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High Rates of Human Fecal Carriage of mcr-1–Positive Multidrug-Resistant Enterobacteriaceae Emerge in China in Association With Successful Plasmid Families

Zhong, LL; Phan, HTT; Shen, C; Vihta, KD; Sheppard, AE; Huang, X; Zeng, KJ; ... Tian, GB; + view all (2018) High Rates of Human Fecal Carriage of mcr-1–Positive Multidrug-Resistant Enterobacteriaceae Emerge in China in Association With Successful Plasmid Families. Clinical Infectious Diseases , 66 (5) pp. 676-685. 10.1093/cid/cix885. Green open access

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Abstract

Background: mcr-1–mediated colistin resistance in Enterobacteriaceae is concerning, as colistin is used in treating multidrug-resistant Enterobacteriaceae infections. We identified trends in human fecal mcr-1-positivity rates and colonization with mcr-1–positive, third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae in Guangzhou, China, and investigated the genetic contexts of mcr-1 in mcr-1–positive 3GC-R strains. / Methods: Fecal samples were collected from in-/out-patients submitting specimens to 3 hospitals (2011–2016). mcr-1 carriage trends were assessed using iterative sequential regression. A subset of mcr-1–positive isolates was sequenced (whole-genome sequencing [WGS], Illumina), and genetic contexts (flanking regions, plasmids) of mcr-1 were characterized. / Results: Of 8022 fecal samples collected, 497 (6.2%) were mcr-1 positive, and 182 (2.3%) harbored mcr-1–positive 3GC-R Enterobacteriaceae. We observed marked increases in mcr-1 (0% [April 2011] to 31% [March 2016]) and more recent (since January 2014; 0% [April 2011] to 15% [March 2016]) increases in human colonization with mcr-1–positive 3GC-R Enterobacteriaceae (P < .001). mcr-1–positive 3GC-R isolates were commonly multidrug resistant. WGS of mcr-1–positive 3GC-R isolates (70 Escherichia coli, 3 Klebsiella pneumoniae) demonstrated bacterial strain diversity; mcr-1 in association with common plasmid backbones (IncI, IncHI2/HI2A, IncX4) and sometimes in multiple plasmids; frequent mcr-1 chromosomal integration; and high mobility of the mcr-1–associated insertion sequence ISApl1. Sequence data were consistent with plasmid spread among animal/human reservoirs. / Conclusions: The high prevalence of mcr-1 in multidrug-resistant E. coli colonizing humans is a clinical threat; diverse genetic mechanisms (strains/plasmids/insertion sequences) have contributed to the dissemination of mcr-1, and will facilitate its persistence.

Type: Article
Title: High Rates of Human Fecal Carriage of mcr-1–Positive Multidrug-Resistant Enterobacteriaceae Emerge in China in Association With Successful Plasmid Families
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/cid/cix885
Publisher version: https://doi.org/10.1093/cid/cix885
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: mcr-1, genomic epidemiology, China, ESBL
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10022862
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