Helicobacter pylori therapy: first-line options and rescue regimen

In the present paper, several points regarding Helicobacter pylori treatment are reviewed, with the following conclusions: (1) all different proton pump inhibitors (PPIs) are equivalent when prescribed with antibiotics; (2) ranitidine bismuth citrate is equal to or, in some cases with antibiotic resistance, more effective than PPI; (3) previous treatment with PPI does not seem to affect the rate of eradication obtained with PPI plus two antibiotics; (4) just 1 week of PPI is enough to obtain duodenal ulcer healing, provided that H. pylori eradication is achieved; (5) the eradication rates seem to be higher in peptic ulcer than in nonulcer dyspepsia; (6) in areas where the prevalence of metronidazole resistance is high, triple therapy including a PPI, clarithromycin, and amoxicillin is the best option, and (7) quadruple therapy (PPI, bismuth, tetracycline, and metronidazole) is the recommended second-line therapy after PPI-clarithromycin-amoxicillin failure, although replacing the PPI and the bismuth compound by ranitidine bismuth citrate achieves also good results.     

'Rescue' therapies for the management of Helicobacter pylori infection

Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer and gastric cancer and should be considered as a major public health issue. According to several international guidelines, first-line therapy for treating H. pylori infection consists of proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) with any two antibiotics of amoxicillin, clarithromycin or metronidazole given for 7-14 days. However, even with the recommended treatment regimens, approximately 20% of patients will fail to obtain H. pylori eradication. The proportion of patients with first-line H. pylori therapy failure may be higher in clinical practice and it may increase thanks to diffusion of H. pylori treatment. The recommended second-line therapy is the quadruple regimen composed by tetracycline, metronidazole, bismuth salts and a PPI. However, the efficacy of this regimen is limited by poor patient's compliance due to its side effects, number of tablets per day, and long duration. Moreover, bismuth and metronidazole are not available in all countries. Alternatively, a longer-lasting (i.e. 10-14 days) PPI or RBC triple therapy with two antibiotics has generally been used. In an empirical strategy, the choice of second line depends on the treatment initially used. If a clarithromycin-based regimen was administered in first line, a quadruple regimen or PPI (or RBC) triple therapy with metronidazole and amoxicillin (or tetracycline) should be suggested as a second line. In case of second-line treatment failure, the patient should be evaluated by a case-by-case approach. A susceptibility-guided strategy, if available, is recommended in order to choose the best third-line treatment. Culture can reveal the presence of H. pylori-sensitive strains to clarithromycin (the best effective) or other antimicrobials (such as amoxicillin, metronidazole and tetracycline). Conversely, in an empirical strategy, a third-line not yet used therapy, can reach a high success rate. PPI or RBC, amoxicillin and a new antimicrobial (e.g. rifabutin, levofloxacin or furazolidone) could be used. Several studies have obtained relatively good results with triple therapy combining PPI, rifabutin, and amoxicillin, although a reversible myelotoxicity as leukopenia and thrombocytopenia has been described. Preliminary good results were also achieved with triples PPI regimens combining levofloxacin and amoxicillin without important adverse effects. Furazolidone has also shown efficacy for H. pylori eradication, although untoward reactions could limit its use, especially when high doses are employed. Finally, in more than one H. pylori treatment failure, non-antimicrobial add-on medications (such as lactoferrin, probiotics and others) could be used with the aim either to improve the eradication rate or to minimize side effects.     

Third-line rescue therapy for Helicobacter pylori infection

H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to H pylori infection and therefore can be treated with antibiotics is an important medical advance. Currently, a first-line triple therapy based on proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) plus two antibiotics (clarithromycin and amo-xicillin or nitroimidazole) is recommended by all consensus conferences and guidelines. Even with the correct use of this drug combination, infection can not be eradicated in up to 23% of patients. Therefore, several second line therapies have been recommended. A 7 d quadruple therapy based on PPI, bismuth, tetracycline and metronidazole is the more frequently accepted. However, with second-line therapy, bacterial eradication may fail in up to 40% of cases. When H pylori eradication is strictly indicated the choice of further treatment is controversial. Currently, a standard third-line therapy is lacking and various protocols have been proposed. Even after two consecutive failures, the most recent literature data have demonstrated that H pylori eradication can be achieved in almost all patients, even when antibiotic susceptibility is not tested. Different possibilities of empirical treatment exist and the available third-line strategies are herein reviewed.     

An update on anti-Helicobacter pylori treatment in children.

Previous consensus statements have recommended one- to two-week proton pump inhibitor (PPI)-based triple therapies with clarithromycin and either amoxicillin or metronidazole as first-line treatments for children with Helicobacter pylori infection. The objective of the present review was to summarize data from pediatric studies that have examined treatment efficacy, safety, drug resistance and reinfection rates related to anti-H. pylori therapies. Data from a recent meta-analysis of pediatric studies were used along with the authors' existing databases and searches of individual studies. Regimens that were identified as greater than 80% efficacious in children included a two-week therapy with a nitroimidazole and amoxicillin in Europe; a two-week regimen of bismuth, amoxicillin and metronidazole in developed countries (except Spain); a one- to two-week regimen of a PPI, clarithromycin and amoxicillin in Northern Europe, Asia and the Middle East; and a two-week regimen of a PPI, clarithromycin and metronidazole in Canada. Although recommended as a first-line treatment in adults, two-week treatment with a PPI, clarithromycin and amoxicillin eradicated only 68% of H. pylori infections in North American children. Treatment efficacy was reduced in the presence of metronidazole and/or clarithromycin resistance. Further studies of anti-H. pylori treatments in children in North America and developing countries are warranted.     

Ranitidine bismuth citrate-based triple therapies as a second-line therapy for Helicobacter pylori in Turkish patients

BACKGROUND: Quadruple therapy with a proton pump inhibitor, bismuth, metronidazole and tetracycline is recommended as the optimal second-line therapy of Helicobacter pylori infection in the Maastricht Consensus Report. The aim of the present paper was to evaluate the efficacy of ranitidine bismuth citrate (RBC)-based regimens as second-line therapies after failure of the standard Maastricht triple therapy. MATERIALS AND METHODS: One hundred and sixteen H. pylori-positive patients were given omeprazole 20 mg b.d., clarithromycin 500 mg b.d., and amoxicillin 1 g b.d for 10 days. Patients remaining H. pylori-positive (n = 29) were combined with 27 patients enrolled after an initial eradication failure from proton-pump inhibitor (PPI), amoxicillin and clarithromycin therapy for at least 7 days and were randomly given one of the following second-line 10-day treatments: RBC 400 mg b.d., amoxicillin 1 g b.d and clarithromycin 500 mg b.d. (RAC group, n = 28) and RBC 400 mg b.d., metronidazole 500 mg b.d and tetracycline 500 mg b.d. (RMT group, n = 28). Eradication was assessed by either histology and rapid urease test or (13)C urea breath test 8 weeks after therapy. RESULTS: The eradication rate of first-line Maastricht therapy was 67% for intention-to-treat analysis (95% confidence interval [CI]: 58-75). Per-protocol and intention-to-treat eradication was achieved in 60.7% of patients (95%CI: 42-79) in the RAC group and in 85.7% of patients (95%CI: 73-98) in the RMT group (P = 0.03). Fifty-three percent of patients in the RAC and 50% of patients in the RMT group experienced at least one slight side-effect (P = 0.6). CONCLUSIONS: RMT is an effective and well-tolerated second-line therapy after H. pylori eradication failure from PPI, amoxicillin, and clarithromycin.     

Helicobacter pylori infection: treatment options

After two decades of progress the best current approach to treatment of Helicobacter pylori infection is a strategy that combines two consecutive complementary treatments. Current guidelines recommend a first-line triple therapy - 7-10 days of a proton-pump inhibitor (PPI), clarithromycin and amoxicillin - followed by a quadruple therapy combining a PPI, metronidazole, tetracycline and a bismuth salt for treatment failures. Regrettably, present cure rates for first-line triple therapy are below 80%, and many patients require second-line treatment with further testing and control visits. Although most compliant patients are cured by the second-line treatment, patients often do not complete the full process and, as a result, final cure rates for the whole strategy often fall below 90%. This means that more effective first-line therapies are required. Promising recent developments include using quadruple therapy as first-line therapy, the use of adjuvant lactoferrin with triple therapy and a newly devised combination of a PPI, clarithromycin, amoxicillin and metronidazole, known as sequential treatment. Additional future developments will require the incorporation of new antibiotic weapons in the anti-H. pylori arsenal. The new quinolones and rifamycin derivates have recently demonstrated their efficacy in the treatment of H. pylori infection.     

The efficacy of levofloxacin based triple therapy for Helicobacter pylori eradication]

BACKGROUND/AIMS: The failure rates of first and second line therapies of Helicobacter pylori (H. pylori) eradication range from 15 to 20%. This study was aimed to evaluate the efficacy and safety of levofloxacin based triple therapy compared with standard triple or quadruple therapy for H. pylori eradication in Korea. METHODS: We enrolled two hundred and sixty seven patients with presence of H. pylori infection. One hundred and forty-one patients were treated with levofloxacin based triple therapy (LAP; levofloxacin, amoxicillin, proton pump inhibitor; PPI), and 126 patients were treated with standard triple therapy (CAP; clarithromycin, amoxicillin, PPI). We retreated the patients who had failed in H. pylori eradication with standard quadruple second-line therapy (MTPB; metronidazole, tetracycline, PPI, bismuth subcitrate) or levofloxacin based therapy (LAP or LCP; levofloxacin, clarithromycin, PPI). RESULTS: In first line therapy of H. pylori eradication, the eradication rates of levofloxacin based triple therapy and standard triple therapy were 69.8% and 74.0% respectively (p=0.52). In second-line therapy, the eradication rate of levofloxacin based triple therapy and standard quadruple therapy were 62.5% and 40.0% respectively (p=0.34). CONCLUSIONS: Levofloxacin based triple therapy is effective as standard regimen to eradicate H. pylori infection and is useful for an alternative rescue therapy as well.     

Randomized Comparison of Ranitidine Bismuth Citrate-Based Triple Therapies for Helicobacter pylori

Objectives: In an attempt to increase the efficacy and simplicity of FDA-approved regimens for Helicobacter pylori , we studied (1) addition of an inexpensive antibiotic (amoxicillin) to twice-daily ranitidine bismuth citrate (RBO-clarithromycin dual therapy, and (2) substitution of RBC for bismuth subsalicylate + H2-receptor antagonist in bismuth-based triple therapy. Methods : Subjects with previously untreated Helicobacter pylori infection documented by ¹³C-urea breath test plus either endoscopic biopsy or serology were randomly assigned to a 2-wk course of (1) RBC 400 mg b.i.d. , amoxicillin 1 g b.i.d. , and clarithromycin 500 mg b.i.d. (RAC), or (2) RBC 400 mg b.i.d. , metronidazole 250 mg t.i.d. , and tetracycline 500 mg t.i.d. (RMT). Repeat breath test was performed 4 wk after the completion of therapy. Results : Intent-to-treat and per-protocol cure rates for RAC were 46 of 50 patients (92%) and 45 of 47 patients (96%); for RMT they were 40 of 50 patients (80%) and 37 of 42 patients (88%). Study drugs were stopped due to side effects in three patients (6%) taking RAC and six patients (12%) taking RMT. Conclusions : Twice-daily RBC-based triple therapy with clarithromycin and amoxicillin produces Helicobacter pylori eradication rates over 90%, which is comparable to rates seen with proton pump inhibitor-based triple therapies. RBC also may be substituted for bismuth subsalicylate and an + H2-receptor antagonist in standard bismuth-based triple therapy.     

Helicobacter pylori diagnosis and management

H pylori is a global human pathogen and is the major cause of gastritis and the gastritis-associated diseases: gastric ulcer, duodenal ulcer, gastric cancer, and primary gastric B-cell lymphoma (MALToma). Although several reliable diagnostic tests are widely available, the ideal regimen for treating the infection re-mains to be established. The current first-line or legacy triple therapy regimens fail in 20% to 40% of patients. Causes of treatment failure include antibiotic resistance, poor compliance, short (7-10 days) duration of therapy, and drug-related side effects. Fourteen-day triple therapy has an approximately 12% better cure rate than does 7-day therapy; therefore, shorter durations can no longer be recommended. Recent studies confirmed older observations that the success rate of legacy triple regimens (PPI plus two antibiotics) can be improved if the duration is extended to 14 days or if a third antibiotic is given. Sequential therapy (PPI plus amoxicillin followed by a PPI plus clarithromycin plus metronidazole) requires further evaluation although the concept appears very promising and therapy should probably replace the legacy triple therapies. More studies are needed to examine doses, durations, and the need for sequential administration of the drugs, which extends the duration to 14 days. Nonetheless, sequential quadruple therapy probably should replace the legacy triple therapies. Classic quadruple therapy contains bismuth, a PPI, 1500 mg of metronidazole, and 1500 mg of tetracycline. It provides the highest average eradication rates and in many regions should be considered as the initial approach. Confirmation of eradication using noninvasive diagnostic tests, such as a urea breath test or stool antigen assay, is now the standard of care. The diagnosis of latent or symptomatic H pylori like the diagnosis of latent or symptomatic syphilis, always should prompt treatment. Because of decreasing cure rates, new and improved therapies are needed.     

幽门螺杆菌不同治疗方案的疗效评估

目的 对本院门诊患者根除幽门螺杆菌(Hp)的不同治疗方案进行疗效比较.方法 选择2005年1月～2007年7月我院就诊的幽门螺杆菌治疗前后资料完整的患者522例,质子泵抑制剂(PPI) 克拉霉素 硝基咪唑类121例,PPI 克拉霉素 阿莫西林135例,PPI 硝基咪唑类 阿莫西林80例;枸橼酸铋雷尼替丁 克拉霉素 硝基咪唑类63例,枸橼酸铋雷尼替丁(RBC) 克拉霉素 阿莫西林81例,RBC 硝基咪唑类 阿莫西林42例.结果 PPI 两种抗生素的治疗方案中,PPI 克拉霉素 阿莫西林的Hp根除率显著高于PPI 克拉霉素 硝基咪唑组,而与PPI 阿莫西林 硝基咪唑组比较无显著性差异;RBC 两种抗生素的治疗方案中,RBC 克拉霉素 阿莫西林的Hp根除率最高;在使用相同的抗生素的情况下,PPI组与RBC组根除Hp比较无显著性差异.结论 选择PPPI/RBC 克拉霉素 阿莫西林能更有效地根除Hp.     

Effectiveness of triple therapy and quadruple therapy for Helicobacter pylori eradication]

BACKGROUND/AIMS: Quadruple therapy can be considered as a first-line therapy in areas where the resistance rate to clarithromycin is high. Comparison study of triple therapy and quadruple therapy for Helicobacter pylori (H. pylori) eradication is still lacking in Korea despite the increasing prevalence of antibiotic resistance. This study was conducted to compare the efficacy of triple and quadruple therapy as a first-line treatment in H. pylori infected patients with peptic ulcer. METHODS: Consecutive 149 cases of peptic ulcer disease associated with H. pylori infection were randomized either to proton pump inhibitor (PPI, bid), amoxicillin (1,000 mg, bid), and clarithromycin (500 mg, bid) (PAC group) or to PPI (bid), bismuth subcitrate (300 mg, qid), metronidazole (500 mg, tid), and tetracycline (500 mg, qid) (PBMT group) eradication treatments for 7 days. Outcome of eradication therapy was assessed by 13C-urea breath test performed 4-6 weeks after eradication. RESULTS: Eradication rates in PAC and PBMT group were 78.7% (59/75) and 71.6% (53/74) by intention to treat analysis, respectively (p=0.424). By per protocol analysis, eradication rates of PAC and PBMT group were 85.5% (59/69) and 85.5% (53/62), respectively (p=1.012). Adverse reactions occurred in 5 (6.6%) and 7 (9.5%) patients in PAC and PBMT group, respectively (p=0.346). CONCLUSIONS: One week-quadruple therapy as a first-line treatment for H. pylori infection does not offer any advantage over PPI-based triple therapy in Korean patients.     

One-week ranitidine bismuth citrate versus colloidal bismuth subcitrate-based anti-Helicobacter triple therapy: a prospective randomized controlled trial

OBJECTIVE: The efficacy of 1 wk bismuth triple therapy is adversely influenced by the presence of metronidazole resistance. In vitro studies suggest that ranitidine bismuth citrate (RBC) plus metronidazole exhibit synergistic activity against metronidazole resistant strains of Helicobacter pylori (H. pylori). Whether this confers a superior clinical efficacy remains unproven. This study compared the efficacy of RBC-based triple therapy with bismuth triple therapy in eradication of H. pylori. METHODS: Patients with H. pylori-related ulcer disease or gastritis were randomized to receive either 400/mg of RBC twice daily plus 400/mg of metronidazole and 500/mg of tetracycline four times daily for 1 wk (RMT) or 120/mg of colloidal bismuth subcitrate, 400/mg of metronidazole, and 500/mg of tetracycline, all given four times daily for 1 wk (BMT). Metronidazole susceptibility was determined by the E-test and pretreatment resistance was defined as minimum inhibitory concentration > or = 32/mg/L. RESULTS: Of 100 consecutive patients randomized, two patients were lost to follow-up in each group. Forty-three of 85 (51%) H. pylori isolates were metronidazole resistant. Per-protocol cure rate for RMT and BMT was 40 of 41 (98%) and 37 of 44 (84%), respectively (p = 0.058). Intent-to-treat cure rate for RMT and BMT was 46 of 50 and 41 of 50, respectively (92% vs 82%, p = 0.23). A significantly higher eradication of metronidazole resistant H. pylori was observed in the RMT group (25 of 25, 100%) than in the BMT group (12 of 16, 75%), (p = 0.018). Side effects observed in the two treatment groups were comparable. CONCLUSIONS: One week of RBC triple therapy with metronidazole and tetracycline is an effective anti-Helicobacter therapy. This regimen is more appropriate in areas of high prevalence of metronidazole resistance.     

Helicobacter pylori eradication therapy is more effective in peptic ulcer than in non-ulcer dyspepsia.

AIM: To evaluate whether eradication therapy is more effective in peptic ulcer disease (PUD) than in non-ulcer dyspepsia (NUD). METHODS: We retrospectively studied 481 patients with NUD (183 patients) or PUD (298 patients) infected with Helicobacter pylori included in several prospective clinical trials. Three eradication regimens were given: (1) proton pump inhibitor (PPI) plus clarithromycin, plus either amoxycillin or metronidazole for 7 days (297 patients); (2) ranitidine bismuth citrate (RBC) plus clarithromycin plus amoxycillin for 7 days (79 patients); and (3) RBC plus clarithromycin plus amoxycillin plus metronidazole for 5 days (105 patients). H. pylori eradication was defined as a negative 13C-urea breath test 4 weeks after completing treatment. RESULTS: H. pylori eradication rates were 82% (95% CI 78-87%) with PPI plus two antibiotics for 7 days, 85% (95% CI 75-91%) with RBC plus two antibiotics for 7 days, and 91% (95% CI 86-97%) with RBC plus three antibiotics for 5 days (P < 0.05 compared with the first regimen). Overall, the H. pylori eradication rate in patients with NUD was 78% (95% CI 71-84%), while in patients with PUD it was 89% (95% CI 86-93%) (P < 0.001). Both the combination of PPI plus two antibiotics for 7 days and the combination of RBC plus three antibiotics for 5 days were more effective in PUD than in NUD patients. However, RBC plus clarithromycin plus amoxycillin for 7 days was equally effective in both diseases. RBC plus two antibiotics for 7 days achieved better results than the same therapy with PPI only in NUD patients (84% v. 59%, P < 0.01), but both regimens were similar when prescribed in PUD patients (86% v. 88%). In the multivariate analysis, the type of therapy, the diagnosis (NUD v. PUD), and the product variable of therapy (with RBC plus 2 antibiotics for 7 days) and diagnosis (interaction variable) were the only variables that influenced H. pylori eradication. The odds ratio (OR) for the effect of RBC versus PPI plus two antibiotics for 7 days in patients with NUD was 4 (95% CI 1.7-9.7; P < 0.01), whereas in patients with PUD no statistical significance was achieved (OR 0.79; 95% CI 0.2-3.9). CONCLUSION: Overall, H. pylori eradication therapy is more effective in PUD than in NUD patients. This advantage of eradication therapies in PUD patients seems to be observed with 7-day PPI-based triple regimens, and with 5-day RBC-based quadruple therapy, while the 7-day RBC-based triple regimen seems to be equally effective in both diseases.     

How to proceed in Helicobacter pylori-positive chronic gastritis refractory to first- and second-line eradication therapy

Helicobacter pylori is a widespread disease causing most of the peptic ulcer diseases and low-grade mucosa-associated lymphoreticular tissue (MALT) lymphoma. Moreover, H. pylori is a proven environmental risk factor for gastric carcinoma and it has been recognized as a type 1 carcinogen factor. A combination of drugs has been proposed, using a proton pump inhibitor (PPI), amoxicillin, clarithromycin, metronidazole and tetracycline to treat the infection. Since 1996, according to the European guidelines, the first-line approach using PPI, amoxicillin and clarithromycin or metronidazole has been suggested. Seven days of quadruple therapy with PPI (or ranitidine), tetracycline, bismuth salts and metronidazole has been reserved as second-line treatment. To improve the eradication rate of the triple therapy, a different combination of the available antibiotics has been proposed, consisting of a 10-day sequential regimen. A second-line levofloxacin-amoxicillin-based triple therapy given for 10 days has been proposed, obtaining a high eradication rate, suggesting this regimen to be a suitable retreatment option in eradication failure. A third-line treatment with rifabutin-based regimen has been proposed.     

Development of Helicobacter pylori treatment: How do we manage antimicrobial resistance?

Helicobacter pylori(H. pylori) antimicrobial resistance is an urgent, global issue. In2017, the World Health Organization designated clarithromycin-resistant H.pylori as a high priority bacterium for antibiotic research and development. In addition to clarithromycin, resistance to metronidazole and fluoroquinolones has also increased worldwide. Recent international guidelines for management of H.pylori infection recommend bismuth or non-bismuth quadruple therapy for 14 d as a first-line treatment for H. pylori in areas of high clarithromycin and/or metronidazole resistance. Although these treatment regimens provide acceptable H. pylori eradication rates, the regimens used should not contribute to future resistance of H. pylori to antimicrobials. Moreover, these regimens can promote resistance, due to prolonged therapy with multiple antibiotics. A new strategy that can eradicate H. pylori as well as reduce the antibiotics used is required to prevent future antimicrobial resistance in H. pylori. Dual-therapy with vonoprazan and amoxicillin could be a breakthrough for H. pylori eradication in an era of growing antimicrobial resistance. This regimen may provide a satisfactory eradication rate of H. pylori and also minimize antimicrobial resistance due to single antibiotic use and the strong inhibitory effect of vonoprazan on gastric acid secretion.     

Optimal therapy for Helicobacter pylori infections

Although Helicobacter pylori infection is both a common and a serious bacterial infection, antimicrobial therapies have rarely been optimized, are prescribed empirically, and provide inferior results compared with antimicrobial therapies for other common infectious diseases. The effectiveness of many of the frequently recommended H. pylori infection treatment regimens has been increasingly compromised by antimicrobial resistance. Regional data on the susceptibility of strains of H. pylori to available antimicrobials are sorely needed. Noninvasive molecular methods are possible to assess clarithromycin susceptibility in isolates obtained from stool specimens. As a general rule, clinicians should prescribe therapeutic regimens that have a ≥90% or, preferably, ≥95% eradication rate locally. If no available regimen can achieve a ≥90% eradication rate, clinicians should use the most effective regimen(s) available locally. Eradication of infection should always be confirmed after treatment in order to provide feedback regarding local effectiveness and an early warning of increasing resistance. In most regions of the world, four-drug treatment regimens, including a PPI plus three antimicrobials (clarithromycin, metronidazole/tinidazole and amoxicillin), or a PPI plus a bismuth plus tetracycline and metronidazole provide the best results. Standard triple therapy (a PPI, amoxicillin and clarithromycin) should now be avoided owing to increasing resistance to this treatment.     

A meta-analysis of the success rate of Helicobacter pylori therapy in Canada.

BACKGROUND AND AIM: Helicobacter pylori treatment success rates have varied. A systematic review of the success rate of anti- H pylori therapy in Canada was performed. METHODS: All clinical trials containing Canadian data on the success rate of H pylori treatment were identified using MEDLINE searches, through review of references of retrieved studies and by contacting key investigators. Both randomized and open-label trials were included. Treatment effect size was calculated using a variation of Cochran's Q method. RESULTS: Seventeen papers met the inclusion criteria. Both triple therapies consisting of a proton pump inhibitor (PPI), clarithromycin and either amoxicillin or metronidazole performed well, achieving a success rate of 84% and 82%, respectively. The cure rate of PPI-amoxicillin + metronidazole was 76%. Quadruple therapy consisting of a PPI, bismuth, metronidazole and tetracycline, given for seven to 10 days, achieved a success rate of 87%. CONCLUSION: Both PPI-based triple therapy and quadruple therapy perform well in Canada for the treatment of H pylori infection.     

以泮托拉唑为基础的三联和四联疗法根除幽门螺杆菌疗效比较——一项单中心、随机、开放、平行对照研究

背景：近年质子泵抑制剂（PPI）＋阿莫西林＋克拉霉素标准三联疗法对幽门螺杆菌（H.pylori）的根除率有所降低,PPI＋铋剂＋甲硝唑＋四环素的四联疗法能否成为一线治疗的首选以及适当延长疗程能否提高根除率尚有待明确。目的：比较以泮托拉唑为基础的7d标准三联疗法与7d、10d四联疗法根除H.pylori的疗效。方法：133例非溃疡性消化不良的H.pylori感染患者随机分配至7d三联组（45例,泮托拉唑40mgbid＋阿莫西林1.0gbid＋克拉霉素500mgbid,PAC方案）以及7d、10d四联组（43例和45例,泮托拉唑40mgbid＋枸橼酸铋钾220mgbid＋甲硝唑400mgtid＋四环素750mgbid,PBMT方案）。治疗结束后至少间隔4周行13C-尿素呼气试验复查H.pylori,评估治疗结果。结果：共129例患者按方案完成治疗。三组H.pylori根除率按意图治疗（ITT）分析分别为73.3%、79.1%和88.9%,按方案（PP）分析分别为75.0%、82.9%和90.9%。7dPAC方案的PP根除率显著低于10dPBMT方案（P〈0.05）。除四联组中有2例患者分别因头晕和腹泻而未完成治疗外,其余患者的不良反应相似且均能耐受。结论：在7d标准三联疗法H.pylori根除疗效降低的情况下,含泮托拉唑、铋剂、甲硝唑和四环素的10d四联疗法可考虑作为根除治疗的首选方案。     

Evaluation of triple and quadruple Helicobacter pylori eradication therapies in Iranian children: a randomized clinical trial

BACKGROUND: Clinical trials in children concerning Helicobacter pylori eradication treatments are scarce. The purpose of this study was to assess the efficacy of proton pump inhibitor (PPI)-based triple therapy using PPI, amoxicillin and clarithromycin in Iranian children. We also evaluated the efficacy of quadruple therapy with PPI, metronidazole, amoxicilin and bismuth citrate in Iranian children. METHODS: This was a randomized clinical trial performed in Emam Khomeini Hospital between 2003 and 2004. Patients with confirmed H. pylori infection by histology were divided into two groups in a randomized 1:1 scheme: the triple regimen group (omeprazole, clarithromycin and amoxicillin for 10 days) and the quadruple regimen group (omeprazole, amoxicillin, metronidazole and bismuth citrate for 10 days). The eradication was assessed by the C-urea breath test 4 weeks after the end of treatment and analyzed by per-protocol and intention-to-treat approaches. RESULTS: One hundred and twenty-two patients (mean age 12.36+/-3.06 years) were entered into the study. Only 100 patients completed the study (50 patients in each regimen group). The eradication rates by triple therapy were 92% and 75.5% for the "per-protocol" and "intention-to-treat" approaches, respectively. In the quadruple regimen group, the eradication rates were 84% by the per-protocol approach and 68.8% in the intention-to-treat approach. Symptom responses to therapy were reported in all patients with successful eradication (88% of all patients). CONCLUSION: With regard to recent recommendations, we also suggest PPI, amoxicillin and clarithromycin triple therapy as a first-line eradication treatment, and quadruple therapies as a second-line option, in Iranian children.     

Ranitidine bismuth citrate.

Recognition of the relationship between Helicobacter pylori infection and the development of gastroduodenal disease has increased greatly in recent years. To avoid complications of H pylori infection, such as the development of recurrent duodenal and gastric ulcers, effective therapies are required for eradication of the infection. This article reviews ranitidine bismuth citrate (RBC), a novel complex of ranitidine, bismuth and citrate, which was developed specifically for the purpose of eradicating H pylori. Dual therapy with RBC in combination with clarithromycin for 14 days yields eradication rates of 76%. Triple therapy bid for one week with a proton pump inhibitor, clarithromycin and either amoxicillin or a nitroimidazole (tinidazole or metronidazole) is advocated as the treatment of choice for H pylori eradication. Analogous regimens with RBC in place of proton pump inhibitors show effective eradication rates in comparative studies and with pooled data. RBC, used alone or in combination with other antibiotics, appears to be a safe and effective drug for the treatment of H pylori infection. Bismuth levels do not appear to rise to toxic levels.