Yang Wang1, Chunyan Xu1, Rong Zhang2, Yiqiang Chen3, Yingbo Shen4, Fupin Hu5, Dejun Liu1, Jiayue Lu2, Yan Guo5, Xi Xia1, Junyao Jiang1, Xueyang Wang1, Yulin Fu1, Lu Yang1, Jiayi Wang3, Juan Li6, Chang Cai7, Dandan Yin5, Jie Che6, Run Fan1, Yongqiang Wang1, Yan Qing2, Yi Li8, Kang Liao9, Hui Chen10, Mingxiang Zou11, Liang Liang12, Jin Tang13, Zhangqi Shen1, Shaolin Wang1, Xiaorong Yang14, Congming Wu1, Shixin Xu15, Timothy R Walsh16, Jianzhong Shen17. 1. Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China. 2. The Second Affiliated Hospital of Zhejiang University, Zhejiang University, Hangzhou, China. 3. State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China. 4. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. 5. Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China. 6. State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. 7. School of Veterinary and Life Sciences, Murdoch University, Perth, WA, Australia. 8. Henan Provincial People's Hospital, Zhengzhou, China. 9. The First Affiliated Hospital of Sun-Yat Sen University, Guangzhou, China. 10. Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China. 11. Xiangya Hospital, Central South University, Changsha, China. 12. Guangxi Zhuang Autonomous Region Peoples Hospital, Nanning, China. 13. Hanzhong Central Hospital, Hanzhong, China. 14. Sichuan Provincial Center for Disease Control and Prevention, Chengdu, China. 15. China Institute of Veterinary Drug Control, Beijing, China. Electronic address: xushixin6315@qq.com. 16. Department of Zoology, University of Oxford, Oxford, UK. Electronic address: walshtr@cardiff.ac.uk. 17. Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China. Electronic address: sjz@cau.edu.cn.
Abstract
BACKGROUND: Following the discovery and emergence of the plasmid-mediated colistin resistance gene, mcr-1, the Chinese government formally banned colistin as an animal growth promoter on April 30, 2017. Herein, we report patterns in colistin resistance and mcr-1 abundance in Escherichia coli from animals and humans between 2015 and 2019, to evaluate the effects of the colistin withdrawal. METHODS: We did an epidemiology comparative study to investigate: annual production and sales of colistin in agriculture across mainland China according to data from the China Veterinary Drug Association from 2015 to 2018; the prevalence of colistin-resistant E coli (CREC) in pigs and chickens in 23 Chinese provinces and municipalities as reported in the China Surveillance on Antimicrobial Resistance of Animal Origin database from Jan 1, 2015, to Dec 31, 2016, and Jan 1, 2017, to Dec 31, 2018; the presence of residual colistin and mcr-1 in faeces from 118 animal farms (60 pig, 29 chicken, and 29 cattle) across four provinces over July 1, 2017, to August 31, 2017, and July 1, 2018 to August 31, 2018; the prevalence of mcr-1-positive E coli (MCRPEC) carriage in healthy individuals attending routine hospital examinations across 24 provinces and municipalities from June 1 to July 30, 2019, comparing with equivalent 2016 data (June 1 to September 30) from our previous study in the same hospitals; and the patterns in CREC prevalence among hospital E coli infections across 26 provinces and municipalities from Jan 1, 2015, to Dec 31, 2016, and Jan 1, 2018, to Dec 31, 2019, reported on the China Antimicrobial Surveillance Network. FINDINGS: After the ban on colistin as a growth promoter, marked reductions were observed in the production (27 170 tonnes in 2015 vs 2497 tonnes in 2018) and sale (US$71·5 million in 2015 vs US$8·0 million in 2018) of colistin sulfate premix. Across 118 farms in four provinces, mean colistin residue concentration was 191·1 μg/kg (SD 934·1) in 2017 versus 7·5 μg/kg (50·0) in 2018 (p<0·0001), and the median relative abundance of mcr-1 per 16S RNA was 0·0009 [IQR 0·0001-0·0059] in 2017 versus 0·0002 [0·0000-0·0020] in 2018 (p=0·0001). Across 23 provinces and municipalities, CREC was identified in pig faeces in 1153 (34·0%) of 3396 samples in 2015-16 versus 142 (5·1%) of 2781 in 2017-18 (p<0·0001); and in chickens in 474 (18·1%) of 2614 samples in 2015-16 versus 143 (5·0%) of 2887 in 2017-18 (p<0·0001). In hospitals across 24 provincial capital cities and municipalities, human carriage of MCRPEC was identified in 644 (14·3%) of 4498 samples in 2016 versus 357 (6·3%) of 5657 in 2019 (p<0·0001). Clinical CREC infections in 26 provinces and municipalities comprised 1059 (1·7%) of 62 737 E coli infections in 2015-16 versus 794 (1·3%) of 59 385 in 2018-19 (p<0·0001). INTERPRETATION: The colistin withdrawal policy and the decreasing use of colistin in agriculture have had a significant effect on reducing colistin resistance in both animals and humans in China. However, continuous colistin monitoring is essential, in particular to act as an early warning system for colistin stewardship in Chinese hospitals. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, and UK Medical Research Council.
BACKGROUND: Following the discovery and emergence of the plasmid-mediated colistin resistance gene, mcr-1, the Chinese government formally banned colistin as an animal growth promoter on April 30, 2017. Herein, we report patterns in colistin resistance and mcr-1 abundance in Escherichia coli from animals and humans between 2015 and 2019, to evaluate the effects of the colistin withdrawal. METHODS: We did an epidemiology comparative study to investigate: annual production and sales of colistin in agriculture across mainland China according to data from the China Veterinary Drug Association from 2015 to 2018; the prevalence of colistin-resistant E coli (CREC) in pigs and chickens in 23 Chinese provinces and municipalities as reported in the China Surveillance on Antimicrobial Resistance of Animal Origin database from Jan 1, 2015, to Dec 31, 2016, and Jan 1, 2017, to Dec 31, 2018; the presence of residual colistin and mcr-1 in faeces from 118 animal farms (60 pig, 29 chicken, and 29 cattle) across four provinces over July 1, 2017, to August 31, 2017, and July 1, 2018 to August 31, 2018; the prevalence of mcr-1-positive E coli (MCRPEC) carriage in healthy individuals attending routine hospital examinations across 24 provinces and municipalities from June 1 to July 30, 2019, comparing with equivalent 2016 data (June 1 to September 30) from our previous study in the same hospitals; and the patterns in CREC prevalence among hospital E coli infections across 26 provinces and municipalities from Jan 1, 2015, to Dec 31, 2016, and Jan 1, 2018, to Dec 31, 2019, reported on the China Antimicrobial Surveillance Network. FINDINGS: After the ban on colistin as a growth promoter, marked reductions were observed in the production (27 170 tonnes in 2015 vs 2497 tonnes in 2018) and sale (US$71·5 million in 2015 vs US$8·0 million in 2018) of colistin sulfate premix. Across 118 farms in four provinces, mean colistin residue concentration was 191·1 μg/kg (SD 934·1) in 2017 versus 7·5 μg/kg (50·0) in 2018 (p<0·0001), and the median relative abundance of mcr-1 per 16S RNA was 0·0009 [IQR 0·0001-0·0059] in 2017 versus 0·0002 [0·0000-0·0020] in 2018 (p=0·0001). Across 23 provinces and municipalities, CREC was identified in pig faeces in 1153 (34·0%) of 3396 samples in 2015-16 versus 142 (5·1%) of 2781 in 2017-18 (p<0·0001); and in chickens in 474 (18·1%) of 2614 samples in 2015-16 versus 143 (5·0%) of 2887 in 2017-18 (p<0·0001). In hospitals across 24 provincial capital cities and municipalities, human carriage of MCRPEC was identified in 644 (14·3%) of 4498 samples in 2016 versus 357 (6·3%) of 5657 in 2019 (p<0·0001). Clinical CREC infections in 26 provinces and municipalities comprised 1059 (1·7%) of 62 737 E coli infections in 2015-16 versus 794 (1·3%) of 59 385 in 2018-19 (p<0·0001). INTERPRETATION: The colistin withdrawal policy and the decreasing use of colistin in agriculture have had a significant effect on reducing colistin resistance in both animals and humans in China. However, continuous colistin monitoring is essential, in particular to act as an early warning system for colistin stewardship in Chinese hospitals. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, and UK Medical Research Council.
Authors: María Bernad-Roche; Alejandro Casanova-Higes; Clara María Marín-Alcalá; Raúl Carlos Mainar-Jaime Journal: Animals (Basel) Date: 2022-06-23 Impact factor: 3.231