Helicobacter pylori cagE,cagG, and cagM can be a prognostic marker for intestinal and diffuse gastric cancer

It is known that Helicobacter pylori is the main cause of peptic ulceration and gastric cancer. However, there is a lack of information on whether H. pylori strains may differ in gastric cancer histological subtypes. This study aimed to investigate different H. pylori strains considering six cag Pathogenicity Island - cagPAI genes (cagA, cagE, cagG, cagM, cagT, and virb11), and vacuolating cytotoxin - vacA alleles, and their relation to gastric cancer histologic subtypes. For this purpose, tumor samples from 285 patients with gastric carcinoma were used. H. pylori infection and genotypes were determined by polymerase chain reaction (PCR). H. pylori was detected in 93.9% of gastric tumors. For comparative analyzes between histopathological subtypes considering H. pylori cagPAI genes the strains were grouped according to the vacA s1/s2 alleles. In the vacAs1 group, the strains cagA(−)cagE(+), cagA(+)cagE(+)cagG(+), cagA(+)cagM(+), or only cagE(+) strains were more frequent in the intestinal subtype (P = .009; P = .024; P = .046, respectively). In contrast, cagM(+)cagG(+)cagA(−) and cagE(−) were associated with diffuse tumors (P = .036), highlighting the presence of cagE in the development of intestinal tumors, and the presence of cagG and absence of cagE in diffuse tumors. Furthermore, WEKA software and Decision Tree (CART) analyses confirmed these findings, in which cagE presence was associated with intestinal tumors, and cagE absence and cagG(+) with diffuse tumors. In conclusion our results showed that vacAs1 (cagG + cagM) strains, mainly cagG positive with cagE absence, were relevant in the studied population for the diffuse outcome, while the presence of cagE was relevant for the intestinal outcome. These findings suggest the relevance of these H. pylori genes as potential markers for gastric cancer histological outcomes.     

Helicobacter pylori heterogeneity in patients with gastritis and peptic ulcer disease

Genetic diversification allows Helicobacter pylori to persist during chronic colonization/infection. We investigated the intra-host variation of several markers that suggested microevolution in patients with chonic gastritis (CG) and peptic ulcer disease (PUD). One-hundred twenty-six isolates recovered from 14 patients with CG and 13 patients with PUD were analysed. cag pathogenicity island (cagPAI), oipA, vacA, bab gene status and the presence of jhp0926, jhp0945, jhp0947, jhp0949 and jhp0940 genes from the genomic Plasticity Zone (PZ) were taken into accout to investigate intra-host variation. lspA-glmM-RFLP was performed to identify mixed infections. Only one patient was colonised/infected by two ancestrally unrelated strains. Among the 126 isolates, a significant association among cagPAI genotypes, oipA status and vacA alleles was indicated. Complete cagPAI, oipA “on”, and vacA s1-m1 variants were significantly found in patients with PUD, without intra-host variations. Isolates from 7/14 patients with CG lacked babA in all chromosomal loci. In contrast, isolates from all or several biopsies of PUD patients carried babA, but in one patient only, the isolates showed positive Lewis b (Leb) binding assay. Considering cagPAI, vacA, oipA, bab genotypes, intra-host variation was also significantly higher in patients with CG. Conversely, a similarly high intra-host variation in almost PZ genes was observed in isolates from patients with CG and PUD.In conclusion, the lowest intra-host variation in cagPAI, oipA, vacA, and bab genes found in patients with PUD suggests the selection of a particular variant along the bacteria-host environment interplay during ulceration development. However, the predominance of this variant may be a refletion of the multifactorial etiology of the disease rather than the cause, as it was also found in patients with CG. The intra-host variation in PZ genes may predict that this genomic region and the other markers of microevolution studied evolve under diverse pressure(s).     

幽门螺杆菌的毒力基因、vacA基因亚型与上消化道疾病关系的研究

目的研究镇海地区幽门螺杆菌(Hp)尿素酶基因(ureA)、细胞毒素相关基因(cagA)、空泡细胞毒素基因(vacA)及vacA基因亚型与上消化道疾病之间的关系。方法用普通聚合酶链反应(PCR)技术,测定84株从上消化道疾病患者胃窦黏膜中分离获得的Hp的ureA基因、cagA基因、vacA基因、vacA基因亚型。结果84株Hp中,ureA、cagA、vacA基因的阳性率分别为100.00%、90.48%、95.24%,cagA、vacA在胃炎、消化性溃疡的阳性率高于胃癌(P<0.05);vacAm2基因的阳性率为79.76%,明显高于vacAm1a(20.24%)、vacAm1b(8.33%)及vacAm1bm2(4.76%),vacAm2在胃炎、消化性溃疡的阳性率高于胃癌(P<0.05),其余3个基因亚型阳性率差异均无统计学意义(均P>0.05)。结论镇海地区Hp相关性上消化道疾病患者感染Hp以ureA阳性、cagA阳性、vacAm2亚型占优势,且均在消化性溃疡及胃炎中的检出率更高。     

浙江地区幽门螺杆菌优势基因型研究

目的研究浙江地区幽门螺杆菌(Helicobacter pylori,Hp)的优势基因型并探讨各基因在不同胃十二指肠疾病患者中Hp的差异。方法从胃十二指肠疾病患者的胃粘膜活检组织中分离培养到Hp 129株,抽提基因组DNA后用PCR检测Hp的cagA、vacA、iceA及babA2等基因的分布,用卡方检验分析各基因在不同胃十二指肠疾病中Hp的差异。结果129株Hp中cagA的阳性率为99.2%(128/129),vacA sla基因型阳性率为94.6%(122/129),vacA m2为83.7%(108/129),iceA1为84.5%(109/129),iceA2为46.5%(60/129),babA2阳性率为81.4%(105/129)。消化性溃疡患者Hp的vacAm2基因阳性率高于慢性胃炎患者Hp(P<0.05),其余基因在不同类型疾病中的分布无统计学差异(P>0.05)。结论浙江地区Hp菌株的优势基因型为cagA,vacAsla/m2,iceAl,babA2;消化性溃疡患者Hp的vacAm2基因阳性率明显高于慢性胃炎患者。     

Molecular epidemiology of Helicobacter pylori: separation of H. pylori from East Asian and non-Asian countries

The predominant H. pylori strain circulating among geographic locations differs with regard to the genomic structure. This study determined whether structural subtypes of the cagA 3' repeat region could be used to identify the population of origin of H. pylori isolates. We examined 600 cagA-positive H. pylori (Colombia, 100; USA, 100; France, 100; Canada, 20; Italy, 20; Korea, 100; Japan, 100; Hong Kong, 20; Taiwan, 20; Vietnam, 20). The cagA 3' region was amplified by PCR using primers specific to Japanese and Western 3' cagA gene sequences. PCR using Japanese cagA primers resulted in PCR products in 99-6 % of strains from East Asia but no non-Asian strains. Conversely, PCR using Western cagA primers resulted in amplicons in 100% of non-Asian strains, and only one from East Asia. cagA genotyping is useful for molecular epidemiological studies as strains can be completely separated by differences in the cagA 3' region.     

淮南地区学生幽门螺杆菌vacA和cagA基因分布特征

目的研究淮南地区学生幽门螺杆菌(Helicobacter pylori,H.pylori)cagA和vacA基因分布特征,为防治工作提供理论依据。方法对74例有消化道症状,年龄在7~24岁的在校学生进行胃镜检查,并在胃窦部取活检粘膜作H.pylori的分离培养,利用聚合酶链反应技术(PCR)测定分离培养出的H.pylori菌株的cagA和vacA基因并进行分型。结果74例学生中,分离培养出H.pylori菌株24例,基因测定结果显示,24株H.pylori临床分离株中,94.7%(23/24)含vacA基因,70.8%(17/24)含cagA基因;其中慢性胃炎vacA和cagA基因检出率分别为94.7%(18/19),70.6%(12/17);2例胃溃疡及3例十二指肠球部溃疡均全部为vacA和cagA阳性;进一步分型发现89.5%(17/19)的慢性胃炎为vacA 和cagA ,而5例溃疡患者均为vacA 和cagA 。结论淮南地区学生H.pylori感染多为vacA 和cagA 菌株,应充分重视H.pylori毒力因子的监测。     

Determination of cagA, vacA genotypes of Helicobacter pylori with real-time PCR-method

Presence of cagA gene of Helicobacter pylori (H. pylori) increases proliferation of stomach mucosa and it is an index of raised virulence of the bacteria. The vacA gene of H. pylori induces a serious inflammation of stomach. The purpose of this study was to determine cagA and vacA genotypes of H. pylori using real-time polymerase chain reaction (PCR) method with the double strain DNA-(dsDNA) binding SYBR Green I. dye. Results were compared with those of two immunohistochemical methods. 43 patients' paraffin embedded biopsy tissue samples were examined by histology, epidermal growth factor receptor (EGFR), proliferating cell nuclear antigen (PCNA) immunohistochemistry and melting curve analysis of real-time PCR using LightCycler instrument. Results of histology and real-time PCR from gastric biopsies correlated in 57% of cag acases and in 58% of vac cases. Significant difference was detected between normal and gastritis cases in the presence of cagA gene (p = 0.003) and between normal epithelial and intestinal metaplasia cases in the presence of vacA gene (p = 0.045) by investigation of association of histology and genotype of bacterium. Statistically significant difference (p = 0.02) was found between increased cell proliferation and the presence of gastritis. Significant correlation was found between the presence of cagA gene and EGFR expression in intestinal metaplasia cases (p = 0.0418). Results underlie the statistics that infection with cagA positive H. pylori strain increases the cell proliferation on the stomach mucosa and raises the chance of development of intestinal metaplasia. Infection with vacA positive H. pylori inhibits the signal-transduction pathway of EGFR, which influences mechanisms of mucosa repair. The role of EGFR and H. pylori infection is yet unclear in intestinal metaplasia and cancer. The authors' method seem to be suitable for determination of genotypes of H. pylori.     

genoBASE pylori: a genotype search tool and database of the human gastric pathogen Helicobacter pylori.

Helicobacter pylori is the pathogenic bacterium linked to gastric and duodenal ulcers and gastric carcinoma. Genomic diversity of the organism has enabled new insights into its population biology through comparative genomics. genoBASE pylori is an online databank of several virulence-linked and phylogenetic markers of H. pylori strains obtained from different human populations. This knowledgebase is built upon a relational database management system which is connected to visualize the presence of known, pathogenicity markers such as the co-ordinates within the cag pathogenicity island (cagPAI), the cagA gene and motifs surrounding it, the vacA allotypes and the oipA gene frame status, together with genotypic details in the form of DNA profiling traces and candidate gene sequences for individual strains. This flexible search tool allows inter-laboratory comparison of DNA fingerprinting data in the form of fluorescent amplified fragment length polymorphism (FAFLP), enterobacterial repetitive intergenic consensus (ERIC) and repetitive extragenic palindromic (REP) signature profiles. Besides this, the database also displays diversity of strains based on nucleotide sequences of several house keeping genes and two membrane proteins. Being the first of its kind, genoBASE pylori is expected to be a helpful online tool in strengthening the concept of 'geographic genomics' and will be useful to molecular epidemiologists, clinical laboratory scientists and those interested in diagnostic development for H. pylori. The database can be accessed through its website (http://www.cdfd.org.in/amplibase/HP).     

浙江人群幽门螺杆菌cagA/vacA优势基因型和不同基因型混合感染的调查

目的　了解消化性溃疡和慢性胃炎患者感染的幽门螺杆菌 (Hp)cagA vacA优势基因型及不同基因型Hp感染、混合感染与疾病的关系。 方法　选择胃窦、胃体双份活检标本均培养出Hp的 42例慢性胃炎 (CG)和 3 6例消化性溃疡 (PU )患者作为研究对象 ,采用聚合酶链反应 (PCR)检测156份Hp分离株的cagA基因、vacA基因的信号区 (s)和中间区 (m )亚型 ,分析Hp基因型及多株Hp混合感染在CG和PU中的分布。结果　胃窦标本cagA基因的检测中 78例患者中有 75例 (96.2 % )为cagA阳性 ,相应的胃体标本中 ,76例患者 (97.4% )为cagA阳性 ,有 1例 (1.3 % )患者胃窦、胃体检出cagA状态不一的Hp混合菌株。在胃窦标本的vacA基因分型中 ,s1a m1、s1a m2、s1a m1b、s1a m1b m2 4种vacA基因型在 78例患者中所占比例分别为 6.4% (5 78)、55.1% (43 78)、2 6.9% (2 1 78)和 1.3 % (1 78) ,多株混合感染为 3 .8% (3 78) ;而相应的胃体标本中 ,前述四种vacA基因型所占比例依次为 6.4% (5 78)、53 .8% (42 78)、2 5.6% (2 0 78)和 3 .8% (3 78) ,多株混合感染为 5.1% (4 78)。cagA+ s1a m2和cagA+ s1a m1b在胃窦标本中占 51.3 % (40 78)和 2 6.9% (2 1 78) ,而在相应的胃体标本中占 52 .6% (41 78)和 2 5.6% (2 0 78)。少量胃窦、胃体     

Relation between Helicobacter pylori cagA status and risk of peptic ulcer disease

Although colonization with any Helicobacter pylori strain is associated with peptic ulcer, it is uncertain whether the risk is greater with cagA(+) or cagA(-) strains, which differ in their biology. A nested case-control study was done, based on a cohort of 5,443 Japanese-American men examined on the Hawaiian island of Oahu from 1967 to 1970. A total of 150 men with gastric ulcer, 65 with duodenal ulcer, and 14 with both diseases were identified. The authors matched the 229 cases with 229 population controls and tested their serum for immunoglobulin G antibodies to H. pylori and immunoglobulin G antibodies to the cagA product of H. pylori using enzyme-linked immunosorbent assays. Persons with H. pylori positivity had an odds ratio of 4.0 (95% confidence interval (CI): 1.9, 8.5) for gastric ulcer and 2.5 (95% CI: 0.8, 7.4) for duodenal ulcer. For CagA positivity, the odds ratios were 1.4 (95% CI: 0.9, 2.4) for gastric ulcer and 2.6 (95% CI: 1.1, 5.8) for duodenal ulcer. Subjects who were seropositive for both H. pylori and CagA had an odds ratio of 4.4 (95% CI: 1.8, 10.5) for gastric ulcer and 5.8 (95% CI: 1.1, 30.0) for duodenal ulcer. The results suggest that colonization with a cag(+) H. pylori strain elevates the risk beyond that of a cag(-) H. pylori strain for both gastric and duodenal ulcers.     

幽门螺杆菌中国菌株致病相关基因cagA、iceA、vacA及HP0519分布分析

目的分析中国不同人群及不同胃部疾病病例来源的幽门螺杆菌致病相关基因cagA、iceA、vacA及HP0519的分布.方法采用特异引物聚合酶链式反应（PCR）方法分析150株幽门螺杆菌上述基因的多态性分布特点,并对其分布作初步统计分析.结果93%（139/150）中国菌株cagA基因3′端重复序列的PCR产物具有东方菌株特征.75%（113/150）菌株iceA基因为iceA1,19%（29/150）为iceA2,不同地区间iceA基因的分布差异无统计学意义.云南菌株iceA1、iceA2的分布与菌株分离个体的种族特点及临床疾病类型无显著关系.96%中国菌株（144/150）vacA基因s区的等位基因为s1;m区等位基因m2、m1b和m1b-m2的比例分别为57%（85/150）、27%（41/150）和11%（16/150）,仅2株福建菌株为m1a.不同地区间vacA s1、m2、m1b分布的差异无统计学意义.云南菌株m1b-m2的分布高于福建和北京菌株.云南菌株vacA s区等位基因的多样性与分离个体的种族及临床疾病类型无显著关系.vacA m区等位基因的多样性与分离个体的临床疾病类型无显著关系,但不同民族间m2的分布有显著差异,白族人群m2的分布显著少于汉族和纳西族.93%（140/150）的中国菌株HP0519基因具有24 bp和15 bp DNA插入和缺失的多态性特点.不同地区间HP0519基因的多态性无显著不同.云南菌株HP0519的多态性与菌株分离个体的临床疾病类型无显著关系,但来源不同民族菌株的HP0519基因存在差异.结论幽门螺杆菌中国菌株cagA 3′端JF/TR特异引物的扩增结果具有东亚菌株特点.中国菌株vacA基因多为s1,其分布与菌株分离个体的临床疾病类型无关.中国菌株vacA基因m区的分布具有多样性.中国菌株HP0519基因具有24 bp和15 bp插入和缺失的多态性特点.     

中国香港地区幽门螺杆菌毒力基因型与十二指肠溃疡关系的研究

目的：研究幽门螺杆菌（Hp）的重要毒力因子vacA，cagA，iceA及插入序列IS在中国香港地区分离菌株中的分布特征及其与十二指肠溃疡的关系。方法：采用聚合酶链反应（PCR）和Southern blot方法，对72例证实为Hp感染的胃十二指肠疾病患者的胃黏膜标本直接进行检测。结果：72例患者中，69例（95.8％）感染的Hp菌株为vacA sIc型，3例（4.2％）为sIa型；23例（31.9％）为vacAm1b型，46例（63.9％）为vacAm2型；6例（8.3％）为混合型。63.9％（46/72）的患者感染菌株为iceA1型，29.2％（21/72）为iceA2型。CagA的阳性率为88.9％（64/72）。结论：Hp毒力因子vacA，cagA和iceA在香港菌株中的分布有自己的特点；未发现特定cagA，vacA和iceA基因型别与DU相关。     

不同类型慢性胃炎患者幽门螺杆菌的分离培养、耐药与毒力基因研究

目的 研究不同类型慢性胃炎患者幽门螺杆菌（Helicobacter pylori,Hp）的感染情况,检测分离株的耐药性与毒力基因。方法 采集患者胃黏膜,分离Hp并进行药敏试验。PCR扩增克拉霉素、左氧氟沙星耐药相关基因23S rRNA、gyrA及毒力基因cagA、vacA、iceA,测序并分析23S rRNA和gyrA扩增产物的突变位点。分析慢性胃炎类型与Hp的分离率、耐药性和毒力基因的关系。结果 120例患者共分离获得45株Hp（37.5%）。Hp对甲硝唑、克拉霉素、左氧氟沙星、阿莫西林、呋喃唑酮和四环素的耐药率分别为97.8%、28.9%、28.9%、4.4%、0和0。在克拉霉素和左氧氟沙星耐药菌株中,23S rRNA、gyrA基因最常见的突变位点分别为A2143G（76.9%）和N87K（38.5%）。cagA、vacA s1a、vacA s1b、vacA s1c、vacA s2、vacA m1、vacA m2、iceA1、iceA2阳性率分别为97.8%、97.8%、0、95.6%、0、37.7%、62.2%、71.1%、24.4%。在不同类型慢性胃炎组间,Hp的分离率差异有统计学意义（χ2 = 13.299,P＜0.05）,分离株的耐药率差异均无统计学意义（均P＞0.05）,iceA1、iceA2的分布差异有统计学意义（均P＜0.05）。结论 不同类型慢性胃炎患者Hp的分离率不同,Hp感染治疗可选呋喃唑酮和四环素,iceA1和iceA2毒力基因可能与胃炎类型有关。     

A study of Helicobacter pylori outer-membrane proteins (hom) A and B in Iraq and Turkey

Helicobacter pylori outer-membrane proteins (hom), especially the homB gene, have been suggested as a novel virulence factor. However, no study has been conducted in Middle Eastern countries regarding the association between these genes and clinical outcome. Gastric biopsies were obtained from 70 and 64 unselected H. pylori+ patients from Iraq and Turkey, respectively. PCR was performed to study the presence of the homA, homB, and cagA. No association was found between homA or homB and clinical outcomes. When Iraqi and Turkish strains were combined as Middle Eastern samples, cagA positivity was significantly higher in patients with peptic ulcer disease (PUD) than those with non-peptic ulcer disease (NPUD) (p=0.003, OR=3.6, CI=1.5-8.8). Two Iraqi strains showed intermediate, non-homA non-homB, length PCR products. The function of such gene is yet to be determined. In conclusion, hom genes might not be a good indicator for disease prediction in the Middle East. More studies are needed to confirm these results and determine the function of intermediate length hom.     

幽门螺杆菌密度和细胞毒素相关基因A在胃部疾病中的检测

目的探讨H.pylori的定植密度及cagA分布与慢性胃疾病病理类型的相互关系。方法胃镜直视下,取胃黏膜组织,经分离培养、快速尿素酶试验和W-S银染对H.pylori感染进行定性、定量诊断,用PCR检测H.pylori的cagA基因,以SPSS软件分析数据。结果①H.pylori在慢性胃部疾病的阳性率为84.6%。cagA阳性率为62.5%,在慢性胃炎,不典型增生,胃癌中的分布分别为:58.0%,70.6%,72.2%,3组间差异无统计学意义(χ2(2,104)=1.804,P=0.406);②H.pylori定植密度在胃黏膜中的分布分别为:1级16(13.0%),2级44(35.8%),3级44(35.8%)。其中慢性胃炎组的分布分别为:1级13(15.9%),2级24(29.3%),3级32(39.0%);不典型增生组的分布分别为:1级1(5.0%),2级8(40.0%),3级8(40.0%);胃癌组中的分布分别为:1级2(9.5%),2级12(57.1%),3级4(19.0%)。密度级别在慢性胃炎、不典型增生、胃癌组的分布差异无统计学意义(χ2(2,123)=7.724,P=0.259)。结论①太原地区慢性胃部疾病患者中H.pylori呈高感染率,且cagA阳性率较高,后者随着疾病的严重程度有增高趋势,但差异无统计学意义,提示ca-gA可能不是影响胃部疾病病理类型的独立因素;②胃部疾病患者中,H.pylori定植密度级别与胃部疾病病理类型无一定的规律。     

Synthesis and preliminary evaluation of some N-[5-(2-furanyl)-2-methyl-4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]-carboxamide and 3-substituted-5-(2-furanyl)-2-methyl-3H-thieno[2,3-d]pyrimidin-4-ones as antimicrobial agents

Two series of N-[5-(2-furanyl)-2-methyl-4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]-carboxamide (4a-m) and 3-substituted-5-(2-furanyl)-2-methyl-3H-thieno[2,3-d]pyrimidin-4-ones (5a-m) were synthesised using appropriate synthetic route. All the test compounds 4a-m and 5a-m were assayed in vitro for antibacterial activity against two different strains of Gram-negative (Escherichia coli and S. typhi) and Gram-positive (S. aureus, B. subtilis) bacteria and the antimycobacterial activity was evaluated against M. tuberculosis and M. avium strains. The minimum inhibitory concentration (MIC) was determined for test compounds as well as for reference standards. The test compounds have shown significant antibacterial and antimycobacterial activity against all the microbial strains used, when tested in vitro. In general, along with the thienopyrimidinone ring, substituted amido or imino side chain at position 3 is essential for antimicrobial activity. Among the compounds tested, compounds 4c, 4e and 4g in N-[5-(2-furanyl)-2-methyl-4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]-carboxamide series and compounds 5c, 5e and 5g in 3-substituted-5-(2-furanyl)-2-methyl-3H-thieno[2,3-d]pyrimidin-4-ones series were found to be the most potent. Further the toxicity of most potent compounds 4c, 4e and 4g and 5c, 5e and 5g were assessed using hemolytic assay and minimal hemolytic concentration (MHCs) were determined. In general, test compounds were found to be non-toxic up to a dose level of 200 micromol L(-1) (MHC).     

Organization of the Helicobacter pylori genome

Helicobacter pylori is a Gram-negative, spiral-shaped pathogenic bacterium that was firstly isolated and cultured from biopsy specimens by Marshall and Warren in 1983. This organism is a human gastric pathogen associated with peptic ulcer disease as well as chronic gastritis. Recent epidemiological studies have demonstrated that H. pylori is a primary risk factor for the development of intestinal type gastric adenocarcinoma. H. pylori is the first bacterium for which the genomes of two unrelated strains (26695 and J99) have been sequenced. The genome of H. pylori is relatively low in size (1.6-1.73 Mb). In this review, we compare the organization of two sequenced H. pylori genomes. A special emphasis on genetic diversity of H. pylori including plasticity zone and cag pathogenicity island has been placed.     

革兰阴性杆菌对亚胺培南耐药率的变迁

目的调查革兰阴性杆菌对亚胺培南的耐药率变化。方法收集2003年10月-2006年6月从住院患者各种临床标本中分离的革兰阴性杆菌,使用VITEK-32全自动微生物分析仪进行菌种的鉴定和药敏试验,对结果进行回顾性调查。结果共分离出革兰阴性杆菌2045株,35个细菌种,肠杆菌科细菌912株,占44.6%;非发酵菌1120株,占54.8%;分离率前5位的病原菌分别是铜绿假单胞菌、大肠埃希菌、鲍氏不动杆菌、肺炎克雷伯菌和洋葱伯克霍尔德菌;肠杆菌科细菌对亚胺培南的耐药率非常低,除弗氏柠檬酸杆菌外,其他肠杆菌科细菌对亚胺培南的耐药率均<1.0%;嗜麦芽寡养单胞菌、洋葱伯克霍尔德菌、脑膜脓毒金黄杆菌、铜绿假单胞菌和鲍氏不动杆菌对亚胺培南的耐药率分别为100.0%、98.6%、98.3%、22.3%和20.6%。结论临床分离的革兰阴性杆菌以非发酵菌为主,亚胺培南对肠杆菌科细菌具有非常强的体外抗菌活性,对非发酵菌的体外抗菌活性较差,铜绿假单胞菌和鲍氏不动杆菌对亚胺培南的耐药率呈上升趋势。     

70株浙江省结核分枝杆菌临床分离株Spoligotyping基因分型研究

目的了解结核分枝杆菌临床分离株相关基因型的分布情况，并分析北京家族菌株与耐药的相关性。方法收集浙江省结核分枝杆菌临床分离株，常规罗氏培养基培养，应用Spoligotyping进行基因分型研究，聚类分析采用BioNumerics软件，统计学分析采用卡方检验。结果70株浙江省结核分枝杆菌临床分离株可分为2个基因群，即北京家族（Beijing family）和非北京家族（Non-Beijing family），分别占70％（49／70）和30％（21／70），18种基因型，其中12株为独特类型，剩余58株分为6簇。北京家族菌株中，89．8％（44／49）为典型北京家族（typical Beijing family），非北京家族菌株表现为高度的基因多态性，可分为13个基因型，9株为独特的基因型。北京家族菌株中表现为全敏感者71．4％（35／49），表现为耐药者为28．6％（14／49）；而非北京家族菌株中表现为全敏感者为66．7％，表现为耐药者为33．3％，经卡方检验，两者问的差异无统计学意义（X^2=0．158，P〉0．05）。结论北京家族菌株为浙江的流行优势菌株。北京基因犁与耐药无明显相关性。     

Hydrazones of 1,2-benzisothiazole hydrazides: synthesis,antimicrobial activity and QSAR investigations

A series of hydrazones of 1,2-benzisothiazole hydrazides 1a-m, 2a-m, 3a-m, 4a-m, 5a-m as well as their cyclic (1 and 4) and acyclic (2, 3 and 5) 1,2-benzisothiazole parent hydrazides, were synthesised and evaluated as antibacterial and antifungal agents. All of the 2-amino-1,2-benzisothiazol-3(2H)-one derivatives, belonging to series I and IV, showed a good antibacterial activity against Gram positive bacteria. Most of them were active against yeasts too. Compounds 1 and 4, together with 1l, proved to be the most effective compounds. Quantitative structure-activity relationship (QSAR) investigation with a 2D-QSAR analysis was applied to find a correlation between different experimental or calculated physicochemical parameters of the compounds studied. A 3D-QSAR study was performed, applying Comparative Molecular Similarity Indices Analysis (CoMSIA) method, to derive quantitative models relating the structural features of 1,2-benzisothiazole derivatives 1, 1a-m and 4, 4a-m and their antimicrobial activity against Bacillus subtilis, resulted the most sensitive micro-organism.