Phage therapy in people with cystic fibrosis: A systematic review

BACKGROUND: Despite advances in cystic fibrosis management, chronic infections caused by multidrug-resistant bacteria remain a major clinical challenge. Bacteriophage therapy, which uses viruses that selectively infect and lyse bacteria while sparing host cells, has emerged as a promising approach against biofilm-associated and/or multidrug-resistant pathogens, although current clinical evidence is still limited. METHODS: A systematic review was conducted in four major databases up to December 2025 for randomized controlled trials, case reports and case series reporting outcomes in cystic fibrosis patients receiving phage therapy, focusing on microbiological outcomes, changes in forced expiratory volume in one second (FEV₁) and adverse events. RESULTS: Nineteen studies involving 51 cystic fibrosis patients and 52 phage treatment courses were analyzed. Pseudomonas aeruginosa was the predominant target (46%). Overall microbiological improvement with bacterial load reduction was achieved in 35/51 cases (68.6%), while FEV1 improvement was documented in 74% (20/27). Safety profile was favorable, with 41 of 52 patients experiencing no adverse events. Two serious adverse events were reported, with uncertain association with phage therapy. Stratified analysis suggests similar results in pediatric and adult efficacy outcomes. DISCUSSION AND CONCLUSIONS: Phage therapy appears generally safe and well tolerated in cystic fibrosis patients, with severe adverse events being rare but worthy of attention. Clinical and microbiological improvements were observed in most patients. Evidence of synergistic effects with antibiotics and variable immune responses highlight the complexity of treatment. Considering protocol heterogeneity and small sample sizes, these findings support further well-designed studies to optimize safety and efficacy.