临床分离志贺菌耐药性及其对β-内酰胺类和氟喹诺酮类抗菌药物耐药机制的研究
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摘要
目的
了解本省志贺菌耐药情况,以指导合理用药;
了解安徽地区临床分离志贺菌中产超广谱β-内酰胺酶(ESBLs)和质粒介导AmpC型β-内酰胺酶情况;
探讨临床分离志贺菌螺旋酶A亚单位gyrA基因及拓扑异构酶ⅣC亚单位parC基因突变与志贺菌对氟喹诺酮类药物的耐药表型的关系;
研究临床分离志贺菌中主动外排系统acrAB-tolC结构基因的分布和acrAB基因表达水平。
材料与方法菌株来源
收集我省35所医院2005年9月份临床标本中分离的志贺菌91株,并常规保存于-70℃。药敏试验质控菌大肠埃希菌ATCC25922。方法
采用平皿琼脂对倍稀释法检测我省35所医院2005年9月份收集的91株志贺菌对多种抗菌药物的敏感性。
用煮沸法提取细菌总DNA,碱裂解法提取质粒。用聚合酶链反应(PCR)方法扩增CTX-M组、OXA组、blaTEM-1、blaSHV-1、ampC基因。PCR产物纯化测序法明确β-内酰胺酶基因型。
用细菌总DNA为摸板,PCR技术扩增gyrA和parC基因的喹诺酮耐药决定区(QRDR)相关序列和acrAB-tolC基因,用DNA直接测序的方法对26株(其中19株对环丙沙星耐药,7株对环丙沙星敏感)志贺菌的gyrA及parC基因序列进行测序分析,结果至GenBank进行比对。
用RT-PCR测定15株多重耐药株和13株敏感株的acrAB基因mRNA表达水平。结果
91株志贺菌中,有福氏志贺菌57株、宋内志贺菌31株、鲍氏志贺菌3株;91株志贺菌对头孢哌酮/舒巴坦和哌拉西林/他唑巴坦的耐药率明显低于其他头孢类抗菌药物,对碳青霉烯类敏感率达100%,对喹诺酮类环丙沙星及帕珠沙星的耐药率分别是27.47%、32.97%。
91株志贺菌产β-内酰胺酶的检出率为58株( 63.74%),产β-内酰胺酶菌中blaTEM-1、blaCTX-M-1、blaCTX-M-13、blaOXA-1和blaampc扩增阳性率分别为62.07%(36/58)、17.24%(10/58)、24.14%(14/58)、36.21%(21/58)和10.34%(6/58),产Ampc中全为EBC型;携带2种耐药基因的菌株占20.88%,携带3种耐药基因的为5.49%,未测出CTX-M-2、CTX-M-8、CTX-M-25、OXA-2、OXA-10、SHV-1型。
20株发生gyrA第83位氨基酸改变,7株发生gyrA第87位改变;9株发生parC第80位氨基酸改变(Ser80→Ile),3株发生parC第57位改变(Ser57→Thr),3株parC第64位氨基酸突变(Ala64→Cys, Ala64→Asp)。其中志贺菌gyrA83(Ser→Ile),parC57(Ser→Thr)及parC64(Ala→Cys, Ala→Asp)的改变在国内外尚属首次报道,这些测序结果已递交GenBank,获得的序列号为DQ898178、DQ898179、DQ898180、DQ898305。同时具gyrA和parC突变菌株的MIC值是仅具gyrA突变菌株MIC值的2～8倍,gyrA突变合并parC64位突变菌株比gyrA突变合并parC57或parC80位突变菌株的耐药更严重。多重耐药株acrAB基因mRNA表达水平高于敏感野生株(P<0.05)。
结论
本地区志贺菌对喹诺酮类和第三代头孢类抗菌药物有一定耐药性,应加强耐药性监测和防治。
本地区志贺菌β-内酰胺酶的检出率较高,以TEM-1型, OXA-1型和CTX-M型基因为主。
在研究耐氟喹诺酮类药物志贺菌螺旋酶A亚单位gyrA基因及拓扑异构酶ⅣC亚单位parC基因方面检测到可引起氨基酸改变的四个新基因型已递交GenBank,获得的序列号为DQ898178、DQ898179、DQ898180、DQ898305。gyrA83、87位突变参与志贺菌对氟喹诺酮类药物耐药,合并parC57、64、80位突变后会导致高度耐药。
acrAB基因高表达与志贺菌多重耐药有关。
Objective:
To investigate the resistance of Shigella isolates against 16 antimicrobial agents in Anhui province and offer the resistance data to clinical therapy.
To investigate the production of extended-spectrumβ-lactamases (ESBLs) and plasmid-mediated AmpCβ-lactamases in the clinical Shigella isolates in Anhui province.
To investigate the correlation between the alterations of DNA gyrase gyrA and TopoisomeraseⅣparC genes and fluoroquinolone resistance in Shigella isolates.
To detect the distribution of the energy-dependent multidrug efflux pump gene acrAB-tolC and expression level of acrAB gene in Shigella isolates.
Materials and Methods:
Isolates:
From September 1 to September 30, 2005, a total of 91 Shigella isolates were collected in 31 hospitals in Anhui of China.
Method:
The MICs of the following agents were determined by the agar dilution method recommended by CLSI (Clinical Laboratory Standard Institute), 2005. Total DNA was extracted by suspending a few overnight colonies in 0.5 mL of double-distilled water and heating the mixture at 100°C for 10 min. Plasmid DNA was extracted and purified by Qiagen plasmid Mini Kit. The extracted DNA was subjected to amplification by PCR for the quinolone resistance-determining regions of gyrA, parC on 26 Shigella isolates (19strains showing ciprofloxacin≥4 ug/mL, and 7 strains selected showing ciprofloxacin < 4 ug/mL), the multidrug efflux pump acrAB-tolC genes on 91 strains were also identified by PCR. PCR analysis was also used to investigate the distribution ofβ-lactamases and Qnr present in Shigella strain. Reverse transcription PCR (RT-PCR) of acrAB genes were used to confirm the presence of acrAB.
Results:
There were 57 strains of S. flexnery, 31 strains S. sonnei and 2 strains S. boydii among 91 strains of Shigella isolates. The resistance rates of Shigella isolates to cefoperazone-sulbactam and piperacillin-tazobactam were remarkably lower than other third generation cephalosporins. The susceptible rates to carbopenems were 100%. The resistance rates to ciprofloxacin and pazufloxacin were 27.47% and 32.97%, respectively. 14 of 91 isolates were susceptible to all tested antimicrobial agents in this study. In this study we did not found the qnr genes.β-lactamases-producing Shigella isolates were 63.74% (58/91), the genes of blaTEM-1, blaCTX-M-1, blaCTX-M-13, blaOXA-1 group and ampC were detected in 62.07%(36/91), 17.24%(10/91), 24.14%(14/91), 36.21%(21/91) and 10.24% (6/91) among 91 isolates. 20 strains had a mutation at codon 83 of gyrA, 7 strains had a mutation at codon 87 of gyrA. 9 strains had a mutation at codon 80 (Ser80→Ile) of parC. Three of the ciprofloxacin-resistance isolates had a novel mutation at codon 64 (Ala64→Cys, Ala64→Asp) of parC, the mutation at codon 57 (Ser57→Thr) of parC and the mutations at codon 83 of gyrA (Ser→Ile) were firstly reported in Shigella isolates. The partial sequences of gyrA and parC genes reported in this article have been deposited in the GenBank database and assigned accession no. DQ898178, DQ898179, DQ898180, DQ898305. The strains with both gyrA and parC mutations were two to eight times more resistant than the strains which had only gyrA mutations. Isolates with a single gyrA mutation were less resistant to fluoroquinolones than those with an additional parC mutation, the novel mutation at codon 64 plus one other gyrA mutation conferred higher level resistance to fluoroquinolones than the mutation at codon 57 or 80 of parC together with one other gyrA mutation. The levels of mRNA expression of acrAB in multidrug-resistant strains were significantly higher than those in wild susceptible strains.
Conclusion:
There was a certain resistance rate of the Shigella isolates to fluoroquinolones and the third generation cephalosporins. More attention should be paid to the surveillance and control of such resistance. The prevalence ofβ-lactamases among clinical Shigella isolates was high, theβ-lactamase-genes possibly were the TEM-1, OXA-1 and CTX-M types in Shigella isolates in our locality.
The mutations of gyrA at codon 83 and 87 were related to fluroquinolone resistance,and they woμLd make higher resistance together with additional parC mutation. The partial sequences of gyrA and parC genes reported in this article have been deposited in the GenBank database and assigned accession no. DQ898178, DQ898179, DQ898180, DQ898305.
Overexpression of the acrAB genes was responsible for resistance to fluoroquinolones in Shigella isolates.
了解本省志贺菌耐药情况,以指导合理用药;
了解安徽地区临床分离志贺菌中产超广谱β-内酰胺酶(ESBLs)和质粒介导AmpC型β-内酰胺酶情况;
探讨临床分离志贺菌螺旋酶A亚单位gyrA基因及拓扑异构酶ⅣC亚单位parC基因突变与志贺菌对氟喹诺酮类药物的耐药表型的关系;
研究临床分离志贺菌中主动外排系统acrAB-tolC结构基因的分布和acrAB基因表达水平。
材料与方法菌株来源
收集我省35所医院2005年9月份临床标本中分离的志贺菌91株,并常规保存于-70℃。药敏试验质控菌大肠埃希菌ATCC25922。方法
采用平皿琼脂对倍稀释法检测我省35所医院2005年9月份收集的91株志贺菌对多种抗菌药物的敏感性。
用煮沸法提取细菌总DNA,碱裂解法提取质粒。用聚合酶链反应(PCR)方法扩增CTX-M组、OXA组、blaTEM-1、blaSHV-1、ampC基因。PCR产物纯化测序法明确β-内酰胺酶基因型。
用细菌总DNA为摸板,PCR技术扩增gyrA和parC基因的喹诺酮耐药决定区(QRDR)相关序列和acrAB-tolC基因,用DNA直接测序的方法对26株(其中19株对环丙沙星耐药,7株对环丙沙星敏感)志贺菌的gyrA及parC基因序列进行测序分析,结果至GenBank进行比对。
用RT-PCR测定15株多重耐药株和13株敏感株的acrAB基因mRNA表达水平。结果
91株志贺菌中,有福氏志贺菌57株、宋内志贺菌31株、鲍氏志贺菌3株;91株志贺菌对头孢哌酮/舒巴坦和哌拉西林/他唑巴坦的耐药率明显低于其他头孢类抗菌药物,对碳青霉烯类敏感率达100%,对喹诺酮类环丙沙星及帕珠沙星的耐药率分别是27.47%、32.97%。
91株志贺菌产β-内酰胺酶的检出率为58株( 63.74%),产β-内酰胺酶菌中blaTEM-1、blaCTX-M-1、blaCTX-M-13、blaOXA-1和blaampc扩增阳性率分别为62.07%(36/58)、17.24%(10/58)、24.14%(14/58)、36.21%(21/58)和10.34%(6/58),产Ampc中全为EBC型;携带2种耐药基因的菌株占20.88%,携带3种耐药基因的为5.49%,未测出CTX-M-2、CTX-M-8、CTX-M-25、OXA-2、OXA-10、SHV-1型。
20株发生gyrA第83位氨基酸改变,7株发生gyrA第87位改变;9株发生parC第80位氨基酸改变(Ser80→Ile),3株发生parC第57位改变(Ser57→Thr),3株parC第64位氨基酸突变(Ala64→Cys, Ala64→Asp)。其中志贺菌gyrA83(Ser→Ile),parC57(Ser→Thr)及parC64(Ala→Cys, Ala→Asp)的改变在国内外尚属首次报道,这些测序结果已递交GenBank,获得的序列号为DQ898178、DQ898179、DQ898180、DQ898305。同时具gyrA和parC突变菌株的MIC值是仅具gyrA突变菌株MIC值的2～8倍,gyrA突变合并parC64位突变菌株比gyrA突变合并parC57或parC80位突变菌株的耐药更严重。多重耐药株acrAB基因mRNA表达水平高于敏感野生株(P<0.05)。
结论
本地区志贺菌对喹诺酮类和第三代头孢类抗菌药物有一定耐药性,应加强耐药性监测和防治。
本地区志贺菌β-内酰胺酶的检出率较高,以TEM-1型, OXA-1型和CTX-M型基因为主。
在研究耐氟喹诺酮类药物志贺菌螺旋酶A亚单位gyrA基因及拓扑异构酶ⅣC亚单位parC基因方面检测到可引起氨基酸改变的四个新基因型已递交GenBank,获得的序列号为DQ898178、DQ898179、DQ898180、DQ898305。gyrA83、87位突变参与志贺菌对氟喹诺酮类药物耐药,合并parC57、64、80位突变后会导致高度耐药。
acrAB基因高表达与志贺菌多重耐药有关。
Objective:
To investigate the resistance of Shigella isolates against 16 antimicrobial agents in Anhui province and offer the resistance data to clinical therapy.
To investigate the production of extended-spectrumβ-lactamases (ESBLs) and plasmid-mediated AmpCβ-lactamases in the clinical Shigella isolates in Anhui province.
To investigate the correlation between the alterations of DNA gyrase gyrA and TopoisomeraseⅣparC genes and fluoroquinolone resistance in Shigella isolates.
To detect the distribution of the energy-dependent multidrug efflux pump gene acrAB-tolC and expression level of acrAB gene in Shigella isolates.
Materials and Methods:
Isolates:
From September 1 to September 30, 2005, a total of 91 Shigella isolates were collected in 31 hospitals in Anhui of China.
Method:
The MICs of the following agents were determined by the agar dilution method recommended by CLSI (Clinical Laboratory Standard Institute), 2005. Total DNA was extracted by suspending a few overnight colonies in 0.5 mL of double-distilled water and heating the mixture at 100°C for 10 min. Plasmid DNA was extracted and purified by Qiagen plasmid Mini Kit. The extracted DNA was subjected to amplification by PCR for the quinolone resistance-determining regions of gyrA, parC on 26 Shigella isolates (19strains showing ciprofloxacin≥4 ug/mL, and 7 strains selected showing ciprofloxacin < 4 ug/mL), the multidrug efflux pump acrAB-tolC genes on 91 strains were also identified by PCR. PCR analysis was also used to investigate the distribution ofβ-lactamases and Qnr present in Shigella strain. Reverse transcription PCR (RT-PCR) of acrAB genes were used to confirm the presence of acrAB.
Results:
There were 57 strains of S. flexnery, 31 strains S. sonnei and 2 strains S. boydii among 91 strains of Shigella isolates. The resistance rates of Shigella isolates to cefoperazone-sulbactam and piperacillin-tazobactam were remarkably lower than other third generation cephalosporins. The susceptible rates to carbopenems were 100%. The resistance rates to ciprofloxacin and pazufloxacin were 27.47% and 32.97%, respectively. 14 of 91 isolates were susceptible to all tested antimicrobial agents in this study. In this study we did not found the qnr genes.β-lactamases-producing Shigella isolates were 63.74% (58/91), the genes of blaTEM-1, blaCTX-M-1, blaCTX-M-13, blaOXA-1 group and ampC were detected in 62.07%(36/91), 17.24%(10/91), 24.14%(14/91), 36.21%(21/91) and 10.24% (6/91) among 91 isolates. 20 strains had a mutation at codon 83 of gyrA, 7 strains had a mutation at codon 87 of gyrA. 9 strains had a mutation at codon 80 (Ser80→Ile) of parC. Three of the ciprofloxacin-resistance isolates had a novel mutation at codon 64 (Ala64→Cys, Ala64→Asp) of parC, the mutation at codon 57 (Ser57→Thr) of parC and the mutations at codon 83 of gyrA (Ser→Ile) were firstly reported in Shigella isolates. The partial sequences of gyrA and parC genes reported in this article have been deposited in the GenBank database and assigned accession no. DQ898178, DQ898179, DQ898180, DQ898305. The strains with both gyrA and parC mutations were two to eight times more resistant than the strains which had only gyrA mutations. Isolates with a single gyrA mutation were less resistant to fluoroquinolones than those with an additional parC mutation, the novel mutation at codon 64 plus one other gyrA mutation conferred higher level resistance to fluoroquinolones than the mutation at codon 57 or 80 of parC together with one other gyrA mutation. The levels of mRNA expression of acrAB in multidrug-resistant strains were significantly higher than those in wild susceptible strains.
Conclusion:
There was a certain resistance rate of the Shigella isolates to fluoroquinolones and the third generation cephalosporins. More attention should be paid to the surveillance and control of such resistance. The prevalence ofβ-lactamases among clinical Shigella isolates was high, theβ-lactamase-genes possibly were the TEM-1, OXA-1 and CTX-M types in Shigella isolates in our locality.
The mutations of gyrA at codon 83 and 87 were related to fluroquinolone resistance,and they woμLd make higher resistance together with additional parC mutation. The partial sequences of gyrA and parC genes reported in this article have been deposited in the GenBank database and assigned accession no. DQ898178, DQ898179, DQ898180, DQ898305.
Overexpression of the acrAB genes was responsible for resistance to fluoroquinolones in Shigella isolates.
引文
1. KotloffK L, W inickoffJ P, Ivanoff B, et al. Global burden of Shigella infections: implications for vaccined evelopment and implementation of control strategies. [J]. BμL. W.H.0, 1999; 77(8): 651一666
2. Trofa AF, Ueno-Olsen H, Oiwa R, et al. Dr. Kiyoshi Shiga: discovery of the dysentery bacillus. [J]. Clin. Infect. Dis, 1999; 29(5): 1303-1306
3. Pupo GM, Lan R, Reeves PR.MμLtiple independent origins of Shigella clones of Escherichia coli and convergent evolution of many of their characteristics. [J]. Pro. Natl. Acad.Sci, 2000; 97(19): 10567-10572
4. Navia MM, Capitano L, Ruiz J, et al. Typing and characterization of mechanisms of resistance of Shigella spp.isolated from feces of children under 5 years of age from Ifakara, Tanzania. [J]. J. Clin. Microbial, 1999; 37(10): 3113-3117
5. Davies J. Bacteria on the rampage. [J]. Nature, 1996; 383(6597): 219-220
6. Clinical and Laboratory Standards Institute/NCCLS. Performance standards for antimicrobial susceptibility testing; Fifteenth informational supplement. CLSI/NCCLS document M100-S15. [R]. Clinical and Laboratory Standards Institute, Wayne, Pennsylvania, 2005; 25:1-167
7. 丁建强,马亦林,龚飞,等.志贺菌流行菌株耐药性及R质粒的研究.[J].中华传染病杂志,1998; 16 (3): 161-163
8. Chu YW, Houang TS, Lyon DJ, et al. Antimicrobial resistance in Shigella flexneri and Shigella sonnei in Hong Kong, 1986 to 1995. [J]. Antimicrob Agents Chemother, 1998; 42(2): 440-443
9. Lima AAM, Lima NL, Pinho MCN, et al. High frequency of strains multiply resistance to ampicillin, trimethoprim-sμLfametheoxazole, streptomycin, chloramphenicol, and tetracycline isolated from patients with shigellosis in northeastern Brazil during the period 1988 to 1993. [J], Antimicrob AgentsChemother, 1995; 39(1): 256-259
10.吴成. 小儿痢疾杆菌菌群分布及耐药性分析.[J] .医学基础与药学研究, 2004; 3 (4): 64-66
11. Kim S, Kim J, Kang Y, et al.Occurrence of extended-spectrum beta-lactamases in members of the genus Shigella in the Republic of Korea. [J]. J Clin Microbiol, 2004; 42(11): 5264-5269
12. Clinical and Laboratory Standards Institute/NCCLS. 2006. Performance standards for antimicrobial susceptibility testing; Sixteenth informational supplement. CLSI/NCCLS document M100-S16. Clinical and Laboratory Standards Institute, Wayne, Pennsylvania. 26, 1~174
13. 李景云,马越,陈洪波,等. 志贺菌的耐药性分析.[J] .世界感染杂志, 2002; 2(2):12-14
14. 杨海燕, 段广才, 郗园林.主动外排系统acrAB在志贺菌中分布和表达.[J] .中国公共卫生, 2005; 21(6): 685-687
15. Ashkenazi S, Levy I, Kazaronovski V, et a l. Growing antimicrobial resistance of Shigella isolates. [J]. J AntimicrobC hemother, 2003; 51(2): 427-429
16. 王晓红,乔欣宇,宋学枯,等. 90年代上海地区痢疾杆菌菌群分布及耐药性变 迁 [J].上海医科大学学报,1997; 24 (6): 425-427
17. Dutta S, Kawamura Y, Ezaki T, et al. Alteration in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV in quinolone-resistant Shigella dysenteriae serotype 1 clinical isolates from Kolkata, India. [J]. Antimicrob. Agents Chemothe, 2005; 49(4): 1660–1661
18. Robicsek A, Strahilevitz J, Sahm DF, et al. qnr pevalence in ceftazidime-resistant Enterobacteriaceae isolates from the United States. [J]. Antimicrob. Agents Chemother, 2006; 50(8): 2872–2874
19. Robicsek A, Strahilevitz J, Jacoby GA, et al. Fluoroquinolonemodifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase. [J]. Nat Med, 2006;12(1): 83–88
20. Pérez-Pérez FJ and Hanson ND. Detection of Plasmid-Mediated AmpC β-Lactamase Genes in Clinical Isolates by Using MμLtiplex PCR. [J]. J Clin Microbiol, 2002; 40(6): 2153-2162
21. Siu LK, Lo JYC, Yuen KY, et al. β-Lactamases in Shigella flexneri isolates from Hong Kong and Shanghai and a novel OXA-1-like β-lactamase, OXA-30. [J]. Antimicrob. Agents Chemother. 2000; 44(8): 2034–2038
22. 陆志檬. 细菌性痢疾.见: 彭文伟,主编.传染病学[M].第六版.北京: 人民卫生出版社,2004: 144-15.
23. Dupont H L. Shigella Species (Bacillary Dysentery). In: Mandell G L, Bennet J E, Dolin R, editors. Mandell, Douglas, and Bennet's Principles and Practice of Infectious Diseases. [M]. 6thed. NewYork: Elsevier/Churchill Livingstone, 2005: 2655-2661
24. Nicolas F, Thierry N, Olivier, G, et al. SHV-type extended-spectrum β-lactamase in a Shigella flexneri clinical isolate. [J]. J Antimicrob Chemother, 2001; 47(5): 685-688
25. Mahbubur R, Shereen S, Harunur R, et al. Extended-spectrum β-lactamase- mediated third generation cephalosporin resistance in Shigella isolates in Bangladesh. [J]. J Antimicrob Chemother, 2004; 54(4): 846-847
26. Jeong YS, Lee JC, Kang HY, et al. Epidemiology of Nalidixic Acid Resistance and TEM-1- and TEM-52-Mediated Ampicillin Resistance of Shigella sonnei Isolates Obtained in Korea between 1980 and 2000. [J]. Antimicrobial Agents and Chemotherapy, 2003; 47(12): 3719-3723
27. Sirot D, Chanal C, Bonnet R, et al. Inhibitor-resistant TEM-33 ? -lactamase in a Shigella sonnei isolate. [J]. Antimicrobial Agents and Chemotherapy, 2001; 45(7): 2179-2180
28. Bou G, Oliver A, Ojeda M, et al. MolecμLar characteriza tion of FOX-4, a new AmpC - type plasmid mediated lactamase from an Escherichia coli strain isolated inspain. [J]. Antimicrob Agents Chemother, 2000; 44 (9): 2549-2553
29. Bhattacharya SK, Sarkar K, Nair BG, et al. MμLtidrug-resistant Shigella dysenteriae type 1 in south Asia. [J]. Lancet Infect. Dis, 2003; 3(12): 755
30. Naheed AP, Kalluri KA, Talukder AS, et al. Fluoroquinolone-resistant Shigella dysenteriae type 1 in northeastern Bangladesh. [J]. Lancet Infect. Dis, 2004; 4(10): 607-608
31. Heisigp H, Schedletzky and Falkenstein-PaμL H. Mutations in the gyrA gene of a highly fluoroquinolone-resistant clinical isolate of Eecherichia coli. [J]. Antimicrob. Agents Chemother, 1993; 37(4): 696-701
32. Heisig P. Genetic evidence for a role of parc mutations in development of high-level fluoroquinolone resistance in Eecherichia coli. [J]. Antimicrob.Agents Chemother, 1996; 40(4): 879-885
33. Hawkey PM. Mechanism of quinolone action and microbial response. [J]. J Antimicrob Chemother, 2003; 51(Suppl) 1: 29-35
34. Ruiz J. Mechanism of resistance to quinolones: target alterations, decreased accumμLation and DNA gyrase protection. [J]. J Antimicrob Chemother , 2003; 51(5): 1109-1117
35. Acar JF and Goldstein FW. Trends in bacterial resistance to Fluoroquinolones. [J]. Cli Infect Dis, 1997; 24(Suppl 1): 67-73
36. Ince D and Hooper DC. Quinolone resistance due to reduced target enzyme expression. [J]. J Bacteriol, 2003; 185(23): 6883-6892
37. Hata M, Suzuki M, Matsumoto M, et al. Cloning of a Novel Gene for Quinolone Resistance from a Transferable Plasmid in Shigella flexneri 2b. [J]. Antimicrob Agents Chemother, 2005; 49 (2): 801-803
38. Hirose k, Terajima J, Izumiya H, et al. Antimicrobial Susceptibility of Shigella sonnei Isolates in Japan and Molecular Analysis of S, sonnei Isolates with Reduced Susceptibility to Fluoroquinolones. [J]. Antimicrob Agents Chemother, 2005, 49 (3):1203–1205.
39. 丁建强, 马亦林, 龚正, 等. 志贺菌对氟喹诺酮类药物耐药机制的研究.[J].中华内科杂志,1999; 38(8): 550-553
40. 唐传玲,朱于莉,赵守军,等.福氏志贺菌喹诺酮类耐药临床分离株gyrA 和parC 的基因突变.[J]. 中华传染病杂志,2005; 23(3):150-153
41. Hiasa, H. The Glu-84 of the ParC subunit plays critical roles in both topoisomerase IV-quinolone and topoisomerase IV-DNA interactions. [J]. Biochemistry, 2002; 41 (39): 11779–11785
42. Anindya SG, Ahamed J, KamLesh K, et al. Involvement of an efflux system in high-level fluoroquinolone resistance of Shigella dysenteriae. [J]. Biochemical and Biophysical Research Communications, 1998; 242 (1): 54-56
1. KotloffK L, Winickoff J P, Ivanoff B, et al. Global burden of Shigella infections: implications for vaccined evelopment and implementation of control strategies. Bul. W.H.0, 1999; 77(8): 651一666
2. TrofaA F, Ueno-Olsen H, Oiwa R, et a l. Dr. Kiyoshi Shiga: discovery of the dysentery bacillus. [J]. Clin. Infect. Dis, 1999; 29(5): 1303-1306
3. Pupo GM, Lan R, Reeves PR. MμLtiple independent origins of Shigella clones of Escherichia coli and convergent evolution of many of their characteristics. [J]. Pro.Natl.Acad.Sci, 2000; 97(19): 10567-10572
4. 丁建强,马亦林,龚飞,等.志贺菌流行菌株耐药性及R质粒的研究.[J].中华传染病杂志,1998,16(3):161-163.
5. 杨珊明.福氏志贺菌感染161例临床特点与耐药性分析.[J].中国实用内科杂志,2006; 26(11):865-866
6. 鲍得霞. 1985-1987痢疾杆菌菌群分布及耐药变化.[J].安徽医科大学报,1986;6(2): 469-470
7. 王小光,汪萍,刘继倩,等.194株志贺菌的流行病学分析及药物敏感调查.[J].疾病监测,2005; 20(2):71-75
8. 顾冠彬.93株痢疾杆菌血清学分类及药敏试验.[J].Chin J Hemorh, 2006; 16(1): 142-143
21. 刘丽红,王辉,李秀娟.118株志贺菌的流行病学调查及药物敏感临床分析.[J].中国初级卫生保健, 2006; 20(7):66-67
22. Hou Fengqin, Sun Xinting, Shen Baoquan, et al. Trends of antibiotic resistance in strains of Shigella isolated in Beijing over 8 years. [J]. J Chin Phar Sci, 2002; 11(1): 51-54
23. 陈群,王兴,张燕.志贺菌耐药分析. [J] .医学伦理与实践,2003; 16(8):878-879
24. Iwalokun BA, Gbenle GO, Smith SI, et al. Epidemiology of shigellosis in Lagos, Negoria: Trends in antimicrobial resistance. [J]. J Health PopμL Nutr, 2001; 19(3): 183-190
25. Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for β-lactamases and its correlation with molecμLar structure. [J].Antimicrob Agent Chemother, 1995; 39(7): 1211
26. Helfand MS, Bonomo RA.Beta-lactamases: a survey of protein diversity. [J]. Curr Brug Target Infect Bisord, 2003; 3(1): 9-23
27. Rosenau A, Cattier B, Gousset N. et al. Capnocytophaga ochracea: characterization of a plasmid-encoded extended-spectrum TEM-17 beta-lactamase in the phylum Flavobacter-bacteroides. [J]. Antimicrob Agents Chemother, 2000; 44(3): 760-762
28. Tzouvelekis LS, Tzelepi E, Tassios PT, et al. CTX-M-type beta-lactamases: an emerging group of extended-spectrum enzymes. [J]. Int J Antimicrob Agents, 2000; 14(2): 137-142
29. Navia MM, Capitano L, Ruiz J, et al. Typing and characterization of mechanisms of resistance of Shigella spp. isolated from feces of children under 5 years of age fromIfakara, Tanzania. [J]. J. Clin. Microbial, 1999; 37(10): 3113-3117
30. Nicolas F, Thierry N, Olivier G, et al. SHV-type extended-spectrum β-lactamase in a Shigella flexneri clinical isolate. [J], Journal of Antimicrobial Chemotherapy, 2001; 47(5): 685-688
31. Mahbubur R, Shereen S, Harunur R, et al. Extended-spectrum β-lactamase- mediated third generation cephalosporin resistance in Shigella isolates in Bangladesh. [J]. Journal of Antimicrobial Chemotherapy. 2004; 54 (4): 846-847
32. Siu LK, Lo JY, Yuen KY, et al. β-Lactamases in Shigella flexneri Isolates from Hong Kong and Shanghai and a Novel OXA-1-Like b-Lactamase, OXA-30. [J]. Antimicrobial Agents and Chemotherapy, 2000; 44 (8): 2034-2038
33. Jeong YS, Lee JC, Kang HY, et al. Epidemiology of Nalidixic Acid Resistance and TEM-1- and TEM-52-Mediated Ampicillin Resistance of Shigella sonnei Isolates Obtained in Korea between 1980 and 2000. [J]. Antimicrobial Agents and Chemotherapy, 2003; 47(12): 3719-3723
34. Sirot D, Chanal C, Bonnet R, et al. Inhibitor-resistant TEM-33 ? -lactamase in a Shigella sonnei isolate. [J]. Antimicrobial Agents and Chemotherapy, 2001; 45(7): 2179-2180
35. Kim S, Kim JY, Kang YH, et al. Occurrence of Extended-Spectrum ?-Lactamases in Members of the Genus Shigella in the Republic of Korea. [J]. J Clin Microbiol. 2004; 42(11): 5264-5269
36. 李家泰.临床药理学[M].第2版.北京:人民卫生出版社.1998,586
37. Tajada P, Gomee-Grace JL. Antimicrobial susceptibilities of campylobacter jejuni and campylobacter coli to 12 beta-lactam agents and combinations with beta-lactamases inhibitors. [J]. Antimicrob Agents Chemother, 1996; 40(8): 1924-1925
38. Drlica K, Zhao X. DNA gyrase, topoisomerase IV, and the 4-quinolones. [J]. Microbiol Mol Biol Rev, 1997; 61(3): 377-392
39. 7Hooper DC. Bacterial topoisomerases, anti-topoisomerases, and anti-topoisomerase resistance. [J]. Clin Infect Dis, 1998; 27 (Suppl 1): 54-63
40. Hawkey PM. Mechanism of quinolone action and microbial response. [J]. J Antimicrob Chemother, 2003; 51( Suppl): 29-35
41. Hirose k, Terajima, J, Izumiya, H, et al. Antimicrobial Susceptibility of Shigella sonnei Isolates in Japan and Molecular Analysis of S, sonnei Isolates with Reduced Susceptibility to Fluoroquinolones. [J]. Antimicrob Agents Chemother, 2005; 49(3): 1203–1205
42. 丁建强,马亦林,龚正,等.志贺菌对氟喹诺酮类药物耐药机制的研究. [J].中华内科杂志,1999; 38(8): 550-553
43. 传玲,朱于莉,赵守军,等.福氏志贺菌喹诺酮类耐药临床分离株gyrA 和parC 的基因突变. [J]. 中华传染病杂志,2005; 23(3):150-153
44. Dutta S , Kawamura Y, Ezaki T, et al. Alteration in the GyrA Subunit of DNA Gyrase and the ParC Subunit of Topoisomerase IV in Quinolone-Resistant Shigella dysenteriae Serotype 1 Clinical Isolates from Kolkata, India. [J]. Antimicrob Agents Chemother, 2005; 49 (4): 1660–1661
45. Levy SB. Active efflux mechanisms of antibacterial resistance. [J]. Antimicrob Agents Chemother, 1992; 43 (5): 1156
46. 杨海燕,段广才,郗园林。主动外排系统acrAB在志贺菌中的分布和表达.[J].中国公共卫生,2005; 21(6): 685-687
47. Munshi MH, Sack DA, Haider K, et al. Plasmid-mediated resistance to nalidixic acid in Shigella dysenteriae type 1. [J]. Lancet, 1987; 2(8556): 419-421
48. Rahman M, Mauff G, Levy J, et al. Detection of 4-quinoloneresistance mutation in gyrA gene of Shigella dysenteriae type 1 by PCR. [J]. Antimicrob Agents Chemother 1994; 38(10): 2488–2491
49. Martínez-Martínez L, Pascual A, Jacoby GA. Quinolone resistance from a transferable plasmid. [J]. Lancet, 1998; 351 (9105): 797-799
50. Robicsek A , Jacoby GA , Hooper DC. The worldwide emergence of plasmid-mediated quinolone resistance. [J]. Lancet Infect Dis 2006; 6(10): 629–40
51. Robicsek A, Strahilevitz J, Jacoby GA, et al. Fluoroquinolonemodifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase. [J]. Nat Med 2006; 12(1): 83–88
64. Rodriguez-Martinez JM, Pascual A, Matin D, et al. Bactericidal activity of fluoroquinolones (FQ) against Klebsiella pneumoniae containing the plasmid -mediated resistance determinant qnr.13th ESCMID (Glasgow, E scocia), 2004; P1555
65. Hedi Mammeri, Marc Van De Loo, Laurent Poirel, et al. Emergence of Plasmid-Mediated Quinolone Resistance in Escherichia coli in Europe. [J]. Antimicrobial agents and chemotherapy, 2005; 49(1): 71-76
2. Trofa AF, Ueno-Olsen H, Oiwa R, et al. Dr. Kiyoshi Shiga: discovery of the dysentery bacillus. [J]. Clin. Infect. Dis, 1999; 29(5): 1303-1306
3. Pupo GM, Lan R, Reeves PR.MμLtiple independent origins of Shigella clones of Escherichia coli and convergent evolution of many of their characteristics. [J]. Pro. Natl. Acad.Sci, 2000; 97(19): 10567-10572
4. Navia MM, Capitano L, Ruiz J, et al. Typing and characterization of mechanisms of resistance of Shigella spp.isolated from feces of children under 5 years of age from Ifakara, Tanzania. [J]. J. Clin. Microbial, 1999; 37(10): 3113-3117
5. Davies J. Bacteria on the rampage. [J]. Nature, 1996; 383(6597): 219-220
6. Clinical and Laboratory Standards Institute/NCCLS. Performance standards for antimicrobial susceptibility testing; Fifteenth informational supplement. CLSI/NCCLS document M100-S15. [R]. Clinical and Laboratory Standards Institute, Wayne, Pennsylvania, 2005; 25:1-167
7. 丁建强,马亦林,龚飞,等.志贺菌流行菌株耐药性及R质粒的研究.[J].中华传染病杂志,1998; 16 (3): 161-163
8. Chu YW, Houang TS, Lyon DJ, et al. Antimicrobial resistance in Shigella flexneri and Shigella sonnei in Hong Kong, 1986 to 1995. [J]. Antimicrob Agents Chemother, 1998; 42(2): 440-443
9. Lima AAM, Lima NL, Pinho MCN, et al. High frequency of strains multiply resistance to ampicillin, trimethoprim-sμLfametheoxazole, streptomycin, chloramphenicol, and tetracycline isolated from patients with shigellosis in northeastern Brazil during the period 1988 to 1993. [J], Antimicrob AgentsChemother, 1995; 39(1): 256-259
10.吴成. 小儿痢疾杆菌菌群分布及耐药性分析.[J] .医学基础与药学研究, 2004; 3 (4): 64-66
11. Kim S, Kim J, Kang Y, et al.Occurrence of extended-spectrum beta-lactamases in members of the genus Shigella in the Republic of Korea. [J]. J Clin Microbiol, 2004; 42(11): 5264-5269
12. Clinical and Laboratory Standards Institute/NCCLS. 2006. Performance standards for antimicrobial susceptibility testing; Sixteenth informational supplement. CLSI/NCCLS document M100-S16. Clinical and Laboratory Standards Institute, Wayne, Pennsylvania. 26, 1~174
13. 李景云,马越,陈洪波,等. 志贺菌的耐药性分析.[J] .世界感染杂志, 2002; 2(2):12-14
14. 杨海燕, 段广才, 郗园林.主动外排系统acrAB在志贺菌中分布和表达.[J] .中国公共卫生, 2005; 21(6): 685-687
15. Ashkenazi S, Levy I, Kazaronovski V, et a l. Growing antimicrobial resistance of Shigella isolates. [J]. J AntimicrobC hemother, 2003; 51(2): 427-429
16. 王晓红,乔欣宇,宋学枯,等. 90年代上海地区痢疾杆菌菌群分布及耐药性变 迁 [J].上海医科大学学报,1997; 24 (6): 425-427
17. Dutta S, Kawamura Y, Ezaki T, et al. Alteration in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV in quinolone-resistant Shigella dysenteriae serotype 1 clinical isolates from Kolkata, India. [J]. Antimicrob. Agents Chemothe, 2005; 49(4): 1660–1661
18. Robicsek A, Strahilevitz J, Sahm DF, et al. qnr pevalence in ceftazidime-resistant Enterobacteriaceae isolates from the United States. [J]. Antimicrob. Agents Chemother, 2006; 50(8): 2872–2874
19. Robicsek A, Strahilevitz J, Jacoby GA, et al. Fluoroquinolonemodifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase. [J]. Nat Med, 2006;12(1): 83–88
20. Pérez-Pérez FJ and Hanson ND. Detection of Plasmid-Mediated AmpC β-Lactamase Genes in Clinical Isolates by Using MμLtiplex PCR. [J]. J Clin Microbiol, 2002; 40(6): 2153-2162
21. Siu LK, Lo JYC, Yuen KY, et al. β-Lactamases in Shigella flexneri isolates from Hong Kong and Shanghai and a novel OXA-1-like β-lactamase, OXA-30. [J]. Antimicrob. Agents Chemother. 2000; 44(8): 2034–2038
22. 陆志檬. 细菌性痢疾.见: 彭文伟,主编.传染病学[M].第六版.北京: 人民卫生出版社,2004: 144-15.
23. Dupont H L. Shigella Species (Bacillary Dysentery). In: Mandell G L, Bennet J E, Dolin R, editors. Mandell, Douglas, and Bennet's Principles and Practice of Infectious Diseases. [M]. 6thed. NewYork: Elsevier/Churchill Livingstone, 2005: 2655-2661
24. Nicolas F, Thierry N, Olivier, G, et al. SHV-type extended-spectrum β-lactamase in a Shigella flexneri clinical isolate. [J]. J Antimicrob Chemother, 2001; 47(5): 685-688
25. Mahbubur R, Shereen S, Harunur R, et al. Extended-spectrum β-lactamase- mediated third generation cephalosporin resistance in Shigella isolates in Bangladesh. [J]. J Antimicrob Chemother, 2004; 54(4): 846-847
26. Jeong YS, Lee JC, Kang HY, et al. Epidemiology of Nalidixic Acid Resistance and TEM-1- and TEM-52-Mediated Ampicillin Resistance of Shigella sonnei Isolates Obtained in Korea between 1980 and 2000. [J]. Antimicrobial Agents and Chemotherapy, 2003; 47(12): 3719-3723
27. Sirot D, Chanal C, Bonnet R, et al. Inhibitor-resistant TEM-33 ? -lactamase in a Shigella sonnei isolate. [J]. Antimicrobial Agents and Chemotherapy, 2001; 45(7): 2179-2180
28. Bou G, Oliver A, Ojeda M, et al. MolecμLar characteriza tion of FOX-4, a new AmpC - type plasmid mediated lactamase from an Escherichia coli strain isolated inspain. [J]. Antimicrob Agents Chemother, 2000; 44 (9): 2549-2553
29. Bhattacharya SK, Sarkar K, Nair BG, et al. MμLtidrug-resistant Shigella dysenteriae type 1 in south Asia. [J]. Lancet Infect. Dis, 2003; 3(12): 755
30. Naheed AP, Kalluri KA, Talukder AS, et al. Fluoroquinolone-resistant Shigella dysenteriae type 1 in northeastern Bangladesh. [J]. Lancet Infect. Dis, 2004; 4(10): 607-608
31. Heisigp H, Schedletzky and Falkenstein-PaμL H. Mutations in the gyrA gene of a highly fluoroquinolone-resistant clinical isolate of Eecherichia coli. [J]. Antimicrob. Agents Chemother, 1993; 37(4): 696-701
32. Heisig P. Genetic evidence for a role of parc mutations in development of high-level fluoroquinolone resistance in Eecherichia coli. [J]. Antimicrob.Agents Chemother, 1996; 40(4): 879-885
33. Hawkey PM. Mechanism of quinolone action and microbial response. [J]. J Antimicrob Chemother, 2003; 51(Suppl) 1: 29-35
34. Ruiz J. Mechanism of resistance to quinolones: target alterations, decreased accumμLation and DNA gyrase protection. [J]. J Antimicrob Chemother , 2003; 51(5): 1109-1117
35. Acar JF and Goldstein FW. Trends in bacterial resistance to Fluoroquinolones. [J]. Cli Infect Dis, 1997; 24(Suppl 1): 67-73
36. Ince D and Hooper DC. Quinolone resistance due to reduced target enzyme expression. [J]. J Bacteriol, 2003; 185(23): 6883-6892
37. Hata M, Suzuki M, Matsumoto M, et al. Cloning of a Novel Gene for Quinolone Resistance from a Transferable Plasmid in Shigella flexneri 2b. [J]. Antimicrob Agents Chemother, 2005; 49 (2): 801-803
38. Hirose k, Terajima J, Izumiya H, et al. Antimicrobial Susceptibility of Shigella sonnei Isolates in Japan and Molecular Analysis of S, sonnei Isolates with Reduced Susceptibility to Fluoroquinolones. [J]. Antimicrob Agents Chemother, 2005, 49 (3):1203–1205.
39. 丁建强, 马亦林, 龚正, 等. 志贺菌对氟喹诺酮类药物耐药机制的研究.[J].中华内科杂志,1999; 38(8): 550-553
40. 唐传玲,朱于莉,赵守军,等.福氏志贺菌喹诺酮类耐药临床分离株gyrA 和parC 的基因突变.[J]. 中华传染病杂志,2005; 23(3):150-153
41. Hiasa, H. The Glu-84 of the ParC subunit plays critical roles in both topoisomerase IV-quinolone and topoisomerase IV-DNA interactions. [J]. Biochemistry, 2002; 41 (39): 11779–11785
42. Anindya SG, Ahamed J, KamLesh K, et al. Involvement of an efflux system in high-level fluoroquinolone resistance of Shigella dysenteriae. [J]. Biochemical and Biophysical Research Communications, 1998; 242 (1): 54-56
1. KotloffK L, Winickoff J P, Ivanoff B, et al. Global burden of Shigella infections: implications for vaccined evelopment and implementation of control strategies. Bul. W.H.0, 1999; 77(8): 651一666
2. TrofaA F, Ueno-Olsen H, Oiwa R, et a l. Dr. Kiyoshi Shiga: discovery of the dysentery bacillus. [J]. Clin. Infect. Dis, 1999; 29(5): 1303-1306
3. Pupo GM, Lan R, Reeves PR. MμLtiple independent origins of Shigella clones of Escherichia coli and convergent evolution of many of their characteristics. [J]. Pro.Natl.Acad.Sci, 2000; 97(19): 10567-10572
4. 丁建强,马亦林,龚飞,等.志贺菌流行菌株耐药性及R质粒的研究.[J].中华传染病杂志,1998,16(3):161-163.
5. 杨珊明.福氏志贺菌感染161例临床特点与耐药性分析.[J].中国实用内科杂志,2006; 26(11):865-866
6. 鲍得霞. 1985-1987痢疾杆菌菌群分布及耐药变化.[J].安徽医科大学报,1986;6(2): 469-470
7. 王小光,汪萍,刘继倩,等.194株志贺菌的流行病学分析及药物敏感调查.[J].疾病监测,2005; 20(2):71-75
8. 顾冠彬.93株痢疾杆菌血清学分类及药敏试验.[J].Chin J Hemorh, 2006; 16(1): 142-143
21. 刘丽红,王辉,李秀娟.118株志贺菌的流行病学调查及药物敏感临床分析.[J].中国初级卫生保健, 2006; 20(7):66-67
22. Hou Fengqin, Sun Xinting, Shen Baoquan, et al. Trends of antibiotic resistance in strains of Shigella isolated in Beijing over 8 years. [J]. J Chin Phar Sci, 2002; 11(1): 51-54
23. 陈群,王兴,张燕.志贺菌耐药分析. [J] .医学伦理与实践,2003; 16(8):878-879
24. Iwalokun BA, Gbenle GO, Smith SI, et al. Epidemiology of shigellosis in Lagos, Negoria: Trends in antimicrobial resistance. [J]. J Health PopμL Nutr, 2001; 19(3): 183-190
25. Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for β-lactamases and its correlation with molecμLar structure. [J].Antimicrob Agent Chemother, 1995; 39(7): 1211
26. Helfand MS, Bonomo RA.Beta-lactamases: a survey of protein diversity. [J]. Curr Brug Target Infect Bisord, 2003; 3(1): 9-23
27. Rosenau A, Cattier B, Gousset N. et al. Capnocytophaga ochracea: characterization of a plasmid-encoded extended-spectrum TEM-17 beta-lactamase in the phylum Flavobacter-bacteroides. [J]. Antimicrob Agents Chemother, 2000; 44(3): 760-762
28. Tzouvelekis LS, Tzelepi E, Tassios PT, et al. CTX-M-type beta-lactamases: an emerging group of extended-spectrum enzymes. [J]. Int J Antimicrob Agents, 2000; 14(2): 137-142
29. Navia MM, Capitano L, Ruiz J, et al. Typing and characterization of mechanisms of resistance of Shigella spp. isolated from feces of children under 5 years of age fromIfakara, Tanzania. [J]. J. Clin. Microbial, 1999; 37(10): 3113-3117
30. Nicolas F, Thierry N, Olivier G, et al. SHV-type extended-spectrum β-lactamase in a Shigella flexneri clinical isolate. [J], Journal of Antimicrobial Chemotherapy, 2001; 47(5): 685-688
31. Mahbubur R, Shereen S, Harunur R, et al. Extended-spectrum β-lactamase- mediated third generation cephalosporin resistance in Shigella isolates in Bangladesh. [J]. Journal of Antimicrobial Chemotherapy. 2004; 54 (4): 846-847
32. Siu LK, Lo JY, Yuen KY, et al. β-Lactamases in Shigella flexneri Isolates from Hong Kong and Shanghai and a Novel OXA-1-Like b-Lactamase, OXA-30. [J]. Antimicrobial Agents and Chemotherapy, 2000; 44 (8): 2034-2038
33. Jeong YS, Lee JC, Kang HY, et al. Epidemiology of Nalidixic Acid Resistance and TEM-1- and TEM-52-Mediated Ampicillin Resistance of Shigella sonnei Isolates Obtained in Korea between 1980 and 2000. [J]. Antimicrobial Agents and Chemotherapy, 2003; 47(12): 3719-3723
34. Sirot D, Chanal C, Bonnet R, et al. Inhibitor-resistant TEM-33 ? -lactamase in a Shigella sonnei isolate. [J]. Antimicrobial Agents and Chemotherapy, 2001; 45(7): 2179-2180
35. Kim S, Kim JY, Kang YH, et al. Occurrence of Extended-Spectrum ?-Lactamases in Members of the Genus Shigella in the Republic of Korea. [J]. J Clin Microbiol. 2004; 42(11): 5264-5269
36. 李家泰.临床药理学[M].第2版.北京:人民卫生出版社.1998,586
37. Tajada P, Gomee-Grace JL. Antimicrobial susceptibilities of campylobacter jejuni and campylobacter coli to 12 beta-lactam agents and combinations with beta-lactamases inhibitors. [J]. Antimicrob Agents Chemother, 1996; 40(8): 1924-1925
38. Drlica K, Zhao X. DNA gyrase, topoisomerase IV, and the 4-quinolones. [J]. Microbiol Mol Biol Rev, 1997; 61(3): 377-392
39. 7Hooper DC. Bacterial topoisomerases, anti-topoisomerases, and anti-topoisomerase resistance. [J]. Clin Infect Dis, 1998; 27 (Suppl 1): 54-63
40. Hawkey PM. Mechanism of quinolone action and microbial response. [J]. J Antimicrob Chemother, 2003; 51( Suppl): 29-35
41. Hirose k, Terajima, J, Izumiya, H, et al. Antimicrobial Susceptibility of Shigella sonnei Isolates in Japan and Molecular Analysis of S, sonnei Isolates with Reduced Susceptibility to Fluoroquinolones. [J]. Antimicrob Agents Chemother, 2005; 49(3): 1203–1205
42. 丁建强,马亦林,龚正,等.志贺菌对氟喹诺酮类药物耐药机制的研究. [J].中华内科杂志,1999; 38(8): 550-553
43. 传玲,朱于莉,赵守军,等.福氏志贺菌喹诺酮类耐药临床分离株gyrA 和parC 的基因突变. [J]. 中华传染病杂志,2005; 23(3):150-153
44. Dutta S , Kawamura Y, Ezaki T, et al. Alteration in the GyrA Subunit of DNA Gyrase and the ParC Subunit of Topoisomerase IV in Quinolone-Resistant Shigella dysenteriae Serotype 1 Clinical Isolates from Kolkata, India. [J]. Antimicrob Agents Chemother, 2005; 49 (4): 1660–1661
45. Levy SB. Active efflux mechanisms of antibacterial resistance. [J]. Antimicrob Agents Chemother, 1992; 43 (5): 1156
46. 杨海燕,段广才,郗园林。主动外排系统acrAB在志贺菌中的分布和表达.[J].中国公共卫生,2005; 21(6): 685-687
47. Munshi MH, Sack DA, Haider K, et al. Plasmid-mediated resistance to nalidixic acid in Shigella dysenteriae type 1. [J]. Lancet, 1987; 2(8556): 419-421
48. Rahman M, Mauff G, Levy J, et al. Detection of 4-quinoloneresistance mutation in gyrA gene of Shigella dysenteriae type 1 by PCR. [J]. Antimicrob Agents Chemother 1994; 38(10): 2488–2491
49. Martínez-Martínez L, Pascual A, Jacoby GA. Quinolone resistance from a transferable plasmid. [J]. Lancet, 1998; 351 (9105): 797-799
50. Robicsek A , Jacoby GA , Hooper DC. The worldwide emergence of plasmid-mediated quinolone resistance. [J]. Lancet Infect Dis 2006; 6(10): 629–40
51. Robicsek A, Strahilevitz J, Jacoby GA, et al. Fluoroquinolonemodifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase. [J]. Nat Med 2006; 12(1): 83–88
64. Rodriguez-Martinez JM, Pascual A, Matin D, et al. Bactericidal activity of fluoroquinolones (FQ) against Klebsiella pneumoniae containing the plasmid -mediated resistance determinant qnr.13th ESCMID (Glasgow, E scocia), 2004; P1555
65. Hedi Mammeri, Marc Van De Loo, Laurent Poirel, et al. Emergence of Plasmid-Mediated Quinolone Resistance in Escherichia coli in Europe. [J]. Antimicrobial agents and chemotherapy, 2005; 49(1): 71-76