药物饲料添加剂杆菌肽耐药性风险评估

doi:10.16431/j.cnki.1671-7236.2020.11.039

摘要/Abstract

摘要： 本研究旨在为监管部门制定动物源细菌耐药风险管理措施提供理论依据。利用2014年国民体质监测数据、第五次中国总膳食研究数据和欧洲药品管理局官方网站数据，采用抗菌药物风险评估模型，对中国居民经动物性食品摄入杆菌肽的耐药性风险进行点评估。用估算每日摄入量作为杆菌肽膳食暴露量，用危害指数（HQ）进行风险特征描述，反映杆菌肽耐药对人体健康损害的风险等级。结果表明，危害识别得杆菌肽经口毒性极低，但肠球菌、产气荚膜梭菌等致病菌已对杆菌肽产生耐药性，耐药基因可转移至人体肠道菌群。经危害特征描述可知，杆菌肽毒理学每日允许摄入量（ADI）为0.055 mg/（kg·BW），微生物学ADI为3.9 μg/（kg·BW）。暴露评估发现，中国居民中2~7岁人群杆菌肽的膳食暴露量最高，女性通过摄入乳类的杆菌肽膳食暴露量高于男性。2~7岁人群中，杆菌肽的膳食暴露量以乳类贡献最大，8岁以上人群杆菌肽的膳食暴露量以肉类贡献最大。风险特征描述发现，中国居民中通过摄入肉、蛋、乳等动物性食品的杆菌肽耐药性风险，2~7岁人群HQ分别为男性1.4901、女性1.4121；其他年龄人群均<1。不确定性分析发现，结果不确定性源自缺乏动物性食品杆菌肽残留量监测数据、权威数据发布的滞后性、未考虑水产品等因素。综上动物性食品中药物饲料添加剂杆菌肽耐药性风险，2~7岁人群为高风险，其他年龄段人群为中等风险。针对杆菌肽的耐药性风险，必要时修订动物性食品中杆菌肽的最大残留限量，同时加强对进口动物性食品的杆菌肽耐药性风险管理。

关键词: 杆菌肽; 饲料添加剂; 食品安全; 风险评估

Abstract: The aim of this study was to provide theoretical basis for regulatory departments to formulate risk management measures for bacterial resistance of animal origin.The point assessment method was applied to assess the risk of bacitracin resistance in animal origin foods of Chinese residents,according to the model of risk assessment analysis,based on the data from the monitoring report of the citizen's physiques in China in 2014,the fifth Chinese total diet study and the official website of European Medicine Agency.Dietary exposure to bacitracin was calculated by estimated daily intake,and hazard quotient (HQ) was used in risk characterisation to indicate risk level of health damage exposed to bacitracin.Firstly,through the way of hazard identification,the toxicity of bacitracin by oral ingestion was very low.But the pathogenic bacteria such as Enterococcus and Clostridium perfringens had developed resistance to bacitracin,with the resistance genes easily transferring to the human intestinal flora through bacteria commonness.Secondly,the hazard characterization indicated the toxicological ADI was 0.055 mg/(kg·BW),and the microbiological ADI was 3.9 μg/(kg·BW).Thirdly,exposure assessment showed that the maximum dietary exposure of bacitracin was in 2 to 7 age group among Chinese residents.And that of women through intake of dairy products was higher than men.Among 2 to 7 age group,dairy products contributed most to the dietary exposure of bacitracin,while meat was the largest contributor above 8 years old.Fourthly,risk characterization hazard quotient was 1.4901 for males and 1.4121 for females among Chinese residents aged 2 to 7 by calculation,and <1 among other age groups.Finally,the uncertainty analysis showed that the lack of monitoring data of bacitracin residues in animal foods,the lag of authoritative data collection and release,the absence of consumption data of aquatic products brought uncertainty to the results.In total,the risk of bacitracin resistance as a medicated feed additive through animal foods exposure was high in children aged 2 to 7 and moderate in other age groups.The maximum residue limit standard should be revised appropriately and risk management of bacitracin resistance need to be strengthened in imported animal foods.

Key words: bacitracin; feed additive; food safety; risk assessment

中图分类号:

S816.3

何梦如, 周旎, 吕晓华. 药物饲料添加剂杆菌肽耐药性风险评估[J]. 中国畜牧兽医, 2020, 47(11): 3749-3756.

HE Mengru, ZHOU Ni, LYU Xiaohua. Risk Assessment of Bacitracin Resistance as a Medicated Feed Additive[J]. China Animal Husbandry and Veterinary Medicine, 2020, 47(11): 3749-3756.

参考文献

[1] 刘利晓.药物饲料添加剂残留对生态环境影响的研究进展[J].畜牧与饲料科学,2019,40(9):82-85. LIU L X.Advances in impacts of medicated feed additives residues on ecological environment[J].Animal Husbandry and Feed Science,2019,40(9):82-85.(in Chinese)
[2] VERMA P,SAMANTA S K.Comparative assessment of antibiotic potency loss with time and its impact on antibiotic resistance[J].Comparative Clinical Pathology,2016,25(6):1163-1169.
[3] RUKMINI M,SAHOO D,DALEI J,et al.Production,purification and characterization of bacitracin from Bacillus subtilis[J].Electronic Journal of Biotechnology,2015,3(12):77-82.
[4] FDA.New animal drugs for use in animal feeds;Bacitracin methylenedisalicylate[EB/OL].https://www.federalregister.gov/articles/2015/12/22/2015-32000/new-animal-drugs-for-use-in-animal-feeds-bacitracin-methylenedisalicylate.
[5] FDA.CVM GFI #120 Veterinary feed directive regulation questions and answers[EB/OL].https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-120-veterinary-feed-directive-regulation-questions-and-answers
[6] e-CFR.PART 558-New animal drugs for use in animal feeds[EB/OL].https://www.ecfr.gov/cgi-bin/text-idx?SID=b8e74620d2b65cd5c35fb00efa6dbcd9&mc=true&node=pt21.6.558&rgn=div5%20-%20se21.6.558_14.
[7] 孙磊,裘鹏,刘晓琳,等.细菌耐药性产生对毒力影响的研究进展[J].畜牧与兽医,2016,48(11):120-123. SUN L,QIU P,LIU X L,et al.Research progress on bacterial resistance influencing virulence[J].Animal Husbandry & Veterinary Medicine,2016,48(11):120-123.(in Chinese)
[8] 国家体育总局.2014年国民体质监测公报[EB/OL].http://www.sport.gov.cn/n315/n329/c216784/content.html. GENERAL ADMINISTRATION OF SPORT OF CHINA.The monitoring report of the citizen's physiques in China in 2014[EB/OL].http://www.sport.gov.cn/n315/n329/c216784/content.html.(in Chinese)
[9] 吴永宁,赵云峰,李敬光,等.第五次中国总膳食研究[M].北京:科学出版社,2018. WU Y N,ZHAO Y F,LI J G,et al.The Fifth Chinese Total Diet Study[M].Beijing:Science Press,2018.(in Chinese)
[10] EMA.Bacitracin:Summary report (2)-Committee for veterinary medicinal products[EB/OL].https://www.ema.europa.eu/documents/mrl-report/bacitracin-summary-report-2-committee-veterinary-medicinal-products_en.pdf.(EMEA/MRL/768/00-FINAL)
[11] SALISBURY J G,NICHOLLS T J,LAMMERDING A M,et al.A risk analysis framework for the long-term management of antibiotic resistance in food-producing animals[J].International Journal of Antimicrobial Agents,2002,20(3):153-164.
[12] 聂晓玲,郭荣,刘宇,等.陕西省居民膳食中铝暴露风险评估[J].中国食品卫生杂志,2017,29(4):499-504. NIE X L,GUO R,LIU Y,et al.Dietary assessment on dietary exposure of aluminium residents in Shaanxi province[J].Chinese Journal of Food Hygiene,2017,29(4):499-504.(in Chinese)
[13] 孙晓红,王海香,陈娟,等.动物性食品中抗菌药物残留对肠道菌群的影响及其微生物学ADI[J].中国食品卫生杂志,2010,22(5):92-96. SUN X H,WANG H X,CHEN J,et al.Impact of antibiotics residues in animal-derived foods on intestinal microflora and the microbiological ADI[J].Chinese Journal of Food Hygiene,2010,22(5):92-96.(in Chinese)
[14] KABIR M H,ELATY A M A,RAHMAN M M.Dissipation kinetics,pre-harvest residue limits,and hazard quotient assessments of pesticides flubendiamide and fluopicolide in Korean melon (Cucumis melo L.var. makuwa) grown under regulated conditions in plastic greenhouses[J].Environmental Science & Pollution Research International,2017,24(28):22241-22250.
[15] ABBASSY M A,SALIM Y M M,SHAWIR M S,et al.Disappearance and hazard quotient of chlorpyrifos-methyl,fipronil,and imidacloprid insecticides from dates[J].Journal of Consumer Protection & Food Safety,2017,12:223-230.
[16] 朱秀辉,曾巧云,解启来,等.广州市北郊蔬菜基地土壤四环素类抗菌药物的残留及风险评估[J].农业环境科学学报,2017,36(11):2257-2226. ZHU X H,ZENG Q Y,XIE Q L,et al.Residues and risk assessment of tetracycline antibiotics in vegetable-growing soils from suburban areas of northern Guangzhou[J].Journal of Agro-Environment Science,2017,36(11):2257-2266.(in Chinese)
[17] CAO M,HELMANN J D.Regulation of the Bacillus subtilis bcrC bacitracin resistance gene by two extracytoplasmic function factors[J].Journal of Bacteriology,2002,184(22):6123-6129.
[18] NEVADO R,FORCEN R,LAYUNTA E,et al.Neomycin and bacitracin reduce the intestinal permeability in mice and increase the expression of some tight-junction proteins[J].Revista Española de Enfermedades Digestivas,2015,107(11):672-676.
[19] 刘瑾,陈申申,张越,等.猪链球菌2型SstF蛋白对杆菌肽耐药性及毒力的影响[J].畜牧与兽医,2018,50(6):74-79. LIU J,CHEN S S,ZHANG Y,et al.Influence of SstF on bacitracin resistance and virulence in Streptococcus suis serotype 2[J].Animal Husbandry & Veterinary Medicine,2018,50(6):74-79.(in Chinese)
[20] TIAN X L,SALIM H,DONG G,et al.The BceABRS four-component system that is essential for cell envelope stress response is involved in sensing and response to host defence peptides and is required for the biofilm formation and fitness of Streptococcus mutans[J].Journal of Medical Microbiology,2018,67(6):874-883.
[21] HAN X Y,DU X D,LUKE S,et al.Functional analysis of a bacitracin resistance determinant located on ICECp1, a novel Tn916-like element from a conjugative plasmid in Clostridium perfringens[J].Antimicrobial Agents & Chemotherapy,2015,59(11):6855-6865.
[22] 曾俊棋,岳万福.猪源大肠杆菌耐药性与毒力的研究[J].现代畜牧兽医,2016,1:38-44. ZENG J Q,YUE W F.Study on drug resistance and virulence of porcine originated Escherichia coli strains[J].Modern Journal of Animal Husbandry and Veterinary Medicine,2016,1:38-44.(in Chinese)
[23] QIN J J,LI R Q,RAES J,et al.A human gut microbial gene catalogue established by metagenomic sequencing[J].Nature,2010,464(7285):59-65.
[24] CLEMENTI F,AQUILANTI L.Recent investigations and updated criteria for the assessment of antibiotic resistance in food lactic acid bacteria[J].Anaerobe,2011,17(6):394-398.
[25] 闫静辉,李玉静.杆菌肽(锌)及其应用进展[J].畜牧与饲料科学,2009,30(6),170-172. YAN J H,LI Y J.Advance on zinc bacitracin premin and its application[J].Animal Husbandry and Feed Science,2009,30(6):170-172.(in Chinese)
[26] 贺文庆.亚甲基水杨酸杆菌肽预混剂对鸭的促生长、靶动物安全性和残留消除研究[D].扬州:扬州大学,2014. HE W Q.Effects on the growtn promotion,target animal safety and residues elimination of BMD premix in ducks[D].Yangzhou:Yangzhou University,2014.(in Chinese)
[27] CARABALLO J,BINKLEY E,HAN I,et al.Intraoperative anaphylaxis to bacitracin during scleral buckle surgery[J].Annals of Allergy,Asthma & Immunology, 2017,119(6):559-560.
[28] YILMAZ E R,GURER B,KERTMEN H,et al.The histopathological and ultrastructural effects of topical application of bacitracin on to the cerebral cortex in rats[J].Turkish Neurosurgery,2015,25(1):78-84.
[29] 孙长颢,凌文华,刘烈刚,等.营养与食品卫生学[M].第8版.北京:人民卫生出版社,2017. SUN C H,LING W H,LIU L G,et al.Nutrtrion and Food Hygiene[M].8th Edition.Beijing:People's Medical Publishing House,2017.(in Chinese)
[30] CHEREAU F,OPATOWSKI L,TOURDJMAN M,et al.Risk assessment for antibiotic resistance in South East Asia[J].British Medical Association,2017,358(Supple 1):j3393.
[31] 王正彬,刘永涛,董靖,等.水产品中杆菌肽残留的微生物法检测[J].华中农业大学学报,2015,34(5):105-110. WANG Z B,LIU Y T,DONG J,et al.Microbiological inhibition method for determination of bacitracin residues in muscles of aquatic products[J].Journal of Huazhong Agricultural University,2015,34(5):105-110.(in Chinese)