Comparative in vitro activities of eravacycline and tigecycline against carbapenem-resistant Acinetobacter baumannii: Insights from whole genome sequencing analysis

Abstract

Objectives: Eravacycline (ERV), a novel tetracycline-class antibiotic, has demonstrated efficacy against carbapenem-resistant Acinetobacter baumannii (CRAB) in Europe and the United States but has not been evaluated in Singapore. The objectives of this study are to evaluate the activity of ERV against CRAB clinical isolates from Singapore and to investigate the genetic profiles of these isolates, exploring novel potential ERV resistance mechanisms through whole genome sequencing (WGS) analysis.

Methods: Three hundred CRAB clinical isolates collected from Singapore General Hospital (SGH) between 2012 and 2021 were tested for their susceptibility to ERV and other antibiotics. The genomic profile, including sequence type (ST), antimicrobial resistance, and virulence factor (VF) genes of these isolates, was determined. Isolates exhibiting high ERV minimum inhibitory concentrations (MICs) were further analysed to identify potential genetic mutations associated with reducing ERV susceptibility.

Results: ERV demonstrated strong in vitro activity against CRAB, with an MIC₉₀ of 2 µg/mL. WGS analysis revealed that the 300 CRAB isolates belonged to 23 STs, with ST2 being the predominant population and frequently harbouring intrinsic bla_OXA-type β-lactamases and tetracycline-class efflux pumps (tet(B)). VF analysis shows extensive genetic diversity, with variations beyond simple presence/absence patterns. Notably, the emergence of ERV resistance (elevated MIC, and MIC > MIC₉₀) was detected, and genetic analysis of high-MIC isolates identified novel mutations in the resistance-nodulation-cell division (RND) efflux pump genes (adeABC, adeFGH, and adeIJK) and their regulatory elements (adeS/R and adeL/N).

Conclusions: ERV is a promising therapeutic option for managing CRAB infections in Singapore. However, the emergence of resistance mediated by novel genetic mutations highlights the need for continuous surveillance and further investigation. © 2025 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.

Keywords: Carbapenem-resistant Acinetobacter baumannii; Eravacycline activities; Whole genome sequencing.