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Pharmacodynamic individualization of phage therapy against a KPC-5-producing <i>Pseudomonas aeruginosa</i>

2025/12/19 by Thomas D. Nguyen, Jacob T. Sanborn, Brian M. Ho +5 · 1 voice
Environmental Science · Medicine · Immunology and Microbiology · #Bacteriophages and microbial interactions #Monoclonal and Polyclonal Antibodies Research #Invertebrate Immune Response Mechanisms

paper · doi:10.1093/jacamr/dlaf257

openalex publication_date 2025/12/19 · openalex created_date 2026/01/08 · openalex updated_date 2026/08/01

Abstract

Abstract Background There is a resurgence of interest in bacteriophage (phage) therapy as antimicrobials, resulting from growing antimicrobial resistance to small-molecule antibiotics. Phages are bacterial viruses long studied, but there is a need for high resolution and systematic assessment of clinical dosing strategies for phages to better inform therapy. Methods We hypothesized that empirical in vitro assessment of clinically relevant phages facilitates pharmacodynamic-driven individualization. Three clinically relevant phage strains (LUZ19, PYO2 and E215) were evaluated as mono- or dual-phage therapy against a clinical Pseudomonas aeruginosa in 24 h static time kills and in 7-day hollow fibre infection model. Results PYO2 single-bolus administration achieved a bacterial log reduction of 6.82 log10 cfu/mL, with eradication at 4 h. Dual-phage therapy (LUZ19 + PYO2) achieved a bacterial log reduction of 6.81 log10 cfu/mL, with delayed eradication at 12 h. Conclusions This highlights the potential of reverse translational pharmacokinetic/pharmacodynamic-driven approaches to guide rational phage selection strategies against individual clinical isolates while identifying potential antagonistic phage–phage interactions.

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