Novel therapies for Helicobacter pylori infection

Background:

Increasing antibiotic resistance has begun to impair our ability to cure Helicobacter pylori infection.

Aim:

To evaluate orally administered novel therapies for the treatment of H. pylori infection.

Methods:

Healthy H. pylori infected volunteers received: (a) hyperimmune bovine colostral immune globulins, (b) an oligosaccharide containing an H. pylori adhesion target, Neu5Aca2-3Galb1–4Glc-(3′-sialyllactose), or (c) recombinant human lactoferrin. Outcome was assessed by urea breath test or histological assessment of the number of H. pylori present.

Results:

None of the novel therapies appeared effective and no adverse events occurred.

Conclusion:

Although in vitro data appeared promising, in vivo results were disappointing. Higher doses, longer duration of therapy, adjunctive acid suppression, or a combination could possibly yield better results.

     

Seven-day therapy for Helicobacter pylori in the United States

BACKGROUND: The ideal duration of Helicobacter pylori treatment in the United States and whether eradication therapy is as successful in nonulcer dyspepsia as in peptic ulcer disease are controversial topics. AIM: This study compared the efficacy of 3-, 7- and 10-day triple therapies with rabeprazole to a 10-day omeprazole control triple therapy for the eradication of Helicobacter pylori in patients with and without peptic ulcer disease in the United States. METHODS: This was a multicentre, double-blind, randomized, parallel-group trial. A total of 803 patients with H. pylori infection (determined by [13C]urea breath test and rapid urease test or culture) received either rabeprazole 20 mg b.d., amoxicillin 1000 mg b.d., and clarithromycin 500 mg b.d. for 3, 7, or 10 days, or 10 days of omeprazole 20 mg b.d. with the same antibiotic regimen (control). H. pylori status was assessed by [13C]urea breath test > or =6 weeks after completing treatment. RESULTS: In intent-to-treat patients, the eradication percentages achieved for the rabeprazole-based treatments were: 3-day, 27% (95% confidence interval: 21%-34%); 7-day, 77% (95% confidence interval: 71%-83%); and 10-day, 78% (95% confidence interval: 72%-84%). The eradication percentage with the 10-day omeprazole-based treatment was 73% (95% confidence interval: 67%-79%). There was no statistically significant difference between the 7-day rabeprazole-based regimen and the 10-day rabeprazole- and omeprazole-based regimens. CONCLUSIONS: Seven-day therapy with rabeprazole, clarithromycin, and amoxicillin is similar in efficacy to 10-day therapies and had similar efficacy in patients with and without ulcer disease.     

Furazolidone-containing short-term triple therapies are effective in the treatment of Helicobacter pylori infection

BACKGROUND: A furazolidone-containing therapeutic regimen for Helicobacter pylori infection has attracted special interest in the face of a rising world-wide metronidazole resistant H. pylori, and the expense of currently used antimicrobial regimens. AIM: To evaluate the efficacy of furazolidone-containing regimens in eradicating H. pylori. METHODS: One-hundred and forty H. pylori positive patients with endoscopically confirmed duodenal ulcer or functional dyspepsia received one of four different regimens to eradicate H. pylori. In the first trial, the patients were randomly assigned to receive a 1-week course of furazolidone 100 mg b.d. and clarithromycin 250 mg b.d., with either tripotassium dicitrato bismuthate (TDB) 240 mg b.d. (FCB group) or lansoprazole 30 mg daily (FCL group). In the second trial, the patients were randomly assigned to receive a 1-week course of clarithromycin 250 mg b.d. and omeprazole 20 mg daily, with either furazolidone 100 mg b.d. (FCO group) or metronidazole 400 mg b.d. (MCO group). Endoscopy was repeated 4 weeks following completion of therapy with re-assessment of H. pylori status on gastric biopsies by histology and culture. RESULTS: Four patients (1 in FCB, 1 in FCO and 2 in MCO groups) dropped out because they refused a follow-up endoscopy. Eradication rates of H. pylori on an intention-to-treat basis in the FCB, FCL, FCO and MCO groups were 91% (32/35, 95% CI: 82-99%), 91% (32/35, CI: 82-99%), 86% (30/35, CI: 74-97%) and 74% (26/35, CI: 60-89%) (all P > 0.05), respectively. Mild side-effects occurred in 15% of the 140 patients. In MCO group, the eradication rate in the patients infected with metronidazole-sensitive isolates of H. pylori was 86%, but dropped to 67% in those with metronidazole-resistance strains (P = 0.198). CONCLUSION: One-week regimens containing furazolidone and clarithromycin in combination with TDB or a proton pump inhibitor fulfil the criteria for successful H. pylori therapy.     

Efficacy of two one-week rabeprazole/levofloxacin-based triple therapies for Helicobacter pylori infection

BACKGROUND: One-week low-dose proton pump inhibitor-based triple therapies have usually proved to be effective treatments for Helicobacter pylori infection. AIM: To investigate the eradication efficacy, safety profile and patient compliance of two triple therapies containing a standard dose of rabeprazole and a new fluoroquinolone, levofloxacin. METHODS: One hundred patients referred to us for gastroscopy, who were H. pylori-positive, were consecutively recruited in a prospective, open-label study. The enrolled patients were randomised to receive a seven-day course of rabeprazole 20 mg o.d. plus levofloxacin 500 mg o.d. and either amoxycillin 1 g b.d. (RLA group) or tinidazole 500 mg b.d. (RLT group). Their H. pylori status was assessed by means of histology and rapid urease test at entry, and by 13C-urea breath test 8 weeks after the end of treatment. RESULTS: All 100 enrolled patients completed the study. Forty-six of 50 patients treated with RLA (both PP and ITT analysis: 92%; 95% CI: 81-98%) and 45 of 50 with RLT (both PP and ITT analysis: 90%: 95% CI: 78-97%), became H. pylori-negative. Slight or mild side-effects occurred in 4 (8%) patients of the RLA group and in 5 (10%) of the RLT group. CONCLUSIONS: This study demonstrates the efficacy of two 1-week rabeprazole-based triple therapies including levofloxacin to eradicate H. pylori. These regimens prove to be safe, well-tolerated, and achieved good eradication rates. Levofloxacin may be an effective alternative to clarithromycin in triple therapy regimens.     

2种低剂量短程三联疗法根除幽门螺旋杆菌的疗效比较

目的：比较２种低剂量短程三联疗法根除幽门螺旋杆菌（ＨＰ）的疗效及其不良反应。方法：８６例ＨＰ阳性的消化性溃疡或糜烂性胃窦炎病人，随机分为Ａ组（４２例，男性３４例，女性８例，年龄５６±ｓ１６ａ）和Ｂ组（４４例，男性４０例，女性４例，年龄５９±１５ａ）。Ａ组以兰索拉唑３０ｍｇ，ｐｏ，ｑｄ，替硝唑５００ｍｇ及克拉霉素２５０ｍｇ，ｐｏ，ｂｉｄ，疗程７ｄ。Ｂ组以奥美拉唑２０ｍｇ，替硝唑５００ｍｇ及克拉霉素２５０ｍｇ，ｐｏ，ｂｉｄ，疗程７ｄ。疗程结束１ｍｏ后复查胃镜及ＨＰ。结果：Ａ，Ｂ２组ＨＰ根除率分别为８８％和９１％；不良反应发生率分别为１９％和１４％，但均能耐受；组间比较Ｐ＞０．０５。结论：这２种三联疗法根除ＨＰ均有良好疗效，且根除率相近，均无严重不良反应。     

Clarithromycin for Helicobacter pylori infection

Helicobacter pylori, a Gram-negative organism that survives in the deep mucus layer and attaches to the gastric surface cells, is estimated to be present in up to one-half of the US population. Chronic H. pylori infection causes chronic gastritis, peptic ulcer diseases and even gastric cancer. Cure of the infection leads to healing of gastric inflammation, prevention of development of peptic ulcer, as well as accelerated healing of peptic ulcers, and prevention of ulcer recurrence. Treatment of H. pylori has undergone substantial evolution over the past decade. Despite the in vitro susceptibility, results from single or even dual drug therapy is typically unsatisfactory and the best therapy is yet to be defined. The best current therapies for H. pylori infection consist of a proton pump inhibitor (PPI) or ranitidine bismuth citrate and two antibiotics (triple therapies), or bismuth, tetracycline, metronidazole and a PPI (quadruple therapy). Clarithromycin is one of the most useful antimicrobials against H. pylori. It is an acid-stable macrolide with a broad spectrum of antibacterial activity, well absorbed with a wide tissue distribution and with mild side effects. Clarithromycin has a low minimum inhibitory concentration (MIC50) for H. pylori and its effect is potentiated by acid inhibition. When combined with a PPI or ranitidine bismuth citrate and amoxicillin or metronidazole, eradication rates of more than 95% can be achieved with susceptible organisms. However, the prevalence of primary and acquired clarithromycin resistance, which is due to mutations within a conserved loop of 23S rRNA of H. pylori, is increasing. In practice, the presence of clarithromycin resistance usually implies reduced success when clarithromycin-containing regimes are used. There is a need for improved therapies for H. pylori where antibiotic resistance is less of a problem.     

幽门螺杆菌粪便抗原用于幽门螺杆菌感染检验观察

目的分析幽门螺杆菌粪便抗原（HpSA）对幽门螺杆菌感染的诊断价值。方法收集304例患者粪便标本,运用ELISA法定性检测HpSA,同时对照用快速尿素酶试验、Gram染色镜检联合检测的胃黏膜标本。结果HpSA的敏感度为96．7％（240／249）,特异度为90．1％（44／49）,阳性预测值为96．4％（240／249）,阴性预测值为80．0％（44／55）,准确率为93．4％（284／304）。结论粪便HpSA检测具有操作简便、省时等特点,是较理想的非侵人性的Hp诊断方法。     

Clarithromycin for Helicobacter pylori infection

Helicobacter pylori, a Gram-negative organism that survives in the deep mucus layer and attaches to the gastric surface cells, is estimated to be present in up to one-half of the US population. Chronic H. pylori infection causes chronic gastritis, peptic ulcer diseases and even gastric cancer. Cure of the infection leads to healing of gastric inflammation, prevention of development of peptic ulcer, as well as accelerated healing of peptic ulcers, and prevention of ulcer recurrence. Treatment of H. pylori has undergone substantial evolution over the past decade. Despite the in vitro susceptibility, results from single or even dual drug therapy is typically unsatisfactory and the best therapy is yet to be defined. The best current therapies for H. pylori infection consist of a proton pump inhibitor (PPI) or ranitidine bismuth citrate and two antibiotics (triple therapies), or bismuth, tetracycline, metronidazole and a PPI (quadruple therapy). Clarithromycin is one of the most useful antimicrobials against H. pylori. It is an acid-stable macrolide with a broad spectrum of antibacterial activity, well absorbed with a wide tissue distribution and with mild side effects. Clarithromycin has a low minimum inhibitory concentration (MIC₅₀) for H. pylori and its effect is potentiated by acid inhibition. When combined with a PPI or ranitidine bismuth citrate and amoxicillin or metronidazole, eradication rates of more than 95% can be achieved with susceptible organisms. However, the prevalence of primary and acquired clarithromycin resistance, which is due to mutations within a conserved loop of 23S rRNA of H. pylori, is increasing. In practice, the presence of clarithromycin resistance usually implies reduced success when clarithromycin-containing regimes are used. There is a need for improved therapies for H. pylori where antibiotic resistance is less of a problem.     

含呋喃唑酮三联方案不同疗程治疗幽门螺杆菌的疗效观察

目的:评价含呋喃唑酮三联方案不同疗程治疗幽门螺杆菌的有效性和安全性。方法:将幽门螺杆菌阳性患者随机分成左氧氟沙星组、阿莫西林组和对照组,按疗程再分成亚组,治疗组均包含呋喃唑酮和奥美拉唑,观察其疗效。结果:含呋喃唑酮三联方案与对照组在总根除率上无差异,且随疗程增加而增加;不良反应发生率各组随疗程增加而增加,左氧氟沙星组总发生率要略高于其他组;在临床症状缓解上,3组间无差异,各组缓解率随疗程增加而增加。结论:含呋喃唑酮三联方案是安全有效的幽门螺杆菌根除方案,10,14日疗程均可获得好的疗效,10日疗程最佳。     

3种短程三联疗法根除幽门螺杆菌感染的疗效比较

目的 :比较 3种短程三联疗法根除幽门螺杆菌 (Hp)的疗效及不良反应。方法 :2 78例Hp阳性的消化性溃疡或慢性糜烂性胃窦炎病人分为 3组。A组 94例 ,以奥美拉唑 2 0mg ,po ,bid× 7d ;B组 82例 ,以兰索拉唑 30mg ,po ,qd× 7d ;C组10 2例 ,以泮托拉唑 4 0mg ,po ,qd× 7d。 3组均加用阿莫西林 10 0 0mg ,po ,bid× 7d及甲硝唑 4 0 0mg ,po ,bid× 7d。疗程结束 1mo后 ,复查胃镜及Hp。结果 :A ,B ,C组Hp根除率分别为 85 % ,88% ,89.2 % ;不良反应率分别为 2 8% ,2 4 % ,30 .4 % ,但均能耐受 ;组间比较P >0 .0 5。结论 :这3种三联疗法根除Hp均有良好疗效 ,且根除率相近 ,均无严重不良反应     

莫西沙星为基础的三联疗法根除幽门螺杆菌疗效观察

目的 观察莫西沙星为基础的三联疗法根除幽门螺杆菌(Hp)的效果.方法 共入选Hp感染的患者117例,根除方案中慢性胃炎者口服雷尼替丁枸橼酸铋,消化性溃疡者口服雷贝拉唑;以上两类患者各随机分为两组,含莫西沙星组同时服用阿莫西林或克拉霉素,对照组口服阿莫西林及克拉霉素.抗生素疗程结束后4周行13C呼气试验判断Hp的根除情况.结果 含莫西沙星组及对照组Hp的根除率在慢性胃炎患者中分别为72.4%、81.3%,在消化性溃疡患者中为80.0%、80.6%;各组间差别无统计学意义.慢性胃炎患者应用阿莫西林者Hp根除率明显高于应用克拉霉素者.结论 莫西沙星可以作为根除Hp的治疗用药;克拉霉素的耐药情况对Hp根除效果的影响较大.     

Clarithromycin-amoxycillin therapy for Helicobacter pylori infection

Background: More convenient therapies are needed to treat Helicobacter pylori infection successfully. Clarithromycin and amoxycillin are effective against H. pylori both in vivo and in vitro. Recent success with a high dose amoxycillin-metronidazole combination therapy led us to evaluate clarithromycin-amoxycillin dual therapy for H. pylori infection. Methods: We tested the combination of clarithromycin 500 mg t.d.s. with meals plus amoxycillin 750 mg t.d.s. with meals for 10 days for its effect on H. pylori infection in 29 patients with documented H. pylori peptic ulcers. There were 27 men and 2 women, ranging in age from 23 to 77 years. H. pylori and ulcer status were evaluated at entry and at least 4 weeks after ending antimicrobial therapy. For ulcer healing, ranitidine 300 mg was given each evening for 6 weeks. H. pylori status was determined by CLOtest and histology. Results: H. pylori infection was cured in 86% (95% CI = 78–99%). Compliance averaged 93% by pill count. Ten patients (34%) experienced mild side effects: eight reported dysgeusia and two had mild diarrhoea; none discontinued therapy because of side effects. Conclusion: We conclude that dual therapy with clarithromycin and amoxycillin is a safe and effective alternative regimen for the successful treatment of H. pylori infections.     

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.     

Furazolidone versus metronidazole in quadruple therapy for eradication of Helicobacter pylori in duodenal ulcer disease

OBJECTIVE: Furazolidone, an old but cheap antibiotic, was shown to be a good alternative to metronidazole in triple therapy for Helicobacter pylori eradication in areas where metronidazole resistant bacteria are common, but randomized studies are lacking. AIM: A randomized controlled trial to determine the efficacy and safety of furazolidone compared to metronidazole in classic quadruple therapy for eradication of H. pylori infection in duodenal ulcer patients. METHODS: Patients with endoscopically proven duodenal ulcer and positive urease test were randomized to receive ranitidine 300 mg, amoxycillin 1000 mg and bismuth subcitrate 240 mg b.d, with either furazolidone 200 mg b.d (RABF), or metronidazole 500 mg b.d. (RABM) for 2 weeks. Compliance and side-effects were monitored and recorded by table diary. H. pylori eradication was assessed at least 4 weeks after the completion of therapy with 14C-urea breath test. RESULTS: A total of 106 patients were enrolled and 101 (59 male, 42 female, mean age=40 +/- 11 years) completed the study. Endoscopic findings and demographic data were comparable in both groups. Intention-to-treat eradication rates were 75% and 55% (P=0.03) and per protocol eradication rates were 82 and 56% (P=0. 006) in the RABF and RABM groups, respectively. Side-effects were reported by 13 patients (27%) in the RABF group (one stopped treatment) compared to five patients (10%) in the RABM group (P=0. 04). CONCLUSION: Quadruple therapy containing furazolidone, instead of metronidazole, results in a significantly higher H. pylori eradication rate in Iranian duodenal ulcer patients.     

Triple therapies plus different probiotics for Helicobacter pylori eradication

The Helicobacter pylori (H. pylori) cure rate following standard triple therapies is decreasing worldwide. Therefore, further approaches aimed to improve standard triple therapy efficacy should be attempted. This prospective, pilot study aimed to evaluate the therapeutic role of either Lactobacillus reuteri (L. reuteri) or a high concentration of probiotics in addition to standard triple therapies for H. pylori eradication. The study enrolled 65 consecutive dyspeptic patients with H. pylori infection. All patients underwent upper endoscopy with gastric biopsies. Patients were assigned to receive one of the following therapies: (a) standard 7-day triple; (b) the same 7-day triple therapy plus L. reuteri supplementation; (c) the same 7-day triple therapy plus a probiotic mixture; and d) a 14-day standard triple therapy plus a probiotic mixture. H. pylori eradication was checked by using a 13C-urea breath test performed 4-6 weeks after treatment. No therapy regimen achieved > 80% eradication rate at both intention-to-treat (ITT) and per protocol (PP) analyses. Although the 14-day therapy plus a probiotic mixture tended to achieve higher eradication rate (71%), no statistically significant difference emerged among the different therapy regimens tested (range: 53-71%). The lowest incidence of side-effects was observed following the 7-day therapy plus L. reuteri (6%) and highest with the 14-day triple therapy plus probiotic mixture (33%), although the difference failed to reach the statistically significance. In conclusion, our data found that 7-14 days triple therapy with or without probiotic supplementation failed to achieved acceptable H. pylori eradication rates.     

Nizatidine in combination with amoxycillin and clarithromycin in the treatment of Helicobacter pylori infection

Background:

The efficacy of H₂-antagonists in combination with antibiotics in curing Helicobacter pylori infection remains controversial, and it is uncertain whether double dose H₂-antagonist therapy is superior to standard dose.

Aim:

To determine the efficacy of two doses of nizatidine in combination with two antibiotics in the treatment of H. pylori.

Methods:

A randomized controlled trial was conducted in 160 patients comparing nizatidine l50 mg with 300 mg b.d. (standard vs. double dose), in combination with clarithromycin (500 mg) and amoxycillin (1000 mg) b.d. for 14 days, in Australia and Taiwan. Compliance was based on a clinical assessment and pill count. H. pylori status was determined by histology (antrum and corpus) and CLO-test.

Results:

Baseline clinical and endoscopic findings were similar in both arms of the study. Based on an intention-to-treat analysis, cure of H. pylori was achieved in 78% (95% CI: 70.4–85.4%) in the standard nizatidine dose arm and 70% (95% CI: 61.6–78.2%) in the double dose arm (P = 0.2). Similar cure rates were observed in ulcer and non-ulcer patient groups. Compliance was excellent in the single and double dose arms (85 and 91%, respectively).

Conclusions:

The combination of nizatidine in standard or double dose with clarithromycin and amoxycillin is similarly efficacious in curing H. pylori infection.

     

Metronidazole, omeprazole and clarithromycin: an effective combination therapy for Helicobacter pylori infection

Background: Successful treatment of Helicobacter pylori infection results in cure of peptic ulcer disease. Multidrug regimens are needed to cure this infection. We studied the effectiveness and side effect profile of two antibiotics active against Helicobacter pylori, metronidazole and clarithromycin, combined with omeprazole. Methods: We evaluated a combination therapy for H. pylori infection consisting of metronidazole (500 mg b.d.), omeprazole (20 mg b.d.), and clarithromycin (250 mg b.d.) for 2 weeks, followed by ranitidine 300 mg daily for 4 weeks. Results: Thirty-three patients with documented H. pylori infection were studied. Twenty had previously failed antimicrobial therapy, including one with metronidazole-based triple therapy and eight with macrolide-based therapy (five with clarithromycinbased therapy), and 11 with amoxycillin, tetracycline, and bismuth. H. pylori status was determined by histopathology using the Genta stain and by culture. H. pylori status was determined at entry and 4 weeks after completing antimicrobial therapy. The H. pylori infection was cured in 88% (95% CI = 72%–96%) including 90% of those who had failed previous anti-H. pylori therapies. Mild side effects were reported by 18%. Conclusion: We conclude that the combination of metronidazole, omeprazole and clarithromycin is an effective treatment for H. pylori infection.