohde Baptiste Gaborieau Laurent Debarbieux Jean-Damien Ricard Martin Witzenrath Matthias Felten Geraldine Nouailles |
| author_facet | Chantal Weissfuss Jingjing Li Ulrike Behrendt Karen Hoffmann Magdalena Bürkle Chunjiang Tan Gopinath Krishnamoorthy Imke H. E. Korf Christine Rohde Baptiste Gaborieau Laurent Debarbieux Jean-Damien Ricard Martin Witzenrath Matthias Felten Geraldine Nouailles |
| author_sort | Chantal Weissfuss |
| collection | DOAJ |
| description | Abstract Bacterial multidrug resistance poses an urgent challenge for the treatment of critically ill patients developing ventilator-associated pneumonia (VAP). Phage therapy, a potential alternative when conventional antibiotics fail, has been unsuccessful in first clinical trials when used alone. Whether combining antibiotics with phages may enhance effectiveness remains to be tested in experimental models. Here, we use a murine model of Pseudomonas-induced VAP to compare the efficacy of adjunctive phage cocktail for antibiotic therapy to either meropenem or phages alone. Combined treatment in murine VAP results in faster clinical improvement and prevents lung epithelial cell damage. Using human primary epithelial cells to dissect these synergistic effects, we find that adjunctive phage therapy reduces the minimum effective concentration of meropenem and prevents resistance development against both treatments. These findings suggest adjunctive phage therapy represents a promising treatment for MDR-induced VAP, enhancing the effectiveness of both antibiotics and phages while reducing adverse effects. |
| format | Article |
| id | doaj-art-095fbf2eef83435e97d2948eeb528eb5 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-095fbf2eef83435e97d2948eeb528eb52025-08-20T03:53:58ZengNature PortfolioNature Communications2041-17232025-05-0116111710.1038/s41467-025-59806-yAdjunctive phage therapy improves antibiotic treatment of ventilator-associated-pneumonia with Pseudomonas aeruginosaChantal Weissfuss0Jingjing Li1Ulrike Behrendt2Karen Hoffmann3Magdalena Bürkle4Chunjiang Tan5Gopinath Krishnamoorthy6Imke H. E. Korf7Christine Rohde8Baptiste Gaborieau9Laurent Debarbieux10Jean-Damien Ricard11Martin Witzenrath12Matthias Felten13Geraldine Nouailles14Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinDepartment of Infectious Diseases, Respiratory Medicine and Critical Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinDepartment of Infectious Diseases, Respiratory Medicine and Critical Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinDepartment of Infectious Diseases, Respiratory Medicine and Critical Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinDepartment of Infectious Diseases, Respiratory Medicine and Critical Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinDepartment of Infectious Diseases, Respiratory Medicine and Critical Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinDepartment of Infectious Diseases, Respiratory Medicine and Critical Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinPharmaceutical Biotechnology, Fraunhofer Institute for Toxicology and Experimental MedicineLeibniz Institute DSMZ-German Collection of Microorganisms and Cell CulturesInstitut Pasteur, Department of Microbiology, Bacteriophage Bacteria Host Laboratory, Université Paris Cité, CNRS UMR6047Institut Pasteur, Department of Microbiology, Bacteriophage Bacteria Host Laboratory, Université Paris Cité, CNRS UMR6047Infection Antimicrobials Modelling Evolution, Université Paris-Cité, Inserm, UMR 1137Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinDepartment of Infectious Diseases, Respiratory Medicine and Critical Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinDepartment of Infectious Diseases, Respiratory Medicine and Critical Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinAbstract Bacterial multidrug resistance poses an urgent challenge for the treatment of critically ill patients developing ventilator-associated pneumonia (VAP). Phage therapy, a potential alternative when conventional antibiotics fail, has been unsuccessful in first clinical trials when used alone. Whether combining antibiotics with phages may enhance effectiveness remains to be tested in experimental models. Here, we use a murine model of Pseudomonas-induced VAP to compare the efficacy of adjunctive phage cocktail for antibiotic therapy to either meropenem or phages alone. Combined treatment in murine VAP results in faster clinical improvement and prevents lung epithelial cell damage. Using human primary epithelial cells to dissect these synergistic effects, we find that adjunctive phage therapy reduces the minimum effective concentration of meropenem and prevents resistance development against both treatments. These findings suggest adjunctive phage therapy represents a promising treatment for MDR-induced VAP, enhancing the effectiveness of both antibiotics and phages while reducing adverse effects.https://doi.org/10.1038/s41467-025-59806-y |
| spellingShingle | Chantal Weissfuss Jingjing Li Ulrike Behrendt Karen Hoffmann Magdalena Bürkle Chunjiang Tan Gopinath Krishnamoorthy Imke H. E. Korf Christine Rohde Baptiste Gaborieau Laurent Debarbieux Jean-Damien Ricard Martin Witzenrath Matthias Felten Geraldine Nouailles Adjunctive phage therapy improves antibiotic treatment of ventilator-associated-pneumonia with Pseudomonas aeruginosa Nature Communications |
| title | Adjunctive phage therapy improves antibiotic treatment of ventilator-associated-pneumonia with Pseudomonas aeruginosa |
| title_full | Adjunctive phage therapy improves antibiotic treatment of ventilator-associated-pneumonia with Pseudomonas aeruginosa |
| title_fullStr | Adjunctive phage therapy improves antibiotic treatment of ventilator-associated-pneumonia with Pseudomonas aeruginosa |
| title_full_unstemmed | Adjunctive phage therapy improves antibiotic treatment of ventilator-associated-pneumonia with Pseudomonas aeruginosa |
| title_short | Adjunctive phage therapy improves antibiotic treatment of ventilator-associated-pneumonia with Pseudomonas aeruginosa |
| title_sort | adjunctive phage therapy improves antibiotic treatment of ventilator associated pneumonia with pseudomonas aeruginosa |
| url | https://doi.org/10.1038/s41467-025-59806-y |
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