Molecular epidemiology and genomic characteristics of clinical Acinetobacter baumannii isolates from patients with hospital-acquired pneumonia in China, 2019–2020: a multicentre retrospective study

Background Carbapenem-resistant Acinetobacter baumannii (CRAB) is a leading cause of hospital-acquired pneumonia (HAP) with high mortality. However, large-scale nationwide data of HAP-causing CRAB in China remain limited. Methods Here, we performed a nationwide multicentre retrospective study to characterise the molecular epidemiology and genomic features of 802 A. baumannii isolates from patients with HAP across 33 tertiary hospitals in China during 2019–2020. Antimicrobial susceptibility testing (AST), whole-genome sequencing (WGS), phylogenetic and comparative genomic analysis were used to investigate molecular epidemiology of HAP-causing CRAB strain. Clinical comparative analyses were carried out on data from 500 patients with HAP stratified by distinct antimicrobial susceptibility and genomic profiles, and a Galleria mellonella infection model was utilised for in vivo virulence assessment. Findings The overall carbapenem resistance rate of A. baumannii was 82.0% (658/802), with marked regional variations. CRAB exhibited high resistance to conventional agents but remained largely susceptible to polymyxin, tigecycline, cefiderocol and sulbactam-durlobactam. Among enrolled patients, CRAB infection was linked to substantially higher mortality (39.0% vs. 17.5%), and multivariate analysis confirmed ICU admission and advanced age as independent risk factors for patients with CRAB infection. Molecular typing revealed ST Pas 2 (96.2%) as the absolutely predominant type; ST Oxf 208, ST Oxf 195, ST Oxf 540, and ST Oxf 369 were the most prevalent Oxford sequence types with obvious geographic stratification and divergent comorbidity profiles among corresponding patients. A total of 654 CRAB isolates harboured carbapenemase genes, with bla OXA-23 dominating at 98.8%. Genomic analysis revealed lineage-specific features: ST Oxf 208 carried more virulence genes, while ST Oxf 540 harboured a broader antimicrobial resistance genes (ARGs). The ST Oxf 208 clone mainly belonged to KL2 (62.1%) and KL7 (36.8%) serotypes, with KL2 strains possessing richer ARGs and virulence factors, and in vivo virulence assays further validated that KL2 strains possessed higher pathogenicity than KL7 strains. Interpretation This study demonstrates the extremely high prevalence and clonal dominance of CRAB in Chinese patients with HAP, providing critical evidence for clinical treatment, antimicrobial stewardship, and targeted infection control. Funding National Key Research and Development Program of China (2024YFE0106200), National Natural Science Foundation of China (U22A20338, 82502763, W2621007), Zhejiang Provincial Natural Science Foundation of China (LQN25H190006), Zhejiang Provincial Postdoctoral Science Foundation (ZJ2025058).