High rates of human fecal carriage of mcr-1-positive multidrug-resistant enterobacteriaceae emerge in China in association with successful plasmid families

Lan Lan Zhong; Hang T.T. Phan; Cong Shen; Karina Doris Vihta; Anna E. Sheppard; Xi Huang; Kun Jiao Zeng; Hong Yu Li; Xue Fei Zhang; Sandip Patil; Derrick W. Crook; A. Sarah Walker; Yong Xing; Jia Lin Lin; Lian Qiang Feng; Yohei Doi; Yong Xia; Nicole Stoesser; Guo Bao Tian

doi:10.1093/cid/cix885

High rates of human fecal carriage of mcr-1-positive multidrug-resistant enterobacteriaceae emerge in China in association with successful plasmid families

Lan Lan Zhong, Hang T.T. Phan, Cong Shen, Karina Doris Vihta, Anna E. Sheppard, Xi Huang, Kun Jiao Zeng, Hong Yu Li, Xue Fei Zhang, Sandip Patil, Derrick W. Crook, A. Sarah Walker, Yong Xing, Jia Lin Lin, Lian Qiang Feng, Yohei Doi, Yong Xia, Nicole Stoesser, Guo Bao Tian

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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.

Original language	English
Pages (from-to)	676-685
Number of pages	10
Journal	Clinical Infectious Diseases
Volume	66
Issue number	5
DOIs	https://doi.org/10.1093/cid/cix885
Publication status	Published - 03-2018
Externally published	Yes

All Science Journal Classification (ASJC) codes

Microbiology (medical)
Infectious Diseases

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10.1093/cid/cix885

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Zhong, L. L., Phan, H. T. T., Shen, C., Vihta, K. D., Sheppard, A. E., Huang, X., Zeng, K. J., Li, H. Y., Zhang, X. F., Patil, S., Crook, D. W., Walker, A. S., Xing, Y., Lin, J. L., Feng, L. Q., Doi, Y., Xia, Y., Stoesser, N., & Tian, G. B. (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), 676-685. https://doi.org/10.1093/cid/cix885

@article{64387eb08e2448ef98f332fd2de33f9d,

title = "High rates of human fecal carriage of mcr-1-positive multidrug-resistant enterobacteriaceae emerge in China in association with successful plasmid families",

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.",

author = "Zhong, {Lan Lan} and Phan, {Hang T.T.} and Cong Shen and Vihta, {Karina Doris} and Sheppard, {Anna E.} and Xi Huang and Zeng, {Kun Jiao} and Li, {Hong Yu} and Zhang, {Xue Fei} and Sandip Patil and Crook, {Derrick W.} and Walker, {A. Sarah} and Yong Xing and Lin, {Jia Lin} and Feng, {Lian Qiang} and Yohei Doi and Yong Xia and Nicole Stoesser and Tian, {Guo Bao}",

note = "Funding Information: 2016A020219002); the 111 Project (grant numbers B13037 and B12003); and Fundamental Research Funds for the Central Universities (grant number 16ykzd09). Additional funding support was provided through a University of Oxford/Public Health England (PHE) Clinical Lectureship to N. S. and the NIHR Oxford Biomedical Research Centre. D. W. C. is an NIHR senior investigator. Funding Information: Financial support. This work was supported by the National Natural Science Foundation of China (grant numbers 81722030 and 81471988); the Science and Technology Planning Project of Guangdong (grant number Publisher Copyright: {\textcopyright} The Author(s) 2017.",

year = "2018",

month = mar,

doi = "10.1093/cid/cix885",

language = "English",

volume = "66",

pages = "676--685",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "5",

}

Zhong, LL, Phan, HTT, Shen, C, Vihta, KD, Sheppard, AE, Huang, X, Zeng, KJ, Li, HY, Zhang, XF, Patil, S, Crook, DW, Walker, AS, Xing, Y, Lin, JL, Feng, LQ, Doi, Y, Xia, Y, Stoesser, N & Tian, GB 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, vol. 66, no. 5, pp. 676-685. https://doi.org/10.1093/cid/cix885

TY - JOUR

T1 - High rates of human fecal carriage of mcr-1-positive multidrug-resistant enterobacteriaceae emerge in China in association with successful plasmid families

AU - Zhong, Lan Lan

AU - Phan, Hang T.T.

AU - Shen, Cong

AU - Vihta, Karina Doris

AU - Sheppard, Anna E.

AU - Huang, Xi

AU - Zeng, Kun Jiao

AU - Li, Hong Yu

AU - Zhang, Xue Fei

AU - Patil, Sandip

AU - Crook, Derrick W.

AU - Walker, A. Sarah

AU - Xing, Yong

AU - Lin, Jia Lin

AU - Feng, Lian Qiang

AU - Doi, Yohei

AU - Xia, Yong

AU - Stoesser, Nicole

AU - Tian, Guo Bao

N1 - Funding Information: 2016A020219002); the 111 Project (grant numbers B13037 and B12003); and Fundamental Research Funds for the Central Universities (grant number 16ykzd09). Additional funding support was provided through a University of Oxford/Public Health England (PHE) Clinical Lectureship to N. S. and the NIHR Oxford Biomedical Research Centre. D. W. C. is an NIHR senior investigator. Funding Information: Financial support. This work was supported by the National Natural Science Foundation of China (grant numbers 81722030 and 81471988); the Science and Technology Planning Project of Guangdong (grant number Publisher Copyright: © The Author(s) 2017.

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

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U2 - 10.1093/cid/cix885

DO - 10.1093/cid/cix885

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AN - SCOPUS:85044184505

VL - 66

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EP - 685

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 5

ER -

High rates of human fecal carriage of mcr-1-positive multidrug-resistant enterobacteriaceae emerge in China in association with successful plasmid families

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