Emergence of tigecycline resistance in Escherichia coli co-producing MCR-1 and NDM-5 during tigecycline salvage treatment
Emergence of tigecycline resistance in Escherichia coli co-producing MCR-1 and NDM-5 during tigecycline salvage treatment
复制标题
替加环素抢救治疗过程中同时产生 MCR-1 和 NDM-5 的大肠杆菌出现替加环素耐药性
DOI：
10.2147/idr.s179618
复制
发表时间：
2018-01-01
影响因子：
3.9
通讯作者：
Yu, Yunsong
中科院分区：
文献类型：
--
作者：
Wang, Qian;Zhang, Ping;Yu, Yunsong
目的报告一例携带mcr-1、bla NDM-5的大肠埃希菌在替加环素挽救治疗过程中发生严重感染并获得性耐药的病例。方法采用药敏试验、Southern杂交和全基因组测序等方法对分离菌株进行鉴定。分析mcr-1和bla NDM-5质粒的遗传特性。完成了含mcr-1质粒的全基因组测序。最后，在替格列汀耐药菌株中推定的单核苷酸多态性和缺失突变进行了预测。结果3株E.从患者的腹水、胸腔积液和粪便中获得大肠杆菌分离株;它们对几乎所有测试的抗生素都具有耐药性。从腹水（E-FQ）和胸水（E-XS）分离的前两个菌株对阿米卡星和替加环素敏感;然而，从粪便（E-DB）分离的第三个菌株在用替加环素治疗近3周后对替加环素耐药。所有三种分离株均具有mcr-1和bla NDM-5。bla NDM-5基因位于IncX 3质粒上，而mcr-1、fosA 3和blaCTX-M-14位于IncHI 2质粒上。acrB和lon突变是替加环素耐药的原因。结论本研究首次报道了一株对粘菌素、碳青霉烯类和替格列汀耐药的大肠埃希菌。coli在中国的分布。替加环素治疗期间获得的替加环素耐药性是我们非常关注的问题，因为替加环素是治疗碳青霉烯类耐药革兰氏阴性菌感染的最后药物。此外，这种广泛耐药菌株的传播可能对公共卫生构成巨大威胁。
Objective Here, we report a case of severe infection caused by Escherichia coli that harbored mcr-1, bla NDM-5, and acquired resistance to tigecycline during tigecycline salvage therapy. Methods Antimicrobial susceptibility testing, Southern blot hybridization, and complete genome sequence of the strains were carried out. The genetic characteristics of the mcr-1 and bla NDM-5 plasmids were analyzed. The whole genome sequencing of mcr-1-containing plasmid was completed. Finally, putative single nucleotide polymorphisms and deletion mutations in the tigecycline-resistant strain were predicted. Results Three E. coli isolates were obtained from ascites, pleural effusion, and stool of a patient; they were resistant to almost all the tested antibiotics. The first two strains separated from ascites (E-FQ) and hydrothorax (E-XS) were susceptible to amikacin and tigecycline; however, the third strain from stool (E-DB) was resistant to tigecycline after nearly 3 weeks’ treatment with tigecycline. All three isolates possessed both mcr-1 and bla NDM-5. The bla NDM-5 gene was found on the IncX3 plasmid, whereas the mcr-1, fosA3 and blaCTX-M-14 were located on the IncHI2 plasmid. Mutations in acrB and lon were the reason for the resistance to tigecycline. Conclusion This is the first report of a colistin-, carbapenem-, and tigecycline-resistant E. coli in China. Tigecycline resistance acquired during tigecycline therapy is of great concern for us because tigecycline is a drug of last resort to treat carbapenem-resistant Gram-negative bacterial infections. Furthermore, the transmission of such extensively drug-resistant isolates may pose a great threat to public health.