Tong Jiepeng, Jiang Yiheng, Xu Hao, Jin Xuehang, Zhang Li, Ying Shuaibing, Yu Wei, Qiu Yunqing
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key Laboratory for Drug Clinical Research and Evaluation, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Clinical Medicine, Nanjing Medical University, Nanjing, People's Republic of China.
Drug Des Devel Ther. 2021 Jul 12;15:3049-3055. doi: 10.2147/DDDT.S315061. eCollection 2021.
The emergence of vancomycin resistant (VRE) is shortening the choices for clinical anti-infective therapy. The aim of this study was to investigate the mechanism of vancomycin resistance and evaluate the effect of fosfomycin (FM), rifampin (RIF), vancomycin (VAN), linezolid (LNZ), daptomycin (DAP) alone or in combination against VRE.
Eight VRE isolates were collected. A total of 18 antibiotics susceptibility tests were further done for VRE. Whole genome sequencing and bioinformatics analysis were performed. The effect of FM, RIF, VNA, LNZ, DAP alone or in combination was determined using anti-biofilm testing and the time-kill assay.
All isolates were susceptible to LNZ and DPA. The high-level resistance determinant of VAN in these strains was due to VanA-type cassette. MLST revealed two different STs for vancomycin-resistant (VREm) and four different STs for vancomycin-resistant (VREs). Virulence genes in VREs were more than VREm, especially for 4942 isolated from blood. Gene and were only identified in VREm, while virulence genes related to cytolysin were only found in E. faecalis. Further in vitro studies indicated FM (83 mg/L) combined with DAP (20.6 mg/L) and DAP monotherapy (47.1 mg/L) had bactericidal effect against VRE isolates at 24h.
High-level resistance determinant of VAN in tested isolates was due to VanA-type cassette. FM combined with DAP is a potential therapeutic option for VRE infections.
耐万古霉素肠球菌（VRE）的出现缩短了临床抗感染治疗的选择范围。本研究旨在探讨万古霉素耐药机制，并评估磷霉素（FM）、利福平（RIF）、万古霉素（VAN）、利奈唑胺（LNZ）、达托霉素（DAP）单独或联合使用对VRE的作用。
收集8株VRE分离株。对VRE进一步进行了总共18种抗生素敏感性试验。进行了全基因组测序和生物信息学分析。使用抗生物膜试验和时间杀菌试验确定FM、RIF、VNA、LNZ、DAP单独或联合使用的效果。
所有分离株对LNZ和DPA敏感。这些菌株中VAN的高水平耐药决定因素是VanA型基因盒。多位点序列分型显示耐万古霉素肠球菌（VREm）有两种不同的序列型，耐万古霉素肠球菌（VREs）有四种不同的序列型。VREs中的毒力基因比VREm更多，尤其是从血液中分离出的4942株。基因 和 仅在VREm中鉴定到，而与溶细胞素相关的毒力基因仅在粪肠球菌中发现。进一步的体外研究表明，FM（83 mg/L）联合DAP（20.6 mg/L）和DAP单药治疗（47.1 mg/L）在24小时时对VRE分离株有杀菌作用。
受试分离株中VAN的高水平耐药决定因素是VanA型基因盒。FM联合DAP是VRE感染的一种潜在治疗选择。
