Ecological and Immune Pressures Shape Outcomes of Precision Phage Therapy in Advanced Cystic Fibrosis Lung Disease
Luong, T.; Kharrat, L.; Champagne-Jorgensen, K.; Melendez, J.; Pride, D. T.; Conrad, D. J.; Roach, D. R.
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Chronic Pseudomonas aeruginosa infection remains a defining and increasingly drug-resistant complication in cystic fibrosis (CF). Here, we report phage-antibiotic co-therapy in an elderly individual with CF and a multidrug-resistant pulmonary exacerbation. Treatment was safe, well-tolerated, and associated with rapid clinical improvement, including enhanced lung function, reduced obstruction, and a 100-fold decrease in bacterial burden. Multi-omic profiling revealed in situ phage replication, transient suppression of non- mucoid P. aeruginosa, and virome restructuring. Bacterial isolates evolved resistance with associated fitness costs, while the host developed phage-specific neutralizing antibodies that limited systemic activity. Despite this, one phage persisted in the lung beyond therapy. These findings offer in vivo insight into phage-host- microbiome dynamics during treatment and underscore the importance of integrating microbial ecology and immune profiling into phage therapy design. This case highlights the potential for phage therapy in late-stage CF and the value of personalized, immune-informed strategies for managing chronic infection.
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