Second-line treatment for Helicobacter pylori infection: 10-day moxifloxacin-based triple therapy versus 2-week quadruple therapy

BACKGROUND AND AIM: The aim of this study was to test the efficacy of 10-day moxifloxacin-based triple therapy versus 2-week quadruple therapy for the second-line treatment of Helicobacter pylori infection. METHODS: One hundred and ninety-two patients who had failed previous H. pylori eradication on standard triple therapy were randomized to one of two regimens: 1, moxifloxacin (400 mg q.d.), amoxicillin (1000 mg b.i.d.), and esomeprazole (20 mg b.i.d.) for 10 days (the 10MEA group), or 2, esomeprazole (20 mg b.i.d.), tripotassium dicitrate bismuthate (300 mg q.i.d.), metronidazole (500 mg t.i.d.), and tetracycline 500 mg (q.i.d.) for 14 days (the 14EBMT group). The eradication rates, drug compliances, and side-effect rates of these two regimens were compared. RESULTS: Eradication rates by intention-to-treat and per-protocol analyses in the 10MEA and 14EMBT groups were 71.9% and 82.6%, and 71.7% and 90.5% (p = .973 and .321), respectively. The 10MEA group was significantly superior to the 14EMBT group in terms of side-effect rates (12.2% vs. 39.6%, p = .001), and discontinuation rates due to side-effects were lower in the 10MEA group than in the 14EMBT group (0.7% vs. 13.2%, p < .001). Moreover, compliance was higher in the 10MEA group (94.2% (131/139)) than in the 14EBMT group (83.0% (44/53)) (p = .014). CONCLUSION: The 10-day moxifloxacin-based triple therapy was found to have a high eradication rate with few side-effects and good drug compliance. These findings suggest that this regimen is a safe and effective second-line treatment option for H. pylori infection in Korea.     

Low efficacy of clarithromycin including sequential regimens for Helicobacter pylori infection

Background: Sequential treatment for Helicobacter pylori (H. pylori) appears to achieve a better eradication rate than triple therapy. However, most of the data have been reported from the Italy, and studies from different population are needed before it is recommended in clinical practice. The present study aimed to assess and compare the efficacy of two separate clarithromycin including sequential regimens in Turkey which is well known with high clarithromycin and metronidazole resistance to H. pylori. Methods: Consecutive H. pylori ‐positive patients with non‐ulcer dyspepsia were randomly allocated to one of the two sequential regimens; the first group was given lansoprazole 30 mg b.i.d. plus amoxicillin 1 g b.i.d. for the first week, followed by lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg t.i.d. for the second week (LA‐CM). The second arm was given the same regimen but tetracycline500 g q.i.d. instead of metronidazole (LA‐CT). H. pylori was detected with urea breath test (UBT) and histology before enrollment. UBT was repeated at 6th weeks after treatment. Results: A total of 200 patients were enrolled in groups and 179 of them completed their protocols. The cumulative per protocol (“PP”) and intention‐to‐treat (“ITT”) eradication rates were 74.3% and 66.5% in all patients, respectively. Both “PP” (78.2% vs 70.1%) and “ITT” (72% vs 61%) eradication rates were better in LA‐CT group than LA‐CM group, but the differences were not statistically significant (p > .05). Both regimens were well tolerated, and the incidence of adverse effects was comparable. Conclusion: Two weeks clarithromycin including sequential regimens with metronidazole or tetracycline were not achieved acceptable eradication rates in Turkey.     

Modified sequential Helicobacter pylori therapy: proton pump inhibitor and amoxicillin for 14 days with clarithromycin and metronidazole added as a quadruple (hybrid) therapy for the final 7 days

Background: Ten‐day sequential therapy with a proton pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole typically achieves Helicobacter pylori eradication rates of 90–94% (Grade B success). Aims: We tested whether prolonging treatment and continuing amoxicillin throughout the 14‐day treatment period would produce a ≥95% result. Methods: This was a multicenter pilot study in which H. pylori‐infected patients received a 14‐day sequential–concomitant hybrid therapy (esomeprazole and amoxicillin for 7 days followed by esomeprazole, amoxicillin clarithromycin, and metronidazole for 7 days). H. pylori status was examined 8 weeks after therapy. Success was defined as achieving ≥95% eradication by per‐protocol analysis. Results: One hundred and seventeen subjects received hybrid therapy. The eradication rate was 99.1% (95% confidence interval (CI), 97.3–100.0%) by per‐protocol analysis and 97.4% by intention‐to‐treat analysis (95% CI, 94.5–100.0%). Adverse events were seen in 14.5%; drug compliance was 94.9%. Conclusions: Fourteen‐day hybrid sequential–concomitant therapy achieved >95%H. pylori eradication (Grade A result). Further studies are needed 1, in regions with different patterns and frequencies of resistance to confirm these findings, and 2, to examine whether Grade A success is maintained with hybrid therapy shorter than 14 days.     

Helicobacter pylori infection: sequential therapy followed by levofloxacin-containing triple therapy provides a good cumulative eradication rate

Background: In the eradication of H. pylori infection, even today, the main international guidelines recommend the triple therapy as first‐line regimen, although its effectiveness is clearly decreasing. As second‐line treatment, the bismuth‐containing quadruple therapy is the most used regimen, although several other therapies are studied. The Italian guidelines recommend, alternatively, sequential therapy or triple therapy as first‐line treatment and levofloxacin‐containing triple therapy as second‐line regimen. We wanted to assess the overall eradication rate of Helicobacter pylori infection in two therapeutic rounds following the Italian guidelines in clinical practice. Materials and Methods: We treated 231 consecutive Helicobacter pylori‐positive patients by sequential therapy and we verified the eradication 8–10 weeks after treatment by stool antigen test. Patients positive for stool antigen test received levofloxacin‐containing triple therapy, as second‐line therapy, according to Italian Guidelines and they were again submitted to the fecal test 8–10 weeks after the end of treatment. Results: In the first‐line regimen, we obtained an eradication rate of 92.6%, in the second‐line of 75.0% and as cumulative result we achieved a 97.8% of eradication, in per‐protocol analysis. Conclusions: Sequential therapy as first‐line and levofloxacin‐containing triple therapy as second‐line represent a good combination to eradicate Helicobacter pylori infection in only two rounds.     

Impact of furazolidone-based quadruple therapy for eradication of Helicobacter pylori after previous treatment failures

Background. One week of quadruple therapy including metronidazole is recommended for Helicobacter pylori treatment failures after first line therapy regardless of resistance status. This study investigated whether a quadruple regimen containing furazolidone could be effective as a third‐line (salvage) therapy. Methods. All patients with previous H. pylori treatment failure after a clarithromycin‐metronidazole ± amoxicillin combination plus acid suppression were given lansoprazole 30 mg twice a day (bid), tripotassiumdicitratobismuthate 240 mg bid, tetracycline 1 g bid, metronidazole 400 mg (PPI‐B‐T‐M) three times a day (tid) for 1 week. In the case of treatment failure with this second‐line therapy, the same regimen was applied for 1 week except for using furazolidone 200 mg bid (PPI‐B‐T‐F) instead of metronidazole (sequential study design). Results. Eighteen consecutive patients were treated with PPI‐B‐T‐M. Eleven of those 18 remained H. pylori positive (38.9% cured). Pretherapeutic metronidazole resistance was associated with a lower probability of eradication success (10% vs. 75%, p= .04). Ten of these 11 patients agreed to be retreated by PPI‐B‐T‐F. Final cure of H. pylori with PPI‐B‐T‐F was achieved in 9/10 patients (90%) nonresponsive to PPI‐B‐T‐M. Conclusions. In the presence of metronidazole resistance, PPI‐B‐T‐M as a recommended second‐line therapy by the Maastricht consensus conference achieved unacceptable low cure rates in our metronidazole pretreated population. In this population, metronidazole based second‐line quadruple therapy may be best suited in case of a metronidazole‐free first line‐regimen (e.g. PPI‐clarithromycin‐amoxicillin) or a low prevalence of metronidazole resistance. Furazolidone in the PPI‐B‐T‐F combination does not have a cross‐resistance potential to metronidazole and is a promising salvage option after a failed PPI‐B‐T‐M regimen.     

A comparison between sequential therapy and a modified bismuth-based quadruple therapy for Helicobacter pylori eradication in Iran: a randomized clinical trial

Background: Sequential regimens have been recently reported to be superior to the standard triple therapies in Helicobacter pylori eradication, but most of these studies were performed in Europe and data from developing countries are lacking. So we designed a study to compare a sequential regimen with a bismuth‐based quadruple therapy that contains a short course of furazolidone, in Iran. Methods: Two hundred and ninety‐six patients with duodenal ulcer and naïve H. pylori infection were randomized into two groups: 148 patients received (PAB‐F) pantoprazole (40 mg‐bid), amoxicillin (1 g‐bid), and bismuth subcitrate (240 mg‐bid) for 2 weeks and furazolidone (200 mg‐bid) just during the first week. And 148 patients received (PA‐CT) pantoprazole (40 mg‐bid) for 10 days, amoxicillin (1 g‐bid) for the first 5 days, and clarithromycin (500 mg‐bid) plus tinidazole (500 mg‐bid) just during the second 5 days. C¹⁴‐urea breath test was performed 8 weeks after the treatment. Results: Two hundred and sixty‐one patients completed the study (137 patients in the PA‐CT and 124 in the PAB‐F group). The results were not statistically different between the two groups in the eradication rates and the severity of side effects. The intention to treat eradication rate was 80.4% in the PAB‐F group and 83.7% in the PA‐CT group. Per‐protocol eradication rates were 88.7% and 89.1%, respectively. Conclusion: Because the two regimens showed acceptable and similar abilities in H. pylori eradication and because of much higher cost of clarithromycin in Iran, the furazolidone containing regimen seems to be superior. Further modifications of sequential therapies are needed to make them ideal regimens in developing countries.     

A modified bismuth-containing quadruple therapy including a short course of furazolidone for Helicobacter pylori eradication after sequential therapy failure

Background: Helicobacter pylori eradication has still remained a challenge, especially in case of failure to novel treatments. Therefore, we designed a study to evaluate the effects of a modified bismuth‐containing quadruple therapy including a short course of furazolidone on a group of patients whose sequential therapy had been unsuccessful. Materials and Methods: Thirty‐six H. pylori‐positive patients who had previously failed a clarithromycin‐containing sequential therapy enrolled the study. They received pantoprazole (40 mg‐bid), amoxicillin (1 g‐bid), and bismuth subcitrate (240 mg‐bid) for 2 weeks and furazolidone (200 mg‐bid) just during the first week. Eight weeks after treatment, H. pylori eradication was reassessed using C14‐urea breath test. Results: Thirty five patients completed the study. H. pylori eradication rates were 80.6% (95% CI = 67.6–93.5) and 82.9% (95% CI = 70.6–95.2) according to intention‐to‐treat and per‐protocol analyses, respectively. All patients had excellent compliance to treatment, and no one interrupted therapy owing to adverse effects. Conclusion: Regarding the eradication rate (>80%), low price, and very low adverse effects, a 2‐week bismuth‐containing quadruple regimen including a short course of furazolidone can be an encouraging regimen for second‐line H. pylori eradication in case of sequential therapy failure. Possibly, it can be improved by alterations in dose, dosing intervals, and/or duration.     

Furazolidone‐containing triple and quadruple eradication therapy for initial treatment for Helicobacter pylori infection: A multicenter randomized controlled trial in China

Background

The efficacy of Helicobacter pylori (H. pylori) eradication has steadily declined, primarily because of antibiotic resistance. This study aimed to evaluate the efficacy and safety of furazolidone eradication therapies as initial treatments for H. pylori infection.

Methods

A national, multicenter, open‐label, randomized controlled trial was performed at 16 sites across 13 provinces in China to evaluate the efficacy and safety of furazolidone‐containing therapies for H. pylori infection. Treatment naïve patients were randomly assigned to: esomeprazole 20 mg, bismuth 220 mg, amoxicillin 1000 mg, and furazolidone 100 mg twice daily for 10 and 7 days (FAB 10 and FAB 7; the same therapy without bismuth (FA 10 and FA 7). The primary and secondary outcomes were the eradication rate and regimen safety, respectively. Treatment success was assessed by the ¹³C urea breath test at least 4 weeks after treatment completion.

Results

Overall, according to intention‐to‐treat (ITT) analysis, the eradication rates for FAB 10 and FAB 7 were 86.6% (95% confidence interval [CI], 79.9%‐93.2%) and 83.6% (95% CI, 76.3%‐90.9%) and for FA 10 and FA 7 were 82.4% (95% CI, 74.9%‐89.8%) and 77.6% (95% CI, 69.4%‐85.8%), respectively. According to per‐protocol analysis, the overall eradication rates for FAB 10 and FAB 7 were 94.7% (95% CI, 90.3%‐99.1%) and 90.8% (95% CI, 85.1%‐96.5%) and for FA 10 and FA 7 were 90.6% (95% CI, 84.9%‐96.3%) and 85.1% (95% CI, 78.2%‐92.1%), respectively. The overall prevalence of side effects was 8.1%.

Conclusions

Furazolidone‐containing therapies, particularly the tested 10‐day quadruple therapy, exhibited satisfactory efficacy and safety. This 10‐day quadruple therapy represents a promising initial treatment strategy for Chinese patients.     

Moxifloxacin-containing triple therapy versus bismuth-containing quadruple therapy for second-line treatment of Helicobacter pylori infection: a meta-analysis

Background: Moxifloxacin‐containing triple therapy has been suggested as an alternative second‐line therapy for Helicobacter pylori infection. Aims: To systematically review the efficacy and tolerance of moxifloxacin‐containing triple therapy in second‐line H. pylori eradication, and to conduct a meta‐analysis of studies comparing this regimen with bismuth‐containing quadruple therapy. Materials and Methods: Electronic databases including Medline, Embase, Cochrane controlled trials register, Web of Science, PubMed, Chinese Biomedical Literature Database (updated to December 2010), and manual searches were conducted. A meta‐analysis of all randomized controlled trials (RCTs) comparing moxifloxacin‐containing triple therapy to bismuth‐containing quadruple therapy in the second‐line treatment of H. pylori infection was performed. Results: Seven RCTs including 787 patients were assessed. The meta‐analysis showed that the eradication rate in the moxifloxacin group was significantly higher than that in the quadruple therapy group (74.9 vs 61.4%, OR 1.89, 95% CI: 1.38–2.58, p < .0001); besides, the rates of side effects and discontinuing therapy because of side effects in the moxifloxacin group were significantly lower than those in the quadruple therapy group (side effects: 10.1 vs 27.8%, OR 0.27, 95% CI: 0.18–0.41, p < .00001; discontinuing therapy because of side effects: 1.4 vs 8.2%, OR 0.18, 95% CI: 0.08–0.40, p < .0001). These results were constant in the sensitivity analyses. Conclusion: Moxifloxacin‐containing triple regimen is more effective and better tolerated than the bismuth‐containing quadruple therapy in the second‐line treatment of H. pylori infection.     

Emergence of clarithromycin-resistant Helicobacter pylori (CRHP) with a high prevalence in children compared with their parents

Background. Clarithromycin‐resistant Helicobacter pylori (CRHP) is increasing worldwide. Clarithromycin resistance in H. pylori from familial members has not been investigated. Materials and Methods. Biopsy specimens were taken from 13 families living in Tokyo, Yokohama, and Niigata between 1998 and 2001. Drug resistance was tested with the replica plating method. The minimum inhibitory concentrations of antimicrobial agents for H. pylori strains were determined by the agar dilution method. Molecular analyses of H. pylori strains were performed by ribosomal RNA gene restriction pattern analysis. The DNA region, associated with clarithromycin resistance, was analyzed by PCR and sequencing. Results. Helicobacter pylori strains isolated from a 5‐year‐old‐son displayed clarithromycin resistance with a mutation (A → G at position 2143) in the 23S ribosomal RNA, whereas H. pylori strains from his parents did not. DNA analyses revealed that the boy was infected with his father's strain. The boy had repeatedly developed otitis media and received clarithromycin since the age of 2 years. Studies on an additional 12 families demonstrated that clarithromycin resistance in the children's strains reached 42.9% and was significantly higher than those of H. pylori strains from their parents (0%) or from adult patients (11.1%) (p < .05). Conclusions. The rate of clarithromycin resistance in H. pylori strains from Japanese children was extremely high, in contrast to those from their parents or adult patients. Prior history of clarithromycin usage in a child suggested development of clarithromycin resistance in resident H. pylori, which was originated from a parent.     

Efficacy of moxifloxacin-based triple therapy as second-line treatment for Helicobacter pylori infection

BACKGROUND AND AIM: Metronidazole and tetracycline-based second-line quadruple therapy, widely used for Helicobacter pylori infection, often ends up in failure due to antibiotic resistance and poor compliance in Korea. Our aim is to evaluate the efficacy and tolerability of moxifloxacin-based triple therapy as an alternative second-line treatment for H. pylori infection. METHODS: The subjects consisted of 85 patients infected with H. pylori, in whom initial proton pump inhibitor triple therapy had failed. They were randomized to receive the following 7-day therapy: 1, moxifloxacin 400 mg q.d., esomeprazole 20 mg b.i.d., and amoxicillin 1 g b.i.d.; and 2, esomeprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d. Eradication rates, drug compliance, and side-effect rates of each group were evaluated. RESULTS: The eradication rates were 75.6 and 83.8% with moxifloxacin triple therapy, and 54.5 and 72.7% with quadruple therapy by intention-to-treat (p = .042) and per-protocol analyses (p = .260), respectively. Moxifloxacin triple therapy was significantly superior to quadruple therapy in terms of side-effect rates (p = .039). Compliance for therapy, i.e., the percentage of tablets taken (> 85%), was 90.2 and 75.0%, numerically higher in moxifloxacin triple therapy group than in quadruple therapy group, but without statistical difference (p = .065). CONCLUSIONS: Moxifloxacin-based triple therapy showed high eradication rates with few side effects and good drug compliance, suggesting this regimen could be a safe and effective option as second-line therapy for H. pylori infection in Korea.     

益生菌四联疗法对比铋剂四联疗法根除幽门螺杆菌感染的Meta分析

目的 系统评价益生菌四联疗法对比铋剂四联疗法根除幽门螺杆菌（H. pylori）感染的疗效和不良反应。方法 计算机检索中英文数据库,收集上述2种方案根除H. pylori感染的随机对照试验（RCT）,检索时间均从建库至2016年10月。由2名评价员独立筛选文献、提取资料、评价纳入研究的偏倚风险,采取RevMan 5.3软件进行Meta分析。结果 最终纳入12个RCT（共1 687例患者）。Meta分析结果显示：益生菌四联组患者对比铋剂四联组的H. pylori根除率按ITT分析为：80.6% vs 81.2%;按PP分析为：81.2% vs 83.7%,差异无统计学意义（ITT分析：RR=0.99,95%CI：0.95~1.04,P=0.76;PP分析：RR=0.97,95%CI：0.93~1.01,P=0.17）;益生菌四联组的总不良反应的发生率明显低于对照组（16.0% vs 34.9%）,且差异有统计学意义（RR=0.46,95%CI：0.37~0.57,P＜0.01）。结论 现有证据显示,益生菌四联疗法与铋剂四联疗法的H. pylori根除率相当,但益生菌四联疗法的不良反应低于铋剂四联疗法。由于纳入研究数量有限,质量不高,上述结论有待高质量的研究予以验证。     

Impact of Quadruple Regimen of Clarithromycin Added to Metronidazole-Containing Triple Therapy Against Helicobacter pylori Infection Following Clarithromycin-Containing Triple-Therapy Failure

Background: The establishment of an optimal second-line regimen for Helicobacter pylori infection is required. Although quadruple therapy should overcome resistance to either clarithromycin or metronidazole, the effects of a quadruple regimen in second-line therapy are unknown. This study aims to evaluate the efficacy of triple therapy composed of proton pump inhibitor/amoxicillin plus metronidazole with the combined additive effects of clarithromycin as a second-line quadruple therapy against H. pylori infection.
Materials and Methods: Participants were 104 patients in whom first-line therapy containing proton pump inhibitor-amoxicillin-clarithromycin failed. Before starting second-line therapy, patients underwent endoscopy to obtain H. pylori strain for antibiotic susceptibility tests. Patients were randomized to receive rabeprazole (10 mg), amoxicillin (750 mg), and metronidazole (250 mg), either with clarithromycin (200 mg; RAMC group) or without (RAM group); all treatments were administered twice daily for 7 days. H. pylori eradication was confirmed by ¹³C-urea breath tests performed 2 to 3 months post-therapy.
Results: As shown by intention-to-treat/per-protocol analyses, the cure rates for H. pylori infection were 88.5%/93.9% and 82.7%/84.3% for the RAMC and RAM groups. Although the study probably had an insufficient power to show a significant difference between the cure rates of the two regimens, the eradication rates showed a clear trend in favor of the RAMC group. There were no severe side-effects in any group.
Conclusions: In Japan, the RAMC regimen is thought to be a promising alternative strategy for second-line eradication of H. pylori infection.