Molecular characteristics and antimicrobial susceptibility profiling of carbapenem-resistant Pseudomonas aeruginosa clinical isolates in Korea: Implications for novel β-lactam therapy.

BACKGROUND: This study investigated the molecular epidemiology, cross-resistance to novel antibiotics, and clonal distribution of carbapenem-resistant Pseudomonas aeruginosa (CRPA) clinical isolates.

METHODS: Forty-three CRPA isolates were collected from sterile clinical specimens in the Republic of Korea between 2015 and 2025. Susceptibility to 14 antibiotics was assessed in vitro by broth microdilution. Carbapenem-resistance mechanisms were characterized by using polymerase chain reaction, real-time quantitative reverse transcription polymerase chain reaction, and sequencing. Clonal diversity and epidemiological trends were examined by multilocus sequence typing.

RESULTS: Among the 43 CRPA isolates, the susceptibility rates were 88.4% for both aztreonam-avibactam and cefiderocol, compared with 46.5% for ceftolozane-tazobactam and 39.5% for ceftazidime-avibactam. Among the 22 difficult-to-treat resistance P. aeruginosa isolates, susceptibility rates were 77.3% for aztreonam-avibactam and 86.4% for cefiderocol. Carbapenemase genes were detected in 46.5% of isolates, predominantly blaNDM (41.9%). Porin loss and efflux pump overexpression were observed in 83.7% and 23.3% of isolates, respectively. Among the 22 P. aeruginosa isolates non-susceptible to both ceftolozane-tazobactam and ceftazidime-avibactam, 90.9% and 77.3% remained susceptible to aztreonam-avibactam and cefiderocol, respectively. Multilocus sequence typing identified 12 sequence types (STs), with predominance of ST773 and ST644, both carrying blaNDM.

CONCLUSIONS: CRPA exhibited multifactorial resistance driven by oprD disruption and blaNDM carriage within a diverse clonal structure dominated by ST773 and ST644. Aztreonam-avibactam and cefiderocol showed promising activity, supporting their role as critical therapeutic options.