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

Abstract

Carbapenem-resistant Acinetobacter baumannii (CR<i>Ab</i>) is a major cause of health care-associated infections. CR<i>Ab</i> is typically multidrug resistant, and infection is difficult to treat. Despite the urgent threat that CR<i>Ab</i> poses, few systematic studies of CR<i>Ab</i> 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<i>Ab</i> 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<i>Ab</i> 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^Pas, 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^Pas/ST281^Ox. Additionally, we identified ST499^Pas as the most common non-CC2 lineage in our study. Our findings suggest a shift within the CR<i>Ab</i> population in the United States during the past 10 years and emphasize the importance of real-time surveillance and molecular epidemiology in studying CR<i>Ab</i> dissemination and clinical impact. <b>IMPORTANCE</b> Carbapenem-resistant Acinetobacter baumannii (CR<i>Ab</i>) constitutes a major threat to public health. To elucidate the molecular and clinical epidemiology of CR<i>Ab</i> in the United States, clinical CR<i>Ab</i> 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^Pas as the dominant non-CC2 CR<i>Ab</i> lineage in U.S. hospitals.