2. Academic Validation
  3. In vitro activity and adaptation strategies of eravacycline in clinical Enterococcus faecium isolates from China

In vitro activity and adaptation strategies of eravacycline in clinical Enterococcus faecium isolates from China

  • J Antibiot (Tokyo). 2022 Sep;75(9):498-508. doi: 10.1038/s41429-022-00546-2.
Zewen Wen  # 1 2,  Fangfang Liu  # 1 2,  Peixing Zhang  # 1 2,  Ying Wei  # 3,  Yiyi Shi 1 2,  Jinxin Zheng 1 2,  Guiqiu Li 2 4,  Zhijian Yu 1 2,  Zhicao Xu 5 6,  Qiwen Deng 7 8,  Zhong Chen 9 10
Affiliations

Affiliations

  • 1 Department of Infectious Diseases and Shenzhen Key Lab of Endogenous Infection, Shenzhen Nanshan People's Hospital and the 6th affiliated hospital of Guangdong Medical University, Shenzhen, 518052, China.
  • 2 Quality Control Center of Hospital Infection Management of Shenzhen, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, China.
  • 3 Heilongjiang Medical Service Management Evaluation Center, Harbin, Heilongjiang, 150031, China.
  • 4 The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
  • 5 Department of Infectious Diseases and Shenzhen Key Lab of Endogenous Infection, Shenzhen Nanshan People's Hospital and the 6th affiliated hospital of Guangdong Medical University, Shenzhen, 518052, China. 954104706@qq.com.
  • 6 Quality Control Center of Hospital Infection Management of Shenzhen, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, China. 954104706@qq.com.
  • 7 Department of Infectious Diseases and Shenzhen Key Lab of Endogenous Infection, Shenzhen Nanshan People's Hospital and the 6th affiliated hospital of Guangdong Medical University, Shenzhen, 518052, China. qiwendeng@hotmail.com.
  • 8 Quality Control Center of Hospital Infection Management of Shenzhen, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, China. qiwendeng@hotmail.com.
  • 9 Department of Infectious Diseases and Shenzhen Key Lab of Endogenous Infection, Shenzhen Nanshan People's Hospital and the 6th affiliated hospital of Guangdong Medical University, Shenzhen, 518052, China. 20024360@163.com.
  • 10 Quality Control Center of Hospital Infection Management of Shenzhen, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, China. 20024360@163.com.
  • # Contributed equally.
PMID: 35896611 DOI: 10.1038/s41429-022-00546-2
Abstract

Eravacycline (Erava) is a synthetic fluorocycline with potent antimicrobial activity against a wide range of Gram-positive bacteria. This study aimed to investigate the in vitro antimicrobial activity and resistance mechanism of Erava in clinical E. faecium isolates from China. Erava minimum inhibitory concentrations (MICs) against clinical E. faecium isolates-including those resistant to linezolid (LZD) or harboring the Tetracycline (Tet) resistance genes was ≤0.25 mg l-1. Moreover, our data indicated that clinical isolates of E. faecium with Erava MIC 0.25 mg l-1 were predominantly shown to belong to Sequence-type 78 (ST78) and ST80. The prevalence of Erava heteroresistance in clinical E. faecium strain was 2.46% (3/122). The increased Erava MIC values of heteroresistance-derived E. faecium clones could be significantly reduced by efflux pump inhibitors (EPIs). Furthermore, comparative proteomics results showed that efflux pumps lmrA, mdlA, and mdlB contributed significantly to the acquisition of Erava resistance in E. faecium. In addition, a genetic mutation in 16 S rRNA (G190A) were detected in resistant E. faecium isolates induced by Erava. In summary, Erava exhibits potent in vitro antimicrobial activity against E. faecium, but mutation of Tet target sites and elevated expression of efflux pumps under Erava selection results in Erava resistance.

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