淋球菌对大观霉素耐药机制的研究进展
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摘要
本文从淋病的流行现状、淋球菌的耐药现状、大观霉素在目前淋病治疗方案中的作用、淋球菌对大观霉素耐药机制等方面进行综述,以期阐述淋球菌与大观霉素相互作用的细胞通路、耐药机制及相关的耐药基因,为淋病的精准治疗、耐药监测和新药开发等提供参考和新思路。
This article overviews the prevalence of gonorrhea, the drug resistance status of NG, and the role of spectionmycin in current NG treatment programs. By expounding the cell pathway, resistant mechanisms and relevant resistant genes of the interactions between NG and spectinomycin, this article provides references and new thoughts for the accurate treatment, drug resistance monitoring, and drug developmentof gonorrhea.
This article overviews the prevalence of gonorrhea, the drug resistance status of NG, and the role of spectionmycin in current NG treatment programs. By expounding the cell pathway, resistant mechanisms and relevant resistant genes of the interactions between NG and spectinomycin, this article provides references and new thoughts for the accurate treatment, drug resistance monitoring, and drug developmentof gonorrhea.
引文
[1]Unemo M,Bradshaw C S,Hocking J S,et al.Sexually transmitted infections:challenges ahead[J].Lancet Infect Dis,2017,17(8):e235-e279.
[2]Newman L,Rowley J,Vander Hoorn S,et al.Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting[J].PLoS One,2015,10(12):e0143304.
[3]https://www.cdc.gov/std/stats17/gonorrhea.htm[EB/OL].Sexually Transmitted Disease Surveillance 2017-Gonorrhoea.
[4]https://www.nhs.uk/conditions/gonorrhoea/[EB/OL].Overview-Gonorrhoea.
[5]Lee H,Unemo M,KimH J,et al.Emergence of decreased susceptibility and resistance to extended-spectrum cephalosporins in Neisseria gonorrhoeae in Korea[J].JAntimicrob Chemother,2015,70(9):2536-2542.
[6]吴晓明,林汉生.1991-2006年全国淋病与梅毒的流行特征分析[J].现代预防医学,2008,35(16):3051-3052.
[7]http://www.nhfpc.gov.cn/jkj/s3578/new_list.shtml[EB/OL].2016年和2017年全国法定传染病疫情概况.
[8]Kubanov A,Vorobyev D,ChestkovA,et al.Molecular epidemiology of drug-resistant Neisseria gonorrhoeae in Russia(Current Status,2015)[J].BMC Infect Dis,2016,16:389.
[9]Herchline T E,InkrottB P.Resistance trends in Neisseria gonorrhoeae in southwestern Ohio[J].Sex Transm Dis,2010,37(2):121-122.
[10]Duplessis C,Puplampu N,Nyarko E,et al.Gonorrhea surveillance in Ghana,Africa[J].Mil Med,2015,180(1):17-22.
[11]Martin I,Jayaraman G,Wong T,et al.Trends in antimicrobial resistance in Neisseria gonorrhoeae isolated in Canada:2000-2009[J].Sex Transm Dis,2011,38(10):892-898.
[12]Cobo F,Cabezas-Fernandez M T,Cabeza-Barrera MI.Antimicrobial susceptibility and typing of Neisseria gonorrhoeae strains from Southern Spain,2012-2014[J].Enferm Infect Microbiol Clin,2016,34(1):3-7.
[13]Kubanova A,Kubanov A,Frigo N,et al.Russian gonococcal antimicrobial susceptibility programme(RU-GASP)--resistance in Neisseria gonorrhoeae during 2009-2012 and NG-MAST genotypes in 2011 and 2012[J].BMC Infect Dis,2014,14(1):342.
[14]Bala M,Kakran M,Singh V,et al.Monitoring antimicrobial resistance in Neisseria gonorrhoeae in selected countries of the WHO South-East Asia Region between 2009 and 2012:a retrospective analysis[J].Sex Transm Infect,2013,89(4):iv28-35.
[15]Cole M J,Spiteri G,Jacobsson S,et al.Is the tide turning again for cephalosporin resistance in Neisseria gonorrhoeae in Europe?Results from the 2013 European surveillance[J].BMC Infect Dis,2015,15(1):321.
[16]Filipiuc S,Nicolae O,Lunca C,et al.The monitoring of Neisseria gonorrhoeae infection incidence and its resistance in Suceava County[J].Rev Med Chir Soc Med Nat Iasi,2009,113(4):1238-1242.
[17]Lahra M M.Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific and South East Asian Regions,2010[J].Commun Dis Intell Q Rep,2012,36(1):95-100.
[18]Tapsall J.Annual report of the Australian Gonococcal Surveillance Programme,2008[J].Commun Dis Intell QRep,2009,33(3):268-274.
[19]湛学军,谢大泽,徐燕萍,等.女性患者淋球菌对抗生素的多重耐药性分析[J].检验医学与临床,2010,7(5):385-386,389.
[20]潘永年,吴正青,彭一凯,等.351例淋病临床流行病学观察[J].中国中西医结合皮肤性病学杂志,2010,9(6):367-368.
[21]时祝帅,王德霞,聂青松.2010-2015年扬州地区淋球菌耐药性和流行株质粒谱的研究[J].蚌埠医学院学报,2016,41(12):1681-1683.
[22]谢俭,陈怀忠.233株淋球菌耐药性的监测与分析[J].中国医学创新,2011,8(17):121-122.
[23]顾华爱.淋病患者156例淋病奈瑟球菌耐药性分析[J].中国乡村医药,2010,17(7):54.
[24]张丽君,何亮,王峰,等.深圳地区淋球菌株耐药性流行趋势分析[J].中国热带医学,2010,10(5):561-562.
[25]曹文苓,黎小东,毕超,等.广州地区2013年淋球菌耐药监测结果分析[J].中国皮肤性病学杂志,2014,28(11):1144-1145.
[26]蒋英,刘键,谢延,等.103株淋球菌耐药性研究[J].实用预防医学,2013,20(3):345-347.
[27]黎小东,曹文苓,宋卫忠,等.2010年广州地区淋球菌耐药监测结果分析[J].中国微生态学杂志,2012,24(6):554-555,560.
[28]黄健,黄美容,黄洋,等.性病患者中淋球菌感染的流行病学调查及耐药性研究[J].国际检验医学杂志,2015,36(17):2554-2555.
[29]余宝珠,龚宇花,黄辉如.惠州地区淋球菌对抗菌药物的耐药性分析[J].检验医学与临床,2013,10(9):1111-1112.
[30]陈晨春.南宁市1993-2013年梅毒及淋病流行特征分析[J].中国皮肤性病学杂志,2015,29(2):158-159.
[31]叶峰山.淋病奈瑟菌耐大观霉素与16S rRNA基因突变发生情况的研究[D].2010,太原:山西医科大学.
[32]梁佩婵,黄海花,吴志周,等.江门市淋球菌对7种抗菌药物耐药性的结果分析[J].国际检验医学杂志,2017,38(2):258-260.
[33]Yin Y P,HanY,Dai X Q,et al.Susceptibility of Neisseria gonorrhoeae to azithromycin and ceftriaxone in China:Aretrospective study of national surveillance data from 2013to 2016[J].PLoS Med,2018,15(2):e1002499.
[34]郭青良,闫圣男,时颍涛,等.我院男科门诊淋球菌药物敏感性及耐药分析[J].中国合理用药探索,2017,14(8):18-20.
[35]黄辉如.惠州地区淋球菌对抗菌药物的敏感性测定及多重耐药分析[J].国际检验医学杂志,2015,36(15):2273-2275.
[36]Nabu S,Lawung R,Isarankura-Na-Ayudhya P,et al.Reference map and comparative proteomic analysis of Neisseria gonorrhoeae displaying high resistance against spectinomycin[J].J Med Microbiol,2014,63(3):371-385.
[37]Unemo M,Shafer W M.Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century:Past,evolution,and future[J].Clin Microbiol Rev,2014,27(3):587-613.
[38]WHO Guidelines Approved by the guidelines review committee.WHO Guidelines for the treatment of Neisseria gonorrhoeae[M].Geneva:World Health Organization,2016.
[39]Bignell C,Unemo M.2012 European guideline on the diagnosis and treatment of gonorrhoea in adults[J].Int J Std Aids,2013,24(2):85-92.
[40]Available from:http://jssti.umin.jp/pdf/guideline-2011.pdf[EB/OL].2011年度版発行に際して.
[41]https://www.egms.de/static/en/journals/id/2014-2/id000010.shtml[EB/OL].Gonorrhoea in adults and in adolescents.
[42]Bignell C,Fitz Gerald M.UK national guideline for the management of gonorrhoea in adults,2011[J].Int J STDAIDS,2011,22(10):541-547.
[43]Available from:http://www.phac-aspc.gc.ca/std-mts/stiits/cgsti-ldcits/assets/pdf/section-5-6-eng.pdf[EB/OL].Guidelines on Sexually Transmitted Infections.
[44]徐金华,王千秋,刘全忠.性传播疾病临床诊疗与防治指南[M].上海:上海科学技术出版社,2014:91-103.
[45]Jerse A E,Sharma N D,Simms A N,et al.A gonococcal efflux pump system enhances bacterial survival in a female mouse model of genital tract infection[J].Infect Immun,2003,71(10):5576-5582.
[46]Unemo M,Nicholas R A.Emergence of multidrug-resistant,extensively drug-resistant and untreatable gonorrhea[J].Future Microbiol,2012,7(12):1401-1422.
[47]Ramirez M S,Tolmasky M E.Aminoglycoside modifying enzymes[J].Drug Resist Updat,2010,13(6):151-171.
[48]Unemo M,Fasth O,Fredlund H,et al.Phenotypic and genetic characterization of the 2008 WHO Neisseria gonorrhoeae reference strain panel intended for global quality assurance and quality control of gonococcal antimicrobial resistance surveillance for public health purposes[J].J Antimicrob Chemother,2009,63(6):1142-1151.
[49]Unemo M,Golparian D,SkogenV,et al.Neisseria gonorrhoeae strain with high-level resistance to spectinomycin due to a novel resistance mechanism(mutated ribosomal protein S5)verified in Norway[J].Antimicrob Agents Chemother,2013,57(2):1057-1061.
[50]Ilina E,Malakhova M,Bodoev I,et al.Mutation in ribosomal protein S5 leads to spectinomycin resistance in Neisseria gonorrhoeae[J].Front Microbiol,2013,4:186.
[2]Newman L,Rowley J,Vander Hoorn S,et al.Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting[J].PLoS One,2015,10(12):e0143304.
[3]https://www.cdc.gov/std/stats17/gonorrhea.htm[EB/OL].Sexually Transmitted Disease Surveillance 2017-Gonorrhoea.
[4]https://www.nhs.uk/conditions/gonorrhoea/[EB/OL].Overview-Gonorrhoea.
[5]Lee H,Unemo M,KimH J,et al.Emergence of decreased susceptibility and resistance to extended-spectrum cephalosporins in Neisseria gonorrhoeae in Korea[J].JAntimicrob Chemother,2015,70(9):2536-2542.
[6]吴晓明,林汉生.1991-2006年全国淋病与梅毒的流行特征分析[J].现代预防医学,2008,35(16):3051-3052.
[7]http://www.nhfpc.gov.cn/jkj/s3578/new_list.shtml[EB/OL].2016年和2017年全国法定传染病疫情概况.
[8]Kubanov A,Vorobyev D,ChestkovA,et al.Molecular epidemiology of drug-resistant Neisseria gonorrhoeae in Russia(Current Status,2015)[J].BMC Infect Dis,2016,16:389.
[9]Herchline T E,InkrottB P.Resistance trends in Neisseria gonorrhoeae in southwestern Ohio[J].Sex Transm Dis,2010,37(2):121-122.
[10]Duplessis C,Puplampu N,Nyarko E,et al.Gonorrhea surveillance in Ghana,Africa[J].Mil Med,2015,180(1):17-22.
[11]Martin I,Jayaraman G,Wong T,et al.Trends in antimicrobial resistance in Neisseria gonorrhoeae isolated in Canada:2000-2009[J].Sex Transm Dis,2011,38(10):892-898.
[12]Cobo F,Cabezas-Fernandez M T,Cabeza-Barrera MI.Antimicrobial susceptibility and typing of Neisseria gonorrhoeae strains from Southern Spain,2012-2014[J].Enferm Infect Microbiol Clin,2016,34(1):3-7.
[13]Kubanova A,Kubanov A,Frigo N,et al.Russian gonococcal antimicrobial susceptibility programme(RU-GASP)--resistance in Neisseria gonorrhoeae during 2009-2012 and NG-MAST genotypes in 2011 and 2012[J].BMC Infect Dis,2014,14(1):342.
[14]Bala M,Kakran M,Singh V,et al.Monitoring antimicrobial resistance in Neisseria gonorrhoeae in selected countries of the WHO South-East Asia Region between 2009 and 2012:a retrospective analysis[J].Sex Transm Infect,2013,89(4):iv28-35.
[15]Cole M J,Spiteri G,Jacobsson S,et al.Is the tide turning again for cephalosporin resistance in Neisseria gonorrhoeae in Europe?Results from the 2013 European surveillance[J].BMC Infect Dis,2015,15(1):321.
[16]Filipiuc S,Nicolae O,Lunca C,et al.The monitoring of Neisseria gonorrhoeae infection incidence and its resistance in Suceava County[J].Rev Med Chir Soc Med Nat Iasi,2009,113(4):1238-1242.
[17]Lahra M M.Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific and South East Asian Regions,2010[J].Commun Dis Intell Q Rep,2012,36(1):95-100.
[18]Tapsall J.Annual report of the Australian Gonococcal Surveillance Programme,2008[J].Commun Dis Intell QRep,2009,33(3):268-274.
[19]湛学军,谢大泽,徐燕萍,等.女性患者淋球菌对抗生素的多重耐药性分析[J].检验医学与临床,2010,7(5):385-386,389.
[20]潘永年,吴正青,彭一凯,等.351例淋病临床流行病学观察[J].中国中西医结合皮肤性病学杂志,2010,9(6):367-368.
[21]时祝帅,王德霞,聂青松.2010-2015年扬州地区淋球菌耐药性和流行株质粒谱的研究[J].蚌埠医学院学报,2016,41(12):1681-1683.
[22]谢俭,陈怀忠.233株淋球菌耐药性的监测与分析[J].中国医学创新,2011,8(17):121-122.
[23]顾华爱.淋病患者156例淋病奈瑟球菌耐药性分析[J].中国乡村医药,2010,17(7):54.
[24]张丽君,何亮,王峰,等.深圳地区淋球菌株耐药性流行趋势分析[J].中国热带医学,2010,10(5):561-562.
[25]曹文苓,黎小东,毕超,等.广州地区2013年淋球菌耐药监测结果分析[J].中国皮肤性病学杂志,2014,28(11):1144-1145.
[26]蒋英,刘键,谢延,等.103株淋球菌耐药性研究[J].实用预防医学,2013,20(3):345-347.
[27]黎小东,曹文苓,宋卫忠,等.2010年广州地区淋球菌耐药监测结果分析[J].中国微生态学杂志,2012,24(6):554-555,560.
[28]黄健,黄美容,黄洋,等.性病患者中淋球菌感染的流行病学调查及耐药性研究[J].国际检验医学杂志,2015,36(17):2554-2555.
[29]余宝珠,龚宇花,黄辉如.惠州地区淋球菌对抗菌药物的耐药性分析[J].检验医学与临床,2013,10(9):1111-1112.
[30]陈晨春.南宁市1993-2013年梅毒及淋病流行特征分析[J].中国皮肤性病学杂志,2015,29(2):158-159.
[31]叶峰山.淋病奈瑟菌耐大观霉素与16S rRNA基因突变发生情况的研究[D].2010,太原:山西医科大学.
[32]梁佩婵,黄海花,吴志周,等.江门市淋球菌对7种抗菌药物耐药性的结果分析[J].国际检验医学杂志,2017,38(2):258-260.
[33]Yin Y P,HanY,Dai X Q,et al.Susceptibility of Neisseria gonorrhoeae to azithromycin and ceftriaxone in China:Aretrospective study of national surveillance data from 2013to 2016[J].PLoS Med,2018,15(2):e1002499.
[34]郭青良,闫圣男,时颍涛,等.我院男科门诊淋球菌药物敏感性及耐药分析[J].中国合理用药探索,2017,14(8):18-20.
[35]黄辉如.惠州地区淋球菌对抗菌药物的敏感性测定及多重耐药分析[J].国际检验医学杂志,2015,36(15):2273-2275.
[36]Nabu S,Lawung R,Isarankura-Na-Ayudhya P,et al.Reference map and comparative proteomic analysis of Neisseria gonorrhoeae displaying high resistance against spectinomycin[J].J Med Microbiol,2014,63(3):371-385.
[37]Unemo M,Shafer W M.Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century:Past,evolution,and future[J].Clin Microbiol Rev,2014,27(3):587-613.
[38]WHO Guidelines Approved by the guidelines review committee.WHO Guidelines for the treatment of Neisseria gonorrhoeae[M].Geneva:World Health Organization,2016.
[39]Bignell C,Unemo M.2012 European guideline on the diagnosis and treatment of gonorrhoea in adults[J].Int J Std Aids,2013,24(2):85-92.
[40]Available from:http://jssti.umin.jp/pdf/guideline-2011.pdf[EB/OL].2011年度版発行に際して.
[41]https://www.egms.de/static/en/journals/id/2014-2/id000010.shtml[EB/OL].Gonorrhoea in adults and in adolescents.
[42]Bignell C,Fitz Gerald M.UK national guideline for the management of gonorrhoea in adults,2011[J].Int J STDAIDS,2011,22(10):541-547.
[43]Available from:http://www.phac-aspc.gc.ca/std-mts/stiits/cgsti-ldcits/assets/pdf/section-5-6-eng.pdf[EB/OL].Guidelines on Sexually Transmitted Infections.
[44]徐金华,王千秋,刘全忠.性传播疾病临床诊疗与防治指南[M].上海:上海科学技术出版社,2014:91-103.
[45]Jerse A E,Sharma N D,Simms A N,et al.A gonococcal efflux pump system enhances bacterial survival in a female mouse model of genital tract infection[J].Infect Immun,2003,71(10):5576-5582.
[46]Unemo M,Nicholas R A.Emergence of multidrug-resistant,extensively drug-resistant and untreatable gonorrhea[J].Future Microbiol,2012,7(12):1401-1422.
[47]Ramirez M S,Tolmasky M E.Aminoglycoside modifying enzymes[J].Drug Resist Updat,2010,13(6):151-171.
[48]Unemo M,Fasth O,Fredlund H,et al.Phenotypic and genetic characterization of the 2008 WHO Neisseria gonorrhoeae reference strain panel intended for global quality assurance and quality control of gonococcal antimicrobial resistance surveillance for public health purposes[J].J Antimicrob Chemother,2009,63(6):1142-1151.
[49]Unemo M,Golparian D,SkogenV,et al.Neisseria gonorrhoeae strain with high-level resistance to spectinomycin due to a novel resistance mechanism(mutated ribosomal protein S5)verified in Norway[J].Antimicrob Agents Chemother,2013,57(2):1057-1061.
[50]Ilina E,Malakhova M,Bodoev I,et al.Mutation in ribosomal protein S5 leads to spectinomycin resistance in Neisseria gonorrhoeae[J].Front Microbiol,2013,4:186.