中国血流感染中产 ESBLs 大肠埃希菌和肺炎克雷伯菌中 mcr-1 的流行：一项多中心纵向研究。

Prevalence of mcr-1 in Escherichia coli and Klebsiella pneumoniae recovered from bloodstream infections in China: a multicentre longitudinal study.

机构信息

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

Centre of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, China.

出版信息

Lancet Infect Dis. 2017 Apr;17(4):400-410. doi: 10.1016/S1473-3099(16)30528-X. Epub 2017 Jan 28.

DOI:10.1016/S1473-3099(16)30528-X

PMID:28139430

Abstract

BACKGROUND

Polymyxin antibiotics are used as last-resort therapies to treat infections caused by multidrug-resistant Gram-negative bacteria. The plasmid-mediated colistin resistance determinant MCR-1 has been identified in Enterobacteriaceae in China. We did this study to investigate the prevalence of the mcr-1 gene in clinical isolates from patients with bloodstream infections in China.

METHODS

Clinical isolates of Escherichia coli and Klebsiella pneumoniae were collected from patients with bloodstream infections at 28 hospitals in China, then screened for colistin resistance by broth microdilution and for the presence of the mcr-1 gene by PCR amplification. We subjected mcr-1-positive isolates to genotyping, susceptibility testing, and clinical data analysis. We established the genetic location of mcr-1 with Southern blot hybridisation, and we analysed plasmids containing mcr-1 with filter mating, electroporation, and DNA sequencing.

FINDINGS

2066 isolates, consisting of 1495 E coli isolates and 571 K pneumoniae isolates were collected. Of the 1495 E coli isolates, 20 (1%) were mcr-1-positive, whereas we detected only one (<1%) mcr-1-positive isolate among the 571 K pneumoniae isolates. All mcr-1-positive E coli and K pneumoniae isolates were resistant to colistin, with minimum inhibitory concentrations values in the range of 4-32 mg/L, except for one E coli isolate that had a minimum inhibitory concentration less than or equal to 0·06 mg/L. All 21 mcr-1-positive isolates were susceptible to tigecycline and 20 isolates (95%) were susceptible to the carbapenem and β-lactamase inhibitor combination piperacillin and tazobactam. One mcr-1-positive E coli isolate also produced NDM-5, which confers resistance to beta-lactam antibiotics. The 21 mcr-1-positive isolates were clonally diverse and carried mcr-1 on two types of plasmids, a 33 kb IncX4 plasmid and a 61 kb Inc12 plasmid. The 30 day mortality of the patients with bloodstream infections caused by mcr-1-positive isolates was zero.

INTERPRETATION

mcr-1-positive isolates from bloodstream infections were rare, sporadic, and remained susceptible to many antimicrobial agents. E coli, rather than K pneumoniae, was the main host of the mcr-1 gene. Further studies are needed to clarify the clinical impact of this novel resistance gene.

FUNDING

National Natural Science Foundation of China.

摘要

背景

多黏菌素类抗生素被用作治疗多重耐药革兰氏阴性菌感染的最后手段。在中国肠杆菌科中已经发现了质粒介导的黏菌素耐药决定因子 MCR-1。我们进行这项研究是为了调查 mcr-1 基因在中国血流感染患者临床分离株中的流行情况。

方法

从中国 28 家医院的血流感染患者中收集大肠埃希菌和肺炎克雷伯菌的临床分离株，通过肉汤微量稀释法筛选出对黏菌素耐药的菌株，并通过 PCR 扩增筛选 mcr-1 基因。我们对 mcr-1 阳性分离株进行基因分型、药敏试验和临床数据分析。我们通过 Southern 印迹杂交确定 mcr-1 的遗传位置，并通过滤膜交配、电穿孔和 DNA 测序分析携带 mcr-1 的质粒。

结果

共收集了 2066 株分离株，包括 1495 株大肠埃希菌和 571 株肺炎克雷伯菌。在 1495 株大肠埃希菌分离株中，有 20 株（1%）为 mcr-1 阳性，而在 571 株肺炎克雷伯菌分离株中，我们只检测到 1 株（<1%）mcr-1 阳性。所有 mcr-1 阳性的大肠埃希菌和肺炎克雷伯菌分离株均对黏菌素耐药，其最低抑菌浓度值在 4-32 mg/L 范围内，除一株大肠埃希菌分离株的最低抑菌浓度值小于或等于 0.06 mg/L 外。所有 21 株 mcr-1 阳性分离株均对替加环素敏感，20 株（95%）分离株对碳青霉烯类和β-内酰胺酶抑制剂复合制剂哌拉西林他唑巴坦敏感。一株 mcr-1 阳性大肠埃希菌分离株还产生了 NDM-5，可导致β-内酰胺类抗生素耐药。21 株 mcr-1 阳性分离株的克隆多样性不同，携带 mcr-1 的质粒有两种类型，一种是 33 kb 的 IncX4 质粒，另一种是 61 kb 的 Inc12 质粒。由 mcr-1 阳性分离株引起的血流感染患者的 30 天死亡率为零。