The sequential therapy regimen for Helicobacter pylori eradication

Importance of the field: Standard triple therapy (STT) is the most used treatment for Helicobater pylori infection. The prevalence of antibiotic resistance has increased substantially in recent years and there has been a corresponding decrease in efficacy.

Areas covered in this review: Bibliographical searches were performed in MEDLINE and international congresses up to 2009 for ‘Helicobacter pylori’ AND ‘sequential regimen/therapy’.

What the reader will gain: Several meta-analyses have demonstrated that sequential therapy (SQT) is more effective than STT. SQT is not affected by bacterial and host factors that have, until now, predicted the outcome of STT. Primary clarithromycin resistance is the only factor reducing the efficacy of SQT; however, even in these patients an acceptable >?75% eradication can be achieved. So far, almost all the studies have been performed in Italy. The advantages of SQT over STT should be confirmed in different countries. Whether it is necessary to provide the drugs sequentially or if the four components of SQT can be given concurrently is unclear.

Take home message: SQT is a promising new treatment approach that deserves consideration as a treatment strategy for H. pylori infection. However, further robust assessment across a much broader range of patients is required before SQT could supplant existing treatment regimens and be generally recommended in clinical practice.     

High rate of Helicobacter pylori eradication with sequential therapy in elderly patients with peptic ulcer: a prospective controlled study

BACKGROUND: Helicobacter pylori eradication rates with triple therapies are decreasing, and few data in elderly patients are available. A 10-day sequential regimen succeeded in curing such H. pylori infection in unselected patients. AIM: To compare this sequential regimen and the standard triple therapy for H. pylori eradication in geriatric patients with peptic ulcer. METHODS: Overall, 179 H. pylori-infected patients with peptic ulcer were enrolled (mean age: 69.5 years; range: 65-83). Patients were randomized to 10-day sequential therapy (rabeprazole 20 mg b.d. plus amoxicillin 1 g b.d. for the first 5 days, followed by rabeprazole 20 mg, clarithromycin 500 mg and tinidazole 500 mg, all b.d., for the remaining 5 days) or standard 7-day triple regimen (rabeprazole 20 mg, clarithromycin 500 mg and amoxicillin 1 g, all b.d.). Helicobacter pylori status was assessed by histology and rapid urease test at baseline and 4-6 weeks after completion of treatment. RESULTS: The sequential regimen achieved eradication rates significantly higher in comparison with the standard regimen at both intention-to-treat (94% vs. 80%; P = 0.008) and per-protocol (97% vs. 83%; P = 0.006) analyses. In both treatment groups, compliance to the therapy was high (> 95%), and the rate of mild side-effects was similarly low (< 12%). At repeated upper endoscopy, peptic ulcer lesions were healed in 97% patients, without a statistically significant difference between the sequential regimen and the standard triple therapy. CONCLUSIONS: In elderly patients with peptic ulcer disease, the 10-day sequential treatment regimen achieved significantly higher eradication rates in comparison with standard triple therapy.     

改良序贯疗法在溃疡活动期根除幽门螺杆菌疗效观察

目的：观察改良序贯疗法在溃疡活动期根除幽门螺杆菌（Hp）的疗效。方法：将确诊为Hp阳性的90例患者分两组,其中标准三联治疗方案45例,奥美拉唑静脉点滴＋克拉霉素＋阿莫西林,每日2次口服,共10d;改良序贯疗法方案45例,前5d奥美拉唑＋左氧氟沙星静脉点滴,后5d奥美拉唑静脉点滴＋阿莫西林＋甲硝唑,每日2次口服。疗程结束后4周复查Hp检测。结果：三联疗法组Hp根除率为80.0%（36/45）,序贯疗法组Hp根除率为95.6%（43/45）,两组疗效比较,差异具有统计学意义（P〈0.05）。结论：改良序贯疗法在根除溃疡活动期Hp感染疗效上明显优于标准三联疗法,可以达到尽早、尽快、有效地根除Hp的目的。     

序贯疗法治疗十二指肠溃疡穿孔幽门螺杆菌感染的疗效

目的研究序贯疗法与标准三联药物疗法治疗幽门螺杆菌感染的根除率之间的差异。方法根据胃镜检查及尿素酶试验筛选幽门螺旋杆菌感染的十二指肠溃疡穿孔患者61例,随机分成两组,分别接受标准的三联药物疗法或序贯疗法。标准三联药物疗法包括奥美拉唑,克拉霉素和阿莫西林,疗程10d。序贯疗法包括奥美拉唑和阿莫西林或前5d口服奥美拉唑和阿莫西林,后5d改用克拉霉素。2个月后利用胃镜检查评估每个疗程的根除率及不良反应。结果标准三联疗法和序贯疗法的根除率分别为83.3%和90.3%(P=0.473)。序贯疗法的费用较低,两组的不良反应发生率相似。结论序贯疗法和标准三联疗法根除幽门螺旋杆菌的疗效相似,但序贯疗法比较经济可替代标准三联疗法。     

三种序贯用药方案根除幽门螺杆菌的成本-效果分析

目的：比较3种10d序贯用药方案根除幽门螺杆菌（Hp）感染的成本-效果。方法：快速尿素酶试验和14 C尿素呼气试验发现Hp阳性病人156例,随机分成3组：前5d,3组病人均给予奥美拉唑20mg＋阿莫西林1.0g,bid。后5d,A组（n=54）给予奥美拉唑20mg＋左氧氟沙星200mg＋呋喃唑酮200mg,bid;B组（n=50）给予奥美拉唑20mg＋加替沙星200mg＋克拉霉素500mg,bid;C组（n=52）给予奥美拉唑20mg＋替硝唑1.0g,bid以及莫西沙星400mg,qd。疗程结束4周后,行14 C尿素呼气试验,阴性者为根除。比较3组病人Hp根除率、不良反应上报率,并进行成本-效果分析。结果：A、B、C组病人的Hp根除率分别为90.7%、92.0%和92.3%,差异无统计学意义（P〉0.05）;总成本分别为102.02、132.72和149.62元,成本-效果比分别为1.12、1.44和1.62,差异有统计学意义（P〈0.01）。结论：3种治疗方案中,A方案为根除Hp感染的较优方案。     

High Helicobacter pylori eradication rate with a 1-week regimen containing ranitidine bismuth citrate

Background:

High Helicobacter pylori eradication rates have consistently been reported with 2-week dual therapy regimens of ranitidine bismuth citrate plus clarithromycin. Ranitidine bismuth citrate with two antibiotics may provide an alternative 1-week eradication regimen.

Methods:

This double-blind, randomized, parallel group, international, multicentre study compared ranitidine bismuth citrate 400 mg b.d. and clarithromycin 500 mg b.d. for 2 weeks (RC) with ranitidine bismuth citrate 400 mg b.d., clarithromycin 500 mg b.d. and metronidazole 400 mg b.d. for 1 week (RCM) for eradication of H. pylori in 350 patients with dyspepsia.

Results:

Treatment with RC and RCM eradicated H. pylori (established by the combination of two negative results from two discrete ¹³C-UBTs at nominal weeks 4 and 12) from 89% (95% CI: 84–94) and 92% (95% CI: 88–97) of the observed population, and from 78% (95% CI: 72–84) and 80% (95% CI: 75–86) of the intention-to-treat population. When established only by one negative ¹³C-UBT result at least 28 days after the end of treatment, the respective intention-to-treat rates were 85% (95% CI; 79–90) and 88% (95% CI: 83–93). Both regimens were well-tolerated, only 6% of patients given RC and 4% given RCM discontinued treatment. Median plasma bismuth concentrations at the end of the second week of study were low, at 3.5 and 0.4 ng/mL, respectively.

Conclusions:

Ranitidine bismuth citrate triple therapy for 1 week (RCM) and dual therapy for 2 weeks (RC) were equally effective for the eradication of H. pylori infection.

     

儿童序贯疗法与传统三联疗法根除儿童幽门螺杆菌的疗效比较

目的探讨儿童序贯疗法在儿童幽门螺杆菌（H.pylori）感染根治治疗中的临床疗效及可行性。方法将有上消化道症状,并经13碳-尿素呼气试验（13C-UBT）检测H.pylori为阳性的患儿150例随机分为治疗组和对照组,每组75例,治疗组采用10d序贯疗法,对照组采用传统三联疗法,两组患儿疗程结束停药4周后复查13C-UBT,并判断H.pylori的根除率。结果治疗组与对照组的总有效率分别为93.33%和82.67%,H.pylori根除率分别为93.33%和62.67%,两组差异均有统计学意义（P〈0.05）;治疗组的不良反应发生率为13.33%,对照组为14.67%,差异无统计学意义（P〉0.05）。结论儿童序贯疗法根除H.pylori的临床疗效明显优于传统三联疗法,且不良反应少,是目前根除H.pylori感染的首选新方案。     

Meta-analysis: Helicobacter pylori eradication treatment efficacy in children

BACKGROUND: Several meta-analyses assessing the efficacy of anti-Helicobacter pylori treatment in adults have been published but a comparable meta-analysis in children is lacking. AIMS: To summarize the efficacy of treatments aimed at eradicating H. pylori in children and to identify sources of variation in treatment efficacy across studies. METHODS: We searched Medline, reference lists from published study reports, and conference proceedings for anti-H. pylori treatment trials in children. Weighted meta-regression models were used to find sources of variation in efficacy. RESULTS: Eighty studies (127 treatment arms) with 4436 children were included. Overall, methodological quality of these studies was poor with small sample sizes and few randomized-controlled trials. The efficacy of therapies varied across treatment arms, treatment duration, method of post-treatment assessment and geographic location. Among the regimens tested, 2-6 weeks of nitroimidazole and amoxicillin, 1-2 weeks of clarithromycin, amoxicillin and a proton pump inhibitor, and 2 weeks of a macrolide, a nitroimidazole and a proton pump inhibitor or bismuth, amoxicillin and metronidazole were the most efficacious in developed countries. CONCLUSIONS: Before worldwide treatment recommendations are given for eradication of H. pylori, additional well-designed randomized placebo-controlled paediatric trials are needed, especially in developing countries where both drug resistance and disease burden is high.     

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.     

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.     

Discontinuation rates of Helicobacter pylori treatment regimens: a meta-analysis

We conducted a meta-analysis to determine what factors in treatment regimens for Helicobacter pylori are associated with increased discontinuation rates. Studies were selected from the 1990-1996 MEDLINE data base, and references in published articles and reviews were obtained. Each article was uniformally abstracted for factors that could potentially affect dropout rates. Drug regimens with high numbers of doses per day had highest dropout rates (p=0.0001). The total dropout rate was lowest for regimens containing a proton pump inhibitor (OR = 0.75, CI 0.57, 0.98). The rate was high in regimens containing a bismuth compound due to side effects (OR = 2.79, CI 1.78, 4.36). The main finding was that drug regimens for eradication of H. pylori that have a high number of doses per day result in higher discontinuation rates than regimens with fewer doses per day.     

Age-dependent eradication of Helicobacter pylori with dual therapy

Background: Combined treatment using an acid-inhibiting drug with antibiotics can cure Helicobacter pylori infection. However, eradication rates are highly variable, especially if a proton pump inhibitor is used with amoxycillin. Therefore it is important to define factors/predictors of the clinical outcome. Methods: In a single-blind study, 60 H. pylori-positive patients prospectively matched for diagnosis (erosive gastritis, duodenal and gastric ulcer), age (above and below 50 years) and smoking habits were randomly treated (each group n = 20) for 2 weeks with amoxycillin (1 mg b.d.) and either omeprazole (20 mg b.d.), lansoprazole (30 mg b.d.) or ranitidine (300 mg b.d.). Intragastric pH and plasma levels of the administered drugs were monitored over a dosing interval of 12 h. Results: The overall eradication rates were 45% (intention-to-treat, ITT, 27/60) or 47% (per protocol 27/58); they did not differ (ITT) between omeprazole (50%), lansoprazole (40%) and ranitidine (45%). Median pH and time at which intragastric pH was above 4 was slightly lower for ranitidine (4.0 ± 1.7; 51 ± 25%) than for omeprazole (5.4 ± 1.1; 77 ± 25%; P < 0.05) or lansoprazole (4.4 ± 1.6; 68 ± 32%). Plasma concentrations of amoxycillin were comparable in all three treatment groups. Post-treatment H. pylori status was not dependent on those levels, or the drug-induced extent or duration of increased intragastric pH. However, H. pylori-eradicated patients were significantly (P < 0.05) older (56 ± 13 years) than patients still H. pylori-positive (47 ± 14 years). In addition, in patients older than 50 years (n = 33), eradication was higher (P < 0.01) than in patients (n = 25) below 50 years (65 vs. 24%). Eradication rate was highest (75–83%) in subgroups of patients (>50 years and history of peptic ulcer or smokers). Neither activity/grade of peptic ulcer or erosive gastritis nor initial diagnosis were predictors for clinical outcome. Conclusion: The age of patients must be regarded as a major determinant of H. pylori eradication rate and may represent an important factor contributing to the highly variable clinical results.     

Meta-analysis: the effect of supplementation with probiotics on eradication rates and adverse events during Helicobacter pylori eradication therapy

BACKGROUND: Recent evidence found probiotics could inhibit Helicobacter pylori colonization from both in vitro and in vivo studies. AIM: To systematically evaluate whether adding probiotics to anti-H. pylori regimens could improve eradication rates and reduce side effects during anti-H. pylori treatment. METHODS: Eligible articles were identified by searches of electronic databases. We included all randomized trials comparing probiotics supplementation to placebo or no treatment during anti-H. pylori regimens. Statistical analysis was performed with Review Manager 4.2.8. Subanalysis/Sensitivity analysis was also performed. RESULTS: We identified 14 randomized trials (n = 1671). Pooled H. pylori eradication rates were 83.6% (95% CI = 80.5-86.7%) and 74.8% (95% CI = 71.1-78.5%) for patients with or without probiotics by intention-to-treat analysis, respectively, the odds ratio (OR) was 1.84 (95% CI = 1.34-2.54); the occurrence of total side effects were 24.7% (95% CI = 20.0-29.4%) and 38.5% (95% CI = 33.0-44.1%) for groups with or without probiotics, especially for diarrhoea, the summary OR was 0.44 (95% CI = 0.30-0.66). CONCLUSIONS: Our review suggests that supplementation with probiotics could be effective in increasing eradication rates of anti-H. pylori therapy, and could be considered helpful for patients with eradication failure. Furthermore, probiotics show a positive impact on H. pylori therapy-related side effects.     

Rapid eradication of Helicobacter pylori infection

Background/aims: Current Helicobacter pylori eradication therapy for peptic ulcer disease usually involves a 2-week course of either a bismuth preparation or omeprazole in combination with antibiotics. We have studied a shorter, 7-day course of treatment to assess efficacy and tolerability. Methods: Four hundred and thirty-six patients, in three non-randomized groups, received omeprazole (40 mg mane), amoxycillin (500 mg t.d.s.) and metronidazole (400 mg t.d.s.): 308 patients received the triple combination for 14 days; 80 patients were treated for 7 days; and 48 patients received omeprazole and amoxycillin for 7 days but metronidazole for only 5 days. Results: Helicobacter pylori was eradicated in 89.5%, 91.1% and 87.5%, respectively (98.3%, 92.9% and 100% of metronidazole-sensitive isolates and 75.6% and 88.2% of metronidazole-resistant isolates in the first two groups). Side effects were significantly more frequent in patients who received 14 days (49%) compared with 7 days of treatment (33%); only 8/308 and 1/128 patients, respectively, failed to complete the course. Conclusions: On the basis of efficacy, tolerability and cost, we conclude that a 7-day course of the omeprazole (40 mg mane), amoxycillin (500 mg t.d.s.) plus metronidazole (400 mg t.d.s.) combination is effective therapy for the eradication of H. pylori.     

幽门螺杆菌个体化精准根治的研究进展

幽门螺杆菌（Helicobacter pylori,Hp）感染与消化道疾病及全身多个系统的发病相关,其感染率高、致病力强,威胁着人们的身体健康。近年来由于抗生素的滥用,抗生素耐药呈逐年上升趋势,从而导致Hp根除率下降,成为临床棘手的问题。近年来,为了努力提高Hp根除率,国内外学者做了积极探索,提出了“个体化”精准根除治...     

A systematic review of Helicobacter pylori eradication therapy—the impact of antimicrobial resistance on eradication rates

BACKGROUND: We systematically reviewed all available data in the literature to determine the overall eradication rates of currently advised Helicobacter pylori eradication regimens and to resolve conflicting evidence on the impact of antimicrobial resistance on the eradication rates. METHODS: A comprehensive search of all published trials on H. pylori eradication therapy was carried out via an electronic database search, hand-searching and checking reference lists of pharmaceutical companies and other reviews. Full papers and abstracts in the English language which study currently advised eradication regimes were included. RESULTS: 770 study-arms were analysed. Mean eradication rates for bismuth based triple, proton pump inhibitor triple, quadruple and ranitidine bismuth citrate combination therapies vary from 65 to 92%. In case of nitroimidazole resistance, a drop in efficacy of up to 50% was found for bismuth-based triple and proton pump inhibitor-based triple therapies. For quadruple therapy, a significant difference in efficacy was found in the equal-effects analysis; however, this could not be confirmed in the random-effects analysis. In case of clarithromycin resistance, a mean drop in efficacy of 56% was found for one- and two-week clarithromycin containing proton pump inhibitor-triple therapies and of 58% for two-week ranitidine bismuth citrate combined with clarithromycin therapies. For ranitidine bismuth citrate combined with clarithromycin and nitroimidazole, no difference in efficacy was found in case of nitroimidazole or clarithromycin resistance, but data are still scarce. CONCLUSIONS: The cure rate with most regimens dropped significantly, in case of nitroimidazole-resistant strains, compared to nitroimidazole-susceptible strains. In case of clarithromycin resistance, the efficacy of most regimens is also decreased; however, data are still scarce. These data should allow physicians to make a better choice of an appropriate therapy for their patients.     

Helicobacter pylori eradication in patients with non-ulcer dyspepsia

Epidemiological and pathophysiological studies, as well as clinical trials, attempting to identify a relationship between Helicobacter pylori infection and non-ulcer dyspepsia (NUD), or a subset of NUD, have produced inconsistent and confusing results. While it is possible that H. pylori eradication may be beneficial for symptom relief in a small proportion of patients, routine H. pylori testing and treatment in documented NUD is not currently widely accepted. Despite the lack of convincing evidence, the European Helicobacter pylori Study Group, an Asian Pacific Consensus Meeting, the American Digestive Health Foundation and the American Gastroenterology Association have all recommended considering H. pylori eradication in patients with NUD on a patient-by-patient basis. Recently, large prospective, randomised, double-blind, controlled clinical trials applying highly effective antimicrobial therapy have been conducted with 12 months follow-up. Although these well-designed studies have reached differing conclusions, the results have been largely negative. H. pylori eradication therapy in NUD will fail to relieve symptoms in most patients in the long term.     

A lyophilized and inactivated culture of Lactobacillus acidophilus increases Helicobacter pylori eradication rates

BACKGROUND: Acid suppression plus two antibiotics is considered the reference anti-Helicobacter pylori treatment. Reported eradication rates are around 65-80%. Human Lactobacillus acidophilus shows an in vitro inhibitory effect on the attachment of H. pylori to gastric epithelial cell lines. Culture supernatant of this bacillus seems to decrease the in vitro viability of H. pylori. AIM: To evaluate whether the supplementation with an inactivated preparation of L. acidophilus could improve the efficacy of a standard anti-H. pylori therapy. METHODS: One-hundred and twenty H. pylori-positive patients were randomly assigned to a 7-day triple therapy based on rabeprazole (20 mg b.d.), clarithromycin (250 mg t.d.s.) and amoxicillin (500 mg t.d.s.) (RCA group: 60 subjects), or to the same regimen supplemented with a lyophilized and inactivated culture of Lactobacillus acidophilus (t.d.s.) (RCAL group: 60 subjects). RESULTS: In the RCA group, eradication was successful in 72% (42 out of 58 patients) from a per protocol (PP) analysis, or 70% (42 out of 60 patients) using an intention-to treat (ITT) analysis. In the RCAL group a significant increase in the eradication rate was observed: 88% (52 out of 59 patients) from PP analysis (P=0.03), 87% (52 out of 60 patients) from ITT analysis (P=0.02). CONCLUSIONS: These results seem to confirm the in vitro anti-H. pylori effect of L. acidophilus, suggesting that the inactivated L. acidophilus could be effective in increasing eradication rates of a standard anti-H. pylori therapy.     

New strategies for Helicobacter pylori eradication

Helicobacter pylori infection is highly prevalent worldwide and is a major cause of diseases occurring in the upper gastrointestinal tract. Successful eradication therapy improves H. pylori-related symptoms in functional dyspepsia, cures peptic ulcer disease and may prevent gastric cancer. During the past decade, the success rate of recommended eradication regimens declined from over 90% to about 80%, a critical threshold for effectiveness of the therapy according to the current guidelines. This is mainly because of the rising antimicrobial resistance and underlines that it is imperative to develop new treatment approaches. The prevention of the initial infection by a suitable vaccination might be the new therapeutic strategy for the future.