Jiang Yan, Zhang Ying, Lu Jun, Wang Qihui, Cui Yushan, Wang Yanfei, Quan Jingjing, Zhao Dongdong, Du Xiaoxing, Liu Haiyang, Li Xi, Wu Xueqing, Hua Xiaoting, Feng Ye, Yu Yunsong
Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, Zhejiang, China.
Center for Clinical Laboratory Medicine, PLA General Hospital, Beijing, China.
Lancet Microbe. 2020 May;1(1):e24-e33. doi: 10.1016/S2666-5247(20)30001-X. Epub 2020 May 11.
Although the emergence of the plasmid-mediated colistin resistance gene, mcr-1, caused global concern, little is known about its clinical implications and transmission characteristics over time. We aimed to investigate the clinical relevance of infection with mcr-1-positive Escherichia coli isolates and to investigate long-term plasmid dynamics.
We did a multicentre case-control study and molecular epidemiological survey of mcr-1-positive E coli infections. E coli isolates from four hospitals in China in 2008 to 2017 were collected and screened for mcr-1 by PCR and Sanger sequencing. Patients with mcr-1-positive E coli infections and matched controls with mcr-1-negative E coli infections were included in a 1:4 ratio, considering age, sex, living environment, comorbidities, antimicrobials used, and clinical sample type as potential risk factors in a regression model. 28-day mortality was also observed. The genomes of all mcr-1-positive E coli were sequenced to explore their genetic background and map IS Apl1 elements. Plasmids carrying mcr-1 were characterised by their resistance profile and incompatibility group.
29 100 isolates were collected across all hospitals and during the study period, 300 (1·03%) of which were mcr-1-positive E coli. The overall proportion of mcr-1-positive isolates significantly increased from 0·42% (1 of 240) in 2008 to 1·39% (66 of 4748; p<0·0001) in 2017. Factors related to health-care contact, including receiving cancer care, indwelling central venous catheter, and hospitalisation in the past 3 months, and some sample types (pus secretion and sputum) were significantly associated with mcr-1-positive E coli infection. 28-day mortality was low in both mcr-1-positive (11 [4·4%] of 248 patients) and mcr-1-negative (39 [3·8%] of 1030 patients) groups and did not significantly differ. Although the genetic background of mcr-1-positive E coli was diverse, most of the mcr-1-encoding plasmids occurred in three dominant Inc groups (IncX4, IncI2, and IncHI2). Only the large IncHI2 plasmids conferred multiple resistances and probably integrated with other resistance plasmids. In 205 (68%) of 300 mcr-1-positive E coli isolates, mcr-1 genes lost their capacity for mobilisation because of loss of flanking IS Apl1 elements.
The prevalence of mcr-1-positive E coli infection among patients increased over the study period, although it remained low. Health-care contact was the most probable risk factor. Plasmids are likely to have played a critical role in mcr-1 transmission, rather than clone dissemination and lateral transfer of IS Apl1. Our findings underscore the importance of continued surveillance of E coli strains positive for mcr-1 and potentially other resistance-associated genes, particularly in hospital settings.
National Natural Science Foundation of China.
尽管质粒介导的黏菌素耐药基因mcr - 1的出现引起了全球关注，但对其临床意义和随时间的传播特征知之甚少。我们旨在研究感染mcr - 1阳性大肠杆菌分离株的临床相关性，并研究长期的质粒动态变化。
我们对mcr - 1阳性大肠杆菌感染进行了多中心病例对照研究和分子流行病学调查。收集了2008年至2017年中国四家医院的大肠杆菌分离株，通过PCR和桑格测序筛选mcr - 1。将mcr - 1阳性大肠杆菌感染患者与配对的mcr - 1阴性大肠杆菌感染对照按1:4的比例纳入研究，在回归模型中考虑年龄、性别、生活环境、合并症、使用的抗菌药物和临床样本类型作为潜在风险因素。还观察了28天死亡率。对所有mcr - 1阳性大肠杆菌的基因组进行测序，以探索其遗传背景并绘制IS Apl1元件图谱。携带mcr - 1的质粒通过其耐药谱和不相容群进行表征。
在研究期间，所有医院共收集了29100株分离株，其中300株（1.03%）为mcr - 1阳性大肠杆菌。mcr - 1阳性分离株的总体比例从2008年的0.42%（240株中的1株）显著增加到2017年的1.39%（4748株中的66株；p<0.0001）。与医疗接触相关的因素，包括接受癌症治疗、留置中心静脉导管以及过去3个月内住院，以及一些样本类型（脓液分泌物和痰液）与mcr - 1阳性大肠杆菌感染显著相关。mcr - 1阳性组（248例患者中的11例[4.4%]）和mcr - 1阴性组（1030例患者中的39例[3.8%]）的28天死亡率均较低，且无显著差异。尽管mcr - 1阳性大肠杆菌的遗传背景多样，但大多数编码mcr - 1的质粒出现在三个主要的Inc组（IncX4、IncI2和IncHI2）中。只有大型IncHI2质粒赋予多重耐药性，并且可能与其他耐药质粒整合。在300株mcr - 1阳性大肠杆菌分离株中的205株（68%）中，由于侧翼IS Apl1元件的缺失，mcr - 1基因失去了移动能力。
在研究期间，患者中mcr - 1阳性大肠杆菌感染的患病率有所增加，尽管仍然较低。医疗接触是最可能的风险因素。质粒可能在mcr - 1传播中起关键作用，而不是克隆传播和IS Apl1的侧向转移。我们的研究结果强调了持续监测mcr - 1阳性及潜在其他耐药相关基因的大肠杆菌菌株的重要性，特别是在医院环境中。
中国国家自然科学基金。
