Low efficacy rate of moxifloxacin-containing Helicobacter pylori eradication treatment: in an observational study in a Turkish population

BACKGROUND: Standard triple therapy for Helicobacter pylori has an eradication rate of about 50% in Turkey. It may be due to an increased resistance of H. pylori to antibiotics. Therefore, we aimed to investigate the effectiveness of a new second-generation fluoroquinolone, moxifloxacin-containing triple therapy in H. pylori eradication. MATERIAL AND METHODS: This is an open-label, prospective, single-center, pilot study. We studied 71 dyspeptic patients infected with H. pylori diagnosed by both histology and rapid urease test. Out of 71 dyspeptic patients, 64 had non-ulcer dyspepsia and seven had peptic ulcer. Patients received pantoprazole (40 mg b.i.d.) plus moxifloxacin (400 mg/day) and amoxicillin (1000 mg b.i.d.) for 14 days. Eradication was assessed 4 weeks after completing the therapy by histology and rapid urease test. Per-protocol and intention-to-treat eradication rates were determined. RESULTS: The eradication rate was 42.2% for the intention-to-treat analysis and 47.6% for the per-protocol analysis. Of all patients included in the study, 29.5% had side-effects and only 2.8% of the patients discontinued the treatment because of side-effects. Most of the complications were mild and self-limiting. CONCLUSION: Triple therapy with pantoprazole, moxifloxacin, and amoxicillin for 14 days yielded unacceptably low eradication rates. However, using tests of susceptibility to antibiotics, further studies with larger sample sizes are needed to judge these eradication rates of moxifloxacin containing eradication treatment.     

Comparison of 7-day and 14-day proton pump inhibitor-containing triple therapy for Helicobacter pylori eradication: neither treatment duration provides acceptable eradication rate in Korea

BACKGROUND AND AIMS: Although triple combination therapy containing a proton pump inhibitor (PPI) and two antibiotics is considered as a standard regimen for the first-line anti-Helicobacter pylori treatment, there are still debates on the ideal duration of treatment. The aim of this study was to compare the efficacies of 7-day and 14-day PPI-containing triple therapy. MATERIALS AND METHODS: This study was performed in a randomized, multicenter, prospective manner. After upper gastrointestinal endoscopy, H. pylori-infected patients with a gastric ulcer and/or a duodenal ulcer were randomly assigned to a PAC7 group (omeprazole 20 mg or equivalent dose of other PPIs, amoxicillin 1000 mg, and clarithromycin 500 mg twice daily for 7 days) or to a PAC14 group (the same regimen as the PAC7 group but for 14 days). H. pylori status was evaluated by (13)C urea breath test 5 weeks after anti-ulcer treatment completion. RESULTS: A total of 598 patients were enrolled; 337 were randomized to the PAC7 group and 261 to the PAC14 group. The two groups were comparable in terms of baseline characteristics. The eradication rates of the PAC7 group were not inferior to those of the PAC14 group in both intention-to-treat analysis (71.2% vs. 75.5%) and per-protocol analysis (83.6% vs. 86.6%). Incidences of adverse events were comparable. CONCLUSIONS: Although the 7-day PPI-containing triple anti-H. pylori therapy is not inferior to the 14-day therapy, neither treatment duration provides acceptable eradication rate reaching 90% in per-protocol analysis. New combination regimen with higher efficacy should be developed as a first-line eradication therapy for H. pylori in Korea.     

Twice-a-day bismuth-containing quadruple therapy for Helicobacter pylori eradication: a randomized trial of 10 and 14 days

Background: Bismuth‐containing quadruple therapy given twice a day for 14 days has been shown to be an excellent first‐line H. pylori eradication therapy. Aim: To compare the efficacy and tolerability of twice‐a‐day bismuth‐containing quadruple H. pylori eradication therapy for 10 versus 14 days in a noninferiority trial. Methods: Dyspeptic patients with H. pylori infection and naïve to H. pylori treatment were randomly assigned to: pantoprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate caplets 240 mg given b.i.d. (with the midday and evening meals) for 10 or 14 days. Eradication was defined by negative UBT and/or histology 4–6 weeks posttherapy. Efficacy and side effects were determined. Results: A total of 417 patients were randomized (153 men, 264 women; median age 52). Per protocol (PP) treatment success with 14 and 10 days was essentially identical [i.e., 96% (95% CI: 92–98) vs 95% (95% CI: 91–98) for 14 days versus 10 days, respectively. Results with intention‐to‐treat (ITT) analysis were also similar (92% (95% CI, 87–95) vs 92% (95% CI, 88–96)) for 14 and 10 days, respectively. Compliance was excellent in both groups. Side effects were generally mild and similar between groups. Fatigue, discomfort, and vomiting were more common in those in the 14‐day group. The 10‐day regimen costs € 17.65 (ie, approximately 25%) less than the 14‐day regimen. Conclusions: Bismuth‐containing quadruple therapy remained highly effective (i.e., ≥95% PP and >90% ITT) despite reducing the duration from 14 to 10 days.     

Brazilian green propolis on Helicobacter pylori infection. a pilot clinical study

Recent in vitro studies suggest that propolis and some of its phenolic components are able to inhibit Helicobacter pylori growth. To date, there are no clinical studies. AIMS: To evaluate the effect of Brazilian green propolis on H. pylori-infected individuals. PATIENTS AND METHODS: Eighteen (11 females, 7 males, mean age 47 years) participants were included. Before treatment, all participants were submitted to gastroscopy, and H. pylori infection was confirmed by histology, urease test, and (13)C-urea breath test (UBT). Participants with UBT showing a delta over baseline (DOB) value higher than 4 per thousand were considered positive for H. pylori infection. Twenty drops from an alcoholic preparation of Brazilian green propolis were administered three times a day for 7 days. Clinical evaluation and UBT were performed at 1-3 days and at 40 days after the end of therapy to evaluate H. pylori suppression or eradication, respectively. RESULTS: All participants took all medication and completed the study. Eighty-three percent of the subjects did not succeed in suppressing or eradicating H. pylori. Two participants reached partial suppression after treatment, but became positive again at UBT performed 40 days after treatment. Another participant presented negative at UBT 40 days after treatment, not confirmed by a second UBT performed 100 days after treatment. CONCLUSIONS: Brazilian green propolis used in popular dose showed minimal effect on H. pylori infection. Larger studies with longer duration, larger dose, and different frequency of administration of propolis extract should be undertaken to define its role on H. pylori therapy.     

幽门螺杆菌相关胃癌发生不同阶段miRNAs表达与临床研究

目的 观察幽门螺杆菌（Helicobacter pylori, H. pylori）感染的慢性非萎缩性胃炎（no-atrophic gastritis,NAG）→萎缩性胃炎（chronic atrophic gastritis,CAG）→肠上皮化生（intestinal metaplasia,IM）→非典型增生（dysplasia,DYS）→胃癌（gastric cancer,GC）五个不同阶段miR-1、miR-20a、miR-34a、miR-423-5p表达变化规律及其与临床的关系。方法 收集胃镜及病理证实的上述胃癌发生五个不同阶段且H. pylori感染的患者（依次为44、47、43、50、45例）,胃癌无H. pylori感染者46例,胃黏膜正常（normal gastric mucose,NGM）63例的血清标本,采用Real-time PCR法检测无H. pylori感染者miR-1、miR-20a、miR-34a、miR-423-5p表达。结果 H. pylori感染NAG→GC不同阶段,miR-1、miR-20a、miR-34a、miR-423-5p表达逐渐升高（P<0.05）,GC阶段最高,miR-1、miR-20a CAG→GC阶段均高于NGM（P<0.05）,与NGM比较差异有统计学意义（P<0.05）;其表达程度与GC发生阶段呈正相关（P<0.001）;GC组H. pylori感染者较无H. pylori感染者miR-1、miR-20a、miR-34a、miR-423-5p表达升高（P<0.05）。结论 H. pylori感染CAG→GC阶段miR-1、miR-20a、miR-34a、miR-423-5p表达升高,向胃癌演进中呈逐渐升高趋势,miR-1、miR-20a、miR-34a、miR-423-5p高表达可能是H. pylori感染后导致胃癌发生发展的重要机制,miR-1、miR-20a、miR-34a可作为诊断早期胃癌的标记物。     

Comparison of stool antigen immunoassay and serology for screening for Helicobacter pylori infection in intellectually disabled children

Diagnosis of active Helicobacter pylori infection in intellectually disabled (ID) children is problematic because they are unable to cooperate with performance of invasive tests. In this study, the non‐invasive methods of measuring serum IgG antibody concentrations and performing stool antigen tests were used to screen for H. pylori infection in ID children. Eighty‐seven children with intellectual disabilities were studied. The amount of serum IgG antibody against H. pylori was measured by the ELISA method. Stool samples were examined using an amplified IDEIA HpStAR kit. To assess categorical variables, X², Fisher's exact and Kappa tests were used. The stool antigen tests showed that 93.1% of the children had H. pylori antigen and the serology test that 85.1% of children were positive for H. pylori IgG antibodies. Agreement between results of H. pylori stool antigen (HpSA) testing and IgG antibody serology was 82.8%; however, according to the kappa measure of agreement this agreement is not statistically significant (value, 0.128; P = 0.19). Discordant results were observed for 15 children (17.2%): 11 (12.6%) who were positive on HpSA test but negative by serology and 4 (4.6%) who were IgG seropositive but had negative HpSA tests. This study showed a notably higher rate of H. pylori infection in ID children than has been reported by others for non‐ID children from the same geographical area. The HpSA test is a valid method for primary screening for H. pylori infection in ID children; it detects the specific antigens shed during active infections and has less cross‐reactivity than serological tests that detect antibodies. HpSA is a sensitive non‐invasive method for detecting infection in ID children and may serve as an accurate alternative to serology.     

Comparison of two different stool antigen tests for the primary diagnosis of Helicobacter pylori infection in turkish patients with dyspepsia

AIM: To assess the reliability of two different enzyme immunoassays in detecting the Helicobacter pylori status in stool specimens of Turkish patients with dyspepsia. MATERIALS AND METHODS: One hundred and fifty-one patients [74 with nonulcer dyspepsia (NUD), 64 with duodenal ulcer (DU) and 13 with gastric cancer] who were admitted to the endoscopy unit of Istanbul University, Cerrahpasa Medical Faculty for upper gastrointestinal endoscopy because of dyspepsia were enrolled in the study. Helicobacter pylori infection was confirmed in all patients by histology, rapid urease test and culture. A patient was classified as being H. pylori-positive if the culture alone or both the histology and the rapid urease test were positive and as negative only if all of these tests remained negative. Stool samples were obtained from patients to assess the reliability of a monoclonal (FemtoLab H. pylori) and a polyclonal (Premier Platinum HpSA) stool antigen test and to compare the diagnostic accuracies of these two tests. A chi2 test was used for statistical comparisons. RESULTS: Using cut-off values of 0.19 for FemtoLab H. pylori and 0.16 for Premier Platinum HpSA, the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 93%, 90%, 98%, 68% and 93% for the monoclonal test and 84%, 67%, 94%, 40% and 81% for the polyclonal test, respectively. The sensitivity, specificity, negative predictive value and diagnostic accuracy of the monoclonal test were significantly greater than those of the polyclonal test (chi2 = 3.98; p < .05 for sensitivity and chi2 = 15.67; p = .000 for specificity, chi2 = 15.78; p = .000 for negative predictive value and chi2 = 6.37; p = .012 for diagnostic accuracy). The bacterial load did not affect the sensitivity of either test. CONCLUSIONS: The monoclonal FemtoLab H pylori test, using a cut-off 0.19, is a very sensitive, specific and easy to perform diagnostic tool for the primary diagnosis of H. pylori infection in Turkish patients with dyspepsia.     

The TETRA study: a prospective evaluation of Helicobacter pylori 'test-and-treat' strategy on 736 patients in clinical practice

AIMS: To prospectively evaluate the effectiveness of the test-and-treat strategy in a large group of dyspeptic patients in clinical practice. METHODS: Patients with ulcer-like dyspepsia, < 45 years, without alarm symptoms, were prospectively studied. Helicobacter pylori infection was diagnosed with the 13C-urea-breath-test, and eradication or symptomatic treatment was prescribed accordingly. 'Symptomatic improvement' was defined as the percentage of patients with a decrease of > or = 2 levels in the dyspepsia-severity-score or with no symptoms after treatment. Health status and use of health resources were also assessed. Endoscopy was performed in therapeutic failures. RESULTS: Out of 736 patients initially included, 422 received eradication, and 314 symptomatic therapy; 87% returned at 6 weeks and 67% at 6 months. At 6 months, 'symptomatic improvement' was achieved in 73% and 54% of the patients, in eradication and symptomatic groups, respectively (p < .001), and overall in 66%. A reduction of 78% in mean self-assessment visual analogical score was observed at 6 months. More than 50% of patients were 'much better' at control visits. Endoscopy (18%) and physician's visits (13%) were the main health resources used. No gastric or oesophageal cancer was diagnosed. CONCLUSION: This large prospective study shows that the test-and-treat strategy is effective and safe for management of dyspeptic patients in clinical practice.     

Quantitative analysis of representative proteome components and clustering of Helicobacter pylori clinical strains

BACKGROUND: Several Helicobacter pylori proteins have been reported to be associated with severe symptoms of gastric disease. However, expression levels of most of these disease-associated proteins require further evaluation in order to clarify their relationships with gastric disease patterns. Representative proteome components of 71 clinical isolates of H. pylori were analyzed quantitatively to determine whether the protein expression levels were associated with gastric diseases and to cluster clinical isolates. METHODS: After two-dimensional electrophoresis (2-DE) of H. pylori isolates, spot intensities were analyzed using pdquest 2-D Gel Analysis Software. The intensities of 10 representative protein spots, identified by peptide fingerprinting using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) or peptide sequencing using quadrupole TOF MS, were subjected to the nonparametric Mann-Whitney test and hierarchical agglomerative cluster analysis. The relationship between clusters and gastric diseases was analyzed by the chi-squared test. RESULTS: Although the spot intensities of the 10 representative proteins were highly variable within each gastric disease group, the expression levels of CagA, UreB, GroEL, EF-Tu, EF-P, TagD, and FldA showed some significant differences among the gastric disease patterns. On the basis of the 10 target protein intensities, hierarchical agglomerative cluster analysis generated a dendrogram with clusters indicative of chronic gastritis/gastric cancers and gastric/duodenal ulcers. CONCLUSION: These results indicated that quantitative analysis of proteome components is a feasible method for examining disease-associated proteins and clustering clinical strains of H. pylori.     

Total family unit Helicobacter pylori eradication and pediatric re-infection rates

BACKGROUND: Re-infection with Helicobacter pylori is more common in children than adults, and it is generally accepted that the family unit plays a significant role in primary childhood infection. We investigated whether the family unit plays a significant role in pediatric re-infection and if eradication of H. pylori from the entire family reduces the risk of childhood re-infection. METHODS: Fifty families, each with an H. pylori-infected pediatric index case (mean age 9.48 years), were recruited. A 13carbon urea breath test was performed on all family members in the same house as the index case. Each family unit was randomized into a 'family unit treatment' group (all infected family members treated) or an 'index case treatment' group (index case only treated). RESULTS: At long-term follow-up (mean 62.2 months), there were three re-infected children in the 'index case treatment' group compared with one in the 'family unit treatment' group. The re-infection rate was 2.4% per patient per year in the 'index case treatment' group and 0.7% per patient per year in the 'family unit treatment' group (p = .31). CONCLUSIONS: This study is the first to evaluate the effect of total family unit H. pylori eradication on pediatric re-infection rates and reports the longest period of re-infection follow-up in children. In childhood, re-infection with H. pylori is not significantly reduced by family unit H. pylori eradication.     

幽门螺杆菌动物模型研究进展

幽门螺杆菌动物模型用于HP相关疾病和HP疫苗作用的研究。常规实验动物包括悉生猪、悉生狗、非人类灵长动物、猫、雪貂、小鼠、大鼠、沙鼠等。猫螺杆菌和雪貂螺杆菌感染也被用于模型研究。最近,转基因小鼠和基因敲除小鼠也被用作幽门螺杆菌动物模型研究。     

乳杆菌治疗幽门螺杆菌感染疗效的Meta分析

目的 系统评价乳杆菌治疗幽门螺杆菌（H. pylori）感染的有效性。方法 计算机检索PubMed、Cochrane Central Register of Controlled Trials、Clinicatrials.gov、中国临床试验注册中心（http://www.chictr.org.cn/）、中国知网（CNKI）、万方数据库。检索时间从建库至2016年6月30日。此外追索已纳入文献和综述的参考文献。经两位研究者独立筛选文献、提取资料和评价质量,交叉核对后,采用Stata 12.0进行Meta分析。结果 最终纳入17个RCT,共1 758例患者。Meta分析结果：乳杆菌联合常规三联疗法能提高H. pylori根除率[OR=2.762,95%CI(2.163,3.526),P<0.001],降低不良反应发生率[OR=0.334,95%CI(0.242,0.461),P<0.001],但乳杆菌单独应用对H. pylori根除率结果与对照组比较差异无统计学意义。根据乳杆菌给药疗程的亚组分析结果,0~14（含14）d乳杆菌联合给药方案显著提高了H. pylori根除率[OR=2.893,95%CI(2.187,3.827),P<0.05],14~28（含28）d给药疗程也显著提高了H. pylori根除率[OR=2.619,95%CI(1.652,4.153),P<0.05]。乳杆菌联合三联疗法在欧洲人群及亚洲人群的亚组分析中,均提高了H. pylori根除率。结论 乳杆菌联合三联疗法有利于提高H. pylori根除率,并能降低总不良反应的发生,在H. pylori感染相关疾病的治疗中具有一定意义。     

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.     

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.     

Comparison of lafutidine and rabeprazole in 7-day second-line amoxicillin- and metronidazole-containing triple therapy for Helicobacter pylori: a pilot study

Background: Lafutidine is an H2‐receptor antagonist with gastroprotective action through capsaicin‐sensitive afferent neurons and relatively inexpensive compare to proton‐pump inhibitors (PPIs). A 7‐day course of PPIs–amoxicillin–metronidazole is recommended as standard second‐line Helicobacter pylori therapy and is covered by national health insurance in Japan. The aim of this study was to determine the efficacy and safety of second‐line eradication using the H2‐receptor antagonist lafutidine as a substitute for a PPI. Materials and Methods: Fifty‐two patients who failed in first‐line eradication using PPI–amoxicillin–clarithromycin were randomly assigned to a 7‐day course of rabeprazole at 10 mg b.i.d., amoxicillin at 750 mg b.i.d., and metronidazole at 250 mg b.i.d. (RPZ‐AM) or a 7‐day course of lafutidine at 10 mg t.i.d., amoxicillin at 750 mg b.i.d., and metronidazole at 250 mg b.i.d. (LFT‐AM) as second‐line therapy. Eradication was assessed by the ¹³C urea breath test. A drug susceptibility test was performed before the second‐line therapy. Results: Prior to second‐line H. pylori eradication, the rate of resistance to clarithromycin was 86.5% and the rate of resistance to metronidazole was 3.8%. The eradication rates for both LFT‐AM and RPZ‐AM groups were 96% (95%CI = 88.6–100%). There were no severe adverse events in either group. Conclusions: Lafutidine plus metronidazole–amoxicillin as second‐line therapy provided a high eradication rate and safe treatment similar to a PPI‐based regimen. Lafutidine‐based eradication therapy is therefore considered to be a promising alternative and is also expected to reduce health care costs in H. pylori eradication.