幽门螺杆菌耐药株研究进展

现在已公认幽门螺杆菌(Helicobacter pylori,下称Hp)与下述4种疾病密切相关：①慢性胃炎;②消化性溃疡病;③MALT淋巴瘤;④胃癌。所以Hp感染的治疗一直是胃肠病领域里研究最热门的课题。随着抗生素在Hp根除治疗中的广泛应用,Hp耐药株的发生率不断上升,以致当前Hp根除难度愈来愈大,特别是对甲硝唑的耐药株在迅速增加。应用不久的克拉霉素亦开始耐药,因而导致Hp根治的失败。要重视Hp耐药株的研究,首先应该寻找导致Hp耐药株产生的原因和探讨其发生机制,并且研究如何避免和克服Hp耐药株产生将是在Hp根治中亟待解决的问题。     

贵州省幽门螺杆菌临床菌株的抗生素耐药现状

目的检测贵州省幽门螺杆菌(Helicobacter pylori,H.pylori)临床菌株对多种抗生素的耐药率,并分析甲硝唑(MTZ)、克拉霉素(CLA)、阿莫西林(AMO)耐药菌株的临床特征。方法以贵州地区30株培养成功的H.pylori临床菌株为研究对象,采用Kirby-Bauer及E-test法测定菌株对MTZ、CLA、AMO等多种抗生素的耐药性。分析MTZ、CLA、AMO耐药菌株与敏感菌株患者性别、年龄及疾病种类的差异。结果 Kirby-Bauer法显示H.pylori临床菌株对AMO、左氧氟沙星、庆大霉素、CLA、四环素、头孢呋肟、复方新诺明的耐药率分别为20.00%、3.33%、13.33%、30.00%、6.67%、0、0;E-test法显示H.pylori临床菌株对MTZ、AMO、CLA耐药率分别为63.33%、26.67%、33.33%;两种检查方法检测结果无明显差异;男性患者MTZ的耐药率(77.78%)较女性患者(41.67%)高(P<0.05);30～60岁年龄组患者MTZ的耐药率更高(P<0.05);CLA和AMO的耐药率与疾病种类、性别、年龄无明显关系(P>0.05)。结论贵州地区H.pylori临床菌株的耐药现状不容忽视,以男性消化性溃疡患者年龄在30～60岁对MTZ的耐药率较高。     

幽门螺杆菌对抗生素耐药研究进展

幽门螺杆菌(H pylori)是一种存在于人类胃黏膜的G-的螺旋形细菌,是胃十二指肠溃疡、慢性活动性胃炎的主要病因,并与黏膜相关性淋巴组织(MALT)淋巴瘤及胃癌的关系密切.因此,H pylori的根治成为大家关注的问题.但是临床上H pylori根除率却不高,其原因主要是日益突出的抗生素耐药问题.本文就有关H pylori对抗生素耐药性的研究近况作一阐述.     

幽门螺杆菌耐药现状及临床治疗对策

随着治疗根除幽门螺杆菌(Hp)抗生素的广泛使用,中国2006～2010年间幽门螺杆菌(Hp)对甲硝唑、克拉霉素、阿莫西林的耐药率逐年上升.治疗上强调地区化、个体化、序贯疗法和四联方案延长疗程法等,应用呋喃唑酮、四环素和喹诺酮类(如左氧氟沙星和莫西沙星)抗生素,采取时间间隔3～6个月的治疗策略能提高幽门螺杆菌的根除率.     

中国幽门螺杆菌耐药研究现状

中国是一个幽门螺杆菌（H．pylori）感染率较高的国家，H．pylori的感染率42％～90％，所以H．pylori感染的治疗是H．pylori研究领域中的重点，而H．pylori感染治疗失败主要原因是H．pylori对抗生素的耐药性，所以H．pylori感染治疗中核心问题是日．pylori对抗生素的耐药性，其耐药性也是H．pylori感染研究中的重点课题。近年我国对H．pylori耐药研究已有新j生展，本文重点介绍如下5个方面：①H．pylori对常用抗生素耐药情况及地区差异性；②H．pylori对常用抗生素耐药性随时间变迁而逐渐上升；⑧H．pylori对四环素和左氧氟沙星耐药情况；④H．pylori耐药对H．pylori根除效果的影响；⑤如何克服H．pylori对抗生素耐药性。     

海岛地区就医患者幽门螺杆菌对常用抗生素的耐药特点分析

浙江省舟山市为海岛地区,其胃肠道疾病发病率明显高于全国其他地区,幽门螺杆菌(HP)根除治疗显得愈发重要.随着根除治疗的普及,HP的耐药情况日益严重.我们通过对舟山海岛地区幽门螺杆菌的耐药状况进行分析,以探讨适合本地区HP根除治疗的方案:     

昆明地区幽门螺杆菌耐药分析

目的了解昆明地区幽门螺杆菌(Hp)菌株对甲硝唑、克拉霉素、阿莫西林耐药的流行病学情况,观察Hp耐药菌株对不同抗Hp治疗方案的影响。方法选取Hp感染阳性的消化性溃疡和慢性活动性胃炎门诊患者80人,年龄18～68岁。于胃镜下从患者胃窦取2块胃黏膜组织,进行Hp培养及E-test药敏试验。患者随机分为LCA和LCM两治疗组,各40人,疗程1周。疗程结束1月后复查14C尿素呼气试验。结果甲硝唑耐药率为77.1%(54/70),MIC范围0.016～>256mg/L。克拉霉素耐药率为11.4%(8/70),MIC范围0.016～24mg/L。阿莫西林耐药率为0%(0/70),MIC范围<0.016～0.125mg/L。甲硝唑和克拉霉素同时耐药率为5.7%(4/70)。结论昆明地区Hp对甲硝唑耐药严重(耐药率达77.1%),克拉霉素耐药已经存在(耐药率为11.4%),未见阿莫西林耐药(耐药率为0%)。     

上海地区幽门螺杆菌对抗生素耐药率的变迁

甲硝唑和克拉霉素是根除幽门螺杆菌 (Ｈｐ)感染的主要抗生素 ,Ｈｐ对这些抗生素耐药是治疗失败的主要原因。我们调查了上海地区 1995～ 1999年间Ｈｐ对甲硝唑和克拉霉素耐药率的变化情况 ,现报道如下。1.Ｈｐ菌株 :Ｈｐ菌株分离自我们在上海地区几家工厂职工胃镜普查所取的胃黏膜活检标本。随机选取 1995、1997和1999年分离、保存的Ｈｐ菌株各 5 0株 ,均接种于含 7%马血的Ｓｋｉｒｒｏｗ培养基中 ,微氧条件培养 3～ 5ｄ ,经生化、涂片鉴定为典型的Ｈｐ。2 .药敏试验 :应用Ｅ ｔｅｓｔ(ＡＢＢｉｏｄｉｓｋ ,Ｓｏｌｗａ,Ｓｗｅｄｅｎ)测定Ｈｐ…     

幽门螺杆菌体外诱导耐药试验和耐药率监测

目的 抗生素耐药越来越被公认为是根除幽门螺杆菌（Hp)治疗失败的主要原因。比较根除Hp常用抗生素耐药性发生倾向和监测耐药率。方法 选用7株敏感菌株（其中2株为标准菌株）进行阿莫西林，四环素，呋喃唑酮，甲硝唑和克拉霉素5种抗生素的体外诱导耐药试验。随机选取2000-2001年间保存的165株菌株，用琼脂稀释法测定最低抑菌浓度（MIC），对上述5种抗生素进行耐药监测。结果 体外诱导试验显示，7株Hp中5株诱导出甲硝唑耐药，且可诱导倍数最高。5株诱导出四环素耐药。虽未诱导出克拉霉素耐药，但有1株可诱导倍数较高。未诱导出阿莫西林或呋喃唑酮耐药，呋喃唑酮可诱导倍数最低。耐药监测甲硝唑耐药率为49.7%(82/165)，克拉霉素为7.3%(12/165)，阿莫西林为1.2%(2/165)，四环素为2.4%(4/165)，呋喃唑酮为1.2%(2/165)。结论 Hp对甲硝唑很容易产生耐药，对克拉霉素可产生耐药，对呋喃唑酮和阿莫西林不易产生耐药。除四环素外，Hp对其他4种抗生素发生耐药的难易程度与实际监测的耐药率高低相关，这有助于预测感染Hp后抗生素耐药率变迁的倾向。     

幽门螺杆菌耐药机制研究近况

随着幽门螺杆菌(Hp)根除治疗中抗生素的广泛应用，Hp的耐药问题日益突出。目前用于治疗Hp的抗生素主要有甲硝唑、替硝唑、大环内酯类(克拉霉素、阿奇霉素等)、阿莫西林、呋喃唑酮和喹诺酮类等。大多数Hp菌株对抗生素的耐药由突变引起。本文就幽门螺杆菌耐药机制的研究近况作一简要综述。     

幽门螺杆菌耐药分子机制研究进展

幽门螺杆菌(Helicobactef pylon,H pvlori)是慢性活动性胃炎的病原菌,是慢性胃炎和消化性溃疡的主要病因,与人体胃、十二指肠的疾病密切相关,并诱发胃癌的发生.随着抗生素药物的广泛使用,H pylori耐药株也日异增多,给临床H pylori的治疗带来巨大的困难.本文对H pylori的耐药现状与趋势进行分析,系统地综述了大环内酯类药物、硝基咪唑类药物、四环素类、β-内酰胺类物药物、喹诺酮类药物对H pylori的耐药情况.探讨对于每种药物的耐药机制及耐药类型检测的不同手段,为与H pylori导致的相关疾病的临床诊断、治疗提供可靠的依据,积累临床资料.     

Recent trends in the antibiotic resistance of Helicobacter pylori in patient with dyspepsia

The aim of this study was to determine the resistance status and to identify the point mutations conferring resistance to clarithromycin and fluoroquinolones among dyspeptic patients in Manisa, Turkey.The study included a sample of 140 patients with an indication for upper gastrointestinal endoscopy randomly selected from 2100 dyspeptic patients attending to the Gastroenterology and Endoscopy Unit at Manisa Celal Bayar University Hafsa Sultan Hospital between April 2016 and May 2018. A commercially available GenoType Helico DR test was used to detect the presence of Helicobacter pylori and mutations associated with resistance to clarithromycin and fluoroquinolones in biopsy specimens.In total, 116 (82.9%) of 140 biopsies obtained from the same number of dyspeptic patients were positive for H pylori and 82 (approximately 71%) of them harbored resistance mutations in 23SrRNA and/or gyrA. Resistance to clarithromycin, levofloxacin, or both were detected in 43.1% (50/116), 27.6% (32/116), and 16/116 (13.8%) of tested biopsies, respectively. The most common mutation conferring resistance to clarithromycin was A2147G (96%, 48/50). Resistance to fluoroquinolones was frequently due to mutation in codon 91 and the most common mutation detected was D91G (34.4%). Heteroresistance patterns were observed in 48.0% (24/50) of clarithromycin-resistant samples and 28.1% (9/32) of levofloxacin-resistant samples.The resistance rates and detected mutations in this study are in line with the country data. However, to achieve better H pylori eradication and to prevent the spread of multidrug-resistant strains in Turkey, the molecular-based susceptibility tests should be considered routinely. Further studies are needed to determine the various mutations among resistant strains.     

幽门螺杆菌临床分离株耐药特性分析及嗜酸乳杆菌对耐药幽门螺杆菌的抑制作用

目的 对84株临床分离幽门螺杆菌 (Helicobacter pylori,Hp)菌株进行耐药特性分析,并同时观察抗Hp嗜酸乳杆菌(Lactobacillus acidophilus,La)4和La6对不同抗生素耐药Hp的抑制效应.方法 从84例不同胃病(慢性胃炎25例,胃溃疡24例,十二指肠溃疡19例,胃癌16例)患者胃黏膜中分离培养Hp菌株,采用E-test法测定甲硝唑、克拉霉素和阿莫西林3种常用抗生素对临床Hp菌株的最小抑菌浓度(MIC值),了解临床Hp菌株对3种抗生素的耐药状况.以标准La作对照,将抗Hp La4和La6上清液加入含不同Hp菌株培养板的孔中,固体培养72 h,记录抑菌环;抗Hp La菌液加入含不同Hp 菌株的培养液中,液体培养,于不同时间点(4、8、12、24和48 h)分别取培养液,计算菌落形成单位和测定尿素酶活性.结果 84株临床分离Hp菌株中对甲硝唑、克拉霉素和阿莫西林的耐药率分别为67.9%、17.9%和1.2%.其中11株为混合耐药,包括 10株甲硝唑和克拉霉素混合耐药和1株甲硝唑和阿莫西林混合耐药.在固体培养条件下抗Hp La4和La6上清液对抗生素耐药和非耐药Hp菌株均产生明显的抑菌效应.液体培养条件下抗Hp La4和La6菌液能抑制抗生素耐药和非耐药Hp菌株的增殖,其拮抗Hp的作用明显强于标准La菌株(P<0.01).抗Hp La4和La6在混合培养4 h就能抑制抗生素耐药Hp菌株尿素酶活性,随着培养时间的延长Hp尿素酶活性逐渐降低,其抑制作用明显强于标准La组(P＜0.05).结论 84株临床分离Hp菌株中甲硝唑耐药株为常见,其次为克拉霉素耐药和甲硝唑克拉霉素混合耐药株.抗Hp La4和La6在体外对抗生素耐药和非耐药Hp菌株均具有明显的抑制作用.

Abstract：

Objective To analyze the drug resistant characteristics of 84 clinical isolated Helicobacter pylori (Hp) strains, and to observe the inhibitory effects of anti-Hp Lactobacillus acidophilus (La)4 and La6 on different antibiotic-resistant Hp strains. Methods Hp strains were isolated and cultured from gastric mucosa of 84 different gastropathy patients (20 patients with chronic gastritis, 24 with gastric ulcer, 19 with duodenal ulcer and 16 with gastric cancer). The minimum inhibitory concentration (MIC) of metronidazole, clarithromycin and amoxicillin were tested by E-test in order to determine the resistance of these three antibiotics in clinical isolated Hp strains. With standard La as control, the supernatant of anti-Hp La4 and La6 was added into Hp strains culture wells. Hp strains were cultured in solid media for 72 hours, and then inhibition ring were recorded. Anti-Hp Lactobacillus acidophilus liquid was also added to culture medium of different Hp strains, which were in liquid culture, culture medium were taken at different time points (4,8,12,24,48 hrs) to calculate bacteria colony number and test urease activity. Results In 84 clinical isolated Hp strains, the resistant rates of metronidazole, clarithromycin and amoxicillin resistance rates were 67.9%, 17.9% and 1.2% respectively. Of those 11 strains were mixed drug resistance, which included 10 strains of metronidazole and clarithromycin mixed drug resistance, and one of metronidazole and amoxicillin mixed drug resistance. In solid culture conditions, supernatant of anti-Hp Lactobacillus acidophilus La4 and La6 had obvious inhibitory effect on antibiotic-resistant and non-resistant Hp strains. In liquid culture conditions, anti-Hp Lactobacillu acidophilus La4 and La6 bacterium liquid could inhibit the proliferation of antibiotic-resistant and non-resistant Hp strains, the antagonistic role was significantly stronger than the standard Lactobacillus acidophilus strains (P<0.05). The urease activity of antibiotic-resistant Hp strains was inhibited since mixed cultured with anti-Hp Lactobacillu acidophilus La4 and La6 for 4 hours, the urease activity gradually decreased as culture time extended, and the inhibitory role was significantly stronger than the standard Lactobacillus acidophilus strains (P<0.05). Conclusions In 84 Hp strains, most were metronidazole resistant strains, followed by clarithromycin resistant strains, metronidazole and clarithromycin mixed resistance strains. In vitro, anti-Hp Lactobacillu acidophilus La4 and La6 had obvious inhibitory effects on antibiotic-resistant and non-resistant Hp strains.     

幽门螺杆菌临床分离株耐药性研究

目的　分析石家庄地区幽门螺杆菌临床分离株对多种抗生素的药物敏感性情况。方法　 2 0 0 2 - 11～2 0 0 3- 12河北医科大学第三医院消化科采用滤纸片琼脂扩散法检测 5 5株临床分离株。对甲硝唑、奥硝唑、阿奇霉素、克拉霉素 ,阿莫西林、四环素、呋喃唑酮的药物敏感性。结果　甲硝唑耐药率 92 73% ,奥硝唑耐药率85 4 5 % ,阿奇霉素耐药率 4 5 4 5 % ,克拉霉素耐药率 9 0 9% ,阿莫西林、四环素、呋喃唑酮耐药率均为 0。结论　石家庄地区幽门螺杆菌对甲硝唑、奥硝唑、阿奇霉素耐药率较高 ,同时存在克拉霉素耐药 ,未发现阿莫西林、四环素、呋喃唑酮耐药株。     

对甲硝唑耐药幽门螺杆菌中rdxA基因的表达

目的 探讨对甲硝唑耐药幽门螺杆菌(Hp)株中rdxA基因表达的差异。方法 随机收集51例快速尿素酶试验阳性患者的胃窦部黏膜,体外微需氧培养。甲硝唑耐药率检测分别用E试验和临界点药敏法。选取对甲硝唑高度耐药菌株(MIC值>256 mg/L),在含16 mr/L甲硝唑及不含甲硝唑培养基中分组培养,半定量RT-PCR法检测rdxA基因的表达,用galE基因作外参照。结果 共分离出Hp临床分离菌47株。E试验法甲硝唑耐药率为34％(16/47),临界点药敏法为32％(15/47),其中15株(包括5株高度耐药菌株)2种方法均耐药。5株高度耐药菌中rdxA基因在甲硝唑存在的情况下表达量减少,而参照galE基因表达均不变。结论rdxA基因的表达减少在Hp对甲硝唑高度耐药形成中起了一定的作用。     

Clarithromycin resistance in Helicobacter pylori and its clinical relevance

SubjectheadingsHelicobacterpylon;Helicobacterinfections;clarithromycinresistanceINTRODUCTIONThemacrolideclarithromycinhasemergedasthemostimportantantibioticincombinedtherapyforeradicationofH.Pyloninfection[1'2).HOwever,concernsaboutincreasingclarithromycinresistanceinH.PylonanditsimpactontheefficacyoferadicationtherapyhavebeenraisedsinceitswidespreadacceptanceinH.Pylontherapy""'.Here,wesoughttoreviewthegeographicprevalenceofclarithromycinresistanceinH.Pylonanditsmolecularmechanisms,an…     

儿童幽门螺杆菌的抗生素耐药性及其与细胞毒素相关蛋白的关系

目的体外观察温州地区儿童幽门螺杆菌（Hp）菌株对临床常用8种抗生素的耐药性及其与细胞毒素相关蛋白（CagA）的关系。方法对分离的的41株Hp行药物敏感试验，并用免疫印迹法检测患儿血清Cag,a抗体。结果CagA阳性Hp菌株中替硝唑、克拉霉素、呋喃唑酮、羟氨苄青霉素、阿齐霉素、庆大霉素、诺氟沙星和头孢哌酮耐药菌株分别为100．0％、55．6％、48．3％、38．7％、32．3％、32．3％、25．8％和0．0％，而在Ca舭阴性Hp菌株中耐药菌株分别为90．0％、50．0％、40．0％、50．0％、30．0％、20.0％、0．0％和0．0％，两组差异无统计学意义。结论该地区儿童耐药Hp菌株多见，其耐药性与CagA无明显相关。     

幽门螺杆菌对克拉霉素耐药的分子机制研究

目的：研究幽门螺杆菌（Hp)对克拉霉素耐的分子机制。方法：用E－test进行克拉霉素药敏试验,选取治疗前敏感、治疗后耐药的配对菌株及原发耐药Hp菌株进行研究;应用随机扩增多态性DNA（RAPD）分析,确定治疗前后菌株的同一性;用PCR－限制性片段长度多态性（RFLP）分析探讨克拉霉素耐药机制。结果9株克拉霉素耐药菌23SrRNA基因功能区V PCR扩增片段,8株被BsaI酶切,9株均未被BbsI酶切,提示8株在2144位点有A→G突变。结论上海地区大多数克拉霉素耐药Hp菌株存在23SrRNA基因功能区V2144位点A→G突变。