Pharmacodynamic individualization of phage therapy against a KPC-5-producing Pseudomonas aeruginosa

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.

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.

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.

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.