In vitro activity of vancomycin and other commonly used Antibiotics against clinical isolates of Enterococcus faecalis and Enterococcus faecium: Data from the antimicrobial testing leadership and surveillance (ATLAS) program from 2019 to 2023

• First global analysis of 18,043 Enterococcus isolates (2019-2023) from 59 countries. • E. faecium exhibits high VRE (25.4%) and extensive multidrug cross-resistance. • North America leads in vancomycin-resistant E. faecium (53.25%); Asia has the highest linezolid resistance in E. faecium (2.9%). • Resistance elevated in ICU/non-pediatric patients and genitourinary sites. • Tigecycline and linezolid remain highly effective in vitro against most enterococcal isolates globally. Enterococci are significant hospital pathogens, posing a serious global public health threat. This study aimed to analyze the in vitro susceptibility of enterococcal isolates to eight commonly used antibiotics and to explore cross-resistance patterns in vancomycin-resistant enterococci (VRE), including their heterogeneity across geographic regions, clinical wards, and infection sites. Utilizing data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program (2019-2023), this study analyzed 18,043 enterococcal isolates (12,007 Enterococcus faecalis and 6,036 Enterococcus faecium ) from 59 countries across six continents. We assessed in vitro susceptibility to eight common antibiotics and evaluated VRE cross-resistance patterns. E. faecalis showed susceptibility rates greater than 95% to ampicillin, daptomycin, linezolid, teicoplanin, tigecycline, and vancomycin. In contrast, E. faecium exhibited susceptibility greater than 90% only for linezolid and tigecycline. The vancomycin resistance rate in E. faecium was 25.4%, significantly higher than in E. faecalis (1.22%), with notable multidrug cross-resistance. Geographically, North America displayed the highest vancomycin resistance rate in E. faecium (53.25%), while Asia showed the highest linezolid resistance rate in this species (2.9%). ICU and non-pediatric patients generally exhibited higher resistance rates, and genitourinary specimens showed slightly higher resistance than those from other sites. Enterococcal resistance varies significantly across species, regions, and clinical environments. The extensive cross-resistance in VRE poses a major challenge to clinical treatment. Tigecycline and linezolid remain highly effective in vitro globally. To slow the spread of resistant strains, it is crucial to enhance resistance monitoring in high-risk regions and populations, while optimizing antibiotic usage strategies.