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替加环素挽救治疗期间同时产生MCR-1和NDM-5的替加环素耐药性的出现。

Emergence of tigecycline resistance in co-producing MCR-1 and NDM-5 during tigecycline salvage treatment.

作者信息

Wang Qian, Zhang Ping, Zhao Dongdong, Jiang Yan, Zhao Feng, Wang Yanfei, Li Xi, Du Xiaoxing, Yu Yunsong

机构信息

Department of General Practice, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China,

出版信息

Infect Drug Resist. 2018 Nov 13;11:2241-2248. doi: 10.2147/IDR.S179618. eCollection 2018.

Abstract

OBJECTIVE

Here, we report a case of severe infection caused by that harbored , , 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 and plasmids were analyzed. The whole genome sequencing of -containing plasmid was completed. Finally, putative single nucleotide polymorphisms and deletion mutations in the tigecycline-resistant strain were predicted.

RESULTS

Three 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 and . The gene was found on the IncX3 plasmid, whereas the , and were located on the IncHI2 plasmid. Mutations in and were the reason for the resistance to tigecycline.

CONCLUSION

This is the first report of a colistin-, carbapenem-, and tigecycline-resistant 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.

摘要

目的

在此,我们报告一例由携带 blaNDM-1、blaOXA-48 和在替加环素挽救治疗期间获得对替加环素耐药性的菌株引起的严重感染病例。

方法

对菌株进行药敏试验、Southern 印迹杂交和全基因组测序。分析 blaNDM-1 和 blaOXA-48 质粒的遗传特征。完成含 blaNDM-1 质粒的全基因组测序。最后,预测替加环素耐药菌株中假定的单核苷酸多态性和缺失突变。

结果

从一名患者的腹水、胸腔积液和粪便中分离出三株鲍曼不动杆菌;它们对几乎所有测试抗生素均耐药。从腹水(E-FQ)和胸腔积液(E-XS)中分离出的前两株菌株对阿米卡星和替加环素敏感;然而,在接受替加环素近 3 周治疗后,来自粪便的第三株菌株(E-DB)对替加环素耐药。所有三株分离株均同时携带 blaNDM-1 和 blaOXA-48。blaNDM-1 基因位于 IncX3 质粒上,而 blaOXA-48、blaCTX-M-15 和 blaTEM-1 位于 IncHI2 质粒上。blaOXA-48 和 blaTEM-1 的突变是对替加环素耐药的原因。

结论

这是中国首例对黏菌素、碳青霉烯类和替加环素耐药的鲍曼不动杆菌报告。在替加环素治疗期间获得的替加环素耐药性值得我们高度关注,因为替加环素是治疗耐碳青霉烯革兰阴性菌感染的最后一道防线药物。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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce79/6239116/0755358a9438/idr-11-2241Fig1.jpg

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