Personalized inhaled bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis

Bacteriophage (phage) therapy, which uses lytic viruses as antimicrobials, is a potential strategy to address the antimicrobial resistance crisis. Cystic fibrosis, a disease complicated by recurrent Pseudomonas aeruginosa pulmonary infections, is an example of the clinical impact of antimicrobial resistance. Here, using a personalized phage therapy strategy that selects phages for a predicted evolutionary trade-off, nine adults with cystic fibrosis (eight women and one man) of median age 32 (range 22-46) years were treated with phages on a compassionate basis because their clinical course was complicated by multidrug-resistant or pan-drug-resistant Pseudomonas that was refractory to prior courses of standard antibiotics. The individuals received a nebulized cocktail or single-phage therapy without adverse events. Five to 18 days after phage therapy, sputum Pseudomonas decreased by a median of 10<sup>4</sup> CFU ml<sup>-1</sup>, or a mean difference of 10<sup>2</sup> CFU ml<sup>-1</sup> (P = 0.006, two-way analysis of variance with Dunnett's multiple-comparisons test), without altering sputum microbiome, and an analysis of sputum Pseudomonas showed evidence of trade-offs that decreased antibiotic resistance or bacterial virulence. In addition, an improvement of 6% (median) and 8% (mean) predicted FEV<sub>1</sub> was observed 21-35 days after phage therapy (P = 0.004, Wilcoxon signed-rank t-test), which may reflect the combined effects of decreased bacterial sputum density and phage-driven trade-offs. These results show that a personalized, nebulized phage therapy trade-off strategy may affect clinical and microbiologic endpoints, which must be evaluated in larger clinical trials.

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Publication Details

Journal
Nature Medicine
Published
2025-04-29
DOI
https://doi.org/10.1038/s41591-025-03678-8
Citations
58
Primary Topic
Bacteriophages and microbial interactions
Type
article
Field-Weighted Citation Impact
99.54

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article

Personalized inhaled bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis

Kaitlyn E. Kortright, Clemente J. Britto, Bradley S. Quon, Jill R. Stewart et al.
58 citations
Nature Medicine
Bacteriophages and microbial interactions
99.54
article

Personalized inhaled bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis

Kaitlyn E. Kortright, Clemente J. Britto, Bradley S. Quon, Jill R. Stewart, Silvia Würstle, Paul E. Turner, John M. Reynolds, Isabel M. Ott, Mrinalini Modak, Barbara I. Kazmierczak, Jaideep S. Talwalkar, Albert C. Vill, Adaobi Kanu, Raksha Jain, Z.M. Harris, Ying Hui Sun, Nauman Chaudary, Casey Grun, Jonathan L. Koff, Charlotte C. Tenebäck, Veronika Shabanova, Casey R. Appell, Benjamin K. Chan, Govindarajan Rajagopalan, Gail Stanley, Sugeet Jagpal, Quynh-Anh Mai
article en
58 citations

Abstract

Bacteriophage (phage) therapy, which uses lytic viruses as antimicrobials, is a potential strategy to address the antimicrobial resistance crisis. Cystic fibrosis, a disease complicated by recurrent Pseudomonas aeruginosa pulmonary infections, is an example of the clinical impact of antimicrobial resistance. Here, using a personalized phage therapy strategy that selects phages for a predicted evolutionary trade-off, nine adults with cystic fibrosis (eight women and one man) of median age 32 (range 22-46) years were treated with phages on a compassionate basis because their clinical course was complicated by multidrug-resistant or pan-drug-resistant Pseudomonas that was refractory to prior courses of standard antibiotics. The individuals received a nebulized cocktail or single-phage therapy without adverse events. Five to 18 days after phage therapy, sputum Pseudomonas decreased by a median of 10<sup>4</sup> CFU ml<sup>-1</sup>, or a mean difference of 10<sup>2</sup> CFU ml<sup>-1</sup> (P = 0.006, two-way analysis of variance with Dunnett's multiple-comparisons test), without altering sputum microbiome, and an analysis of sputum Pseudomonas showed evidence of trade-offs that decreased antibiotic resistance or bacterial virulence. In addition, an improvement of 6% (median) and 8% (mean) predicted FEV<sub>1</sub> was observed 21-35 days after phage therapy (P = 0.004, Wilcoxon signed-rank t-test), which may reflect the combined effects of decreased bacterial sputum density and phage-driven trade-offs. These results show that a personalized, nebulized phage therapy trade-off strategy may affect clinical and microbiologic endpoints, which must be evaluated in larger clinical trials.

Nature MedicineVol. 31(5)
University of Vermont (US), Northwestern University (US), Goethe University Frankfurt (DE), Texas Tech University (US), University of British Columbia (CA), Duke University (US), Virginia Commonwealth University (US), Johnson University (US), Yale University (US), University Hospital Frankfurt (DE), St. Paul's Hospital (CA), The University of Texas Southwestern Medical Center (US), Texas Tech University Health Sciences Center (US)
Cystic Fibrosis Foundation, Office of Extramural Research, National Institutes of Health
Openalex Percentile: Top 0%
Bacteriophages and microbial interactions
99.54
DOIOpen Access PDFOpenAlex
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