含利福布汀的三联或四联疗法在幽门螺杆菌根除失败后的应用

根除幽门螺杆菌(Hp)是防治消化性溃疡、慢性活动性胃炎等疾病的主要措施,作为一线治疗的三联或四联方案的根除率逐年降低。抗分枝杆菌药物利福布汀有较强的抗Hp活性,国内外陆续有将含利福布汀方案作为Hp感染一线治疗失败后的补救或三/四线方案的报道。本文对利福布汀的作用机制、药动学特点及含利福布汀方案的疗效和安全性作一综述。     

用三联法根除幽门螺杆菌失败后的补救方案

目的探讨三联疗法(质子泵抑制剂 阿莫西林 克拉霉素)根除幽门螺杆菌(HP)治疗失败后的补救方案。方法将95名HP感染且三联疗法根除HP治疗失败的患者,随机分为试验组与对照组,并分别用新三联法(质子泵抑制剂 阿莫西林 左氧氟沙星)与四联法(质子泵抑制剂 铋剂 四环素 甲硝唑)比较,在治疗结束时和结束后4周,检测HP,并评价耐受性。结果在HP根除率和耐受性,试验组优于对照组。结论以左氧氟沙星为基础的新三联方案是有效的补救方案,优于四联方案。     

埃索美拉唑为基础的三联一线治疗幽门螺杆菌的疗效

目的 观察埃索美拉哗联合左氧氟沙星和阿莫西林一线治疗幽门螺杆菌的疗效.方法 163例幽门螺杆菌阳性患者,随机分为3组,分别应用埃索美拉唑20mg每13 2次(A组),埃索美拉唑40 mg每13 2次(B组),埃索美拉唑40 mg每日1次(C组),3组均加用左氧氟沙星500 mg每日1次和阿莫西林1000 mg每日2次,疗程7 d.并且对幽门螺杆菌根除率分别按意愿治疗(ITT)分析和方案(PP)分析进行评估.结果 A、B、C组各治疗方案的根除率:ITT法为82.98%、87.10%、70.37%;PP法为86.67%、88.52%,73.08%.B组明显高于C组(P<0.05).结论 埃索美拉唑联合左氧氟沙星和阿莫西林一线治疗能显著提高幽门螺杆菌根除率.     

Efficacy of low-dose clarithromycin triple therapy and tinidazole-containing triple therapy for Helicobacter pylori eradication

BACKGROUND: Proton pump inhibitor-based triple therapies are recommended as the first-line treatment for Helicobacter pylori eradication. AIM: To evaluate the efficacies of low-dose clarithromycin triple therapy and tinidazole-containing triple therapy in a metronidazole resistance prevalent area and to compare the efficacies with standard triple therapy. METHODS: In a randomized, multicentre, prospective study, a total of 352 patients with duodenal ulcer or non-ulcer dyspepsia were randomly divided into three groups according to the administered regimen: OAC250 group (omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 250 mg), OAC500 group (omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg) and OTC group (omeprazole, 20 mg, tinidazole, 500 mg, and clarithromycin, 500 mg). The three groups received each regimen twice daily for 7 days. Upper gastrointestinal endoscopy was performed before and 4 weeks after treatment. H. pylori status was determined by rapid urease test and 13C urea breath test. RESULTS: The eradication rates in the OAC250, OAC500 and OTC groups were 76.2%, 65.7% and 64.8% (95% confidence interval: 67.9-84.4%, 56.7-74.8% and 55.7-73.9%), respectively, by intention-to-treat analysis (P=0.149) and 92.8%, 87.2% and 84.1% (95% confidence interval: 84.4-97.3%, 77.9-93.8% and 73.9-91.2%), respectively, by per protocol analysis (P=0.088). All regimens were well tolerated and compliance was excellent. CONCLUSIONS: Both low-dose clarithromycin triple therapy and tinidazole-containing triple therapy are effective and safe regimens for H. pylori eradication.     

First-line triple therapy with levofloxacin for Helicobacter pylori eradication

BACKGROUND: At present, the efficacy of proton pump inhibitor-clarithromycin-amoxicillin regimen is relatively low. AIM: To evaluate the efficacy and tolerability of a first-line triple clarithromycin-free regimen including ranitidine bismuth citrate, levofloxacin and amoxicillin. METHODS: Design: Prospective study. Patients: Helicobacter pylori-positive patients complaining of dyspeptic symptoms referred for gastroscopy. Intervention: Levofloxacin (500 mg b.d.), amoxicillin (1 g b.d.) and ranitidine bismuth citrate (400 mg b.d.) was prescribed for 10 days. Outcome: Eradication was confirmed by a (13)C-urea breath test 8 weeks after therapy. Compliance with therapy was determined by questioning and the recovery of empty envelopes of medications. Incidence of adverse effects was evaluated by means of a specific questionnaire. RESULTS: Sixty-four patients were included (30% peptic ulcer, 70% functional dyspepsia). Almost all (97%) patients took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 88.5% (95% CI =78-95%) and 84.4 (74-91%). Adverse effects were reported in 9.5% of the patients, mainly including diarrhoea (7.9%); none of them were severe. CONCLUSION: This new 10-day levofloxacin-based combination represents an alternative to clarithromycin-based therapy, as it meets the criteria set for regimens used as primary H. pylori treatment: effectiveness (>80%), simplicity (twice-daily dosing and excellent compliance) and safety (low incidence of adverse effects).     

Prospective evaluation of ranitidine bismuth citrate-based triple therapy for the treatment of Helicobacter pylori infection

BACKGROUND: There is a need for effective and inexpensive therapy for Helicobacter pylori with good patient compliance. AIM: To evaluate a simplified twice daily schedule for treating H. pylori. METHODS: Patients infected with H. pylori (positive by CLO- and 13C-urea breath tests [UBT]) and not previously treated with anti-H. pylori therapy were treated with ranitidine bismuth citrate (RBC) and two inexpensive antibiotics (metronidazole, tetracycline) twice daily for 14 days in an open-label study. Eradication was established by a negative UBT 4 weeks after ending therapy. RESULTS: Twenty men and 30 women (age 54+/-14 years, range 26-74) were included in the study. Five patients were prematurely withdrawn (side-effects 2, took additional antibiotics 2 and surgery 1) and one patient was lost to follow-up; therefore, 44 (88%) patients completed the H. pylori eradication protocol. Per protocol (PP) cure rate was 82% (36/44 patients, 95% CI: 68-95%), and intention-to-treat cure rate was 72% (36/50 patients, 95% CI: 58-82%). Five patients (10%) developed side-effects during therapy, most commonly nausea (3 patients). Four weeks after the end of treatment, 78% (PP) of patients were symptomatically improved. CONCLUSIONS: A 2-week course of twice-daily RBC-based triple therapy was well tolerated, eradicated H. pylori in 72% (ITT) and 82% (PP) of patients, respectively, and relieved symptoms in 78%.     

三联疗法治疗胃幽门螺杆菌感染50例疗效观察

目的探讨奥美拉唑、左氧氟沙星、呋喃唑酮与奥美拉唑、阿莫西林、甲硝唑两种不同三联疗法治疗胃幽门螺杆菌感染的临床疗效。方法选取2011年10月～2012年10月本院收治的胃幽门螺杆菌感染患者100例,将其按照随机双盲原则分为观察组和对照组各50例,观察组采用奥美拉唑、左氧氟沙星、呋喃唑酮i联疗法治疗,对照组采用奥美拉唑、阿莫西林、甲硝唑三联疗法治疗,两组均以2周为1个疗程,疗程结束后比较两组的临床疗效及药物不良反应情况。结果观察组Hp根除率为96．OO％,明显高于对照组的82．00％,两组比较差异有统计学意义（χ2=4．986,P=0．037〈0．05）。观察组药物不良反应发生率为8．00％,对照组药物不良反应发生率为18．00％,两组比较差异无统计学意义（χ2=3．014,P=0．178〉0．05）。结论奥美拉唑、左氧氟沙星、呋喃唑酮三联疗法治疗胃幽门螺杆菌感染疗效优于奥美拉唑、阿莫西林、甲硝唑三联疗法,可以明显提高Hp根除率,无严重不良反应,值得临床推广应用。     

One-week clarithromycin triple therapy regimens for eradication of Helicobacter pylori

Background:

One-week triple therapies have been endorsed as the treatment regimens of choice for eradication of Helicobacter pylori infection. Those that include clarithromycin appear to be the most effective.

Aim:

To review reports of triple therapies that include clarithromycin.

Methods:

Reports were identified from the literature to May 1998. The variation between study designs prevents a formal meta-analysis. A measure of the relative efficacies of regimens has, however, been gained by comparison and by pooling of intention-to-treat eradication rates.

Results:

One hundred and ninety-two studies were identified which included 264 treatment arms of a 1-week triple therapy composed of clarithromycin with amoxycillin or a nitroimidazole (metronidazole or tinidazole), and either ranitidine bismuth citrate or a proton pump inhibitor (omeprazole, lansoprazole or pantoprazole). From reports of these studies, an intention-to-treat H. pylori eradication rate could be determined from 210 treatment arms of 151 studies.

Conclusions:

There is little to choose between the efficacies of 1-week clarithromycin-based triple therapy eradication regimens. However, those comprising clarithromycin, a nitroimidazole and either ranitidine bismuth citrate or a high dose of omeprazole are, in general, the most effective. Against antibiotic-resistant strains of H. pylori, regimens including ranitidine bismuth citrate may be more effective than those including a proton pump inhibitor.

     

Bismuth-containing single-antibiotic 1-week triple therapy for Helicobacter pylori eradication

Background:

Although bismuth was both the first drug shown to alter the natural history of peptic ulcer disease and also a constituent of the first very effective eradication regimens, it has been excluded from the newer regimens, despite its safety and low cost, in favour of two antibiotics.

Aim:

To asses a novel 1-week regimen consisting of bismuth, clarithromycin and a proton pump inhibitor in routine clinical practice.

Methods:

One hundred and three consecutive patients with peptic ulcer disease and antral biopsies containing Helicobacter pylori were given a 7-day course of treatment with bismuth (tripotassium dicitrato bismuthate chelate) 120 mg q.d.s., clarithromycin 500 mg t.d.s. and lansoprazole 30 mg o.d. Completeness of eradication was assessed by a ¹³C-urea breath test, in all except three patients, at least 4 months later.

Results:

Of the 100 patients who were assessed in this open treatment study 84 (84%; 95% CI: 77–91%) had a negative breath test. Minor side-effects were reported by 14% and more troublesome side-effects (nausea, vomiting, diarrhoea, hallucinations, nasty taste and body pains) were reported by 10%.

Conclusions:

A 1-week course of triple therapy including bismuth, clarithromycin and a proton pump inhibitor is effective in routine clinical practice and is well tolerated.

     

Low- versus high-dose azithromycin triple therapy for Helicobacter pylori infection

Background

We report a clinical trial which evaluated the effectiveness of triple therapy containing low- and high-dose azithromycin to treat Helicobacter pylori infection.

Methods

From March 1997 to March 1998, patients infected with H. pylori were assigned to receive either: Treatment 1: ranitidine bismuth citrate (RBC) (400 mg b.d.) and amoxycillin (1 g b.d.) for 10 days with azithromycin 500 mg o.m. for 3 days; or Treatment 2: RBC and amoxycillin for 10 days with azithromycin 1 g o.m. for 3 days. H. pylori eradication was established by a urea breath test at least 4 weeks after therapy. Side-effects and compliance were assessed using a diary.

Results

Sixty-eight patients were enrolled. Fifty-seven per cent of patients were treated for active peptic ulcer disease or a history of peptic ulcer disease. Treatment 1 cured H. pylori in 44% and 44% by per protocol and intention-to-treat analysis, respectively. The corresponding eradication rates for Treatment 2 were 79% and 75%. Two patients taking Treatment 2 dropped out of the study because of side-effects.

Conclusions

With RBC and amoxycillin for 10 days, azithromycin at a dose of 1 g/day for 3 days was significantly better at curing H. pylori infection than azithromycin 500 mg/day for 3 days.

     

A review of rescue regimens after clarithromycin-containing triple therapy failure (for Helicobacter pylori eradication)

Introduction: Helicobacter pylori infection is generally treated with therapies that include a proton pump inhibitor (PPI) and, at least, two antibiotics being clarithromycin one of the most used. Antibiotic resistance, mainly to clarithromycin, seems to be increasing in many geographical areas, and this factor is considered a main cause leading to a treatment failure when the later therapies contain this antibiotic again. As clarithromycin is a key antibiotic in the eradication of H. pylori, the election of the rescue treatment is a matter of debate.

Areas covered: The aim of this study is to systematically review the efficacy of the second-line rescue therapies after the failure of a first-line clarithromycin-containing regimen, and to link this information with the previous first-line treatment. Also, authors performed meta-analyses and inverse variance analyses with studies that met the inclusion criteria: first-line treatment must specify type and dosage; diagnosis and eradication confirmation must be performed by generally accepted tests; and second-line treatment must not be assigned depending on the antibiotic susceptibility or resistance.

Expert opinion: In a routine clinical practice setting, the most adequate second-line treatment consists in a 10-day regimen of levofloxacin– amoxicillin–PPI given twice daily, unless regional or new data show high quinolone resistance. Other good options are the bismuth quadruple regimen and a metronidazole–amoxicillin–PPI therapy.     

Rabeprazole-based 3-day and 7-day triple therapy vs. omeprazole-based 7-day triple therapy for the treatment of Helicobacter pylori infection

BACKGROUND: Rabeprazole is a new proton pump inhibitor with more potent acid suppressive and anti-Helicobacter effects. AIM: To compare two different regimens of rabeprazole-based triple therapy vs. 7-day omeprazole-based triple therapy for the eradication of Helicobacter pylori infection. METHOD: Patients with proven H. pylori infection were randomized to receive: (i) 7-day rabeprazole, 10 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; (ii) 3-day rabeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; or (iii) 7-day omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily. Endoscopy (CLO test, histology) was performed before randomization and 6 weeks after drug treatment. RESULTS: One hundred and seventy-three patients were randomized. H. pylori eradication rates (intention-to-treat, n=173/per protocol, n=167) were 88%/91% for 7-day rabeprazole-based therapy, 72%/72% for 3-day rabeprazole-based therapy and 82%/89% for 7-day omeprazole-based therapy, respectively. The per protocol eradication rate was significantly better in the 7-day rabeprazole-based therapy and 7-day omeprazole-based therapy groups when compared to the 3-day rabeprazole-based therapy group (P=0.01 and P=0.04, respectively). Compliance was excellent and all three regimens were well tolerated. CONCLUSIONS: The efficacy of seven-day rabeprazole-based triple therapy is similar to 7-day omeprazole-based triple therapy for the eradication of H. pylori infection.     

左氧氟沙星三联疗法根除幽门螺杆菌的临床研究

目的 研究含左氧氟沙星的三联疗法对幽门螺杆菌(HP)根除的疗效和安全性.方法 选择有HP感染的消化性溃疡、慢性胃炎伴胃黏膜糜烂萎缩的患者60例,随机均分为治疗组和对照组.治疗组选择埃索美拉唑+阿莫西林+左氧氟沙星三联疗法,疗程7 d;对照组选择埃索美拉唑+阿莫西林+克拉霉素经典三联疗法,疗程7 d.观察HP的根除率和不良反应情况.结果 含左氧氟沙星三联疗法与经典疗法均取得较好的HP根除率,分别为86.7%、82.1%,无明显差异,耐受性均较好.结论 含左氧氟沙星三联疗法可作为HP感染根除治疗的一线方案.     

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。     

One-week triple therapy with omeprazole, amoxycillin and clarithromycin for treatment of Helicobacter pylori infection

Background : Multi-drug regimens are generally required to reliably cure H. pylori infection. We previously demonstrated that a 2-week three-times-a-day regimen of amoxycillin and clarithromycin was effective against H. pylori infection.
Objectives : To evaluate the efficacy and side-effects of a 1-week twice-daily dosing schedule for the treatment of H. pylori infection.
Methods : We studied the efficacy of 1-week of therapy with 20 mg of omeprazole, 1 g of amoxycillin and 250 mg of clarithromycin, all twice daily H. pylori status was determined at entry and 4 or more weeks after completing antimicrobial therapy using histology (Genta stain) and culture.
Results : Thirty-one patients with documented peptic ulcer disease and H. pylori infection were treated. The H. pylori infection was cured in 24 (77%, 95% CI= 58–90%) (intention-to-treat). In a per protocol analysis the cure rate was 23 of 29 patients (79%, 95% CI= 60–92%). One patient took only 43% of the study drugs and another withdrew following development of an anaphylactic reaction to study medication. Mild side-effects were reported by 16% including diarrhoea, headache and altered taste. Compliance averaged 95%. Pretreatment clarithromycin resistance averaged 5% and had not been acquired by any strains post-therapy.
Conclusion : This combination of omeprazole, amoxycillin and low-dose clarithromycin resulted in a relatively low cure rate even in patients with clarithromycin-sensitive isolates. Large comparative studies will be needed to define the optimal duration, dose and dosing interval if this combination of drugs is to become competitive.     

A triple therapy regimen after failed Helicobacter pylori treatments

BACKGROUND: Following standard triple therapy, up to 20% of patients require further Helicobacter pylori eradication treatment. Data regarding the efficacy of re-treatment in these patients are scarce. AIM: To evaluate the efficacy of a triple therapy after one or more consecutive treatment failures. METHODS: A total of 51 patients with persistent H. pylori infection after at least one unsuccessful standard 1-week regimen were enrolled in the study. H. pylori infection at entry was assessed by rapid urease test and histology on biopsies from the antrum and the corpus. Patients were given a 2-week triple therapy, comprising ranitidine bismuth citrate 400 mg b.d., tetracycline 500 mg t.d.s., and tinidazole 500 mg b.d. Ranitidine bismuth citrate was given during meals, whilst tetracycline and tinidazole was given after meals. Bacterial eradication was assessed by endoscopy (36 patients) or 13C-urea breath test (15 patients) 4-6 weeks after therapy had ended. RESULTS: All 51 patients completed the study and H. pylori eradication was achieved in 46, with an eradication rate of 90% (95% CI: 82-98). In detail, bacterial eradication was obtained in 96% of patients who had previously failed one course of clarithromycin-amoxicillin based triple therapy, in 88% patients who had failed a clarithromycin-tinidazole based triple therapy, in 83% patients who had failed both treatment schedules, and in the only patient who had failed three consecutive therapeutic attempts. Two patients took the therapy for 9 and 10 days instead of the full 14 day-course. No major side-effects were reported, whilst six (12%) patients complained of mild side-effects. CONCLUSION: This study demonstrates that this triple therapy regimen is effective for re-treatment of H. pylori infection.