Genomic epidemiology and resistance mechanisms of carbapenem-resistant Pseudomonas aeruginosa in Fujian Province, China: a multicenter study

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a major global nosocomial pathogen, and the emergence of difficult-to-treat resistance (DTR-PA) has further constrained therapeutic options. In China, Fujian Province has consistently reported a high burden of CRPA, yet large-scale multicenter genomic surveillance data remain limited. A total of 215 non-duplicate clinical CRPA isolates were collected from nine cities between June and December 2022. Antimicrobial susceptibility testing (AST), whole-genome sequencing (WGS), and phylogenetic analysis were performed to evaluate resistance profiles, clonal distributions, and molecular mechanisms. Among the 215 isolates, 32.6% ( n = 70) were classified as DTR-PA. AST showed that cefepime–zidebactam demonstrated favorable in vitro activity, with all isolates categorized as susceptible according to the proposed pharmacokinetic/pharmacodynamic (PK/PD) breakpoint (≤ 32 mg/L), whereas polymyxin B and amikacin were the next most active agents. Compared with carbapenem-resistant but non–difficult-to-treat resistance Pseudomonas aeruginosa (non-DTR-PA) isolates, DTR-PA strains presented markedly higher resistance rates to ceftazidime–avibactam (52.9% vs. 7.6%) and cefepime–tazobactam (62.9% vs. 6.2%), whereas the increase in resistance to ceftolozane–tazobactam among DTR-PA isolates was relatively modest (37.1% vs. 15.6%). WGS identified 82 distinct sequence types, with high-risk clones including ST235, ST277, and ST244 predominating. Phylogenomic analysis revealed six major clades, demonstrating both regional clustering and evidence of intercity dissemination. The major chromosomal CR-markers included OprD-related CR-markers (69.3%), MexAB-OprM-related CR-markers (47.4%), and AmpC-related CR-markers (41.4%), whereas carbapenemase genes were detected in only 8.8% of isolates. Several acquired resistance genes, including bla VIM−1 , bla CARB−4 , bla CARB−2 , and qnrVC1 , were enriched among the DTR-PA isolates. The CRPA in Fujian Province is genetically diverse and predominantly driven by non-enzymatic resistance mechanisms. The dissemination of high-risk clones and the enrichment of metallo-β-lactamases (MBLs) in DTR-PA isolates pose substantial therapeutic challenges. Cefepime–zidebactam and polymyxin B demonstrated favorable in vitro activity. Notably, although resistance to ceftolozane–tazobactam was higher in DTR-PA isolates than in non-DTR-PA isolates, it remained below 50%, suggesting that it may remain a potential treatment option for selected DTR-PA infections.