Mapping the clinical use of inhaled bacteriophages in respiratory infections caused by multidrug-resistant pathogens: a scoping review.

OBJECTIVE

Inhaled bacteriophage therapy is an emerging adjunctive strategy for treating lower respiratory tract infections caused by multidrug-resistant (MDR) pathogens. However, the clinical evidence base remains fragmented. We conducted a scoping review to map the current landscape of human studies using nebulized, aerosolized, or dry-powder phage therapy for pulmonary infections.

METHODS

We systematically searched PubMed, Scopus, Web of Science, and ClinicalTrials.gov for clinical studies published up to 1 June 2025. Eligible studies included clinical trials, cohort studies, and case reports/series reporting at least one dose of inhaled lytic phage for bacterial respiratory infections. Screening followed PRISMA-ScR guidelines. Key data were extracted on patient characteristics, pathogens, phage preparations, delivery methods, safety, and outcomes.

RESULTS

Of 507 records identified, 31 studies met inclusion criteria: six clinical trials and 25 case reports or series. Target infections included ventilator-associated pneumonia, cystic fibrosis exacerbations, and chronic bronchiectasis, primarily due to Pseudomonas aeruginosa, Acinetobacter baumannii, or Klebsiella pneumoniae. Delivery methods varied widely, including nebulizers, dry-powder inhalers, and endotracheal instillation. Most studies reported clinical or microbiological improvement without major adverse events, though few used standardized outcome measures.

CONCLUSIONS

Inhaled phage therapy has shown promise in compassionate and investigational settings for MDR respiratory infections. Despite heterogeneity in delivery methods and outcome reporting, preliminary data suggests feasibility and safety. Standardized protocols and controlled trials are needed to define its role in pulmonary antimicrobial therapy.