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bioRxiv · 10.64898/2026.09.03.749285

Variable phage susceptibility of Pseudomonas aeruginosa from patients with and without cystic fibrosis following treatment-emergent resistance to ceftolozane-tazobactam

Wallace, N. R.·DiDonato, R. L.·Jackson, B. A.·Kline, E. G.·Squires, K. M.·Dorazio, A. J.·Shields, R. K.·Van Tyne, D.
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Abstract

Background: Pseudomonas aeruginosa is a ubiquitous opportunistic bacterial pathogen associated with nosocomial infections and is a leading cause of infection in persons with cystic fibrosis (pwCF). The front-line treatment for multidrug-resistant P. aeruginosa infections is ceftolozane-tazobactam (C/T). While previous research has characterized clinical P. aeruginosa isolates that evolved resistance to C/T, the collateral effect of evolved resistance on susceptibility to bacteriophages has not been explored. Methods: We collected paired P. aeruginosa clinical isolates from 10 pwCF and 18 non-pwCF who developed treatment-emergent C/T resistance. We compared genetic relatedness, acute and chronic virulence phenotypes, and antibiotic and phage susceptibilities between each pair of susceptible baseline and treatment-emergent C/T-resistant isolates. Results: Treatment-emergent C/T-resistant isolates were genetically closely related to baseline isolates in all patients. Virulence phenotypes did not differ between pre- and post-C/T exposure isolates, but isolates from pwCF demonstrated differences in protease production, twitching motility, and amino acid auxotrophy compared to isolates from non-pwCF. Treatment-emergent C/T resistance was associated with increased resistance to ceftazidime and ceftazidime/avibactam, but no other trends in antibiotic or phage susceptibility were detected. Conclusions: Treatment-emergent resistance to C/T does not cause predictable alterations in phage susceptibility across genotypically and phenotypically diverse multidrug-resistant P. aeruginosa clinical isolates.

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Wallace, N. R., DiDonato, R. L., Jackson, B. A., Kline, E. G., Squires, K. M., Dorazio, A. J., Shields, R. K., Van Tyne, D.. 2026-09-07. Variable phage susceptibility of Pseudomonas aeruginosa from patients with and without cystic fibrosis following treatment-emergent resistance to ceftolozane-tazobactam. https://doi.org/10.64898/2026.09.03.749285

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