Carbapenem-Resistant Acinetobacter baumannii in U.S. Hospitals: Diversification of Circulating Lineages and Antimicrobial Resistance.

Carbapenem-resistant Acinetobacter baumannii (CR) is a major cause of health care-associated infections. CR is typically multidrug resistant, and infection is difficult to treat. Despite the urgent threat that CR poses, few systematic studies of CR clinical and molecular epidemiology have been conducted. The Study Network of Acinetobacter as a Carbapenem-Resistant Pathogen (SNAP) is designed to investigate the clinical characteristics and contemporary population structure of CR circulating in U.S. hospital systems using whole-genome sequencing (WGS). Analysis of the initial 120 SNAP patients from four U.S. centers revealed that CR remains a significant threat to hospitalized patients, affecting the most vulnerable patients and resulting in 24% all-cause 30-day mortality. The majority of currently circulating isolates belonged to ST2, a part of clonal complex 2 (CC2), which is the dominant drug-resistant lineage in the United States and Europe. We identified three distinct sublineages within CC2, which differed in their antibiotic resistance phenotypes and geographic distribution. Most concerning, colistin resistance (38%) and cefiderocol resistance (10%) were common within CC2 sublineage C (CC2C), where the majority of isolates belonged to ST2/ST281. Additionally, we identified ST499 as the most common non-CC2 lineage in our study. Our findings suggest a shift within the CR population in the United States during the past 10 years and emphasize the importance of real-time surveillance and molecular epidemiology in studying CR dissemination and clinical impact. Carbapenem-resistant Acinetobacter baumannii (CR) constitutes a major threat to public health. To elucidate the molecular and clinical epidemiology of CR in the United States, clinical CR isolates were collected along with data on patient characteristics and outcomes, and bacterial isolates underwent whole-genome sequencing and antibiotic susceptibility phenotyping. Key findings included emergence of new sublineages within the globally predominant clonal complex 2 (CC2), increased colistin and cefiderocol resistance within one of the CC2 sublineages, and emergence of ST499 as the dominant non-CC2 CR lineage in U.S. hospitals.