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[Lancet Infect Dis发表论文]:中国禁止含有粘菌素添加剂后动物与人源性大肠杆菌粘菌素耐药性及mcr-1丰度的改变
2020年12月19日 时讯速递, 进展交流 暂无评论

ARTICLES| VOLUME 20, ISSUE 10, P1161-1171, OCTOBER 01, 2020

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

Yang Wang, Chunyan Xu, Rong Zhang, et al

Lancet Infect Dis 2020; 20: 1161-1171

Summary 摘要

Background 背景

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-1abundance in Escherichia coli from animals and humans between 2015 and 2019, to evaluate the effects of the colistin withdrawal.

自从质粒介导的粘菌素耐药基因mcr-1被发现以来,中国政府于2017年4月30日禁止将粘菌素作为动物助长剂使用。我们报告2015年至2019年动物和人源性大肠杆菌对粘菌素的耐药性以及mcr-1丰度,以评价上述政策的影响。

Methods 方法

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.

我们进行了流行病学比较研究:根据中国兽药协会2015年至2018年的数据得到每年农业用粘菌素的产量及销量;中国动物源性抗生素耐药监测数据库2015年1月至2016年12月31日,以及2017年1月1日至2018年12月31日期间报告的中国23个省市猪和鸡中粘菌素耐药大肠杆菌(CREC)检出率;2017年7月1日至8月31日,以及2018年7月1日至8月31日间4个省的118个农场(60只猪,29只鸡和29头牛)动物粪便中残留的粘菌素及mcr-1;2019年6月1日至7月30日间24个省市参加健康体检的健康志愿者mcr-1阳性大肠杆菌(MCRPEC)阳性率,并与我们在相同医院的2016年(6月1日至9月30日)数据进行比较;2015年1月1日至2016年12月31日及2018年1月1日至2019年12月31日间,中国抗生素监测网报告的26个省市医院大肠杆菌感染中CREC的比例。

Findings 结果

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).

禁止将粘菌素作为助长剂后,硫酸粘菌素预混剂的产量(2015年27 170吨 vs 2018年 2497 吨) 及销量 (2015年71·5百万美元 vs 2018年8·0百万美元) 显著降低。在4个省的118家农场中,2017年粘菌素平均残留浓度为191·1 μg/kg (SD 934·1),2018年为7·5 μg/kg (50·0) in 2018 (p<0·0001),2017年每16S RNA中 mcr-1 相对丰度中位数为 0·0009 [IQR 0·0001–0·0059],2018年为 0·0002 [0·0000–0·0020] (p=0·0001)。在23个省市,2015-16年间3396个猪粪标本中1153个 (34·0%) 检测出CREC,2017-18年间2781个标本中 142个 (5·1%) 检测阳性;2015-16年间2614个鸡粪标本中 474个 (18·1%) 检测阳性,2017-18年间2887个鸡粪标本中 143个 (5·0%) 检测阳性。在24个省市的医院中,2016年4498份健康人标本中644个 (14·3%) 携带MCRPEC,2019年5657份标本中 357份 (6·3%) 检测阳性。2015-16年26个省市62 737 例大肠杆菌感染中1059例 (1·7%) 为CREC,2018-19年59 385例大肠杆菌感染中 794例 (1·3%) 为CREC (p<0·0001)。

Interpretation 结论

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.

农业中禁止粘菌素政策及减少粘菌素使用对减少中国动物和人中粘菌素耐药有相助影响。然而,需要对粘菌素耐药进行持续监测,尤其在中国的医院中作为早期预警系统指导粘菌素的合理应用。

Funding 资助

National Key Research and Development Program of China, National Natural Science Foundation of China, and UK Medical Research Council.

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