肝移植术后感染阴沟肠杆菌多重耐药基因研究
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摘要
目的研究肝移植术后感染阴沟肠杆菌的多重耐药基因和耐药性以及两者的相关联系,为防治术后感染提供依据。
方法对40株从肝移植术后患者送检标本中分离到的阴沟肠杆菌进行琼脂稀释法药敏试验;采用三维试验法检测AmpC酶和ESBLs酶,EDTA-亚胺培南纸片增效法检测MBL酶;根据β内酰胺酶各种已知基因序列设计引物,进行聚合酶链反应及序列分析确定AmpC酶基因、ESBLs酶基因以及MBL酶的基因型分布。
结果40株阴沟肠杆菌对多种抗生素耐药。22株ESBLs编码基因PCR结果阳性,经测序分别为SHV-2、CTX-M-3和CTX-M-9型ESBLs;14株ampD和ampC基因PCR扩增均呈阳性;2株金属酶IMP型基因PCR结果阳性;28株Ⅰ类整合酶基因PCR结果阳性。
结论肝移植术后阴沟肠杆菌已呈现出多重耐药和高度耐药,阴沟肠杆菌产金属酶IMP基因在我国大陆为首次报道。
Objective: To investigate multiple-drug-resistant genes antibiotic-resistance of Enterobacter cloacae strains after liver transplantation infection as well as their relationship and to provide evidence for prevention against and treatment of infect ion after liver transplantation.
Methods: 40 strains of Enterobacter cloacae after liver transplantation infection were collected. The minimal inhibitory concentrations (MICs) of them were determined by standard agar dilution. Cephalosporinase (AmpC)β-lactamase and ESBLs were dectected by three-dimensional tests. MBL were detected by comparing the inhibition zones using imipenem containing EDTA. Genotypes and distribution were determined by polymerase chain reaction(PCR) with type-specific primers and sequence analysis.
Results: Sensitivity test shows that they are resistant to the most antibiotics. 22 strains of them carried ESBLs gene: SHV-2, CTX-M-3 and CTX-M-9; 14 isolates carried ampD and ampC gene. 2 isolates carried Metallo-beta-lactamase gene IMP. 28 isolates carried class 1 integron.
Conclusion: This investigation shows that there are multiple-drug-resistance and high degree of drug resistance on E. cloacae isolates in postoperative infection of liver transplation which genes of IMP in E. cloacae was firstly reported in China.
方法对40株从肝移植术后患者送检标本中分离到的阴沟肠杆菌进行琼脂稀释法药敏试验;采用三维试验法检测AmpC酶和ESBLs酶,EDTA-亚胺培南纸片增效法检测MBL酶;根据β内酰胺酶各种已知基因序列设计引物,进行聚合酶链反应及序列分析确定AmpC酶基因、ESBLs酶基因以及MBL酶的基因型分布。
结果40株阴沟肠杆菌对多种抗生素耐药。22株ESBLs编码基因PCR结果阳性,经测序分别为SHV-2、CTX-M-3和CTX-M-9型ESBLs;14株ampD和ampC基因PCR扩增均呈阳性;2株金属酶IMP型基因PCR结果阳性;28株Ⅰ类整合酶基因PCR结果阳性。
结论肝移植术后阴沟肠杆菌已呈现出多重耐药和高度耐药,阴沟肠杆菌产金属酶IMP基因在我国大陆为首次报道。
Objective: To investigate multiple-drug-resistant genes antibiotic-resistance of Enterobacter cloacae strains after liver transplantation infection as well as their relationship and to provide evidence for prevention against and treatment of infect ion after liver transplantation.
Methods: 40 strains of Enterobacter cloacae after liver transplantation infection were collected. The minimal inhibitory concentrations (MICs) of them were determined by standard agar dilution. Cephalosporinase (AmpC)β-lactamase and ESBLs were dectected by three-dimensional tests. MBL were detected by comparing the inhibition zones using imipenem containing EDTA. Genotypes and distribution were determined by polymerase chain reaction(PCR) with type-specific primers and sequence analysis.
Results: Sensitivity test shows that they are resistant to the most antibiotics. 22 strains of them carried ESBLs gene: SHV-2, CTX-M-3 and CTX-M-9; 14 isolates carried ampD and ampC gene. 2 isolates carried Metallo-beta-lactamase gene IMP. 28 isolates carried class 1 integron.
Conclusion: This investigation shows that there are multiple-drug-resistance and high degree of drug resistance on E. cloacae isolates in postoperative infection of liver transplation which genes of IMP in E. cloacae was firstly reported in China.
引文
[1]刘俊,夏强,裘正军,等.肝移植术后细菌感染的常见病原菌及耐药性.实用临床医药杂志,2003;7(1):163-164.
[2]Paterson DL,Bonomo RA.Extended-spectrum beta-lactamase:a clinical update[J].Clin Microbiol Rev,2005,18(4):657.
[3]Pai H,J Y Hong,H Byeon,et al.High prevalence of extended-spectrum β-lactamase-producing strains among blood isolates of Enterobacterspp.Collected in a tertiary hospital during an 8-year period and their antimicrobial susceptibility patterns[J].Antimicrob Agents Chemother.2004,48(3):3159.
[4]Moland Es,Hanson ND,Black JA,et al.Prevalence of newer betalactamase in gram-negative clinical isolates collected in the United States from 2001-2002[J].J Clin Microbiol.2006,44(9):3318.
[5]Katsutoshi Y,Masaru K,Tomonari Y,et al.Production of CTX-M-3extended-spectrum β-lactamase and IMP-1 metallo β-lactamase by five Gram-negative bacilli:survey of clinical isolates from seven laboratories collected in 1998 and 2000,in the Kinki region of Japan[J].Antimicrob Agents Chemother,2003,51(5):631-638.
[6]佘丹阳,刘又宁.AmpC酶和超广谱β-内酰胺酶在阴沟肠杆菌中的表达及对其耐药性的影响,中华医学杂志,2002,82(19):1355-1358.
[7]马健,张延霞,贺立新.超广谱β-内酰胺酶细菌医院感染调查.中华医院感染学杂志,2002,12(6):342-344
[8]Arpin C,Labia R,Dubois V,et al.TEM-80,A novel inhibitor resistant β-lactamase in a clinical isolate of Enterobacter cloacae [J].Antimicrob Agents Chemother,2002,46(5):1183-1189.
[9]Szab D,Melan MA,Hujer AM,et al.Molecular analysis of the simultaneous production of two SHV-type extended spectrum beta - lactamases in a clinical isolate of Enterobacter cloacae by using single- nucleotide polymorphism genotyping[J].Antimicrob Agents Chemother,2005,49(11):4716-4720.
[10]Chanawong A,Zali M,Heritage FH,et al.Three cefotaximases,CTX-M-9,CTX-M-13 and CTX-M-14 among Enterobacteriaceae in the People,s Republic of China[J].Antimicrob Agents Chemother,2002,46(3):630-637.
[11]余方友,傅颖媛,胡龙华,等.多重耐药产PER-1型超广谱β内酰胺酶阴沟肠杆菌的研究.中华检验医学杂志,2005,28(6):642-644.
[12]Cristina L,Elisabetta E,Lucilla D,etal.Molecular Evolution of Metallo-β-Lactamase Producing Pseudomonas aeruginosa in a Nosocomial Setting of High Level Endemicity[J].Clin Microbiol,2006,44(7):2348-2353.
[13]卓超,钱元恕.金属β内酰胺酶的研究进展[M].国外医学抗生素分册,2003,24(1):12-26.
[14]Jing JY,PoRen H,Jang JL,etal.Characterization of acquired β-lactamases and their genetic support in multidrug resistant Pseudom onas aerug inosa isolates in Taiwan:the prevalence of unusual integrons [J].Antimicrob Chemother,2006,58(6):530-536.
[15]JingJouYan,WenChienKo,Chin-LuanChuang,etal.Metallo-β-lactamase-producing Enterobacteriaceae isolates ina university hospital in Taiwan:prevalence of IMP-8 in Enterobacter cloacae and first identification of VIM-2 in Citrobacter freundii[J].Antimicrob Agents Chemother,2002,50:503-11.
[16]Jeong,S.H.,Lee,K.,Chong,Y.etal.Characterization of a new integron containing VIM-2,a metallo-β-lactamase gene cassette,in a clinical isolate of Enterobacter cloacae[J].Antimicrob Agents Chemother,2003,51(3):397-400.
[17]Luzzaro,F.,Docquier,J.D.,Colinon,C.et al.Emergence in glebsiella pneumoniae and Enterobacter cloacae clinical isolates of the VIM-4 metallo-β-lactamase encoded by a conjugative plasmid[J].Antimicrobial Agents and Chemotherapy 2004,48(2):48-50.
[18]Irene Galani,Maria Souli,Zoi Chryssouli,etal.Characterization a new integron containing bla_(VIM-1)and aac(6')-Ⅱc in an Enterobacter cloacae clinical isolate from Greece[J].Antimicrob Agents Chemother,2005,55(5):634-638.
[19]蒋晓飞,洪秀华,倪语星。金属β-内酰胺酶-抗感染治疗面临的新挑战[J].中国抗生素杂志,2002,27(11):700-704.
[20]Yamada M,Fujita T.Analysis ofurinary Nacetyl beta-D-glu-Cosa minidaseusing2,4-dinitrophenyl-1-thio-N-acetyl-beta-D-glucoaminide as the substrate[J].Clin Lab Anal.2003,7(4):127-31.
[21]Fluit AC,Schmitz FJ.Ciass 1 integrons,gene cassettes mobility,and epidemiology[J].Clin Microbiol Infect Dis,1999,18(11):761-770.
[22]Barbolla R,Catalano M,Orman BE,et al.Class 1 integrons increase trimethoprim-sulfamethoxazole MICs against epidemiologically unrelated Stenotrophomonas ma-ltophilia isolates[J].Antimicrob Agents Chemother,2004,48(2):666-669.
[23]桂炳东,王伶,邹叶表,等.高产AmpC酶阴沟肠杆菌的耐药性及同源性分析[J].中华医学感染学杂志,2005,15(12):1332-1334.
[24]Giakkoupi P,Tzouvelekis LS,Tsakris A,et al.IBC21,a novel integron associated class A beta-lactamase wit h extended-spectrum properties produced by an Enterobacter cloacae clinical strain[J].Antimicrob Agents Chemother,2000,44(12):2472-2253.
[25]Irene G,Maria S,Zoi C,et al.Characterization of a new integron containing bla_(VIM-1)and aac(6')-Ⅱc in an Enterobacter cloacae clinical isolate from Greece.[J].Antimicrob Agents Chemother,2005,5(5):634-638.
[26]JONES LA,MCLVER CJ,RIM MJ,et al.The aadB gene cassette is associated with blaSHV genes in Klebsiella species producing extended spectrum beta lactamases[J].Antimicrob Agents Chomother,2005,49(2): 794-797.
[27]GIULIANI F,DOCQUIER JD,RICCIO ML,et al.OXA-46,a new Class D beta- lactamase of narrow substrate specificity encoded by a bla-VIM-lcontaining integron from a Pseudomonas aeruginosa clinical isolate[J].Antimicrobial Agents and Chemotherapy,2005,45(6):1973-1980.
[28]黄支密,诸葛青云,糜祖煌,等.阴沟肠杆菌Ⅰ类整合酶基因及质粒AmpC酶基因检测.江西医学检验,2005,2(23)21-24.
[29]Barlow RS,Pemberton JM,Desmarchelier PM,et al.Isolation and characterization of inter-gron-containing bacteria without antibiotic selection.Antimicrob Agents Chemother,2004,48(3):838-842.
[30]Jones RN.Important and emerging β-lactamase-mediated resistance In hospital-based pathogens:the AmpC enzymes[J].Oiagm Microbiol Infect Dis,1998,31(22):461-466.
[31]Langaee TY,Gagnon L,Huletsky A.Inactivation of the ampD gene in Pse-Udomonas aeruginosa leads to moderate-basal-level and hyperinducible AmpC β-lactamases expression[J].Antimicrob Agents Chemother,2000,44(21):583-589.
[32]吴伟元,陈民钧,王辉.阴沟肠杆菌6株中产超广谱β-内酰胺酶的基因型,中国抗感染化疗杂志,2001,1(3):155-159.
[33]Clinical and Laboratory Standard Insitute.Performance standards for antimicrobial susceptibility testing;fifteenth informational suppliment M100-S15.Wayne.Pennsylvania:CLSI,2005,108.
[34]Coudron PE,Moland ES,Thomson KS Occurrence and detection of AmpC beta-lactamases among Esche-richia coli,Klebsiella pneumoniae and Proteus mirabilis isolates at a vete tans medical,center[J].Clin Microbiol,2000,38(8):1791-1796.
[35]National Committee for Clinical Laboratory Standards.Performance standards for antimicrobial susceptibility testing[S].8th informationl supplemental standard.PA:NCCLS.1999.36
[36]李国雄,赵建萍.亚胺培南-EDTA纸片增效法检测非发酵菌的金属β-内酰胺酶[J].江西医学杂志,2005,23(2):109-111.
[37]Wang H,Wu WY,Chen M J.Study of clinical isolates of Enterobacter -iaceae Enterobacteriaceae extended-spectrum β-lactamases.Chin J Microbiol,2001,1(6):676-681.
[38]ChanawongA,M'Z aliF H,HeritageJ,e tal.Three cefotaximases,CTX-M-9,CTX-M-13,CTX-M-14,among Enterobacteriaceae in the People's Republic of China[J].Antimicrob Agents chemother,2002,46(3):630-635.
[39]肖庆忠,苏丹虹,江洁华等广州地区革兰阴性杆菌CTX-M和OXA型广谱β--内酰胺酶基因分型研究.中华医院感染学杂志,2005,15(12):1321-132.
[40]Marie F L,Laurent P,Patrice N.First Detection of a CarbapenemHydrolyzing Metalloenzyme in an Enterobacteriaceae Isolate in France [J].Antimicrob Agents Chemother.2004,48(12):4929-4930.
[41]Robert SB,John M.P,Patricia MD,et al.Isolation and Characterization of Integron containing Bacteria without Antibiotic Selection[J].Antimicrobial Agents and Chemotherapy,2004,3(12):338-342.
[42]Mario C,Filipa B,Filipa G,et al.Molecular Characterization of a New Class 3 Integron in Klebsiella pneumoniae[J].Antimicrobial Agents and Chemotherapy,2003,9(6):2838-2843.
[43]Robert S.Bzrlow,John M.Pemberton,Patricia M.Desmarchelier,etal.Isolation and Characterization of Integron containing Bacteria without Antibiotic Selection[J].Antimicrobial Agents and Chemotherapy,2004,3(15):838-842.
[44]张永利,顾怡明,,张杰,等.多重耐药阴沟肠杆菌β内酰胺酶编码基因的研究.中华医院感染学杂志,2006,16(5)489-492.
[45]Ploy MC,Lamber T,Couty JP,el al.Integrons an antibiotic resistance gene capture and expression system[J].Clin Chem Lab Med,2000,38(3):483-487.
[46]李岩,许淑珍,苏建荣,等.2002年至2006年阴沟肠杆菌耐药性监测 分析中国实验诊断学,2007,11(2):241-243.
[47]Girlich D,Poirel L,Leelapporn A,et al.Molecular epidemiology of the integron-located VEB-1 extended-spectrum betalactamase in nosocomial enterobacterial isolates in Bangkok,Thai-land[J].Clin Microbiol,2001,39(7):175-182.
[48]Docquier JD,Riccio ML,Mugnaioli C,et al.IMP212,a new plasmid-encoded metallo-beta-lactamase from a Pseudomonas putida clinical isolate[J].Antimicrob Agents Chemother,2003,47(5):1522-1528.
[49]鲍长途,王光,孙利炜,等.随机扩增多态DNA指纹技术的研究及在检测医院感染中的应用[J].中华医院感染学杂志,2000,10(2):97-99.
[50]Hou ST,Wang CC,Chu ML.Ribotyping and random amplification of polymorphic DNA for nosocomial Enterobacter cloacae in a pediatric intensive-care unit[J].Infect Control Hosp Epidemiol,1997,18(11):769-771.
[51]郭永键.随机扩增多态DNA分析在微生物基因分型中的研究进展[J].中国人兽共患杂志,1996,12(4):50-53.
[1] Trepanier S , Knox J R, Clairoux N, et al. Structure—function studies of ser2289 in the class C beta — lactamase from Enterobacter cloacae P99 [J] . Antimicrob Agents Chemother,1999,43:543-548.
[2] Dietz H, Pfeifle D , Wiedemann B. The signal molecule for β — lactamase induction in Enterobacter cloacae is the anhydromu — ramyl — pentapeptide [J] . Antimicrob Agents Chemother, 1997,41:2113—2120.
[3] Kuga A, Okamoto R, Inoue M. ampR gene mutation that greatly increase classC — β — lactamase activity in Enterobacter cloacae [J].Antimicrob Agents Chemother,2000,44:561 -567.
[4] Pfeifle D , J anas E, Wiedemann B. Role of pencillin—binding proteins in the initiation of t he AmpC β —lactamase expression in Enterobacter cloacae [J] .Antimicrob Agents Chemother,2000,44 :169—172.
[5] Bell JM , Turnidge JD Jones RN ,et al. Prevalence of extended—spectrum β—lactamase—producing Enterobacter cloacae in the Asia—Pacific region:results from the STNTRY Antimicrobial Surveillance Program ,1998 to 2001 [J]. Antimicrob Agents Chemother ,2003 ,47 :3989- 3993.
[6] Mat sumoto Y, Inoue M. Characterization of SFO— 1, a plas—Mid—mediated inducible class Aβ-lactamase from Enterobacter cloacae [J] .Antimicrob Agents Chemother,1999,43:307-313.
[7] Giakkoupi P, Tzouvelekis LS , Tsakris A, et al. IBC— 1, a novel integron —associated class A β—lactamase with extended—spectrum properties produced by an Enterobactercloacae clinical strain[J].Antimicrob Agents Chemother, 2000,44 : 2247-2253.
[8] Bonnet R, Sampaio JL, Labia R, et al. A novel CTX—M—β — lactamase ( CTX—M—8 ) in cefotaxime—resistant Enterobactriaceae isolated in Brazil [J] . Antimicrob Agents Chemother,2000,44 :1936 -1942.
[9] Arpin C, Labia R, Dubois V, et al. TEM-80, a novel inhibi-Tor-resistantβ—lactamase in a clinical isolate of Enterobacter cloa—cae[J] . Antimicrob Agents Chemother ,2002 ,46 :1183—1189.
[10] Kartali G, Tzelepi E, Pournaras S , et al. Out break of infections caused by Enterobacter cloacae producing the integron—Associated 8—lactamase IBC— 1 in a neonatal intensive care unit of a Greek hospital [J] . Antimicrob Agents Chemother ,2002 ,46 :1577-1580.
[11] Nordmann P ,Mariotte S ,Naas T ,et al. Biochemical properties of a carba- penem—hydrolyzing β — lactamase from Enterobacter cloacae and cloning of The gene into Escherichia coli[J]. Antimicrob Agents Chemot—her ,1993 ,37 :939-946.
[12] Naas T, Massuard S , Gamier F, et al. AmpD is required for regulation of expression of NmcA, a carbapenem—hydrolyzingβ—lactamase of Enterobacter cloacae [ J ]. Antimicrob Agents Chemother, 2001,45 :2908-2915.
[13] Rasmussen BA, Bush K, Keeney D , et al. Characterization of IMI— 1 β—lactamase , a class A carbapenem2hydrolyzing enzyme from Enterobacter cloac- ae[J]. Antimicrob Agents Chemother ,1996,40 :2080-2086.
[14] Jeong SH , Lee K, Chong Y, et al. Characerization of a new integron containing VIM—2, a metallo—β—lactamase gene casette , in a clinical isolate of Enterobacter cloacae[J]. J Antimicrob Chemother,2003,51:397-400.
[15] Luzzaro F ,Docquier JD ,Colinon C ,et al. Emergence in Kleb—siella pneumoniae and Enterobacter cloacae clinical isolates of the VIM—4 metallo—β — lactamase encoded by a conjugative plasmid [J] .Antimicrob Agents Chemother ,2004,48 :648-650.
[16] Deguchi T, Yasuda M , Nakano M , et al. Detection of mutations in the gyrA and parC genes in quinolone—resistant clinical isolates of Enterobacter cloacae [J]. Antimicrob Chemother, 1997,40 :543-549.
[17] Weigel LM, Steward CD , Tenover FC. gyrA mutations associated with flu- fluoroquinolone resistance in eight species of Enterobacteriaceae [J]. Antimicrob Agent s Chemot her, 1998 ,42 :2661～2667.
[18] Chevalier J , Mallea M , Pages JM. Comparative aspects of the diffusion of norfloxacin , cefepime and spermine through the F porin channel of Enterobacter cloacae [J]. Biochem J ,2000,348 :223-227.
[19] Cornaglia G, Russell K, Satta G, et al. Relative importance of outer membrane permeability and group 1 β—lactamase as determinants of meropenem and imipenem activities against Enterobacter cloacae [J] . Antimicrob Agent s Chemot her ,1995 ,39 :350-355.
[20] Linde HJ , Not ka F , Irtenkauf C , et al. Increase in MICs of ciprofloxacin in vivo in two closely related clinical isolates of Enterobacter cloacae[J] . Antimicrob Chemother ,2002,49 :625-630.
[21] Poole K. Efflux—mediated resistance to fluoroquinolones in gram negative bacteria[J].Antimicrob Agents Chemother,2000,44:2233-2241.
[22]Rowe Magnus DA,Guerout AM,Mazel D.Bacteria resistance evolution by recruitment of super-integron gene cassettes.Molecular Microbiology,2002,43(6):1657-1669.
[23]黄支密,诸葛青云,糜祖煌,等.沟肠杆菌I类整合酶基因及质粒AmpC 酶基因检测.江西医学检验,2005,23(1):21-24.
[24]蔡培泉,王春新,黄支密,等.阴沟肠杆菌耐药性、氯已定-磺胺耐药基因型研究.中华感染学杂志,2006,16(8):841-843.
[2]Paterson DL,Bonomo RA.Extended-spectrum beta-lactamase:a clinical update[J].Clin Microbiol Rev,2005,18(4):657.
[3]Pai H,J Y Hong,H Byeon,et al.High prevalence of extended-spectrum β-lactamase-producing strains among blood isolates of Enterobacterspp.Collected in a tertiary hospital during an 8-year period and their antimicrobial susceptibility patterns[J].Antimicrob Agents Chemother.2004,48(3):3159.
[4]Moland Es,Hanson ND,Black JA,et al.Prevalence of newer betalactamase in gram-negative clinical isolates collected in the United States from 2001-2002[J].J Clin Microbiol.2006,44(9):3318.
[5]Katsutoshi Y,Masaru K,Tomonari Y,et al.Production of CTX-M-3extended-spectrum β-lactamase and IMP-1 metallo β-lactamase by five Gram-negative bacilli:survey of clinical isolates from seven laboratories collected in 1998 and 2000,in the Kinki region of Japan[J].Antimicrob Agents Chemother,2003,51(5):631-638.
[6]佘丹阳,刘又宁.AmpC酶和超广谱β-内酰胺酶在阴沟肠杆菌中的表达及对其耐药性的影响,中华医学杂志,2002,82(19):1355-1358.
[7]马健,张延霞,贺立新.超广谱β-内酰胺酶细菌医院感染调查.中华医院感染学杂志,2002,12(6):342-344
[8]Arpin C,Labia R,Dubois V,et al.TEM-80,A novel inhibitor resistant β-lactamase in a clinical isolate of Enterobacter cloacae [J].Antimicrob Agents Chemother,2002,46(5):1183-1189.
[9]Szab D,Melan MA,Hujer AM,et al.Molecular analysis of the simultaneous production of two SHV-type extended spectrum beta - lactamases in a clinical isolate of Enterobacter cloacae by using single- nucleotide polymorphism genotyping[J].Antimicrob Agents Chemother,2005,49(11):4716-4720.
[10]Chanawong A,Zali M,Heritage FH,et al.Three cefotaximases,CTX-M-9,CTX-M-13 and CTX-M-14 among Enterobacteriaceae in the People,s Republic of China[J].Antimicrob Agents Chemother,2002,46(3):630-637.
[11]余方友,傅颖媛,胡龙华,等.多重耐药产PER-1型超广谱β内酰胺酶阴沟肠杆菌的研究.中华检验医学杂志,2005,28(6):642-644.
[12]Cristina L,Elisabetta E,Lucilla D,etal.Molecular Evolution of Metallo-β-Lactamase Producing Pseudomonas aeruginosa in a Nosocomial Setting of High Level Endemicity[J].Clin Microbiol,2006,44(7):2348-2353.
[13]卓超,钱元恕.金属β内酰胺酶的研究进展[M].国外医学抗生素分册,2003,24(1):12-26.
[14]Jing JY,PoRen H,Jang JL,etal.Characterization of acquired β-lactamases and their genetic support in multidrug resistant Pseudom onas aerug inosa isolates in Taiwan:the prevalence of unusual integrons [J].Antimicrob Chemother,2006,58(6):530-536.
[15]JingJouYan,WenChienKo,Chin-LuanChuang,etal.Metallo-β-lactamase-producing Enterobacteriaceae isolates ina university hospital in Taiwan:prevalence of IMP-8 in Enterobacter cloacae and first identification of VIM-2 in Citrobacter freundii[J].Antimicrob Agents Chemother,2002,50:503-11.
[16]Jeong,S.H.,Lee,K.,Chong,Y.etal.Characterization of a new integron containing VIM-2,a metallo-β-lactamase gene cassette,in a clinical isolate of Enterobacter cloacae[J].Antimicrob Agents Chemother,2003,51(3):397-400.
[17]Luzzaro,F.,Docquier,J.D.,Colinon,C.et al.Emergence in glebsiella pneumoniae and Enterobacter cloacae clinical isolates of the VIM-4 metallo-β-lactamase encoded by a conjugative plasmid[J].Antimicrobial Agents and Chemotherapy 2004,48(2):48-50.
[18]Irene Galani,Maria Souli,Zoi Chryssouli,etal.Characterization a new integron containing bla_(VIM-1)and aac(6')-Ⅱc in an Enterobacter cloacae clinical isolate from Greece[J].Antimicrob Agents Chemother,2005,55(5):634-638.
[19]蒋晓飞,洪秀华,倪语星。金属β-内酰胺酶-抗感染治疗面临的新挑战[J].中国抗生素杂志,2002,27(11):700-704.
[20]Yamada M,Fujita T.Analysis ofurinary Nacetyl beta-D-glu-Cosa minidaseusing2,4-dinitrophenyl-1-thio-N-acetyl-beta-D-glucoaminide as the substrate[J].Clin Lab Anal.2003,7(4):127-31.
[21]Fluit AC,Schmitz FJ.Ciass 1 integrons,gene cassettes mobility,and epidemiology[J].Clin Microbiol Infect Dis,1999,18(11):761-770.
[22]Barbolla R,Catalano M,Orman BE,et al.Class 1 integrons increase trimethoprim-sulfamethoxazole MICs against epidemiologically unrelated Stenotrophomonas ma-ltophilia isolates[J].Antimicrob Agents Chemother,2004,48(2):666-669.
[23]桂炳东,王伶,邹叶表,等.高产AmpC酶阴沟肠杆菌的耐药性及同源性分析[J].中华医学感染学杂志,2005,15(12):1332-1334.
[24]Giakkoupi P,Tzouvelekis LS,Tsakris A,et al.IBC21,a novel integron associated class A beta-lactamase wit h extended-spectrum properties produced by an Enterobacter cloacae clinical strain[J].Antimicrob Agents Chemother,2000,44(12):2472-2253.
[25]Irene G,Maria S,Zoi C,et al.Characterization of a new integron containing bla_(VIM-1)and aac(6')-Ⅱc in an Enterobacter cloacae clinical isolate from Greece.[J].Antimicrob Agents Chemother,2005,5(5):634-638.
[26]JONES LA,MCLVER CJ,RIM MJ,et al.The aadB gene cassette is associated with blaSHV genes in Klebsiella species producing extended spectrum beta lactamases[J].Antimicrob Agents Chomother,2005,49(2): 794-797.
[27]GIULIANI F,DOCQUIER JD,RICCIO ML,et al.OXA-46,a new Class D beta- lactamase of narrow substrate specificity encoded by a bla-VIM-lcontaining integron from a Pseudomonas aeruginosa clinical isolate[J].Antimicrobial Agents and Chemotherapy,2005,45(6):1973-1980.
[28]黄支密,诸葛青云,糜祖煌,等.阴沟肠杆菌Ⅰ类整合酶基因及质粒AmpC酶基因检测.江西医学检验,2005,2(23)21-24.
[29]Barlow RS,Pemberton JM,Desmarchelier PM,et al.Isolation and characterization of inter-gron-containing bacteria without antibiotic selection.Antimicrob Agents Chemother,2004,48(3):838-842.
[30]Jones RN.Important and emerging β-lactamase-mediated resistance In hospital-based pathogens:the AmpC enzymes[J].Oiagm Microbiol Infect Dis,1998,31(22):461-466.
[31]Langaee TY,Gagnon L,Huletsky A.Inactivation of the ampD gene in Pse-Udomonas aeruginosa leads to moderate-basal-level and hyperinducible AmpC β-lactamases expression[J].Antimicrob Agents Chemother,2000,44(21):583-589.
[32]吴伟元,陈民钧,王辉.阴沟肠杆菌6株中产超广谱β-内酰胺酶的基因型,中国抗感染化疗杂志,2001,1(3):155-159.
[33]Clinical and Laboratory Standard Insitute.Performance standards for antimicrobial susceptibility testing;fifteenth informational suppliment M100-S15.Wayne.Pennsylvania:CLSI,2005,108.
[34]Coudron PE,Moland ES,Thomson KS Occurrence and detection of AmpC beta-lactamases among Esche-richia coli,Klebsiella pneumoniae and Proteus mirabilis isolates at a vete tans medical,center[J].Clin Microbiol,2000,38(8):1791-1796.
[35]National Committee for Clinical Laboratory Standards.Performance standards for antimicrobial susceptibility testing[S].8th informationl supplemental standard.PA:NCCLS.1999.36
[36]李国雄,赵建萍.亚胺培南-EDTA纸片增效法检测非发酵菌的金属β-内酰胺酶[J].江西医学杂志,2005,23(2):109-111.
[37]Wang H,Wu WY,Chen M J.Study of clinical isolates of Enterobacter -iaceae Enterobacteriaceae extended-spectrum β-lactamases.Chin J Microbiol,2001,1(6):676-681.
[38]ChanawongA,M'Z aliF H,HeritageJ,e tal.Three cefotaximases,CTX-M-9,CTX-M-13,CTX-M-14,among Enterobacteriaceae in the People's Republic of China[J].Antimicrob Agents chemother,2002,46(3):630-635.
[39]肖庆忠,苏丹虹,江洁华等广州地区革兰阴性杆菌CTX-M和OXA型广谱β--内酰胺酶基因分型研究.中华医院感染学杂志,2005,15(12):1321-132.
[40]Marie F L,Laurent P,Patrice N.First Detection of a CarbapenemHydrolyzing Metalloenzyme in an Enterobacteriaceae Isolate in France [J].Antimicrob Agents Chemother.2004,48(12):4929-4930.
[41]Robert SB,John M.P,Patricia MD,et al.Isolation and Characterization of Integron containing Bacteria without Antibiotic Selection[J].Antimicrobial Agents and Chemotherapy,2004,3(12):338-342.
[42]Mario C,Filipa B,Filipa G,et al.Molecular Characterization of a New Class 3 Integron in Klebsiella pneumoniae[J].Antimicrobial Agents and Chemotherapy,2003,9(6):2838-2843.
[43]Robert S.Bzrlow,John M.Pemberton,Patricia M.Desmarchelier,etal.Isolation and Characterization of Integron containing Bacteria without Antibiotic Selection[J].Antimicrobial Agents and Chemotherapy,2004,3(15):838-842.
[44]张永利,顾怡明,,张杰,等.多重耐药阴沟肠杆菌β内酰胺酶编码基因的研究.中华医院感染学杂志,2006,16(5)489-492.
[45]Ploy MC,Lamber T,Couty JP,el al.Integrons an antibiotic resistance gene capture and expression system[J].Clin Chem Lab Med,2000,38(3):483-487.
[46]李岩,许淑珍,苏建荣,等.2002年至2006年阴沟肠杆菌耐药性监测 分析中国实验诊断学,2007,11(2):241-243.
[47]Girlich D,Poirel L,Leelapporn A,et al.Molecular epidemiology of the integron-located VEB-1 extended-spectrum betalactamase in nosocomial enterobacterial isolates in Bangkok,Thai-land[J].Clin Microbiol,2001,39(7):175-182.
[48]Docquier JD,Riccio ML,Mugnaioli C,et al.IMP212,a new plasmid-encoded metallo-beta-lactamase from a Pseudomonas putida clinical isolate[J].Antimicrob Agents Chemother,2003,47(5):1522-1528.
[49]鲍长途,王光,孙利炜,等.随机扩增多态DNA指纹技术的研究及在检测医院感染中的应用[J].中华医院感染学杂志,2000,10(2):97-99.
[50]Hou ST,Wang CC,Chu ML.Ribotyping and random amplification of polymorphic DNA for nosocomial Enterobacter cloacae in a pediatric intensive-care unit[J].Infect Control Hosp Epidemiol,1997,18(11):769-771.
[51]郭永键.随机扩增多态DNA分析在微生物基因分型中的研究进展[J].中国人兽共患杂志,1996,12(4):50-53.
[1] Trepanier S , Knox J R, Clairoux N, et al. Structure—function studies of ser2289 in the class C beta — lactamase from Enterobacter cloacae P99 [J] . Antimicrob Agents Chemother,1999,43:543-548.
[2] Dietz H, Pfeifle D , Wiedemann B. The signal molecule for β — lactamase induction in Enterobacter cloacae is the anhydromu — ramyl — pentapeptide [J] . Antimicrob Agents Chemother, 1997,41:2113—2120.
[3] Kuga A, Okamoto R, Inoue M. ampR gene mutation that greatly increase classC — β — lactamase activity in Enterobacter cloacae [J].Antimicrob Agents Chemother,2000,44:561 -567.
[4] Pfeifle D , J anas E, Wiedemann B. Role of pencillin—binding proteins in the initiation of t he AmpC β —lactamase expression in Enterobacter cloacae [J] .Antimicrob Agents Chemother,2000,44 :169—172.
[5] Bell JM , Turnidge JD Jones RN ,et al. Prevalence of extended—spectrum β—lactamase—producing Enterobacter cloacae in the Asia—Pacific region:results from the STNTRY Antimicrobial Surveillance Program ,1998 to 2001 [J]. Antimicrob Agents Chemother ,2003 ,47 :3989- 3993.
[6] Mat sumoto Y, Inoue M. Characterization of SFO— 1, a plas—Mid—mediated inducible class Aβ-lactamase from Enterobacter cloacae [J] .Antimicrob Agents Chemother,1999,43:307-313.
[7] Giakkoupi P, Tzouvelekis LS , Tsakris A, et al. IBC— 1, a novel integron —associated class A β—lactamase with extended—spectrum properties produced by an Enterobactercloacae clinical strain[J].Antimicrob Agents Chemother, 2000,44 : 2247-2253.
[8] Bonnet R, Sampaio JL, Labia R, et al. A novel CTX—M—β — lactamase ( CTX—M—8 ) in cefotaxime—resistant Enterobactriaceae isolated in Brazil [J] . Antimicrob Agents Chemother,2000,44 :1936 -1942.
[9] Arpin C, Labia R, Dubois V, et al. TEM-80, a novel inhibi-Tor-resistantβ—lactamase in a clinical isolate of Enterobacter cloa—cae[J] . Antimicrob Agents Chemother ,2002 ,46 :1183—1189.
[10] Kartali G, Tzelepi E, Pournaras S , et al. Out break of infections caused by Enterobacter cloacae producing the integron—Associated 8—lactamase IBC— 1 in a neonatal intensive care unit of a Greek hospital [J] . Antimicrob Agents Chemother ,2002 ,46 :1577-1580.
[11] Nordmann P ,Mariotte S ,Naas T ,et al. Biochemical properties of a carba- penem—hydrolyzing β — lactamase from Enterobacter cloacae and cloning of The gene into Escherichia coli[J]. Antimicrob Agents Chemot—her ,1993 ,37 :939-946.
[12] Naas T, Massuard S , Gamier F, et al. AmpD is required for regulation of expression of NmcA, a carbapenem—hydrolyzingβ—lactamase of Enterobacter cloacae [ J ]. Antimicrob Agents Chemother, 2001,45 :2908-2915.
[13] Rasmussen BA, Bush K, Keeney D , et al. Characterization of IMI— 1 β—lactamase , a class A carbapenem2hydrolyzing enzyme from Enterobacter cloac- ae[J]. Antimicrob Agents Chemother ,1996,40 :2080-2086.
[14] Jeong SH , Lee K, Chong Y, et al. Characerization of a new integron containing VIM—2, a metallo—β—lactamase gene casette , in a clinical isolate of Enterobacter cloacae[J]. J Antimicrob Chemother,2003,51:397-400.
[15] Luzzaro F ,Docquier JD ,Colinon C ,et al. Emergence in Kleb—siella pneumoniae and Enterobacter cloacae clinical isolates of the VIM—4 metallo—β — lactamase encoded by a conjugative plasmid [J] .Antimicrob Agents Chemother ,2004,48 :648-650.
[16] Deguchi T, Yasuda M , Nakano M , et al. Detection of mutations in the gyrA and parC genes in quinolone—resistant clinical isolates of Enterobacter cloacae [J]. Antimicrob Chemother, 1997,40 :543-549.
[17] Weigel LM, Steward CD , Tenover FC. gyrA mutations associated with flu- fluoroquinolone resistance in eight species of Enterobacteriaceae [J]. Antimicrob Agent s Chemot her, 1998 ,42 :2661～2667.
[18] Chevalier J , Mallea M , Pages JM. Comparative aspects of the diffusion of norfloxacin , cefepime and spermine through the F porin channel of Enterobacter cloacae [J]. Biochem J ,2000,348 :223-227.
[19] Cornaglia G, Russell K, Satta G, et al. Relative importance of outer membrane permeability and group 1 β—lactamase as determinants of meropenem and imipenem activities against Enterobacter cloacae [J] . Antimicrob Agent s Chemot her ,1995 ,39 :350-355.
[20] Linde HJ , Not ka F , Irtenkauf C , et al. Increase in MICs of ciprofloxacin in vivo in two closely related clinical isolates of Enterobacter cloacae[J] . Antimicrob Chemother ,2002,49 :625-630.
[21] Poole K. Efflux—mediated resistance to fluoroquinolones in gram negative bacteria[J].Antimicrob Agents Chemother,2000,44:2233-2241.
[22]Rowe Magnus DA,Guerout AM,Mazel D.Bacteria resistance evolution by recruitment of super-integron gene cassettes.Molecular Microbiology,2002,43(6):1657-1669.
[23]黄支密,诸葛青云,糜祖煌,等.沟肠杆菌I类整合酶基因及质粒AmpC 酶基因检测.江西医学检验,2005,23(1):21-24.
[24]蔡培泉,王春新,黄支密,等.阴沟肠杆菌耐药性、氯已定-磺胺耐药基因型研究.中华感染学杂志,2006,16(8):841-843.