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.     

布拉氏酵母菌联合标准三联疗法根治幽门螺杆菌感染的meta分析

目的 系统评价布拉氏酵母菌联合标准三联疗法根治幽门螺杆菌感染的疗效与安全性.方法 通过检索PubMed、EMBASE、Cochrane Central Register of Controlled Trials、MEDLINE等数据库1982年1月至2011年12月相关文献,全面收集应用布拉氏酵母菌联合标准三联疗法治疗Hp感染的随机对照试验,并用RevMan 5.0.2软件进行meta分析.结果 纳入5个试验包括1307例患者.其中4项试验的数据显示,与对照组相比,布拉氏酵母菌联合标准三联疗法能显著提高Hp根除率(n=915,OR=1.66,95％C1:1.22～1.26,P=0.001);有效降低三联疗法相关性不良反应(n=1305,OR=0.32,95％CI:0.17～0.63,P=0.008),特别是腹泻的发生率(4项试验,n=1215,OR=0.42,95％CI:0.27～0.64,P＜0.0001);但2组间的其他不良反应发生率无显著性差异.结论 布拉氏酵母菌联合标准三联疗法可显著性提高Hp感染的根治率,降低三联疗法总体相关性不良反应,特别是腹泻发生率.     

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.     

布拉氏酵母菌对幽门螺杆菌感染根除率的影响

目的：探讨布拉氏酵母菌联合三联疗法(雷贝拉唑、阿莫西林、左氧氟沙星)根除幽门螺杆菌(Hp)的疗效。方法100例慢性胃炎伴幽门螺杆菌感染患者,随机分为对照组和治疗组,各50例。对照组采用三联疗法治疗,治疗组在三联疗法的基础上加用布拉氏酵母菌散口服,疗程均为2周。疗程结束比较两组Hp根除率、不良反应发生率。结果治疗组患者Hp根除率和不良反应发生率与对照组相比,差异均有统计学意义(P<0.05)。结论布拉氏酵母菌可显著减少不良反应发生,并能提高三联疗法的Hp根除率,值得临床推广运用。     

Meta-analysis: efficacy of bovine lactoferrin in Helicobacter pylori eradication

Background  Several randomized-controlled trials (RCTs) have sought to determine the efficacy of bovine lactoferrin in Helicobacter pylori eradication with equivocal results.
Aim  To evaluate the effect of bovine lactoferrin supplementation in H. pylori eradication.
Methods  Electronic databases, reviews, bibliographies, abstracts and conference proceedings were searched. Included trials had to be randomized or quasi-randomized and controlled, using bovine lactoferrin in the intervention group, treating Helicobacter -infected subjects and evaluating eradication of H. pylori as an outcome.
Results  The search identified five eligible RCTs (of 169). Data were available for 682 subjects (bovine lactoferrin group- n  = 316; control group- n  = 366). The pooled odds ratio (five studies) for eradication by intention-to-treat analysis was 2.22 (95% CI 1.44–3.44; P  = 0.0003) using the fixed effects model (FEM) and 2.24 (95% CI 1.15–4.35; P  = 0.0003) using the random effects model (REM) (Cochran's Q  = 6.83; P  = 0.145). The pooled risk difference was 0.11 (95% CI 0.05–0.16; P  = 0.0001) by FEM (Cochran's Q  = 6.67; P  = 0.154) and 0.10 (95% CI 0.04–0.17; P  = 0.0023) by REM. There was no significant difference in incidence of adverse effects.
Conclusion  Bovine lactoferrin potentially improves H. pylori eradication rates without any impact on adverse effects, but available evidence is limited and further research is necessary to confirm the findings.     

High eradication rates of Helicobacter pylori with a new sequential treatment

BACKGROUND: Eradication rates of Helicobacter pylori with standard triple therapy are disappointing, and studies from several countries confirm this poor performance. AIM: To assess the eradication rate of a new sequential treatment regimen compared with conventional triple therapy for the eradication of H. pylori infection. METHODS: One thousand and forty-nine dyspeptic patients were studied prospectively. H. pylori-infected patients were randomized to receive 10-day sequential therapy [rabeprazole (40 mg daily) plus amoxicillin (1 g twice daily) for the first 5 days, followed by rabeprazole (20 mg), clarithromycin (500 mg) and tinidazole (500 mg) twice daily for the remaining 5 days] or standard 7-day therapy [corrected] [rabeprazole (20 mg), clarithromycin (500 mg) and amoxicillin (1 g) twice daily]. H. pylori status was assessed by histology, rapid urease test and 13C-urea breath test at baseline and 6 weeks or more after completion of treatment. RESULTS: Higher eradication rates were found with the sequential regimen compared to the standard regimen (intention-to-treat: 92% vs. 74%, P < 0.0001; per protocol: 95% vs. 77%, P < 0.0001). Higher eradication rates were also seen in patients with peptic ulcer disease and non-ulcer dyspepsia. In both treatments, compliance was similar (> 90%), as was the rate of side-effects, which were mild. CONCLUSIONS: This 10-day sequential treatment regimen achieves high eradication rates in peptic ulcer disease and non-ulcer dyspepsia.     

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。     

Meta-analysis: the influence of pre-treatment with a proton pump inhibitor on Helicobacter pylori eradication

BACKGROUND: There is much debate about the influence of pre-treatment with a proton pump inhibitor on Helicobacter pylori eradication. The few studies investigating the influence of pre-treatment on triple and quadruple therapies did not find differences in eradication rates. However, the high eradication rates make it difficult to study factors associated with therapy failure in small populations. In order to overcome this problem we performed a meta-analysis. METHODS: The literature was searched in order to identify randomized clinical trials comparing modern triple/quadruple therapies for H. pylori eradication without pre-treatment with a proton pump inhibitor with exactly the same regimen with pre-treatment. The overall risk difference (with - without pre-treatment) was calculated by pooling the risk differences of the individual studies weighted by the inverse of their variances. RESULTS: Nine studies, investigating a total of 773 patients, were identified. There was considerable variation regarding therapy regimen and duration. Pooled eradication rates were 81.3% (312 of 384) for patients with pre-treatment and 81.2% (316 of 389) for patients without pre-treatment. The (weighted) overall risk difference was 0.1% (95% CI: -5%; 5%). CONCLUSION: Pre-treatment with a proton pump inhibitor does not influence H. pylori eradication.     

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.     

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.     

Meta-analysis: proton pump inhibitor or H2-receptor antagonist for Helicobacter pylori eradication

AIM: To compare H2-receptor antagonists and proton pump inhibitors as adjuvants to triple therapy for Helicobacter pylori eradication. METHODS: H. pylori-infected patients with peptic ulcer were randomized to receive either 300 mg nizatidine or 30 mg lansoprazole plus 1 g amoxicillin and 500 mg clarithromycin taken b.d. for 7 days. H. pylori eradication was assessed 4 weeks after therapy. Using meta-analytical techniques, we combined the results of this study with other randomized controlled comparisons of H2-receptor antagonists and proton pump inhibitors as adjuvants to triple therapy. RESULTS: One hundred and one patients were randomized. H. pylori eradication was 94% (47/50) [95% confidence interval (CI), 83-99%] (intention-to-treat) in the H2-receptor antagonist group vs. 86% (44/51) (95% CI, 74-94%) in the proton pump inhibitor group (P = 0.3). There has been a total of 12 similar studies (1415 patients). The overall efficacy was similar in intention-to-treat analysis: 78% (549/701) with H2-receptor antagonists vs. 81% (575/714) with proton pump inhibitors (odds ratio, 0.86; 95% CI, 0.66-1.12). A non-significant trend favouring H2-receptor antagonist (79% vs. 69%; odds ratio, 1.14; 95% CI, 0.76-1.71; P = 0.5) was seen in the comparison of clarithromycin-containing regimens. In contrast, in non-clarithromycin-containing trials, there was a slight, but significant, advantage with proton pump inhibitors (85% vs. 78%; odds ratio, 0.64; 95% CI, 0.45-0.92; P = 0.02). CONCLUSION: Overall, proton pump inhibitor and H2-receptor antagonist antisecretory agents appear to be similarly effective as adjuvants for H. pylori triple therapy. It is unlikely that the direct anti-H. pylori effect of proton pump inhibitors is responsible for their ability to enhance anti-H. pylori therapy.     

Meta-analysis: role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users

Aim : To evaluate whether eradication of Helicobacter pylori prevents peptic ulcer in non‐steroidal anti‐inflammatory drug users by means of a meta‐analysis. Material and methods : A systematic search was performed in MEDLINE, EMBASE, the Cochrane Controlled Trials Register and the AGA congress. Randomized trials comparing H. pylori eradication vs. non‐eradication or eradication vs. a proton pump inhibitor in patients receiving a non‐steroidal anti‐inflammatory drug were selected. Results : Five studies and 939 patients were included in the analysis; 34 of 459 (7.4%) patients developed a peptic ulcer in the eradicated group vs. 64 of 480 (13.3%) in the control group. The odds ratio was 0.43 (95% confidence interval: 0.20–0.93). Sub‐analyses showed a significant reduction of risk for non‐steroidal anti‐inflammatory drug‐naive (odds ratio = 0.26; 95% confidence interval: 0.14–0.49) but not for previously treated patients (odds ratio = 0.95, 95% confidence interval: 0.53–1.72). Two studies with a total of 385 patients compared eradication vs. a proton pump inhibitor; five of 196 (2.6%) developed a peptic ulcer in the eradicated group vs. zero of 189 (0%) in the proton pump inhibitor group (odds ratio = 7.43; 95% confidence interval: 1.27–43.6). Conclusion : Helicobacter pylori eradication reduces the incidence of peptic ulcer in the overall population receiving non‐steroidal anti‐inflammatory drugs. It appears to be especially effective when performed in non‐steroidal anti‐inflammatory drug‐naïve patients. Nonetheless, eradication seems less effective than treatment with a maintenance proton pump inhibitor for preventing non‐steroidal anti‐inflammatory drug‐associated ulcers.     

Review article: treatment of Helicobacter pylori infection and factors influencing eradication

Currently available Helicobacter pylori eradication therapies are considered very effective and safe. The most recent eradication guidelines proposed in the Maastricht 2-2000 Consensus Report recommend the use of proton pump inhibitors (standard b.d.) along with clarithromycin (500 mg b.d.) and amoxycillin (1000 mg b.d.) or metronidazole (500 mg b.d.) for a minimum of 7 days. The combination of amoxycillin and clarithromycin is preferred because it may favour best results with a second-line proton pump inhibitor quadruple therapy. The recommended second-line therapy includes a combination of a proton pump inhibitor (standard b.d.) with bismuth salt (subsalicylate/subcitrate 120 mg q.d.s.), metronidazole (500 mg t.d.s.), and tetracycline (500 mg q.d.s.) for a minimum of 7 days. Extended proton pump inhibitor-based triple therapy can be used if bismuth is not available. Specialists should manage subsequent failures. Based on direct and indirect evidence from well-designed studies and clinical experience, eradication is recommended in gastric and duodenal ulcers, MALToma, atrophic gastritis, postgastric cancer resection, and in first-degree relatives of gastric cancer patients. The most common reason for treatment failure is poor compliance with eradication guidelines. Antibiotic resistance may be a significant factor in certain geographical areas. Proton pump inhibitors are an integral part of the eradication regimens as proved by meta-analyses of clinical trials. Novel agents used in secondary failure are few and depend on the use of new antibiotics. The role of H. pylori-specific antibiotics, probiotics, and vaccines is not established as yet. Widespread acceptance of the eradication guidelines should be regarded as the single most important factor in eradication success.     

Meta-analysis: comparative efficacy of different proton-pump inhibitors in triple therapy for Helicobacter pylori eradication

BACKGROUND: It is not known whether certain proton-pump inhibitors are more efficacious than others when used in triple therapy for Helicobacter pylori eradication. AIM: To compare the efficacy of different proton-pump inhibitors in triple therapy by performing a meta-analysis. METHODS: A MEDLINE search was performed. Abstracts of the European Helicobacter pylori Study Group and the American Gastroenterological Association congresses from 1996 to 2002 were also examined. Randomized studies with at least two branches of triple therapy that differed only in terms of type of proton-pump inhibitor were included in a meta-analysis using Review Manager 4.1. RESULTS: Fourteen studies were included. Intention-to-treat cure rates were similar for omeprazole and lansoprazole: 74.7% vs. 76%, odds ratio (OR) 0.91 [95% confidence interval (CI) 0.69-1.21] in a total of 1085 patients; for omeprazole and rabeprazole: 77.9% vs. 81.2%, OR 0.81 (95% CI 0.58-1.15) in a total of 825 patients; for omeprazole and esomeprazole: 87.7% vs. 89%, OR 0.89 (95% CI 0.58-1.35) in 833 patients; and for lansoprazole and rabeprazole: 81% vs. 85.7%, OR 0.77 (95% CI 0.48-1.22) in 550 patients. CONCLUSION: The efficacy of various proton-pump inhibitors seems to be similar when used for H. pylori eradication in standard triple therapy.     

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.     

Meta-analysis: non-pathogenic yeast Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea

BACKGROUND: Antibiotic-associated diarrhoea occurs in up to 30% of patients who receive antibiotics but can be prevented with probiotics. AIM: To systematically evaluate the effectiveness of Saccharomyces boulardii in preventing antibiotic-associated diarrhoea in children and adults. METHODS: Using medical subject headings and free-language terms, the following electronic databases were searched for studies relevant to antibiotic-associated diarrhoea and S. boulardii: MEDLINE, EMBASE, CINAHL and The Cochrane Library. Additional sources were obtained from references in reviewed articles. Only randomized-controlled trials were considered for study inclusion. RESULTS: Of 16 potentially relevant clinical trials identified, five randomized-controlled trials (1076 participants) met the inclusion criteria for this systematic review. Treatment with S. boulardii compared with placebo reduced the risk of antibiotic-associated diarrhoea from 17.2% to 6.7% (RR: 0.43; 95% CI: 0.23-0.78; random effect model). The number needed to treat to prevent one case of antibiotic-associated diarrhoea was 10 (95% CI: 7-16). No side-effects were reported. CONCLUSIONS: A meta-analysis of data from five randomized-controlled trials showed that S. boulardii is moderately effective in preventing antibiotic-associated diarrhoea in children and adults treated with antibiotics for any reason (mainly respiratory tract infections). For every 10 patients receiving daily S. boulardii with antibiotics, one fewer will develop antibiotic-associated diarrhoea.