Personalized Inhaled Bacteriophage Therapy Shows Promise for Cystic Fibrosis: Study

Phage therapy, where lytic viruses are used to infect and kill targeted bacteria, is being considered as a solution to the worldwide antimicrobial resistance problem. Cystic fibrosis is a hereditary disease frequently complicated by chronic Pseudomonas aeruginosa infections that become more resistant to standard antibiotics with time. In this trial, an individualized phage therapy approach was tested in which the phages were chosen not only for their ability to kill the bacteria but also to cause bacterial vulnerabilities—like decreased antibiotic resistance or decreased virulence.

Nine adult CF patients (eight female, one male; median age 32 years, range 22–46 years) with MDR or PDR Pseudomonas infection were enrolled in a compassionate-use treatment protocol. The infections had failed multiple previous antibiotic regimens. Either a nebulized phage cocktail or a single-phage therapy was administered to each patient, chosen on the basis of anticipated evolutionary trade-offs that would compel the bacteria into becoming either less virulent or more antibiotic-sensitive.

Notably, both patients tolerated the phage therapy with no occurrence of adverse effects. The phages were administered via inhalation, which is where the infection was present.

Results

• Patients enrolled: 9 (8 women, 1 man)

• Median age: 32 years (range 22–46)

Type of infection: MDR or PDR Pseudomonas aeruginosa resistant to conventional antibiotics

• Method of delivery: Nebulized cocktail or single phage therapy

• Safety: No adverse effects reported

Reduction of bacteria:

• Median: Reduction in Pseudomonas of 10⁴ CFU/ml

• Mean: Reduction of 10² CFU/ml (P = 0.006)

Improvement of lung function:

• Median FEV1: +6%

• Mean FEV1: +8% (P = 0.004)

• Sputum microbiome: Remains unchanged

• Trade-offs: Compromise loss of antibiotic resistance or virulence of bacteria

Personalized nebulized phage therapy is shown to be a safe and effective method of decreasing bacterial load and enhancing lung function in cystic fibrosis patients with drug-resistant Pseudomonas aeruginosa infection. The novel therapy not only reduces bacterial numbers but also imposes genetic trade-offs on bacteria that can decrease their resistance and virulence.

Reference:

Chan, B.K., Stanley, G.L., Kortright, K.E. et al. Personalized inhaled bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis. Nat Med (2025). https://doi.org/10.1038/s41591-025-03678-8