Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
Eur J Clin Microbiol Infect Dis. 2018 Aug;37(8):1441-1448. doi: 10.1007/s10096-018-3269-8. Epub 2018 Jun 16.
Linezolid is considered as a last-resort antimicrobial agent, the resistance of which is of great concern. The aim of this study was to investigate the mechanisms and transferability of linezolid resistance and molecular epidemiology of linezolid-resistant enterococcal isolates in Wenzhou, China. A collection of 1623 enterococcal strains, including 789 Enterococcus faecalis and 834 Enterococcus faecium, were isolated from our hospital during 2011-2016. Antimicrobial susceptibility testing and clinical data analysis were performed. Molecular mechanisms of linezolid resistance, including the existence of resistance genes cfr and optrA, as well as the mutations in 23S rRNA and ribosomal proteins L3, L4, and L22, were investigated by PCR and sequencing. Conjugation experiments were conducted, and epidemiological characteristics were analyzed by PFGE and MLST. In our study, 31 (3.93%) E. faecalis and 2 (0.24%) E. faecium exhibited resistance to linezolid. Risk factors correlated with linezolid-resistant enterococcal infections included gastrointestinal surgery hospitalization, urogenital disorders, tumor, diabetes, and polymicrobial infections. Among these isolates, 6 (18.18%) harbored cfr, 9 (27.27%) harbored optrA, and 18 (54.55%) co-harbored cfr and optrA. However, mutational mechanisms were not found in this study. Conjugation experiments demonstrated the transferability of cfr and optrA between Gram-positive and Gram-negative bacteria. The clone of these isolates was diverse and scattered. It is noteworthy that cfr and optrA were the main mechanisms of linezolid resistance in this study, posing a potential risk of spread of linezolid resistance. Strikingly, it reported firstly that the two transferable resistance genes cfr and optrA coexisted in the same E. faecalis isolates.
利奈唑胺被认为是一种最后的抗菌药物，其耐药性引起了极大的关注。本研究旨在调查中国温州耐利奈唑胺肠球菌分离株的耐药机制和可转移性以及分子流行病学。收集了我院 2011-2016 年期间分离的 1623 株肠球菌，包括 789 株粪肠球菌和 834 株屎肠球菌。进行了药敏试验和临床数据分析。通过 PCR 和测序研究了利奈唑胺耐药的分子机制，包括耐药基因 cfr 和 optrA 的存在以及 23S rRNA 和核糖体蛋白 L3、L4 和 L22 的突变。进行了接合实验，并通过 PFGE 和 MLST 分析了流行病学特征。在本研究中，31 株（3.93%）粪肠球菌和 2 株（0.24%）屎肠球菌对利奈唑胺表现出耐药性。与耐利奈唑胺肠球菌感染相关的危险因素包括胃肠道手术住院、泌尿生殖系统疾病、肿瘤、糖尿病和混合感染。在这些分离株中，6 株（18.18%）携带 cfr，9 株（27.27%）携带 optrA，18 株（54.55%）同时携带 cfr 和 optrA。然而，本研究未发现突变机制。接合实验表明 cfr 和 optrA 可在革兰阳性和革兰阴性细菌之间转移。这些分离株的克隆多样且分散。值得注意的是，cfr 和 optrA 是本研究中利奈唑胺耐药的主要机制，存在利奈唑胺耐药传播的潜在风险。引人注目的是，本研究首次报道了两种可转移的耐药基因 cfr 和 optrA 同时存在于同一株粪肠球菌分离株中。
