Evolving therapy for Helicobacter pylori infection

Helicobacter pylori infection is a widespread disease causing significant morbidity and mortality, with relevant economic impact. A 7-day triple regimen (proton pump inhibitor together with two antibiotics) is currently suggested as first-line treatment, but the success rate following such a therapy is decreasing. Therefore, new drugs or novel therapeutic approaches are needed. Patents of new antibiotics have been claimed, such as both erythromycin and rifamycin derivatives, and new polycyclic compounds, showing a very powerful antibacterial activity in vitro. Patents of either H. pylori urease inhibitors or new proton pump inhibitors are also of great interest. Several attempts have been made to create vaccines for H. pylori infection, with interesting results in animal models. Experimentation in humans is ongoing.     

艾司奥美拉唑为基础的三联疗法根除幽门螺杆菌的荟萃分析

目的：比较艾司奥美拉唑为基础的和其他质子泵抑制剂(PPI)为基础的三联疗法治疗幽门螺杆菌(Hp)的根除率。方法：通过MEDLINE(1966年1月-2005年6月)和EMBASE(1988年1月-2005年8月)数据库检索公开发表的研究报告,复习检出文章的参考文献,确定有上述2种三联疗法根除Hp,且只有PPI不同的临床随机对照研究进行荟萃分析。按标准提取来源地区、样本数量、研究时间、治疗方案及Hp根除率情况。结果：通过荟萃分析比较,艾司奥美拉唑+克拉霉素+阿莫西林或甲硝唑组成的三联方法,Hp的根除率为82．1％(按意图分析)和86．1％(按试验方案分析),5项质量较高的临床对照研究的Hp的根除率(按意图分析),艾司奥美拉唑为基础的三联疗法Hp的根除率为84．2％,奥美拉唑为82．0％,优势比(OR)为1．17(95％的可信区间：0．88～1．56)。结论：以艾司奥美拉唑为基础的的三联疗法能有效根除Hp,与以奥美拉唑为基础的三联疗法无差异。     

两种疗法根治幽门螺杆菌的疗效比较

目的:评价益生菌联用质子泵抑制剂治疗由幽门螺杆菌感染所致消化性溃疡的疗效。方法:选择临床确诊的由幽门螺杆菌感染所致的消化性溃疡患者96例,分A、B组。A组50例,给予双歧四联活菌剂+奥美拉唑;B组46例,给予克拉霉素+甲硝唑+奥美拉唑。结果:A组幽门螺杆菌根除的有效率和根除率分别为84.0%,88.0%,B组分别为91.3%,89.1%,2组比较差异无显著性(P>0.05);不良反应发生率:A组为4.0%,B组为32.6%,2组有显著差异(P<0.05)。结论:益生菌联合质子泵抑制剂治疗Hp感染安全、有效,值得推广。     

Eradication of Helicobacter pylori: current perspectives

Helicobacter pylori appears to be a necessary cofactor for the majority of non-drug-associated duodenal and gastric ulcers. H. pylori infection is a chronic and transmissible infectious disease whose eradication has proved difficult. The last decade has seen > 1000 clinical trials using different eradication regimens. Many of these trials had severe limitations, some of which will be discussed here. The current review also focuses on the regimens that were used in the past, the present regimens and possibilities for the future. Also highlighted are some other aspects of H. pylori management, such as eradication failures and drug resistance.     

Alternative and rescue treatment regimens for Helicobacter pylori eradication

Eradication therapy has been incorporated into clinical practice. The regimens currently recommended for first-line treatment include a 2-week bismuth-based triple therapy (mainly in developing countries), a 1 – 2 week proton pump inhibitor (PPI)-based triple therapy and a 1-week ranitidine bismuth citrate (RBC)-based triple therapy. However, these regimens fail to eradicate Helicobacter pylori in up to 20% of patients due to poor compliance, inadequate treatment duration, smoking, old age and bacterial resistance to nitroimidazoles and/or macrolides in particular. Therefore, alternative regimens that avoid nitroimidazoles and/or macrolides or overcome bacterial resistance to these drugs, improve compliance, minimise side effects and/or reduce costs have been evaluated. One-week quadruple therapy, which adds a PPI or histamine receptor 2-blocker to bismuth-based triple therapy, usually achieves an eradication rate of 90% when used as an alternative first-line therapy but the efficacy decreases when used as a rescue therapy. Several new triple therapies that may be used as alternative and/or rescue therapies have been evaluated. Among these are furazolidone-based (furazolidone plus an antibiotic and a bismuth salt, a PPI or RBC), fluoroquinolone-based (levofloxacin or moxifloxacin plus an antibiotic and a PPI) and ecabet sodium-based (ecabet plus two antibiotics) triple therapies. Recently, rifabutin has been used in combination with a PPI and amoxycillin as a rescue therapy, with satisfactory eradication rates. In addition, a number of new antimicrobial agents are currently under investigation in in vitro studies but the clinical values of these agents needs to be confirmed.     

Multidrug resistance in Helicobacter pylori: current state and future directions

ABSTRACT

Introduction: Helicobacter pylori antibiotic resistance has increased worldwide and multidrug resistance (MDR), which seriously hampers eradication success of the frequent chronic infection, has often been reported.

Areas covered: H. pylori MDR rates are discussed, mostly from recent articles published since 2015. Present approaches and future directions to counteract the MDR are outlined.

Expert opinion: Alarming presence of triple, quadruple and, in some studies, quintuple and sextuple resistance was detected. Primary MDR rates ranged from <10% in most European countries to >40% in Peru. Post-treatment or overall MDR rates were >23–36% in about half of the studies. MDR prevalence has varied both among and within the countries. Factors linked to the MDR are national antibiotic consumption, antibiotic misuse, treatment failures and bacterial factors such as mutations, efflux pumps, and biofilms. Important directions to counteract the MDR increase can be optimization of present and new eradication regimens, wider use of bismuth-containing regimens, assessment of benefit of vonoprazan, new antibiotics such as newer fluoroquinolones and oxazolidinone analogues, adjuvants involving N-acetylcysteine and probiotics, anti-biofilm approaches using anti-biofilm peptides and rhamnolipid and development of vaccines and non-invasive tests for resistance detection. However, more efforts and studies are required. Strain susceptibility testing is increasingly important.     

综合性医院门诊抗高血压药的药物利用研究

目的了解抗高血压药的临床应用模式,并促进其合理用药。方法利用医院信息系统药房管理子系统,对2008年11月14日—11月18日某综合性医院门诊患者含抗高血压药的处方进行回顾性分析。合理性标准为药品说明书、国内外循证医学研究结果、药物代谢酶学和2007年欧洲高血压治疗指南。结果该院的抗高血压药治疗应用总体较为合理,较好地符合治疗指南。极少量处方在用法用量和合并用药方面的合理性值得商榷。结论临床医生和药师应遵循药物治疗指南,注意鉴别潜在的相互作用,做好患者用药教育和抗高血药药物治疗达标管理。应用药动学原理,可以有效指导临床合理选药。对于多重用药患者可以加强药物治疗监测,必要时换用替代药品等。     

长期应用质子泵抑制药与胃癌的关联性研究进展

质子泵抑制药(PPI)是目前治疗酸相关性疾病的首选药物.近年来,越来越多研究发现长期应用PPI可能与胃黏膜病变相关,甚至导致胃癌的发生.该文通过检索国内外文献,对PPI的药理作用、致癌机制及相关临床研究进行阐述.旨在为临床合理选择和使用PPI,识别胃癌的高危人群,减少PPI相关性胃癌的发生提供参考.     

Strategies to treat patients with antibiotic resistant Helicobacter pylori

Increased resistance to clarithomycin and metronidazole, the two main antibiotics used to treat Helicobacter pylori infection, has led to a search for alternatives to the proton pump inhibitor based triple therapies commonly used. The main rescuse therapy is a bismuth-based quadruple therapy. However, triple therapies with tetracycline and metronidazole or amoxicillin and metronidazole can be considered in the case of clarithomycin resistance. They can also be used in the case of metronidazole resistance by increasing the dose and duration of metronidazole. The only therapy without clarithomycin and metronidazole includes rifabutin and amoxicillin. Dual therapies with amoxicillin and a proton pump inhibitor at high dose can also be used.     

The treatment of Helicobacter pylori infection: the changing picture of a still unresolved problem

More than 20 years from the discovery of Helicobacter pylori there is still a need to eradicate the bacterium. The efficacy of the current preferred first-line therapy – the triple regimen – has progressively decreased over the last 5 – 6 years, paralleling the progressive increase in the prevalence of resistant bacterial strains. Similarly, the quadruple therapy has progressively lost its importance as rescue therapy in some countries where bismuth is no longer available. A large number of studies investigating new combinations of drugs, new antibiotics and new regimens have been published in recent years. The most promising regimens – sequential therapy and triple therapy with lovofloxacin – have progressively gained importance but still need further confirmation of their efficacy before they can replace the old protocols in the everyday treatment of H. pylori infection.     

A novel therapeutic approach for Helicobacter pylori infection: the bismuth-based triple therapy monocapsule

Helicobacter pylori infection causes peptic ulcer disease and must be regarded as a serious infectious disease. Over the past two decades treatment of the infection has been a controversial issue. Treatment is purely empirical and based on combinations of two, three or four existing drugs. Antimicrobial resistance is important and an observed increase in the prevalence of resistance may change the relative importance of certain antibiotics. Bismuth-based triple therapy with bismuth, tetracycline and metronidazole is a well investigated, cheap and FDA approved regimen to cure the infection. Adding a proton pump inhibitor (PPI) increases efficacy. A novel monocapsule (‘Helicide^®’) that contains bismuth, tetracycline and metronidazole simplifies the regimen. This new and patient-friendly drug has been investigated in clinical studies and is expected to be released in North America in 2002.     

左氧氟沙星三联疗法根治幽门螺杆菌感染

目的探讨含左氧氟沙星的三联疗法治疗幽门螺杆菌感染的有效性和安全性。方法选择62例确诊为幽门螺杆菌感染的患者,按照随机原则均分为观察组与对照组,其中观察组患者采用雷贝拉唑、阿莫西林、左氧氟沙星,对照组患者采用雷贝拉唑、阿莫西林、克拉霉素,所有患者均治疗两周后复查胃镜和快速尿素酶试验,比较两组治疗后幽门螺杆菌的根除率以及不良反应的发生率。结果观察组患者的幽门螺杆菌根除率为90.32%,对照组患者幽门螺杆菌根除率为70.97%,前者明显优于后者(P<0.05),两组患者的不良反应发生率无统计学差异(P>0.05)。结论采用左氧氟沙星联合阿莫西林和雷贝拉唑治疗幽门螺杆菌感染根除率高,用药简单方便,不良反应较少,易于患者接受,值得临床推广。     

乳酸菌素根除治疗幽门螺杆菌感染的临床研究

目的:探讨乳酸菌素在幽门螺杆菌(Hp)感染根除治疗中的作用.方法:66例慢性糜烂性胃炎、萎缩性胃炎、消化性溃疡、胃镜胃窦部快速尿素酶试验(RUT),14C-尿素呼气试验(14C-UBT)均阳性的患者随机分为两组:试验组36例,应用乳酸菌素、雷贝拉唑、克拉霉素、阿莫西林,口服7d.对照组30例,应用雷贝拉唑、克拉霉素、阿莫西林,服7 d.结果:4周后复查胃镜RUT及14C-UBT,两者均阴性,试验组31例(86.1%),明显高于对照组19例(63.3%).两组比较有统计学差异(P＜0.05).副作用发生率,试验组2例(5.5%),对照组10例(33.3%),后者明显高于前者(P＜0.01).结论:在雷贝拉唑加阿莫西林、克拉霉素标准三联疗法基础上加用乳酸菌素,可以明显提高Hp根除率.     

利迈先(克拉霉素)等三联疗法根除幽门螺旋杆菌疗效观察

目的 :观察利迈先、洛赛克、羟氨苄青霉素三联疗法根除幽门螺旋杆菌的疗效。方法 :将65例Hp阳性十二指肠溃疡患者随机分为两组。治疗组32例 ,给予利迈先500mg、洛赛克20mg、羟氨苄青霉素1000mg ,bid ,治疗7天 ;洛赛克治疗时间再延长1周。对照组33例 ,给予洛赛克20mg、羟氨苄青霉素1000mg,bid ,治疗7天 ;洛赛克治疗时间亦延长1周。在治疗前和疗程结束4周以后 ,用快速尿素酶试验和免疫组化染色法检测Hp。结果 :治疗组Hp 根除率为90 6 % ,明显高于对照组的69 7 % (P<0 01)。两组不良反应少 ,均能耐受。结论 :利迈先、洛赛克、羟氨苄青霉素三联疗法安全、耐受性好 ,Hp 根除率高     

左氧氟沙星三联治疗根除幽门螺旋杆菌临床疗效观察

目的观察以左氧氟沙星为基础的三联疗法根除幽门螺旋杆菌的疗效。方法选择202例幽门螺旋杆菌感染患者,随机分为2组,治疗组80例采用以左氧氟沙星为基础的三联疗法,对照组采用标准三联疗法,停药4周后进行13C呼气试验,统计幽门螺旋杆菌根除率,并同时记录患者不良反应情况。结果治疗组幽门螺旋杆菌根除率为90%,幽门螺旋杆菌根除率为68.8%,差异有显著性(P<0.05)。治疗组药物不良反应发生为率8.75%,对照组药物不良反应发生为率12.29%,无统计学差异(P>0.05)。结论对于幽门螺旋杆菌感染患者,以左氧氟沙星为基础的三联疗法,幽门螺旋杆菌的清除率明显优于标准三联疗法,而药物不良反应率相当,值得临床推广。     

序贯疗法根除幽门螺杆菌的临床研究

目的:探讨埃索美拉唑镁、克拉霉素、左氧氟沙星与替硝唑10d序贯疗法根除幽门螺杆菌(Hp)的效果及不良反应。方法:将122例经胃镜检查确诊Hp阳性患者随机均分为试验组与对照组。试验组在前5d给予埃索美拉唑镁20mg+克拉霉素500mg,后5d给予埃索美拉唑镁20mg+左氧氟沙星200mg+替硝唑500mg;bid,共10d;对照组给予埃索美拉唑镁20mg+阿莫西林1000mg+呋喃唑酮100mg,bid,共14d。2组均于疗程结束后4周复查检测Hp。结果:试验组Hp根除率为88.1%,对照组为67.2%,2组比较有显著性差异(P<0.05)。试验组有5例(8.5%)、对照组有15例(25.9%)发生不良反应,2组比较有显著性差异(P<0.05)。结论:由埃索美拉唑镁+克拉霉素+左氧氟沙星+替硝唑组成的10d序贯疗法可以明显提高Hp根除率,试验组不良反应发生率较对照组低。     

2种治疗方案根除幽门螺杆菌的疗效观察

目的:比较2种根除幽门螺杆菌(Hp)方案的优劣。方法:将197例因各种上消化道症状行胃镜检查并14C-尿素呼气阳性的患者,随机分为A、B组(均符合根除Hp的条件及排除条件)。A组109例,给予雷贝拉唑10mg,阿莫西林-克拉维酸钾分散片(2:1)2片,甲硝唑0.4g;B组88例,给予雷贝拉唑10mg,阿莫西林1g,甲硝唑0.4g。2组给药方法均为每日2次,连用7d。总疗程结束后2周,再行内镜和14C-尿素呼气试验,判断Hp的根除效果。结果:A组根除率为88.07%,B组为73.90%。2组比较,差异有统计学意义(P<0.05)。结论:2种根除Hp的方案中,A组Hp根除率显著高于B组。     

雷贝拉唑三联疗法治疗消化性溃疡的疗效观察

目的观察雷贝拉唑三联疗法治疗消化性溃疡的临床疗效。方法将92例消化性溃疡患者随机分为治疗组和对照组各46例。治疗组先给予雷贝拉唑10mg、阿莫西林1.0g、克拉霉素500mg;对照组先给予奥美拉唑20mg、阿莫西林1.0g、克拉霉素500mg,2组均每天2次,饭前1h服用,连服7d。然后治疗组单独给予雷贝拉唑10mg,对照组单纯给予奥美拉唑20mg,2组均每天1次,连服7d。治疗后比较2组溃疡愈合率、幽门螺杆菌(Hp)根除率,并观察2组不良反应发生情况。结果治疗组溃疡愈合率为91.30%高于对照组的60.04%,差异有统计学意义(P<0.01)。2组不良反应均轻微,可自行消失。结论雷贝拉唑三联疗法是一种短程、高效、安全的根除Hp及促进溃疡愈合的方案。     

埃索美拉唑肠溶胶囊治疗幽门螺杆菌疗效观察

目的:观察埃索美拉唑肠溶胶囊治疗幽门螺杆菌(Hp)的疗效,并评价其安全性。方法:59例Hp阳性的十二指肠溃疡患者随机分为试验组(29例)与对照组(27例),分别服用埃索美拉唑肠溶胶囊或埃索美拉唑镁肠溶片40mg(qd)及克拉霉素500mg(bid)、替硝唑500mg(bid),连用7d。结果:试验组Hp根除率为62.07%,对照组为37.04%,2组间无显著性差异(P>0.05);2组不良反应发生率相似,试验组为17.24%,对照组为14.81%。结论:埃索美拉唑肠溶胶囊治疗Hp效果与埃索美拉唑镁肠溶片相似,安全性好。     

根除幽门螺杆菌的三联方案中3种质子泵抑制剂的成本-效果分析

目的：对根除幽门螺杆菌（Hp）的三联治疗方案中的3种质子泵抑制剂进行药物经济学评价,为临床用药提供参考。方法：选择2012年9月至2013年9月Hp阳性的消化性溃疡患者106例随机分成3组,A组给予奥美拉唑＋奥硝唑＋克拉霉素,B组给予雷贝拉唑＋奥硝唑＋克拉霉素,C组给予艾普拉唑＋奥硝唑＋克拉霉素,疗程均为10 d。停药4周后运用成本-效果分析方法进行经济学评价。结果：3组治疗方案的总有效率分别为88.57％、91.43％、91.57％,组间差异无统计学意义（P＞0.05）;成本-效果比分别为2.59、2.51、8.88。结论：从药物经济学角度,奥美拉唑和雷贝拉唑的三联疗法成本-效果相当,优于艾普拉唑三联疗法。