Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 27, Number 9—September 2021
Research Letter

Prevalence of mcr-1 in Colonized Inpatients, China, 2011–2019

Cong Shen1, Lan-Lan Zhong1, Zhijuan Zhong1, Yohei Doi, Jianzhong Shen, Yang Wang, Furong Ma, Mohamed Abd El-Gawad El-Sayed Ahmed, Guili Zhang, Yong Xia, Cha Chen, and Guo-Bao TianComments to Author 
Author affiliations: Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, China (C. Shen, L.-L. Zhong, M.A.E.-G.E.-S. Ahmed, G. Zhang, G.-B. Tian); Sun Yat-sen University Key Laboratory of Tropical Diseases Control, Guangzhou (C. Shen, L.-L. Zhong, M.A.E.-G.E.-S. Ahmed, G. Zhang, G. Tian); Guangzhou University of Chinese Medicine The Second Clinic Medical College, Guangzhou (C. Shen, C. Chen); The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou (C. Shen, C. Chen); Sun Yat-Sen University The Fifth Affiliated Hospital, Zhuhai, China (Z. Zhong); University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA (Y. Doi); Fujita Health University School of Medicine, Aichi, Japan (Y. Doi); China Agricultural University, College of Veterinary Medicine, Beijing, China (J. Shen, Y. Wang); China Agricultural University, College of Animal Science and Technology, Beijing (J. Shen, Y. Wang); Third Affiliated Hospital of Guangzhou Medical University, Guangzhou (F. Ma, Y. Xia); Misr University for Science and Technology, Cairo, Egypt (M.A.E.-G.E.-S. Ahmed); Xizang Minzu University School of Medicine, Xianyang, China (G. Tian)

Cite This Article


In response to the spread of colistin resistance gene mcr-1, China banned the use of colistin in livestock fodders. We used a time-series analysis of inpatient colonization data from 2011–2019 to accurately reveal the associated fluctuations of mcr-1 that occurred in inpatients in response to the ban.

Heavy use of antimicrobials in agricultural, human, and veterinary applications correlates directly with emergence and spread of antimicrobial resistance, thereby threatening the effective management of clinical infections (1,2). An example of this association is the global dissemination of the antimicrobial resistance gene (ARG) mcr-1, conferring resistance to the last-line antimicrobial drug colistin. The mcr-1 gene has been prevalent in ecosystems that use colistin as a growth promoter in food-producing animals, as seen in China before 2017 (25).

To counteract the high prevalence of mcr-1 and align with One Health principles, the government in China formally banned colistin as an animal feed additive on April 30, 2017 (6). Previous research demonstrated that colistin resistance rates and mcr-1 prevalence in Escherichia coli from human and animal samples declined substantially in China, according to a regional study conducted in Guangzhou during 2015–2019 (p<0.0001). These data suggest the effectiveness of colistin stewardship in reducing colistin resistance in both livestock and humans (4,5). However, the sampling strategy of these studies was limited to evaluating only several cross-sectional timepoints from before and after the ban, resulting in uncertainty about the exact timing of the effect.


Time series of monthly mcr-1 prevalence in colonized inpatients, China, April 2011–December 2019. The mcr-1 prevalence was recorded each month in observed data (blue histogram) and 3-month moving average data (solid red line). Vertical dashed lines indicate significant changepoints identified in the changepoint analysis: November 2013, May 2015, November 2016, May 2017, and August 2018. The government of China formally banned colistin as an animal feed additive on April 30, 2017. P, time period.

Figure. Time series of monthly mcr-1 prevalence in colonized inpatients, China, April 2011–December 2019. The mcr-1prevalence was recorded each month in observed data (blue histogram) and 3-month...

To characterize the complete prevalence dynamics of human mcr-1 colonization, including the periban period, we constructed a 9-year monthly time series for April 2011–December 2019, over which time 13,630 fecal samples from colonized inpatients were previously taken, by further evaluating mcr-1 prevalence of 3,823 stored fecal samples collected during April–September 2016, January–September 2017–2018, and January–December 2019. We combined these data with those from our previous studies (3,5) (Appendix Table 1). We used a 3-month moving average approach to remove noise and substituted missing data for 7 months of the time series by using the mean values of the 2 months flanking any month with missing data (Appendix). Through changepoint analysis (Appendix) (7), we identified 5 changepoints, dividing the time series into 6 periods (Figure).

We observed that mcr-1 prevalence in human fecal samples was low (<3%) in the early period, before October 2013, demonstrating that the mcr-1 gene was circulating to a limited extent in human populations before late 2013 in period 1 (P1). We observed a significant increase in mcr-1 colonization prevalence after November 2013 in period 2 (P2) that lagged behind increases of mcr-1 prevalence observed in livestock from 2011 (2) and was consistent with dissemination from this reservoir. The third period (P3) showed a sharp increase in mcr-1 human colonization prevalence, followed by a peak in October 2016, suggesting that mcr-1 was rapidly spreading in human settings, potentially attributable to an extremely high mcr-1 prevalence (>60%) in livestock around the time (4,5,8). Beginning in November 2016, in period 4 (P4), pilot decreases in colistin use as an animal feed additive were already being implemented (4) before the complete ban in 2017. We observed declines in human mcr-1 colonization prevalence during this period that were temporally consistent with declines in mcr-1 prevalence observed in livestock (8). The fifth period (P5) showed a dramatic decline in human mcr-1 colonization prevalence, correlating with the complete ban of colistin in animal feed (6). The rapid impact of this intervention is indicative of the dramatic effect that curtailing a selection pressure can have in constraining ARG prevalence and could be a template for combatting other ARGs. In the last period evaluated, period 6 (P6), mcr-1 prevalence fluctuated at a low level (monthly average 5.3%), in accordance with the mcr-1 prevalence observed in healthy human carriers, pigs, and chickens after the colistin ban (5). Alhough currently at low levels, mcr-1 prevalence should be monitored continually to detect any signs of its resurgence, particularly given that colistin was approved for human clinical use in China in January 2017 (9).

In conclusion, we characterized the dynamic landscape of mcr-1 over a 9-year period in China and found that colistin stewardship interventions in livestock were reflected in the mcr-1 prevalence in human fecal colonization samples within a month of a large-scale, national ban on colistin usage. Partial reductions in colistin use beginning in November 2016 rapidly reduced the mcr-1 prevalence and turned around the alarming increases observed during 2015–2016. The complete ban implemented on April 30, 2017, significantly and immediately reduced mcr-1 prevalence to near pre-2015 levels. Of interest, however, the background mcr-1 prevalence in 2019 was still higher than that observed during 2011–2013, perhaps associated with the approval of colistin for human clinical use in China in January 2017 (9). As a result of our findings, we strongly encourage interdisciplinary surveillance involving clinicians, veterinary specialists, and environmentalists to further investigate and evaluate changes in ARG prevalence across different human, animal, and environmental niches to improve holistic understanding of the impact and timeframe of different stewardship interventions.

Mr. Shen is a doctoral student at Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. His primary research interests include infectious disease epidemiology, antimicrobial resistance, microbial population genomics, and genomic epidemiology.



We thank Nicole Stoesser for helpful discussions and review of this manuscript.

This work was supported by the National Natural Science Foundation of China (grant nos. 81722030, 81830103, 8201101256), National Key Research and Development Program (grant no. 2017ZX10302301), Guangdong Natural Science Foundation (grant no. 2017A030306012), project of high-level health teams of Zhuhai at 2018 (The Innovation Team for Antimicrobial Resistance and Clinical Infection), 111 Project (grant no. B12003), and a project funded by China Postdoctoral Science Foundation(BX20200394,2020M683068).



  1. Tang  KL, Caffrey  NP, Nóbrega  DB, Cork  SC, Ronksley  PE, Barkema  HW, et al. Restricting the use of antibiotics in food-producing animals and its associations with antibiotic resistance in food-producing animals and human beings: a systematic review and meta-analysis. Lancet Planet Health. 2017;1:e31627. DOIPubMedGoogle Scholar
  2. Shen  Z, Wang  Y, Shen  Y, Shen  J, Wu  C. Early emergence of mcr-1 in Escherichia coli from food-producing animals. Lancet Infect Dis. 2016;16:293. DOIPubMedGoogle Scholar
  3. Zhong  LL, Phan  HTT, Shen  C, Vihta  KD, Sheppard  AE, Huang  X, et al. High rates of human fecal carriage of mcr-1-positive multidrug-resistant Enterobacteriaceae emerge in China in association with successful plasmid families. Clin Infect Dis. 2018;66:67685. DOIPubMedGoogle Scholar
  4. Wang  Y, Xu  C, Zhang  R, Chen  Y, Shen  Y, Hu  F, et al. Changes in colistin resistance and mcr-1 abundance in Escherichia coli of animal and human origins following the ban of colistin-positive additives in China: an epidemiological comparative study. Lancet Infect Dis. 2020;20:116171. DOIPubMedGoogle Scholar
  5. Shen  C, Zhong  L, Yang  Y, Doi  Y, Paterson  D, Stoesser  N, et al. Dynamics of mcr-1 prevalence and mcr-1-positive Escherichia coli after the cessation of colistin use as a feed additive for animals in China: a prospective cross-sectional and whole genome sequencing-based molecular epidemiological study. Lancet Microbe. 2020;1:e3443. DOIGoogle Scholar
  6. Walsh  TR, Wu  Y. China bans colistin as a feed additive for animals. Lancet Infect Dis. 2016;16:11023. DOIPubMedGoogle Scholar
  7. Killick  R, Eckley  I. Changepoint: an R package for changepoint analysis. J Stat Softw. 2014;58:119. DOIGoogle Scholar
  8. Li  W, Hou  M, Liu  C, Xiong  W, Zeng  Z. Dramatic decrease in colistin resistance in Escherichia coli from a typical pig farm following restriction of colistin use in China. Int J Antimicrob Agents. 2019;53:7078. DOIPubMedGoogle Scholar
  9. Zhang  R, Shen  Y, Walsh  TR, Wang  Y, Hu  F. Use of polymyxins in Chinese hospitals. Lancet Infect Dis. 2020;20:11256. DOIPubMedGoogle Scholar




Cite This Article

DOI: 10.3201/eid2709.203642

Original Publication Date: August 11, 2021

1These authors contributed equally to this article.

Table of Contents – Volume 27, Number 9—September 2021

EID Search Options
presentation_01 Advanced Article Search – Search articles by author and/or keyword.
presentation_01 Articles by Country Search – Search articles by the topic country.
presentation_01 Article Type Search – Search articles by article type and issue.



Please use the form below to submit correspondence to the authors or contact them at the following address:

Guo-Bao Tian, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Rd, Guangzhou 510080, China

Send To

10000 character(s) remaining.


Page created: July 22, 2021
Page updated: August 18, 2021
Page reviewed: August 18, 2021
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.