In Vitro Antibacterial Activity of Sulbactam-Durlobactam and Eravacycline Against Carbapenem-Resistant Acinetobacter baumannii in China and Analysis of Sulbactam-Durlobactam Resistance Mechanisms

The management of carbapenem-resistant Acinetobacter baumannii (CRAB) infections remains a formidable clinical challenge. This study evaluated the in vitro antimicrobial activities of sulbactam-durlobactam (SUL-DUR) and eravacycline (ERV) against CRAB isolates and elucidated the genomic landscapes of resistance and virulence determinants in SUL-DUR-resistant strains to inform therapeutic decision-making. A total of 233 clinical CRAB isolates were collected and screened for susceptibility to SUL-DUR and ERV using the Kirby-Bauer (K-B) disk diffusion assay. Isolates exhibiting resistance to SUL-DUR were further characterized via metagenomic next-generation sequencing (mNGS) to identify key resistance and virulence factors. SUL-DUR and ERV demonstrated robust in vitro activity, with susceptibility rates of 92.3% and 91.4%, respectively. Notably, no isolates exhibited concurrent non-susceptibility to both agents. Genomic analysis of 14 SUL-DUR-resistant strains revealed a complex and heterogeneous distribution of genetic determinants. The presence of bla _NDM-1 was identified as a critical driver of SUL-DUR resistance. Additionally, reduced susceptibility was potentially associated with specific mutations in bla _OXA-23, bla _OXA-66, and bla _TEM-1, while hyperactive efflux systems and altered membrane permeability further synergized to enhance the resistance phenotype. Despite the extensive-drug-resistant (XDR) nature of current CRAB isolates, they maintain high sensitivity to SUL-DUR and ERV. Our findings underscore that SUL-DUR and ERV represent highly promising therapeutic options with significant development potential and broad clinical application prospects for the management of CRAB-related infections.