Emergence of a high-risk multidrug-resistant Acinetobacter baumannii clone ST697 in nosocomial settings

ABSTRACT Acinetobacter baumannii is a critical opportunistic pathogen increasingly linked to hospital-acquired infections due to its ability to acquire multidrug resistance (MDR). Its persistence in clinical environments and resistance to nearly all major antibiotic classes make it a formidable challenge for infection control and treatment. This study investigated the molecular epidemiology and therapeutic strategies for A. baumannii across three hospital campuses. A total of 148 clinical MDR A. baumannii isolates were collected, mostly recovered from respiratory tract specimens in ICU settings. All isolates underwent whole-genome sequencing (WGS), antibiotic susceptibility testing against 16 antibiotics, and in vitro evaluation of 14 antibiotic combinations. WGS confirmed 140 clinical isolates as A. baumannii, and 42.3% were classified as extensively drug-resistant (XDR). High resistance rates were observed for carbapenems (98.6%), fluoroquinolones (100%), and aminoglycosides (91.4%), while susceptibility to polymyxin B (PMB) and tigecycline (TGC) remained largely preserved. Four antibiotic combinations, TGC + cefoperazone/sulbactam (CSL), TGC + PMB, PMB + CSL, and minocycline (MNO) + CSL, demonstrated strong synergistic effects (>90%). The efficacy and safety of the MNO + CSL combination were preliminarily assessed in the mouse model. Genome sequence typing revealed ST2 as the dominant clone (92.9%), while a novel XDR clone, ST697, was identified. Genomic and virulence profiling suggests that ST697 evolved from ST2, representing a high-risk lineage with potential for early, rapid dissemination. A notably high mortality rate (71.4%) was observed among patients infected with ST697. Long-read sequencing assembled complete ST697 genomes revealed that ST697 isolates carry multiple copies of the bla OXA-23 gene, and the Galleria mellonella infection model revealed that ST697 isolates exhibit virulence comparable to the highly virulent ST2 A. baumannii . IMPORTANCE This study reveals the emergence of ST697, a novel, highly drug-resistant, and virulent clone of Acinetobacter baumannii , closely related to ST2. It also identifies potent antibiotic combinations that may serve as effective alternatives to last-line monotherapy. These findings highlight the urgent need for surveillance, infection control, and targeted therapy, especially in ICU and respiratory settings, to curb the spread of this emerging clone.