Abstract
BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) has emerged as a critical threat in bloodstream infections (BSIs), with rising global prevalence and elevated mortality rates. Traditional surveillance methods often lacks resolution for resistance-virulence-transmission interplay, highlighting the importance of high-resolution genomics. Whole-genome sequencing (WGS) has enabled unprecedented resolution in dissecting CRPA's genetic landscape, revealing links between resistance, virulence, and outcomes. RESULTS: This study employed WGS to characterize 61 P. aeruginosa isolates from BSIs, with a focus on 18 CRPA strains. Clinical data linked central venous catheterization to CRPA BSI development (OR = 6.6, p = 0.002) and identified carbapenem exposure, mechanical ventilation, and low hemoglobin as independent mortality risk factors. WGS identified 33.3% (n = 6, 6/18) of the strains harbored β-lactamase genes, and 44.4%(n = 8, 8/18) of the strains carried truncated OprD protein due to frameshift mutations or point mutations inducing translational truncation. Efflux pump overexpression (61.1% with ≥ 2-fold upregulation) further contributed to this resistance phenotype. MLST identified 49 distinct STs (including 2 novel types) and a pattern of endemic diversification. O11 is strongly linked to carbapenem resistance (CRPA: p = 0.02; MDRPA: p = 0.004), correlating with oprD mutations (p = 0.008) and exoU+/exoS-, indicating enhanced nosocomial adaptability. CONCLUSIONS: A very high genetic diversity was noted amongst P. aeruginosa strains isolated from BSIs cases. The mechanism of carbapenem resistance is mainly attributed to oprD mutations and efflux pumps activation, with carbapenemases emerging as an additional mechanism of concern. These resistance mechanisms with high-risk clinical factors collectively indicate that strict policies are essential for in CRPA BSIs management.