Efficacy of omeprazole and amoxicillin with either clarithromycin or metronidazole on eradication of Helicobacter pylori in Chinese peptic ulcer patients

AIM: One-week triple therapy with proton pump inhibitors, clarithromycin and amoxicillin has recently been proposed as the first-line treatment for Helicobacter pylori (H pylori) infection; however, data regarding the effects of this regimen in China are scarce. The aim of this prospective and randomized study was to compare the efficacy of clarithromycin and metronidazole when they were combined with omeprazole and amoxicillin on eradication of H pylori and ulcer healing in Chinese peptic ulcer patients. METHODS: A total of 103 subjects with Hpylori-positive peptic ulcer were randomly divided into two groups, and accepted triple therapy with omeprazole 20 mg, amoxicillin 1 000 mg and either clarithromycin 500 mg (OAC group, n = 58) or metronidazole 400 mg (0AM group, n - 45). All drugs were given twice daily for 7 d. Patients with active peptic ulcer were treated with omeprazole 20 mg daily for 2-4 wk after anti-H pylori therapy. Six to eight weeks after omeprazole therapy, all patients underwent endoscopies and four biopsies (two from the antrum and two others from the corpus of stomach) were taken for rapid urease test and histological analysis (with modified Giemsa staining) to examine H pylori. Successful eradication was defined as negative results from both examination methods. RESULTS: One hundred patients completed the entire course of therapy and returned for follow-up. The eradication rate of H pylori for the per-protocol analysis was 89.3% (50/56) in OAC group and 84.1% (37/44) in 0AM group. Based on the intention-to-treat analysis, the eradication rate of H pylori was 86.2% (50/58) in OAC group and 82.2% (37/45) in 0AM group. There were no significant differences in eradication rates between the two groups on either analysis. The active ulcer-healing rate was 96.7% (29/30) in OAC group and 100% (21/21) in 0AM group (per-protocol analysis, P>0.05). Six patients in OAC group (10.3%) and five in OAM group (11.1%) reported adverse events (P>0.05). CONCLUSION: One-week triple therapy with omeprazole and amoxicillin in combination with either clarithromycin or metronidazole is effective for the eradication of H pylori. The therapeutic regimen comprising metronidazole with low cost, good compliance and mild adverse events may offer a good choice for the treatment of peptic ulcers associated with H pylori infection in China.     

Will H. pylori stagger under the weight of this LOAD? A novel but expensive eradication regimen

In the era of increasing Helicobacter pylori resistance to clarithromycin and metronidazole used in standard treatments, newer well-tolerated regimens with high eradication success rates in practice are urgently needed. In this edition of the American Journal of Gastroenterology, a clinical trial of a novel drug combination is presented, demonstrating significantly more success in comparison with a standard "triple therapy." The new regimen (referred to as LOAD) comprises three antibiotics, levofloxaxin, doxycycline, and nitazoxanide, together with omeprazole. The LOAD regimen had around a 90% eradication rate compared with only 73% with a standard "triple therapy" regimen of amoxicillin, clarithromycin, and lansoprazole. The use of this relatively expensive novel drug combination would represent an absolute increased eradication rate of 17%, with a number needed to treat to achieve one more successful eradication of 5.88. Results from this preliminary study should prompt further evaluation of LOAD in rigorously designed clinical studies.     

Effectiveness of 10 day-sequential therapy for Helicobacter pylori eradication in Korea

BACKGROUND/AIMS: Antibiotic resistance and poor compliance are the main causes of Helicobacter pylori (H. pylori) eradication failure. Proton pump inhibitor (PPI)-based triple therapy is the most preferred regimen in clinical practice. However, a critical fall in the H. pylori eradication rate has been observed in the recent years. A novel 10 day-sequential therapy consists of five days of dual therapy followed by five days of triple therapy regimen has recently been described. We aimed to evaluate whether 10 day-sequential therapy eradicated H. pylori infection better than the PPI-based triple therapy in Korea. METHODS: 158 patients with proven H. pylori infection were randomized to receive either 10 day-sequential therapy (20 mg of omeprazole, 1.0 g of amoxicillin, each administered twice daily for the first 5 days, followed by 20 mg of omeprazole, 500 mg of clarithromycin, 500 mg of metronidazole, each administered twice daily for the remaining 5 days) or PPI-based triple therapy (20 mg of omeprazole, 1.0 g of amoxicillin, 500 mg of clarithromycin, each administered twice daily for 1 week). Outcome of eradication therapy was assessed 8 weeks after the cessation of treatment. RESULTS: Eradication rates of 10 day-sequential therapy and PPI-based triple therapy were 77.9% (60/77) and 71.6% (58/81) by intention to treat analysis, respectively (p=0.361). By per protocol analysis, eradication rates of 10 day-sequential therapy and triple therapy were 85.7% (60/70) and 76.6% (58/76), respectively (p=0.150). There were no significant differences in adverse event rates and treatment compliance between two groups. CONCLUSIONS: The 10 day-sequential therapy regimen failed to achieve significantly higher eradication rates than PPI-based triple therapy.     

Antibiotic treatment for Helicobacter pylori : Is the end coming?

Infection with the Gram-negative pathogen Helicobacter pylori(H. pylori) has been associated with gastroduodenal disease and the importance of H. pylori eradication is underscored by its designation as a groupI carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacil us. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication.     

Comparison of the effectiveness of quadruple salvage regimen for Helicobacter pylori infection according to the duration of treatment]

BACKGROUND/AIMS: At present, triple therapy schemes are recommended by national and international consensus conferences for the treatment of Helicobacter pylori (H. pylori) infection. However, even with the most effective current treatment regimens, about 10-20% of patients fail to eradicate H. pylori, necessitating alternative strategy to eradicate H. pylori in primary treatment failure. Therefore, we performed this study to evaluate the efficacy of quadruple therapy and to compare 1 and 2-week quadruple regimen as a second-line therapy. METHODS: The hospital records of 155 patients who failed to the standard triple therapy (proton pump inhibitor, amoxicillin, clarithromycin) were reviewed retrospectively, and divided the 1 or 2 weeks OBMT regimen (omeprazole 20 mg bid, bismuth salt 120 mg qid, metronidazole 500 mg tid, tetracycline 500 mg qid). Presence of H. pylori infection and side-effects of the treatment regimen were assessed 4 weeks after the cessation of treatment. RESULTS: One hundred and eight male and 47 female (mean age, 52.2+/-15.4) patients were enrolled. The overall eradication rate of H. pylori with quadruple therapy was 83.9% and the eradication rate was similar between 1 and 2 weeks of OBMT regimen (76.8% in OBMT 1 week, 87.9% in OBMT 2 weeks, respectively p=0.110). CONCLUSIONS: Quadruple therapy is an effective salvage regimen for H. pylori eradication after the failure of standard triple therapy. One week quadruple therapy is not significantly different from 2-weeks regimen as the second-line option for H. pylori eradication.     

Comparison of 1 and 2 weeks of omeprazole, amoxicillin and clarithromycin treatment for Helicobacter pylori eradication: the HYPER Study

BACKGROUND: Triple therapy is recommended for Helicobacter pylori eradication, yet consensus on the duration of treatment is lacking. AIM: To compare the efficacy and safety of 1- and 2-week regimens of omeprazole, amoxicillin and clarithromycin in a large, multicentre, double-blind and randomised study. METHODS: A total of 909 H pylori-positive patients with duodenal ulcer, enrolled in 81 endoscopy units in Italy, were randomised to receive omeprazole, amoxicillin and clarithromycin for either 1 week (OAC1W) or 2 weeks (OAC2W) or omeprazole and amoxicillin for 2 weeks. H pylori eradication was assessed by histological examination and carbon-13 urea breath test 4 weeks after treatment. RESULTS: Both the intention-to-treat (ITT; n = 907) and per protocol (PP; n = 661) analyses showed no significant differences between the eradication rates of OAC1W (ITT 79.7%; PP 83.6%) and OAC2W (ITT 81.7%; PP 84.9%; ITT p = 0.53; PP p = 0.71). Both triple omeprazole, amoxicillin and clarithromycin regimens gave significantly higher eradication rates compared with omeprazole and amoxicillin treatment (ITT 44.6%; PP 42.8%; p<0.001). Poor compliance was reported in 18.6%, 17.3% and 15.1% (p = 0.51) of patients for OAC2W, OAC1W and omeprazole and amoxicillin, respectively. Adverse events occurred in 9.9% and 9.6% (p = 0.88) of patients for OAC2W and OAC1W, respectively, and in 5.9% for omeprazole and amoxicillin (p = 0.11). CONCLUSIONS: 1-week and 2-week triple treatments for H pylori eradication are similar in terms of efficacy, safety and patient compliance.     

'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.     

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.     

Azithromycin in one week quadruple therapy for H pylori eradication in Iran

AIM: To investigate eradication rates, patient compliance and tolerability of a 1-wk Azithromycin-based quadruple therapy versus the 2-wk conventional therapy. METHODS: A total of 129 H pylori-positive patients were randomized to either omeprazole 20 mg, bismuth subcitrate 240 mg, azithromycin 250 mg, and metronidazole 500 mg, all twice daily for 1-wk (B-OAzM) or omeprazole 20 mg, bismuth subcitrate 240 mg, amoxicillin 1g, and metronidazole 500 mg all twice daily for 2-wk (B-OAM). H pylori infection was defined at entry by histology and rapid urease test and cure of infection was determined by negative urea breath test. RESULTS: H pylori eradication rates produced by B-OAzM and B-OAM were 74.1% and 70.4% respectively based on an intention to treat analysis, and 78.1% versus 75.7% respectively based on a per-protocol analysis. The incidence of poor compliance was lower, although not significantly so, in patients randomized to B-OAzM than for B-OAM (3.5% versus 4.3%) but intolerability was similar in the two groups ( 35% versus 33.3%). CONCLUSION: 1-wk azithromycin based quadruple regimen achieves an H pylori eradication rate comparable to that of standard 2-wk quadruple therapy, and is associated with comparable patient compliance and complications.     

含铋剂和克拉霉素的四联根除方案在幽门螺杆菌一线治疗中的作用

背景：近年经典三联方案对幽门螺杆菌（H.pylori）感染的根除疗效明显下降,建立新型、安全和高效的一线标准治疗方案是临床工作的当务之急。目的：评估含铋剂和克拉霉素的四联方案作为H.pylori一线治疗方案的疗效和安全性。方法：120例胃镜诊断为非溃疡性消化不良的H.pylori感染患者随机分为3组：7 d三联组（奥美拉唑20 mgbid＋阿莫西林1000 mg bid＋克拉霉素500 mg bid,疗程7 d）、7 d四联组（7 d三联方案＋枸橼酸铋钾220 mg bid,疗程7 d）和2周四联组（方案同7 d四联组,疗程2周）。治疗结束后至少4周行13C-尿素呼气试验以评估根除疗效。H.pylori分离菌株行克拉霉素、甲硝唑和阿莫西林药敏试验。结果：115例患者按方案完成治疗。7 d三联组、7 d四联组和2周四联组按意向治疗（ITT）分析H.pylori根除率分别为70.0%、75.0%和90.0%,按方案（PP）分析分别为73.7%、76.9%和94.7%。2周四联组ITT和PP根除率均显著高于7 d三联组（P〈0.05）,PP根除率显著高于7 d四联组（P=0.026）,而7 d三联组ITT和PP根除率与7 d四联组相比均无明显差异。H.pylori对克拉霉素、甲硝唑和阿莫西林的耐药率分别为24.2%、48.3%和0%,7 d三联组、7 d四联组和2周四联组对克拉霉素耐药菌株的根除率逐渐升高（37.5%、55.6%、80.0%）,但差异无统计学意义。除2周四联组中1例患者因皮肤过敏而未完成治疗外,其余患者的不良反应相似且轻微,耐受性良好。结论：含铋剂和克拉霉素的2周四联方案可明显提高H.pylori根除疗效,且安全性较高,可作为H.pylori一线治疗的标准方案。     

Omeprazole-based triple therapy with low-versus high-dose of clarithromycin plus amoxicillin for H pylori eradication in Iranian population

AIM: To investigate the efficacy and tolerability of H pylori eradication in an omeprazole-based triple therapy with high-and low-dose of clarithromycin and amoxicillin. METHODS: One hundred and sixty H pylori positive patients were randomly assigned to two groups based on the following 2 wk investigation; (1) group A or low-dose regimen received omeprazole 20 mg b.i.d, clarithromycin 250 mg b.i.d and amoxicillin 500 mg b.i.d; and (2) group B or high-dose regimen received omeprazole 20 mg b.i.d, clarithromycin 500 mg b.i.d and amoxicillin 1000 mg b.i.d. During the study H pylori status was assessed by histology and rapid urease test prior and by 13C-urea breath test 6 wk after the therapy. Standard questionnaires were administered to determine the compliance to treatment and possible adverse events of therapy. Data were subject to χ2 to compare the eradication rates in the two groups. The significant level of 95% (P ≤ 0.05) was considered statistically different. RESULTS: We found that the per-protocol eradication rate was 88% (68/77) in group A, and 89% (67/75) in group B. The intension-to-treat eradication rate was 85% (68/80) in group A and 83.75% (67/80) in group B. Overall adverse events were 26% in group A and 31% in group B. The adverse events were generally mild in nature and tolerated well in both groups with a compliance of 98% in group A vs 96% in group B. CONCLUSION: The omeprazole-based low dose regimen of clarithromycin and amoxicillin for two weeks in H pylori eradication is as effective as high dose regimen in Iranian population.     

Levofloxacin-azithromycin combined triple therapy for Helicobacter pylori eradication]

BACKGROUND/AIMS: Antibiotic resistance and poor compliance are the main causes of Helicobacter pylori (H. pylori) eradication failure. This study evaluated the eradication rate, tolerability, and compliance of levofloxacin- azithromycin combined triple therapy for H. pylori eradication. METHODS: 1) First-line eradication: A total of 78 H. pylori-positive patients were enrolled. Seventeen military men in Armed Forces Capital Hospital were treated with 7 days of levofloxacin-azithromycin combined triple therapy (omeprazole 20 mg bid, levofloxacin 500 mg od, and azithromycin 500 mg od), and 61 patients in Kangbuk Samsung Hospital were treated with standard PPI-based triple therapy (omeprazole 20 mg bid, amoxicillin 1.0 g bid, and clarithromycin 500 mg bid) for 7 days. 2) Second-line eradication: A consecutive series of 59 patients who failed H. pylori eradication with standard PPI-based triple therapy in Kangbuk Samsung Hospital were randomized to two groups. Thirty patients were retreated with 7 days of bismuth-based quadruple therapy (omeprazole 20 mg bid, bismuth 120 mg qid, metronidazole 500 mg tid, and tetracycline 500 mg qid), and remaining 29 patients were retreated with levofloxacin-azithromycin combined triple therapy. Patient's compliance and tolerability were evaluated at the end of treatment. The status of H. pylori infection was assessed 8 weeks later then. The successful eradication of H. pylori was defined as negative results from histology and CLO test, or 13C-urea breath test. RESULTS: First-line eradication rate of levofloxacin-azithromycin triple therapy was lower than that of standard PPI-based triple therapy, but there was no statistically significant difference (70.6% vs. 80.3%, p=0.390). Second-line eradication rate of levofloxacin-azithromycin combined triple therapy was significantly lower than that of bismuth-based quadruple therapy (ITT/PP 65.5%/73.1% vs. 90%/90%, p<0.0001). The compliances of all patients were more than 85%. Two of patients with levofloxacin-azithromycin combined triple therapy complained self-limiting side effects (mild dizziness; mild insomnia with general weakness). CONCLUSIONS: Levofloxacin-azithromycin combined triple therapy should not be recommended as the first-line or second-line H. pylori eradication regimen in Korea.     

Triple, standard quadruple and ampicillin-sulbactam-based quadruple therapies for H pylori eradication： A comparative three-armed randomized clinical trial

AIM: To compare the effectiveness of triple, standard quadruple and ampicillin-sulbactam-based quadruple therapies for H pylori eradication in a comparative threearmed randomized clinical trial. METHODS: A total of 360 H pylori-positive patients suffering from dyspepsia and aging 24-79 years with a median age of 42 years were enrolled in the study and randomly allocated into the following three groups: group A (n = 120) received a standard 1-wk triple therapy (20 mg omeprazole b.i.d., 1000 mg amoxicillin b.i.d., 500 mg clarithromycin b.i.d.); group B (n = 120) received a 10-d standard quadruple therapy (20 mg omeprazole b.i.d., 1000 mg amoxicillin b.i.d., 240 mg colloidal bismuth subcitrate b.i.d., and 500 mg metronidazole b.i.d.); group C (n = 120) received the new protocol, i.e. 375 mg sultamicillin (225 mg ampicillin plus 150 mg sulbactam) b.i.d. (before breakfast and dinner), instead of amoxicillin in the standard quadruple therapy for the same duration. Chi-square test with the consideration of P < 0.05 as significant was used to compare the eradication rates by intention-to-treat and per-protocol analyses in the three groups. RESULTS: The per-protocol eradication rate was 91.81% (101 patients from a total of 110) in group A, 85.84% (97 patients from a total of 113) in group B, and 92.85% (104 patients from a total of 112) in group C. The intentionto-treat eradication rate was 84.17% in group A, 80.83% in group B, and 86.67% in group C. The new protocol yielded the highest eradication rates by both per-protocol and intention-to-treat analyses followed by the standard triple and quadruple regimens, respectively. However, the differences were not statistically significant between the three groups. CONCLUSION: The results of this study provide further support for the equivalence of triple and quadruple therapies in terms of effectiveness, compliance and side-effect profile when administered as first-line treatment for H pylori infection. Moreover, the new protocol using ampicillin-sulbactam instead of amoxicillin in the quadruple regimen is a suitable first-line alternative to be used in regions with amoxicillin-resistant H pylori strains.     

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.     

One week of treatment with esomeprazole-based triple therapy eradicates Helicobacter pylori and heals patients with duodenal ulcer disease.

BACKGROUND: Proton pump inhibitor (PPI) monotherapy is commonly continued for 3 weeks after Helicobacter pylori eradication with PPI-based triple therapy regimens to ensure duodenal ulcer (DU) healing. This randomized, double-blind, multicentre study evaluated whether only 1 week of triple therapy with the new PPI esomeprazole was sufficient to ensure high rates of ulcer healing and H. pylori eradication. METHODS: A total of 446 H. pylori-positive patients with active DU received twice daily treatment with esomeprazole 20 mg (n = 222) or omeprazole 20 mg (n = 224) in combination with amoxicillin 1 g and clarithromycin 500 mg for 1 week (EAC and OAC, respectively). Patients in the OAC group then received 3 weeks' monotherapy with omeprazole 20 mg once daily; those treated with EAC received placebo. Ulcer healing was assessed by endoscopy on completion of therapy and H. pylori status was assessed by (13)C-urea breath testing and histology 4-6 weeks later. RESULTS: Ulcer healing rates (95% CI) for intention-to-treat and per-protocol populations were: EAC + placebo 91% (87-95%) and 94% (90-97%); OAC + omeprazole 92% (88-95%) and 96% (92-98%). Corresponding H. pylori eradication rates were: EAC + placebo 86% (81-90%) and 89% (84-93%); OAC + omeprazole 88% (83-92%) and 90% (85-93%). Both eradication regimens were well tolerated, and patient compliance was high. CONCLUSIONS: A 1-week regimen of esomeprazole-based triple therapy is sufficient for DU healing and H. pylori eradication in patients with DU disease.     

Bismuth-based quadruple therapy using a single capsule of bismuth biskalcitrate,metronidazole, and tetracycline given with omeprazole versus omeprazole,amoxicillin, and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a prospective,randomized, multicenter,North American trial

OBJECTIVES: This multicenter, randomized, active-controlled trial assessed efficacy of bismuth-based quadruple therapy with omeprazole, bismuth biskalcitrate, metronidazole, and tetracycline (OBMT) using a single-triple capsule of BMT compared with triple therapy with omeprazole, amoxicillin, and clarithromycin (OAC) in treatment of patients with Helicobacter pylori infection and duodenal ulcers. METHODS: Patients with active duodenal ulcer or diagnosed within the past 5 yr and with infection documented by (13)C-urea breath test plus histology or culture were randomly assigned to 10-day course of OBMT using a single-triple capsule containing bismuth biskalcitrate 140 mg, metronidazole 125 mg, and tetracycline 125 mg given as three capsules q.i.d. with omeprazole 20 mg b.i.d., or a 10-day course of OAC, omeprazole 20 mg plus amoxicillin 1 g plus clarithromycin 500 mg, all b.i.d. Eradication was confirmed by two negative urea breath tests at >1 month and >2 months after therapy. RESULTS: One hundred thirty-eight patients received OBMT and 137 OAC. Modified intent-to-treat eradication rates were 87.7% for OBMT and 83.2% for OAC (95% CI = -3.9%-12.8%; p = 0.29). OBMT eradicated 91.7% metronidazole-sensitive and 80.4% metronidazole-resistant strains (p = 0.06). OAC eradicated 92.1% clarithromycin sensitive and 21.4% clarithromycin-resistant strains (p < 0.001). Adverse events occurred in 58.5% of OBMT patients and 59.0% of OAC patients. CONCLUSIONS: OBMT regimen using the single-triple capsule is as efficacious and well-tolerated as the widely used OAC regimen for H. pylori eradication. This OBMT therapy largely overcomes H. pylori metronidazole resistance, present in 40% of patients in this study.     

Cure of Helicobacter pylori infection and healing of duodenal ulcer: comparison of pantoprazole-based one-week modified triple therapy versus two-week dual therapy

Objective: Eradication of Helicobacter pylori ( H. pylori ) is recommended as the first-line therapeutic concept for reliable long-term prevention of duodenal ulcer (DU) relapse. Current treatment regimens vary in efficacy, complexity, and compliance. To assess the efficacy of pantoprazole in H. pylori eradication in parallel groups of patients using two eradication regimens.
Methods: Patients, (18–85 yr old; intention-to-treat,  n = 286  ) with proven DU, positive rapid urease test (biopsy), and ¹³C-urea breath test (UBT) were included in a prospective, randomized, multicenter study. Modified triple therapy consisted of 40 mg pantoprazole b.i.d ., 500 mg clarithromycin t.i.d ., and 500 mg metronidazole t.i.d . for 7 days (PCM therapy); dual therapy consisted of 40 mg pantoprazole b.i.d . and 500 mg clarithromycin t.i.d . for 14 days (PC therapy). In both groups 40 mg pantoprazole o.d . was given until day 28 when healing of DU was evaluated endoscopically; H. pylori status was assessed by UBT on day 56.
Results: H. pylori eradication rate was 95% in PCM versus 60% in PC therapy groups (per-protocol population,   p < 0.001  ), and 82% in PCM versus 50% in PC therapy in the intention-to-treat patient population (   p < 0.001  ). The DU healing rate was 98% in the PCM and 95% in the PC therapy groups (per-protocol population). Both regimens were similarly well tolerated. Adverse events in both regimens included taste disturbance, diarrhea, and increased serum concentration of liver enzymes, at an incidence of < 10%.
Conclusions: Compared to 2-wk PC therapy (pantoprazole and clarithromycin), the 1-wk PCM therapy (pantoprazole, clarithromycin, and metronidazole) is a significantly superior and highly promising strategy for eradication of H. pylori .     

Esomeprazole versus omeprazole for the eradication of Helicobacter pylori infection: results of a randomized controlled study

BACKGROUND: Esomeprazole has higher oral bioavailability and increased antimicrobial activity against Helicobacter pylori than omeprazole. GOALS: To compare 7 days esomeprazole with 7 days of omeprazole based triple therapies for the eradication of H. pylori, and to assess whether the administration of higher dose of esomeprazole leads to improved eradication rates. STUDY: One hundred and fifty-six dyspeptic patients with H. pylori received either: (1) 1-week treatment including esomeprazole 40 mg once daily, amoxicillin 1 g, and clarithromycin 500 mg, both twice daily (EAC1 group, n = 52); (2) 1-week treatment of omeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg, all administered twice daily (OAC group, n = 52); or (3) 1-week treatment with esomeprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily (EAC2 group, n = 52). RESULTS: H. pylori was eradicated in 37 of 52 patients in the OAC group (Intension to treat [ITT] 71%), and in 42 patients in the EAC1 group (ITT 81%). High eradication rate was achieved by the EAC2 regimen (ITT; 96%), but more patients reported unwanted effects. CONCLUSION: Seven days of esomeprazole based triple therapy is a satisfactory eradication regimen for H. pylori infection. Higher doses of esomeprazole have excellent eradication rates, but they may lead to increased side effects.     

Relationship between eradication therapy and clarithromycin-resistant Helicobacter pylori in Japan

Since clarithromycin is expected to be widely used to treat Helicobacter pylori infection in the near future, it is important to investigate the relationship between resistance to clarithromycin and the regimens of eradication therapy. We investigated: (1) the usefulness of susceptibility tests prior to eradication therapy, and (2) the rate of acquisition of H. pylori resistance to clarithromycin after treatment failure. Drug susceptibility tests to clarithromycin and amoxicillin were conducted by Dry Plate Test or E-test. The subjects in the first part of this study included 112 patients with H. pylori infection who received triple therapy with various combinations of drugs, including clarithromycin. The eradication rate in patients with clarithromycin-susceptible H. pylori was significantly higher than that in patients with clarithromycin-resistant H. pylori. The second part of this study included 21 patients in whom H. pylori was not eradicated by triple therapy and 12 patients in whom H. pylori was not eradicated with dual therapy including clarithromycin. Of the 33 patients showing non-eradication. 90.9% of those treated with dual therapy and 35.7% of those treated with triple therapy acquired secondary resistance of H. pylori to clarithromycin. We conclude that it is important to conduct drug susceptibility tests prior to treatment of H. pylori infection. Since the incidence of acquiring clarithromycin resistance was significantly higher in the patients showing non-eradication, it is important to choose a regimen with a higher eradication rate, such as triple therapy.     

A 10-day levofloxacin-based therapy in patients with resistant Helicobacter pylori infection: a controlled trial.

BACKGROUND & AIMS: Antibiotic resistance is a major issue in anti- Helicobacter pylori treatment. This study was aimed at assessing the efficacy of 2 therapies in patients with resistant H pylori infection. METHODS: Patients who had failed 1 or more eradication regimens underwent upper gastrointestinal endoscopy and 2 antral and 2 corpus biopsy specimens were taken for histology and culture. Metronidazole, clarithromycin, and amoxicillin resistance were determined by E-test. Patients were randomly assigned to 2 therapies: 1 group received pantoprazole 40 mg, amoxicillin 1 g, levofloxacin 250 mg, all twice daily for 10 days, and the other group was treated with omeprazole 20 mg twice daily for the first week and omeprazole 20 mg twice daily, tetracycline 250 mg 4 times daily, metronidazole 500 mg twice daily, and bismuth subcitrate 240 mg twice daily for the second week. Therapeutic success was evaluated by 13C urea breath test after 4 weeks of treatment. RESULTS: We enrolled 44 patients in the levofloxacin-based regimen and 46 patients in the quadruple therapy. The former was successful in 31 of 44 (70%; 95% confidence interval: 53-87) and the latter in 17 of 46 (37%; 95% confidence interval: 23-47) patients, using intention-to-treat (ITT) analysis (P < .001). The rates of H pylori resistance to metronidazole, clarithromycin, and amoxicillin were 46%, 12%, and 0%, respectively. Resistance to both metronidazole and clarithromycin was found in 10% of cases. CONCLUSIONS: Triple therapy containing levofloxacin was better than quadruple therapy. The 70% success rate observed indicates that 10 days of pantoprazole, amoxicillin, and levofloxacin should be considered in patients who had failed 1 or more eradication regimens.