贡鑫然;李志强;吴迪;杨美涛;王彦丁;邹大阳;王勇;

• 1:中国医科大学公共卫生学院
• 2:中国人民解放军疾病预防控制中心

摘要(Abstract)：

目的 对中国人群中携带mcr相关基因的阳性菌流行病学特征总结分析，为相关临床研究及科研人员提供参考。方法 在PubMed和中国知网分别以“mcr,China”和“mcr”搜索2015-2021年中国境内mcr相关文献，对mcr阳性菌株的分布特征进行分析。结果 中国31个省市(区)报告了3 745株mcr阳性菌株，mcr-1(3 684株)和mcr-3(34株)分离数量最多，尚未在中国人群中发现mcr-6和mcr-7,其余型别数量均少于10株。地区分布上呈现南方高于北方，沿海高于内陆的状况，广东省报道数量最多(1 654株),其次是浙江(579株)。埃希菌属中mcr阳性菌最多(1 872株),其中mcr-1基因主要由大肠埃希菌携带(1 869株),mcr-3基因主要由沙门菌属(10株)和气单胞菌属(9株)携带，7株mcr-8基因阳性菌均为肺炎克雷伯菌，3株mcr-9阳性菌分布在肠杆菌科。时间分布上从2008年开始呈现增加后下降再上升的趋势；样本多来源于住院患者(1 615株)和体检人员(1 529株),以肠道门诊和胃肠疾病来源为主。2 882份标本来源于粪便和直肠拭子。结论 mcr基因在中国人群中广泛存在，且阳性菌株仍有增加的趋势，这提示医疗疾控机构应对mcr基因阳性菌进行合理的监测和防控。

关键词(KeyWords)： mcr-1;携带;多黏菌素;耐药基因;质粒

Abstract:

Keywords:

基金项目(Foundation): 国家传染病重大专项基金资助项目(2018ZX10733402-008)

作者(Authors): 贡鑫然;李志强;吴迪;杨美涛;王彦丁;邹大阳;王勇;

参考文献(References)：

• [1] Li J,Nation RL,Turnidge JD,et al.Colistin:the re-emerging antibiotic for multidrug-resistant gram-negative bacterial infections[J].Lancet Infect Dis,2006,6(9):589-601.
• [2] 王明贵.广泛耐药革兰阴性菌感染的实验诊断、抗菌治疗及医院感染控制：中国专家共识[J].中国感染与化疗杂志，2017,17(1):82-93.
• [3] Liu YY,Wang Y,Walsh TR,et al.Emergence of plasmid-mediated colistin resistance mechanism mcr-1 in animals and human beings in China:a microbiological and molecular biological study[J].Lancet Infect Dis,2016,16(2):161-168.
• [4] Ling ZR,Yin WJ,Shen ZQ,et al.Epidemiology of mobile colistin resistance genes mcr-1 to mcr-9[J].J Antimicrob Chemother,2020,75(11):3087-3095.
• [5] Zhang HR,Xiang Y,Huang Y,et al.Genetic characterization of mcr-1-positive multidrug-resistant Salmonella enterica serotype typhimurium isolated from intestinal infection in children and pork offal in China[J].Front Microbiol,2021,12:774797.
• [6] 李天萌，王丽媛，柯唯心，等.2015—2018年黏菌素耐药肺炎克雷伯菌的分子流行病学研究[J].中国临床药理学杂志，2021,37(11):1337-1340.
• [7] 张霞，王莹超，眭阳，等.产碳青霉烯酶肠杆菌科细菌合并多黏菌素耐药基因 mcr-1的研究[J].中华临床感染病杂志，2016,9(5):444-447.
• [8] 王齐晖，刘学佳，胡锦瑞，等.肠杆菌科细菌mcr-1基因筛查及其与多黏菌素耐药表型的相关性[J].中国医科大学学报，2018,47(8):713-716.
• [9] 张雪，谢小芳，王敏，等.碳青霉烯类耐药肠杆菌科细菌多黏菌素耐药性调查及分子机制分析[J].临床检验杂志，2020,38(8):592-596,602.
• [10] 孙丹，姜飞，樊慧丽，等.碳青霉烯耐药肺炎克雷伯菌致泌尿系统医院感染的特点及耐药机制研究[J].中华医院感染学杂志，2018,28(20):3041-3044.
• [11] 曹阳，遇晓杰，韩营营，等.我国非伤寒沙门菌对多粘菌素的耐药现况及mcr-1基因携带概况[J].疾病监测，2017,32(5):365-371.
• [12] 马强，朱永泽，朱建俊，等.血流感染大肠埃希菌对多黏菌素耐药机制研究[J].浙江医学，2021,43(12):1291-1294.
• [13] Sun QL,Hu YY,Zhou HW,et al.Alkaline peptone water-based enrichment method for mcr-3 from acute diarrheic outpatient gut samples[J].Front Med (Lausanne),2018,5:99.
• [14] Li WW,Chen QQ,Zhang ZH,et al.Analysis of drug resistance pattern and genes of Salmonella.spp isolated from human infections in Anhui Province[J].Chin J Prev Med,2020,54(2):187-191.
• [15] Shen YB,Zhou HW,Xu J,et al.Anthropogenic and environmental factors associated with high incidence of mcr-1 carriage in humans across China[J].Nat Microbiol,2018,3(9):1054-1062.
• [16] Patil S,Chen HY,Zhang XL,et al.Antimicrobial resistance and resistance determinant insights into multi-drug resistant gram-negative bacteria isolates from paediatric patients in China[J].Infect Drug Resist,2019,12:3625-3634.
• [17] Li BY,Ke BX,Zhao XY,et al.Antimicrobial resistance profile of mcr-1 positive clinical isolates of Escherichia coli in China from 2013 to 2016[J].Front Microbiol,2018,9:2514.
• [18] Lv DY,Duan R,Fan R,et al.blaNDM and mcr-1 to mcr-5 gene distribution characteristics in gut specimens from different regions of China[J].Antibiotics (Basel),2021,10(3):233.
• [19] Wang Y,Xu CY,Zhang R,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[J].Lancet Infect Dis,2020,20(10):1161-1171.
• [20] Jiang Y,Zhang Y,Lu J,et al.Clinical relevance and plasmid dynamics of mcr-1-positive Escherichia coli in China:a multicentre case-control and molecular epidemiological study[J].Lancet Microbe,2020,1(1):e24-e33.
• [21] Feng SY,Shen C,Chen HT,et al.Co-production of mcr-1 and NDM-5 in Escherichia coli isolated from a colonization case of inpatient[J].Infect Drug Resist,2018,11:1157-1161.
• [22] Hu YY,Wang YL,Sun QL,et al.Colistin resistance gene mcr-1 in gut flora of children[J].Int J Antimicrob Agents,2017,50(4):593-597.
• [23] Huang H,Dong N,Shu LB,et al.Colistin-resistance gene mcr in clinical carbapenem-resistant Enterobacteriaceae strains in China,2014-2019[J].Emerg Microbes Infect,2020,9(1):237-245.
• [24] Wong SC,Tse H,Chen JH,et al.Colistin-resistant Enterobacteriaceae carrying the mcr-1 gene among patients in Hong Kong[J].Emerg Infect Dis,2016,22(9):1667-1669.
• [25] Zhong LL,Zhang YF,Doi Y,et al.Coproduction of mcr-1 and NDM-1 by colistin-resistant Escherichia coli isolated from a healthy individual[J].Antimicrob Agents Chemother,2017,61(1):e01962-e01916.
• [26] Chen X,Zhao XF,Che J,et al.Detection and dissemination of the colistin resistance gene,mcr-1,from isolates and faecal samples in China[J].J Med Microbiol,2017,66(2):119-125.
• [27] Yu H,Qu F,Shan B,et al.Detection of the mcr-1 colistin resistance gene in carbapenem-resistant Enterobacteriaceae from different hospitals in China[J].Antimicrob Agents Chemother,2016,60(8):5033-5035.
• [28] Kang HQ,Zheng W,Kong ZY,et al.Disease burden and molecular epidemiology of carbapenem-resistant Klebsiella pneumonia infection in a tertiary hospital in China[J].Ann Transl Med,2020,8(9):605.
• [29] Hu YF,Liu F,Lin IY,et al.Dissemination of the mcr-1 colistin resistance gene[J].Lancet Infect Dis,2016,16(2):146-147.
• [30] Shen C,Zhong LL,Yang Y,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[J].Lancet Microbe,2020,1(1):e34-e43.
• [31] Liu GY,Qian HM,Lv JW,et al.Emergence of mcr-1-harboring Salmonella enterica serovar sinstorf type ST155 isolated from patients with diarrhea in Jiangsu,China[J].Front Microbiol,2021,12:723697.
• [32] Du H,Chen L,Tang YW,et al.Emergence of the mcr-1 colistin resistance gene in carbapenem-resistant Enterobacteriaceae[J].Lancet Infect Dis,2016,16(3):287-288.
• [33] Shen ZQ,Hu YY,Sun QL,et al.Emerging carriage of NDM-5 and mcr-1 in Escherichia coli from healthy people in multiple regions in China:a cross sectional observational study[J].EClinicalMedicine,2018,6:11-20.
• [34] Elbediwi M,Pan H,Biswas S,et al.Emerging colistin resistance in Salmonella enterica serovar Newport isolates from human infections[J].Emerg Microbes Infect,2020,9(1):535-538.
• [35] Lu X,Zeng M,Xu JL,et al.Epidemiologic and genomic insights on mcr-1-harbouring Salmonella from diarrhoeal outpatients in Shanghai,China,2006-2016[J].EBioMedicine,2019,42:133-144.
• [36] Hameed MF,Chen YN,Wang Y,et al.Epidemiological characterization of colistin and carbapenem resistant Enterobacteriaceae in a tertiary:a hospital from Anhui Province[J].Infect Drug Resist,2021,14:1325-1333.
• [37] Zhong YM,Liu WE,Zheng ZF.Epidemiology and molecular characterization of mcr-1 in Escherichia coli recovered from patients with bloodstream infections in Changsha,central China[J].Infect Drug Resist,2019,12:2069-2076.
• [38] Li ZH,Shi R,Wu H,et al.First identification of a patient with prosthesis-related infection caused by an mcr-1.1-producing ST131 Escherichia coli after rhinoplasty[J].Infect Drug Resist,2021,14:249-257.
• [39] Wang QJ,Sun J,Ding YF,et al.Genomic insights into mcr-1-positive plasmids carried by colistin-resistant Escherichia coli isolates from inpatients[J].Antimicrob Agents Chemother,2017,61(7):e00361-e00317.
• [40] Zhang HM,Seward CH,Wu ZW,et al.Genomic insights into the ESBL and mcr-1-producing ST648 Escherichia[J].Sci Bull,2016,61(11):875-878.
• [41] Zhong LL,Phan HTT,Shen C,et al.High rates of human fecal carriage of mcr-1-positive multidrug-resistant Enterobacteriaceae emerge in China in association with successful plasmid families[J].Clin Infect Dis,2018,66(5):676-685.
• [42] Li Y,Yan WJ,Liu SQ.Investigation of colistin resistance gene mcr in gut bacteria from patients with acute diarrheal[J].Zhonghua Yi Xue Za Zhi,2017,97(47):3720-3723.
• [43] Liang ZW,Pang J,Hu XX,et al.Low prevalence of mcr-1 among clinical Enterobacteriaceae isolates and co-transfer of mcr-1 and blaNDM-1 from separate donors[J].Microb Drug Resist,2021,27(4):476-484.
• [44] Zheng BW,Xu H,Yu X,et al.Low prevalence of mcr-1-producing Klebsiella pneumoniae in bloodstream infections in China[J].Clin Microbiol Infect,2018,24(2):205-206.
• [45] Lei L,Wang Y,Schwarz S,et al.mcr-1 in Enterobacteriaceae from companion animals,Beijing,China,2012-2016[J].Emerg Infect Dis,2017,23(4):710-711.
• [46] Luo QX,Wan F,Yu X,et al.MDR Salmonella enterica serovar Typhimurium ST34 carrying mcr-1 isolated from cases of bloodstream and intestinal infection in children in China[J].J Antimicrob Chemother,2020,75(1):92-95.
• [47] He QW,Xu XH,Lan FJ,et al.Molecular characteristic of mcr-1 producing Escherichia coli in a Chinese university hospital[J].Ann Clin Microbiol Antimicrob,2017,16(1):32.
• [48] Li S,Duan XN,Peng Y,et al.Molecular characteristics of carbapenem-resistant Acinetobacter spp.from clinical infection samples and fecal survey samples in Southern China[J].BMC Infect Dis,2019,19(1):900.
• [49] Zhang JL,Chen L,Wang JW,et al.Molecular detection of colistin resistance genes (mcr-1 to mcr-5) in human vaginal swabs[J].BMC Res Notes,2018,11(1):143.
• [50] Wang X,Liu Y,Qi X,et al.Molecular epidemiology of colistin-resistant Enterobacteriaceae in inpatient and avian isolates from China:high prevalence of mcr-negative Klebsiella pneumoniae[J].Int J Antimicrob Agents,2017,50(4):536-541.
• [51] Yan WJ,Zhang Q,Zhu YJ,et al.Molecular mechanism of polymyxin resistance in multidrug-resistant Klebsiella pneumoniae and Escherichia coli isolates from Henan Province,China:a multicenter study[J].Infect Drug Resist,2021,14:2657-2666.
• [52] Liu YL,Lin YQ,Wang ZW,et al.Molecular mechanisms of colistin resistance in Klebsiella pneumoniae in a tertiary care teaching hospital[J].Front Cell Infect Microbiol,2021,11:673503.
• [53] Ma Q,Huang Y,Wang J,et al.Multidrug-resistant Shigella sonnei carrying the plasmid-mediated mcr-1 gene in China[J].Int J Antimicrob Agents,2018,52(1):14-21.
• [54] Zhang R,Liu L,Zhou H,et al.Nationwide surveillance of clinical carbapenem-resistant Enterobacteriaceae (CRE) strains in China[J].EBioMedicine,2017,19:98-106.
• [55] Lu Y,Feng Y,McNally A,et al.The occurence of colistin-resistant hypervirulent Klebsiella pneumoniae in China[J].Front Microbiol,2018,9:2568.
• [56] Zheng BW,Xu H,Huang C,et al.Occurrence and genomic characterization of two mcr-1-producing Escherichia coli isolates from the same mink farmer[J].mSphere,2019,4(6):e00602-e00619.
• [57] Zheng ZZ,Lei Y,Wang YN,et al.Occurrence of mcr positive strains and molecular characteristics of two mcr-1 positive Salmonella typhimurium and Escherichia coli from a Chinese women′s and children′s hospital[J].Infect Drug Resist,2021,14:2925-2932.
• [58] Wang Q,Wang XJ,Wang J,et al.Phenotypic and genotypic characterization of carbapenem-resistant Enterobacteriaceae:data from a longitudinal large-scale CRE study in China (2012-2016)[J].Clin Infect Dis,2018,67(suppl_2):S196-S205.
• [59] Fan JZ,Zhang LH,He JT,et al.Plasmid dynamics of mcr-1-positive Salmonella spp.in a general hospital in China[J].Front Microbiol,2020,11:604710.
• [60] Li Y,Zhang Y,Chen M,et al.Plasmid-borne colistin resistance gene mcr-1 in a multidrug-resistant Salmonella enterica serovar Typhimurium isolate from an infant with acute diarrhea in China[J].Int J Infect Dis,2021,103:13-18.
• [61] Zhang X,Qu F,Jia W,et al.Polymyxin resistance in carbapenem-resistant Enterobacteriaceae isolates from patients without polymyxin exposure:a multicentre study in China[J].Int J Antimicrob Agents,2021,57(2):106262.
• [62] Cao L,Li XM,Xu Y,et al.Prevalence and molecular characteristics of mcr-1 colistin resistance in Escherichia coli:isolates of clinical infection from a Chinese University Hospital[J].Infect Drug Resist,2018,11:1597-1603.
• [63] Lu J,Quan JJ,Zhao DD,et al.Prevalence and molecular characteristics of mcr-1 gene in Salmonella typhimurium in a tertiary hospital of Zhejiang Province[J].Infect Drug Resist,2019,12:105-110.
• [64] Lu H,Wang C,Dong GF,et al.Prevalence and molecular characterization of Escherichia coli clinical isolates carrying mcr-1 in a Chinese teaching hospital from 2002 to 2016[J].Antimicrob Agents Chemother,2018,62(9):e02623-e02617.
• [65] Cui MQ,Zhang JF,Gu Z,et al.Prevalence and molecular characterization of mcr-1-positive Salmonella strains recovered from clinical specimens in China[J].Antimicrob Agents Chemother,2017,61(5):e02471-e02416.
• [66] Lu JY,Dong N,Liu CC,et al.Prevalence and molecular epidemiology of mcr-1-positive Klebsiella pneumoniae in healthy adults from China[J].J Antimicrob Chemother,2020,75(9):2485-2494.
• [67] Lei L,Wang YQ,He JJ,et al.Prevalence and risk analysis of mobile colistin resistance and extended-spectrum β-lactamase genes carriage in pet dogs and their owners:a population based cross-sectional study[J].Emerg Microbes Infect,2021,10(1):242-251.
• [68] Lv Z,Shen Y,Liu W,et al.Prevalence and risk factors of mcr-1-positive volunteers after colistin banning as animal growth promoter in China:a community-based case-control study[J].Clin Microbiol Infect,2022,28(2):267-272.
• [69] Quan J,Li X,Chen Y,et al.Prevalence of mcr-1 in Escherichia coli and Klebsiella pneumoniae recovered from bloodstream infections in China:a multicentre longitudinal study[J].Lancet Infect Dis,2017,17(4):400-410.
• [70] Bi Z,Berglund B,Sun Q,et al.Prevalence of the mcr-1 colistin resistance gene in extended-spectrum β-lactamase-producing Escherichia coli from human faecal samples collected in 2012 in rural villages in Shandong Province,China[J].Int J Antimicrob Agents,2017,49(4):493-497.
• [71] Shen C,Ma FR,Deng SY,et al.Prevalence,genomic characteristics,and transmission dynamics of mcr-1-positive Salmonella enterica typhimurium from patients with infectious diarrhea[J].Int J Med Microbiol,2021,311(4):151501.
• [72] Wang Y,Tian GB,Zhang R,et al.Prevalence,risk factors,outcomes,and molecular epidemiology of mcr-1-positive Enterobacteriaceae in patients and healthy adults from China:an epidemiological and clinical study[J].Lancet Infect Dis,2017,17(4):390-399.
• [73] Huang B,He YT,Ma XY,et al.Promoter variation and gene expression of mcr-1-harboring plasmids in clinical isolates of Escherichia coli and Klebsiella pneumoniae from a Chinese hospital[J].Antimicrob Agents Chemother,2018,62(5):e00018-e00018.
• [74] Lu S,Li D,Wang LL,et al.Promoter variations associated with expression of mcr-1 gene and level of colistin resistance[J].Int J Antimicrob Agents,2021,58(2):106371.
• [75] Chan WS,Au CH,Ho DN,et al.Prospective study on human fecal carriage of Enterobacteriaceae possessing mcr-1 and mcr-2 genes in a regional hospital in Hong Kong[J].BMC Infect Dis,2018,18(1):81.
• [76] Li Y,Sun QL,Shen YB,et al.Rapid increase in prevalence of carbapenem-resistant Enterobacteriaceae (CRE) and emergence of colistin resistance gene mcr-1 in CRE in a hospital in Henan,China[J].J Clin Microbiol,2018,56(4):e01932-e01917.
• [77] Liao WL,Lin J,Jia HY,et al.Resistance and heteroresistance to colistin in Escherichia coli isolates from Wenzhou,China[J].Infect Drug Resist,2020,13:3551-3561.
• [78] Fan R,Li CC,Duan R,et al.Retrospective screening and analysis of mcr-1 and blaNDM in gram-negative bacteria in China,2010-2019[J].Front Microbiol,2020,11:121.
• [79] Liu XJ,Wang Y,Cui LQ,et al.A retrospective study on mcr-1 in clinical Escherichia coli and Klebsiella pneumoniae isolates in China from 2007 to 2016[J].J Antimicrob Chemother,2018,73(7):1786-1790.
• [80] Chen KC,Chan EWC,Xie MM,et al.Widespread distribution of mcr-1-bearing bacteria in the ecosystem,2015 to 2016[J].Euro Surveill,2017,22(39):17-00206.
• [81] Lin MM,Yang YQ,Yang YX,et al.Co-occurrence of mcr-9 and blaNDM-1 in Enterobacter cloacae isolated from a patient with bloodstream infection[J].Infect Drug Resist,2020,13:1397-1402.
• [82] Sun RY,Ke BX,Fang LX,et al.Global clonal spread of mcr-3-carrying MDR ST34 Salmonella enterica serotype Typhimurium and monophasic 1,4,5,12:i:- variants from clinical isolates[J].J Antimicrob Chemother,2020,75(7):1756-1765.
• [83] Shen YB,Xu CY,Sun QL,et al.Prevalence and genetic analysis of mcr-3-positive Aeromonas species from humans,retail meat,and environmental water samples[J].Antimicrob Agents Chemother,2018,62(9):e00404-e00418.
• [84] Xu Y,Zhong LL,Srinivas S,et al.Spread of mcr-3 colistin resistance in China:an epidemiological,genomic and mechanistic study[J].EBioMedicine,2018,34:139-157.
• [85] Wang CC,Feng Y,Liu LN,et al.Identification of novel mobile colistin resistance gene mcr-10[J].Emerg Microbes Infect,2020,9(1):508-516.
• [86] Xu T,Zhang C,Ji Y,et al.Identification of mcr-10 carried by self-transmissible plasmids and chromosome in Enterobacter roggenkampii strains isolated from hospital sewage water[J].Environ Pollut,2021,268:115706.
• [87] Zhou HW,Wang SH,Wu YC,et al.Carriage of the mcr-9 and mcr-10 genes in clinical strains of the Enterobacter cloacae complex in China:a prevalence and molecular epidemiology study[J].Int J Antimicrob Agents,2022,60(4):106645.
• [88] Manandhar S,Nguyen Q,Pham DT,et al.A fatal outbreak of neonatal sepsis caused by mcr-10-carrying Enterobacter kobei in a tertiary care hospital in Nepal[J].J Hosp Infect,2022,125:60-66.