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2017 IHPWG共识:爱尔兰成人幽门螺杆菌感染的诊断和治疗

时间:2024-09-03

李 健 译,段芳龄 审

1.郑州大学人民医院 河南省人民医院消化内科,河南 郑州 450003; 2.郑州大学第二附属医院 郑州大学消化疾病研究所



2017 IHPWG共识:爱尔兰成人幽门螺杆菌感染的诊断和治疗

李 健1译,段芳龄2审

1.郑州大学人民医院 河南省人民医院消化内科,河南 郑州 450003; 2.郑州大学第二附属医院 郑州大学消化疾病研究所

目前,爱尔兰人群幽门螺杆菌(Helicobacter pylori,H.pylori)根除率不断下降,其耐药菌发生率逐年增加,这一趋势引起研究者对当前H.pylori管理策略的质疑。成立爱尔兰幽门螺杆菌工作组(Irish Helicobacter pylori Working Group,IHPWG)并评估、修订和调整现有推荐建议。邀请胃肠病学和微生物学领域专家参加IHPWG。采用PICO方法提出与诊断、一线和补救治疗相关的问题,并进行文献检索。然后,使用“证据推荐分级的评估、制订与评价”方法对有效证据的质量进行评估,并对推荐结果进行分级。IHPWG关键陈述(Statements,S)如下,S8:不再推荐持续7 d的标准三联疗法(推荐强度:强;证据质量:中等)。S9:推荐14 d克拉霉素三联疗法与大剂量质子泵抑制剂联用作为一线疗法。如果可以,14 d铋剂四联疗法可作为替代疗法(推荐强度:强;证据质量:中等)。S12:二线疗法基于一线治疗而非相同治疗。方案a:14 d左氧氟沙星为基础治疗和大剂量质子泵抑制剂联合;b:14 d克拉霉素三联疗法和大剂量质子泵抑制剂联合;c:14 d铋剂四联疗法(推荐强度:强;证据质量:中等)。S13:两种治疗方案失败后应进行H.pylori培养和药敏试验(推荐强度:弱;证据质量:低或极低)。本文推荐意见旨在为爱尔兰成人H.pylori感染管理提供最相关、最佳的实践指南。

阿莫西林;抗生素耐药性;铋;克拉霉素;幽门螺杆菌;左氧氟沙星;甲硝唑;质子泵抑制剂;四联疗法;三联疗法

幽门螺杆菌(Helicobacter pylori,H.pylori)感染参与慢性胃炎、消化性溃疡、胃癌和胃黏膜相关淋巴组织(MALT)淋巴瘤的发生、发展。尽管全球许多地方的H.pylori感染率在逐渐下降,但H.pylori感染管理已变得具有挑战性[1]。研究[2]显示,H.pylori治疗应旨在根除接受治疗患者的90%以上。

导致H.pylori根除率下降的主要原因包括抗生素耐药和患者依从性差两方面。欧洲幽门螺杆菌研究小组和共识小组近期发布了关于欧洲幽门螺杆菌管理的马斯特里赫特Ⅴ/佛罗伦萨共识报告[3]。由于不同国家H.pylori感染率和抗生素耐药率不同[4-5],马斯特里赫特Ⅴ/佛罗伦萨共识报告中主要治疗推荐是根据当地抗生素耐药流行情况制订的。

因此,为更好管理既定人群中的H.pylori感染,不同国家制定了各自的H.pylori共识意见[6-10]。本共识旨在成立国家爱尔兰幽门螺杆菌工作组(IHPWG),在该领域国际专家协助下审查H.pylori感染管理相关文献,并提供最适合爱尔兰成人H.pylori感染管理的更新意见。

1 方法

1.1 成立爱尔兰幽门螺杆菌工作组(IHPWG) 邀请爱尔兰和欧洲胃肠病学和微生物学领域专家参加IHPWG。根据专业将专家成员分配到3个亚组:(a)有症状成人H.pylori诊断组;(b)一线治疗组;(c)补救治疗组,以解决每个领域的主要问题。

1.2 数据审查和证据评估 首先,每个亚组根据对象、干预措施、对照组和结果(PICO)四个问题提出与本领域相关的主要医疗保健问题。然后,根据PICO提出的相关问题,每个亚组审查当地有效数据,检索已发表文献和目前欧洲、国际指南。

2016年6月22日在爱尔兰都柏林举办的一次会议上,专家们公布了各自领域的相关数据,并对这些数据深入讨论并制订了基于每个PICO相关问题的推荐意见[11]。使用“证据推荐分级的评估、制订与评价”方法[12]对有效证据的质量进行评估,并对推荐结果进行分级。

每项意见的推荐强度和支持证据的强度也使用“证据推荐分级的评估、制订与评价”方法[12]进行评估。整个研究过程中,将每个基于PICO提出的问题作为一个证据进行质量评估。临床实践中与建议实施相关的方面也需考虑在内。每项意见需要得到90%以上专家支持才能达成共识。推荐意见结果如下。

2 推荐意见

2.1 有症状成人H.pylori感染的诊断 陈述1:有上消化道相关症状患者均应接受H.pylori检测

推荐强度:强;证据质量:高。

由于H.pylori感染与消化性溃疡、胃癌和MALT淋巴瘤的发生相关,因此,凡有症状患者建议实施H.pylori检测和治疗。研究[13-14]发现,H.pylori感染根除治疗可使多数与NSAID类使用无关的消化性溃疡患者得到长期治愈。而且,根除H.pylori可减缓萎缩性胃炎的进展、降低无胃癌癌前病变的H.pylori感染个体发生癌症的风险[15-22]。此外,H.pylori感染根除治疗可使局部胃MALT淋巴瘤得到逆转[23-26]。

检测-治疗策略即对有消化不良症状患者进行无创性H.pylori检测,然后对检测到H.pylori感染患者进行治疗。目前,欧洲指南推荐H.pylori患病率≥20%的国家及胃癌风险较低患者实施该项策略。其中胃癌低风险是指年龄达到45岁且无报警症状,如体质量减轻、吞咽困难、显性消化道出血、腹部肿块、缺铁性贫血等[3,27]。

H.pylori无创检测包括尿素呼气试验(UBT)、粪便抗原检测和血清学抗体检测。来自爱尔兰医疗机构的最新数据表明,在接受UBT检测的患者中,H.pylori感染率为36%~37%[28-29],内镜检查为19%~36%[30][还包括Adelaide和Meath医院合并国立儿童医院(AMNCH)及Whitfield诊所的未公布数据]。

建议胃癌高风险患者行内镜-治疗策略。其中,胃癌高风险是指年龄≥45岁,或有报警症状和胃癌家族史。在低H.pylori感染率(<20%)人群中,伴有消化不良患者也应进行内镜-治疗策略[3]。内镜下H.pylori感染的检测方法包括通过组织活检进行快速尿素酶试验、组织病理学和/或H.pylori培养。

陈述2:推荐尿素呼气试验作为H.pylori的一项无创检查

推荐强度:强;证据质量:高。

UBT包括13C或14C标记的尿素呼气试验,原理是指利用H.pylori尿素酶把C标记的尿素分解成标记的CO2,其可在呼吸样本中检测到[31]。建议测试前禁食至少4 h[32]。UBT具有操作简单,灵敏度(88%~96%)和特异度(93%~100%)均高的特点[33-34],对有条件地区推荐该项无创检查。

粪便抗原试验是指利用酶联免疫吸附试验测定粪便中H.pylori抗原,其准确性高。Gisbert等[35]一项Meta分析显示,单克隆粪便抗原酶联免疫吸附测定法测定H.pylori抗原的灵敏度和特异度分别为95%和97%。

AMNCH当地数据[28]显示,粪便抗原试验(Premier Platinum HpSA PLUS test方法,Meridian Bioscience,美国)检测的灵敏度为62%,特异度为99%,与UBT相比较差。HpSA试验灵敏度可能受粪便样本的储存和转运过程的影响。但是设施资源有限,HpSA试验引进得到当地验证和爱尔兰国家鉴定委员会的认可,且要求在检测过程中尽量减少样品存储和运输对该试验准确性的影响。

血清学试验检测H.pylori的IgG抗体,其试剂盒准确性波动明显(灵敏度79%~85%和特异度79%~82%)[36-37]。因此,血清学检测在使用前应在本地进行验证。

陈述3:侵入性H.pylori检测推荐使用胃窦和胃体组织学和快速尿素酶试验的结合

推荐强度:强;证据质量:高

胃镜检查时,H.pylori感染可通过组织活检病理检查、快速尿素酶检测/CLO检测和/或培养得到确诊。尽管活检标本的组织学检查要求技术人员经过严格培训,但该方法可准确检测到细菌,评估炎症程度和诊断慢性活动性胃炎、肠化生或恶性肿瘤。

H.pylori在胃内呈片状分布,组织活检应包括胃窦(幽门前2~3 cm)和胃体[38]。多数情况下组织切片通过HE组化或Giemsa染色可诊断H.pylori感染。对于某些组织化学检测未能诊断H.pylori感染的慢性(活动性)胃炎患者,推荐H.pylori免疫组化染色。组织学正常时,不需要免疫组化染色[3]。

快速尿素酶试验简单易行且诊断迅速,对诊断明确的患者可立即行H.pylori治疗,其灵敏度和特异度分别为78%~97%和94%~100%[39-41]。AMNCH数据显示,与组织学相比,快速尿素酶检测(Tri-Med Distributors Pty Ltd,美国)的灵敏度和特异度分别为80%和90%[42]。

来自布兰察斯镇康诺利医院的数据显示,快速尿素酶试验(Kimberly Clark,美国)的灵敏度和特异度分别为88%和97%,快速检测的灵敏度和特异度分别为78%和97%[43]。尽管快速检测更便宜迅速,但其灵敏度低于CLO试验;仅使用快速检测而未同时进行胃组织病理学检测的H.pylori感染患者中,近1/4未被诊断出H.pylori感染。因此,不推荐行快速尿素酶检测,尤其是快速检测[43]。

组织样本进行H.pylori培养主要用于细菌药敏试验。尽管培养特异性高,但H.pylori生长缓慢且对营养液要求苛刻。因此,培养不但耗时,还需要对相关人员进行专业培训。研究报道,H.pylori培养检出阳性率为55%~93%[44-45]。

陈述4:应取胃体和胃窦活检标本用于快速尿素酶试验

推荐强度:强;证据质量:低或极低

H.pylori在胃内分布不均,呈片状分布,应对胃窦和胃体的活检标本进行快速尿素酶试验。国外和爱尔兰新的证据表明,与单次胃窦活检相比,同一检测试验中分别对胃窦和胃体进行组织活检[40]或联合检测[30,39,43]显著提高快速尿素酶检测的诊断准确性。此外,联合检测减少了测试时间,使诊断更快速[39]。

陈述5:如果需要进行H.pylori培养,应取胃体和胃窦处活检

推荐强度:强;证据质量:低或极低

在爱尔兰,H.pylori培养和药敏试验缺乏广泛实用性,因此,H.pylori培养仅在治疗失败后才被推荐应用(见推荐意见10和13)。与其他侵入性H.pylori诊断试验一样,应从胃窦和胃体进行组织活检,以提高H.pylori检测成功的可能性[46]。值得注意的是胃窦、胃体不同部位分离出来的H.pylori药物敏感性分布有差异[47]。因此,如仅从胃一个解剖部位取出单一样本,可能会遗漏耐药性H.pylori。

为了避免活检标本与空气接触和脱水,应将标本放在特殊传输容器(Portagerm pylori,德国)中运送,而且在胃镜检查之后尽快进行培养,理想时间在6 h内[48]。如果处理过程延迟,建议标本冷藏[46,48]。然后,标本接种在Columbia血琼脂平板(Columbia血琼脂;10%裂解马血)上,并在37 ℃、微需氧条件下连续孵育7~10 d[49](通常情况下,孵育3~5 d即可见到细菌菌落[48])。

将抗微生物制剂加入到生长培养基中以抑制污染细菌和/或真菌的过度生长[49-50]。培养结束后,使用Gram染色法和氧化酶、脲酶和过氧化氢酶检测证实H.pylori的存在[5]。目前的识别技术还包括基质辅助激光解析电离飞行时间质谱。H.pylori药敏试验的临床折点是从欧洲抗菌药敏试验委员会获得(http://www.eucast.org),并于2017年初更新。

陈述6:必须进行根除后检测,如果不需要胃镜检查,建议用尿素呼气试验进行根除后检测

推荐强度:强;证据质量:高

随着H.pylori根除率下降,症状不是判断根除成功的良好指标。患者需要进行H.pylori根除后检测,即患者完成H.pylori治疗后至少间隔4周再进行H.pylori根除检测。UBT被认为是证实H.pylori根除的最佳选择[34,51]。

可选择单克隆粪便抗原检测作为替代方案,但准确性欠佳[35,52],这可能受粪便标本的储存和送检过程的影响。由于抗体于H.pylori感染后可持续数月存在,不推荐血清学检测用于根除后的验证检测。如果需要内镜检查时,应从胃窦和胃体取活检,并进行快速尿素酶检测,该方法的敏感度和特异度分别为44%~88%和98%~100%[39,53]。

陈述7:质子泵抑制剂(PPI)显著降低H.pylori检测试验的准确性,因此,PPI应在检测前14 d停药

推荐强度:强;证据质量:低或极低

PPI提高胃内pH,从而导致细菌负荷降低,因此,在进行UBT、粪便抗原检测或内镜检查诊断前应停药2周[3,27,49,54]。

已有研究[54-57]证明,PPI可降低UBT、HpSA和内镜检测H.pylori的灵敏度和特异度,增加检测假阴性结果。虽然研究证明PPI停药7 d是足够的,但仍建议将14 d作为“安全”间隔[58]。尽管H2受体拮抗剂也可轻微降低H.pylori负荷,在诊断H.pylori时,它的使用并不影响检测结果[3,27]。抗生素能抑制H.pylori感染且降低检测敏感度,应在测试(UBT、HpSA和内镜检测H.pylori)前停用4周[3,27]。

2.2 一线疗法 陈述8:不再推荐连续7 d的标准三联疗法

推荐强度:强;证据质量:中等

近年来,多数国家7 d克拉霉素标准三联疗法的H.pylori根除率已经下降[6],其中西欧国家的根除率低至55%[59]。最近,爱尔兰一项研究[60]表明,克拉霉素三联疗法的根除率仅有57%。共识建议意向性分析(ITT)H.pylori根除率<80%的治疗方案不被接受[27],故7 d标准三联疗法不再被推荐。

陈述9:推荐14 d克拉霉素三联疗法与大剂量PPI联用。如果可以,14 d铋剂四联疗法可作为替代疗法

推荐强度:强;证据质量:中等

H.pylori根除治疗失败原因很多,如细菌高负荷、胃内低pH、黏膜免疫受损、抗生素耐药、患者依从性差,其中后两者是根除失败的主要原因[5,61-63]。马斯特里赫特共识指南[3]建议,当地克拉霉素耐药率>15%并无以往药敏试验,建议直接放弃含克拉霉素的三联疗法。

2010年一项报道[64]显示,爱尔兰的克拉霉素耐药率为9.3%。虽然AMNCH最近的调查[65-66]结果显示,克拉霉素耐药率明显增加,但工作组认为,缺乏关于克拉霉素耐药率的全国数据,故并未放弃应用克拉霉素治疗H.pylori。

一些方案已经显示出可提高标准三联疗法H.pylori根除率。众多荟萃分析和新近观察性研究[67-73]已经表明,增加一线三联疗法疗程可提高根除率,14 d疗程显示根除最为有效。

由于PPIs抑制胃酸分泌且抗生素在低酸环境下更稳定,因此,PPIs可增加H.pylori根除效果。研究[74-75]显示,增加PPIs给药次数(从1次/d到2次/d)可提高H.pylori根除率。此外,与第一代PPIs(奥美拉唑、兰索拉唑、泮托拉唑)相比,新一代PPIs具有更好的H.pylori根除率。已有报道[75-76]显示,口服埃索美拉唑40 mg,2次/d,显示出最显著的临床益处。

欧洲指南[3]推荐铋剂四联疗法可作为克拉霉素三联疗法的有效替代方案。14 d铋剂四联疗法ITT意向分析H.pylori根除率>95%[77]。铋剂四联疗法在克拉霉素和甲硝唑双重耐药地区仍有效[3],而非铋剂四联疗法(序贯疗法、伴同疗法或混合疗法)显示在这些地区受到影响[78]。

然而,铋剂四联疗法在爱尔兰并未广泛应用,故不能作为多数人的选择。De-Noltab(枸橼酸铋钾120 mg;Astellas制药公司,Leiden,荷兰)在英国获得许可和销售,但在爱尔兰被认为是豁免药用产品而未获得许可。

因此,该药由药剂师从专门批发商采购。德诺被列入爱尔兰健康服务执委会的豁免药用产品目录,该目录可根据综合医疗服务计划或药品支付方案为患者报销。Pylera(140 mg枸橼酸铋钾,125 mg甲硝唑,125 mg盐酸四环素,Aptalis制药公司,Houdan,法国)在爱尔兰获得许可但未上市,药剂师很难采购到本药。

工作组认为在爱尔兰不推荐序贯疗法(PPI+阿莫西林5 d,PPI+克拉霉素+甲硝唑5 d),因其疗效并不优于14 d克拉霉素三联疗法[79-80]。最新一项爱尔兰研究报道,序贯疗法H.pylori根除率为69%[60]。一线治疗方案和选择见表1、图1。

陈述10:目前,不推荐在一线治疗前进行培养和药敏试验

推荐强度:弱;证据质量:低或极低

虽然当地[65]和已发表的证据[81-84]在抗菌药敏试验基础上为制定一线疗法提供了依据,但在爱尔兰大多数医院中H.pylori培养和药敏试验并非常规开展。因此,工作组认为,不推荐在一线治疗之前进行抗菌药敏试验检测,但应多鼓励当地爱尔兰医疗机构进行该项检测。

陈述11:可通过分子生物学方法检测克拉霉素耐药性

推荐强度:强;证据质量:中等

H.pylori的分子学检测可作为H.pylori培养的一种具有吸引力的替代方法,可直接从活检标本中进行H.pylori和抗生素耐药的分子基因鉴定,使其进行快速分析和当天诊断成为可能。编码23S核糖体亚基的H.pylorirrl基因单点突变导致克拉霉素耐药,其中三个主要突变位点为:A2146C、A2146G和A2147G(Genbank accession number NC_000915)[85-86]。

通过PCR为基础的分子学方法测得这些突变位点。可用于检测克拉霉素耐药的分子检测试剂盒包括MutaREAL试剂盒(Immunodiagnostik,Benshiem,德国)、ClariRes实时PCR检测(Ingentix,Vienna,奥地利)、the Seeplex ClaR-HP ACE检测系统(Seegene,Eschborn,德国)、GenoTypeHelicoDR测定(Hain Lifescience,Nehren,德国)[5,86]。越来越多的证据显示,分子学检测到的突变存在与培养为基础的抗生素耐药高度吻合[5],当地数据显示有85%的相关性[66]。分子学检测方法被认为是监控全国H.pylori克拉霉素耐药流行的有效方法,也可作为制定个体化治疗的一种手段。

2.3H.pylori补救疗法 陈述12:二线疗法以一线治疗为基础,并非相同治疗。方案a:14 d左氧氟沙星为基础的三联治疗联合大剂量PPI;b:14 d克拉霉素三联疗法联合大剂量PPI;c:14 d铋剂四联疗法

推荐强度:强;证据质量:中等

一线治疗结束后必须进行H.pylori检测。克拉霉素三联治疗根除细菌失败情况下,应假定克拉霉素耐药[3],避免重复给予相同治疗方案。除非本地区数据显示左氧氟沙星耐药,否则左氧氟沙星三联疗法可作为有效的二线治疗方案[87-89]。2008年-2009年检测到爱尔兰左氧氟沙星耐药率为11.7%[90],至今其耐药率未增加[91]。

研究[87-88]表明,同一线治疗类似,延长左氧氟沙星三联疗法持续时间可提高H.pylori根除成功率。最近一项荟萃分析[92]认为,左氧氟沙星三联疗法或含铋剂四联疗法可作为克拉霉素三联疗法治疗失败后的方案选择。文献[93-94]显示,对前次治疗方案无效(包括对甲硝唑耐药)的患者给予铋剂治疗显示高H.pylori根除率。二线治疗方案见表1、图1。

陈述13:两种治疗失败后应进行培养和药敏试验

推荐强度:弱;证据质量:低或极低

如果条件允许,应在两次治疗失败后进行培养和药敏试验检测(见图1),以制定治疗个体化治疗方案并增加根除成功的可能性。

相比于标准疗法,基于药敏试验而制定的一线疗法可提高H.pylori的根除率[81-84],但是针对二次和后续疗法的相关研究较少。尽管如此,目前所进行的有限研究数据[44,95]还是令人鼓舞的。培养和药敏试验应在完成任何治疗后至少4周进行。

陈述14:利福平应用于三线或后续治疗

推荐强度:弱;证据质量:低或极低

原发性H.pylori相关性利福平耐药性低[96],因此,利福平对甲硝唑和克拉霉素双重耐药的患者是有效的[97]。据报道[98],基于利福平的治疗是多次根除失败后的有效补救疗法。但是,应用利福平引起的不良反应需引起人们的关注。在应用利福平行H.pylori根除治疗中,骨髓抑制虽发生率低,但最严重。

Meta分析[96]显示,大多数患者的白细胞减少可在数天内恢复。由于利福平的普遍应用可导致继发结核分枝杆菌耐药菌的产生,因此,我们建议利福平作为三线及后续的H.pylori根除治疗。利福平三联疗法见表1。

陈述15:序贯疗法不能作为补救疗法

推荐强度:强;证据质量:中等

图1 治疗决策示意图Fig 1 Treatment decision schematic

序贯疗法作为H.pylori感染补救治疗的相关数据有限[95,99]。但是,当地数据[60]显示,作为一线治疗的序贯疗法疗效不太理想。此外,研究[80,100]还表明,序贯治疗的疗效受克拉霉素耐药及和甲硝唑双重耐药的影响。

克拉霉素三联疗法治疗失败,应考虑克拉霉素耐药。同样,作为补救治疗的伴随和混合治疗的数据也是有限的,至今尚未在爱尔兰进行调查。因此,序贯、伴随或混合治疗不能被推荐用于补救治疗。

表1 推荐治疗处方

Tab 1 Recommended treatment descriptions

治疗方案处方持续时间(d)克拉霉素三联疗法PPIabid.14500mg克拉霉素bid.1g阿莫西林bid.铋剂四联疗法PPIabid.14120mg枸橼酸铋钾qid.400mg甲硝唑tid.500mg四环素qid.左氧氟沙星三联疗法PPIabid.14250mg左氧氟沙星bid.1g阿莫西林bid.利福平三联疗法PPIabid.14150mg利福平bid.1g阿莫西林bid.

注:a:推荐新一代PPI:埃索美拉唑(40 mg bid)和雷贝拉唑(40 mg bid);bid:2次/d;tid:3次/d;qid:4次/d。

3 结论

本文所提供建议旨在为爱尔兰成年患者的H.pylori感染管理提供最相关、最佳的实践指南,以期提高H.pylori的根除率和预防与H.pylori相关疾病的发生、发展。这些建议需要在实施之后再进一步评估。在爱尔兰,H.pylori感染率相对较低的地区,应该实施非侵入性H.pylori检测诊断的验证。

由于抗生素耐药不断发生,应用H.pylori培养和分子学方法监测抗生素耐药性是未来继续努力的方向,这个方向应基于国家层面建立集中式数据采集以精准监测抗生素耐药。

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The Irish Helicobacter pylori Working Group consensus for the diagnosis and treatment of Helicobacter pylori infection in adult patients in Ireland

LI Jian1, DUAN Fangling2

1.Department of Gastroenterology, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou 450003; 2.Institute of Digestive Diseases, Zhengzhou University, the Second Affiliated Hospital of Zhengzhou University, China

Irish eradication rates for Helicobacter pylori (H.pylori) are decreasing and there is an increase in the prevalence of antibiotic-resistant bacteria. These trends call into question current management strategies. To establish an Irish Helicobacter pylori Working Group (IHPWG) to assess, revise and tailor current available recommendations.Experts in the areas of gastroenterology and microbiology were invited to join the IHPWG. Questions of relevance to diagnosis, first-line and rescue therapy were developed using the PICO system. A literature search was performed. The ‘Grading of Recommendations Assessment, Development and Evaluation’ approach was then used to rate the quality of available evidence and grade the resulting recommendations.Key resultant IHPWG statements (S), the strength of recommendation and quality of evidence include S8: standard triple therapy for 7 days’ duration can no longer be recommended (strong and moderate). S9: 14 days of clarithromycin-based triple therapy with a high-dose proton pump inhibitor (PPI) is recommended as first-line therapy. Bismuth quadruple therapy for 14 days is an alternative if available (strong and moderate). S12: second-line therapy depends on the first-line treatment and should not be the same treatment. The options are (a) 14 days of levofloxacin-based therapy with high-dose PPI, (b) 14 days of clarithromycin-based triple therapy with high-dose PPI or (c) bismuth quadruple therapy for 14 days (strong and moderate). S13: culture and antimicrobial susceptibility testing should be performed following two treatment failures (weak and low/very low).These recommendations are intended to provide the most relevant current best-practice guidelines for the management ofH.pyloriinfection in adults in Ireland.

Amoxicillin; Antibiotic resistance; Bismuth; Clarithromycin; Helicobacter pylori; Levofloxacin; Metronidazole; Proton pump inhibitor; Quadruple therapy; Triple therapy

李健,主任医师,硕士生导师,研究方向:胃肠道疾病的基础与临床。E-mail:jiuwei@163.com

10.3969/j.issn.1006-5709.2017.06.003

R378

A

1006-5709(2017)06-0625-08

2017-05-09

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