质粒介导aac(6′)-Ib基因检测与喹诺酮类耐药

doi:10.3969/j.issn.1673-8640.2013.03.007

摘要/Abstract

摘要： 目的　了解大肠埃希菌临床株对喹诺酮类抗菌药物耐药情况并分析质粒介导aac(6′)-Ib基因存在与喹诺酮类药物耐药性的关系。方法　采用纸片扩散法(K-B)对临床中段尿分离所得121株大肠埃希菌进行耐药性检测，聚合酶链反应(PCR)法检测大肠埃希菌aac(6′)-Ib基因，对aac(6′)-Ib基因阳性菌株扩增片段进行DNA测序并确定基因型。结果　大肠埃希菌临床株对萘啶酸、环丙沙星、诺氟沙星、左氧氟沙星4种喹诺酮类抗菌药物耐药率均高于75%。aac(6′)-Ib基因检出率为14.0%（17/121），经DNA测序确定aac(6′)-Ib基因变异体(cr)有14株，突变率为82.4%(14/17)；aac(6′)-Ib基因阳性株对氨苄西林-舒巴坦、哌拉西林-他唑巴坦、头孢唑啉、头孢克洛、头孢呋辛、阿米卡星、环丙沙星、诺氟沙星、左氧氟沙星耐药率高于阴性株且差异有统计学意义（P<0.05）。结论　仁济医院临床分离大肠埃希菌对喹诺酮类抗菌药物耐药情况严重；质粒介导aac(6′)-Ib基因的存在可使大肠埃希菌对喹诺酮类抗菌药物耐药性提高；质粒介导aac(6′)-Ib基因还可能引起细菌对β-内酰胺酶抑制剂药物和头孢菌素类药物敏感性下降。

关键词: 质粒介导, aac(6′)-Ib基因, 突变株, 喹诺酮类抗菌药物, 耐药机制

Abstract: Objective　To investigate the quinolone resistance to Escherichia coli isolates，and to identify the relationship of existence of plasmid-mediated aac (6′)-Ib genes with the resistance of quinolones. Methods　Kirby-Bauer(k-B) method was performed for 121 Escherichia coli isolates from urine samples collected from March 2010 to March 2011 in Renji Hospital. The aac (6′)-Ib genes in Escherichia coli isolates were determined by polymerase chain reaction(PCR). The amplification fragment of positive isolates were selected to be sequenced，and the genotypes were determined. Results　Escherichia coli isolates′ resistance rates of nalidixic acid，ciprofloxacin，norfloxacin and levofloxacin were all higher than 75%. The determination rate of aac(6′)-Ib gene was 14.0% (17/121)，and the mutation rate was 82.4%(14/17). The aac (6′)-Ib gene positive isolates had higher resistance rates of ampicillin-sulbactam，piperacillin-tazobactam，cefazolin，cefaclor，cefuroxime，amikacin，ciprofloxacin，norfloxacin and levofloxacin than the negative isolates. There was statistical significance(P<0.05). Conclusions　Quinolone resistance to Escherichia coli isolates in Renji Hospital is serious. With the plasmid-mediated aac (6′)-Ib genes，the Escherichia coli isolates may have an increasing resistance rates to quinolones and decreasing susceptibility to beta-lactamase inhibitors and cephalosporins antibiotics.

Key words: Plasmid-mediation, aac(6′)-Ib gene, Mutation isolate, Quinolone antibiotic, Resistance mechanism

赵倩，汪雅萍，应春妹，郑冰，张灏旻，杨俊. 质粒介导aac(6′)-Ib基因检测与喹诺酮类耐药[J]. 检验医学, 2013, 28(3): 199-202.

ZHAO Qian，WANG Yaping，YING Chunmei，ZHENG Bing，ZHANG Haomin，YANG Jun. A study of plasmid-mediated aac(6′)-Ib gene determination and quinolone resistance[J]. , 2013, 28(3): 199-202.

参考文献

[1]叶任高.临床肾脏病学[M].第2版.北京:人民卫生出版社，2007:339.
[2]Chenia HY，Pillay B，Pillay D. Analysis of the mechanisms of fluoroquinolone resistance in urinary tract pathogens[J].J Antimicrob Chemother，2006，58(6):1274-1278. 
[3]Ruiz J. Mechanisms of resistance to quinolones: target alterations，decreased accumulation and DNA gyrase protection[J]. J Antimicrob Chemother，2003，51(5):1109-1117.
[4]Sáenz Y，Ruiz J，Zarazaga M，et al. Effect of the efflux pump inhibitor Phe-Arg-beta-naphthylamide on the MIC values of the quinolones，tetracycline and chloramphenicol，in Escherichia coli isolates of different origin[J].J Antimicrob Chemother，2004，53(3):544-545.
[5]Park CH，Robicsek A，Jacoby GA，et al.Prevalence in the United States of aac(6′)-Ib-cr encoding a ciprofloxacin-modifying enzyme[J]. Antimicrob Agents Chemother，2006，50(11):3953-3955.
[6]肖时超，吕火祥，沈蓓琼，等.2003年至2007年大肠埃希菌的临床分离及耐药趋势分析[J]. 中国微生态学杂志，2008，20(4):407-409.
[7]Robicsek A，Sahm DF，Strahilevitz J，et al. Broader distribution of plasmid-mediated quinolone resistance in the United States[J]. Antimicrob Agents Chemother，2005，49(7):3001-3003.
[8]Morgan-Linnell SK，Becnel Boyd L，Steffen D，et al.Mechanisms accounting for fluoroquinolone resistance in Escherichia coli clinical isolates[J]. Antimicrob Agents Chemother，2009，53(1):235-241.
[9]朱东安，孙景勇，范惠清.一株福氏志贺菌中同时检出CTX-M-3型超广谱β-内酰胺酶和质粒介导的喹诺酮基因qnrS[J].检验医学，2009，24（7）:489-492.
[10]汪雅萍，应春妹，张灏旻，等.氟喹诺酮耐药志贺菌中质粒介导qnr基因的检测[J].检验医学，2011，26（10）：645-647.
[11]Robicsek A，Strahilevitz J，Jacoby GA，et al. Fluoroquinolone-modifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase [J]. Nat Med，2006，12(1):83-88.

[1]	王立新, 苏云福, 王毅. 临床病原菌磷霉素耐药机制研究进展[J]. 检验医学, 2022, 37(10): 993-997.
[2]	王姜琳, 孙杰, 杨慧健, 王冰洁, 潘芬, 张泓. 儿童耐氨苄西林流感嗜血杆菌耐药机制及同源性研究[J]. 检验医学, 2020, 35(6): 513-518.
[3]	张心宇, 杜雪飞, 邹桂玲, 姜晓峰. 鲍曼不动杆菌对替加环素耐药机制研究进展[J]. 检验医学, 2019, 34(7): 656-660.
[4]	李巍, 艾芙琪, 马逸珉, 王蓓, 田月如. 携带bla_NDM-1碳青霉烯类耐药雷极普罗威登斯菌耐药机制研究[J]. 检验医学, 2019, 34(1): 67-70.
[5]	赵虎. 深部真菌的耐药性及其耐药机制研究[J]. 检验医学, 2016, 31(9): 735-738.
[6]	闫文娟, 李轶, 王山梅, 孙明洁. 耐碳青霉烯类抗菌药物大肠埃希菌耐药机制的研究[J]. 检验医学, 2016, 31(1): 56-60.
[7]	魏冰,刘锦燕,史册,项明洁. 白念珠菌对唑类药物耐药机制的研究进展[J]. 检验医学, 2014, 29(9): 978-981.
[8]	张国栋,王莹,朱红胜. 临床分离的美罗培南和环丙沙星共同耐药的铜绿假单胞菌耐药机制的研究[J]. 检验医学, 2014, 29(6): 646-650.
[9]	史册,刘锦燕,魏冰,项明洁. 白念珠菌对唑类药物耐药机制中生物膜作用的研究进展[J]. 检验医学, 2014, 29(6): 692-694.
[10]	侯盼飞;杜坤;应春妹;胡付品;徐晓刚. 亚胺培南耐药鲍曼不动杆菌外排泵机制研究[J]. 检验医学, 2012, 27(2): 95-98.
[11]	李永丽，应春妹. 鲍曼不动杆菌多重耐药机制及耐药基因检测研究进展[J]. 检验医学, 2012, 27(11): 963-968.
[12]	汪雅萍;应春妹;张灏旻;叶杨芹;于嘉屏. 氟喹诺酮耐药志贺菌中质粒介导qnr基因的检测[J]. 检验医学, 2011, 26(10): 645-647.
[13]	罗柳林;应春妹;叶杨芹;汪雅萍;张灏旻 ;于嘉屏;倪培华. 耐碳青霉烯类抗菌药物鲍曼不动杆菌膜蛋白机制研究[J]. 检验医学, 2010, 25(04): 304-308.
[14]	李卿;蒋燕群. 可诱导性质粒ampC基因表达的调控[J]. 检验医学, 2009, 24(10): 764-767.
[15]	汪雅萍;应春妹;史超颖;张灏旻;于嘉屏. 多重聚合酶链反应检测革兰阴性杆菌中质粒介导ampC基因[J]. 检验医学, 2007, 22(04): 380-382.