Combined Activity of Azithromycin and Lansoprazole Against Helicobacter pylori

Background. Due to its unique pharmacokinetic properties, azithromycin may be an attractive combination partner for H. pylori eradication regimens. However, up to 15% of clinical isolates are primarily resistant to azithromycin as well as to other macrolide antibiotics. Combination therapy with lansoprazole, a proton pump inhibitor known to have intrinsic antibacterial activity against H. pylori , may be useful to counteract such resistance. We therefore evaluated the combined effects of azithromycin and lansoprazole in vitro.
Materials and Methods. Minimal inhibitory concentrations (MICs) of azithromycin and lansoprazole alone and in combination were determined for 106 clinical H. pylori isolates by means of an agar dilution technique. Killing kinetics of seven isolates were also studied in fluid medium.
Results. MIC values for 50 and 90% of the isolates (MIC₅₀, MIC₉₀) were 0.19 and 0.5 mg/l for azithromycin, and 44.5 and 104 mg/l for lansoprazole. Nine strains (8.5%) had an MIC of azithromycin ≥ 16 mg/l and were regarded as resistant. An additive interaction between the two drugs was found in 72 (68%), and indifferent effects in 24 strains (23%). Three of 9 azithromycin-resistant strains regained sensitivity in the presence of lansoprazole. In fluid culture, synergism between the two drugs occurred in 6 out of 7 strains tested.
Conclusion. In the majority of strains, lansoprazole and azithromycin interacted in an additive or synergistic manner depending on the test method employed. Addition of lansoprazole restored in vitro sensitivity to azithromycin in 3 out of 9 azithromycin-resistant strains. Such effects may enhance the elimination of H. pylori during clinical eradication therapy.     

Efficacy and safety of faropenem in eradication therapy of Helicobacter pylori

Aims: While triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin is the standard therapy for Helicobacter pylori eradication, it is ineffective against clarithromycin‐resistant strains. To seek a better regimen for eradication therapy, we assessed the sensitivity of clinical strains seen in Japan to faropenem and then evaluated the efficacy and safety of eradication therapy containing this antibiotic. Methods: Minimum inhibitory concentrations (MICs) of faropenem were determined in 78 Japanese clinical H. pylori isolates using the agar dilution method. H. pylori‐positive patients were consecutively assigned to a 7‐day eradication therapy protocol with LAF (lansoprazole 60 mg/day, amoxicillin 2000 mg/day, and faropenem 600 mg/day), and then to a 14‐day protocol. The outcomes of the therapies were assessed by ¹³C‐urea breath tests. Results: All 78 strains showed MICs of faropenem that were equal to or less than 0.2 µg/mL. The eradication rates according to intention‐to‐treat analyses were 46.5% with the 7‐day therapy (n = 43) and 62.5% with the 14‐day therapy (n = 32). No special measures were required to treat the adverse events observed in approximately one‐third of the patients. Conclusions: Faropenem was found to have good antimicrobial action against H. pylori in vitro. The 14‐day LAF therapy successfully eradicated H. pylori in about two‐thirds of the patients although the incidence of adverse events was high.     

幽门螺杆菌尿素酶B单克隆抗体的制备与鉴定

目的:制备稳定分泌抗幽门螺杆菌尿素酶B单克隆抗体(mAb)的杂交瘤细胞系,并对其分泌的mAb进行鉴定。方法:用初步纯化的重组幽门螺杆菌尿素酶B免疫BALB/c小鼠,利用杂交瘤技术制备抗尿素酶B的mAb,用间接ELISA检测mAb的特异性和亲和力,检测mAb腹水效价,鉴定Ig亚类并测定其抗原决定簇。结果:获得8株能稳定分泌抗尿素酶B的mAb杂交瘤细胞系,这8株单抗与能产生尿素酶的小肠结肠耶尔森氏菌、肺炎克雷伯氏菌和普通变形杆菌均无交叉反应,相对亲和力为1.13×10-8～4.66×10-10,腹水mAb效价可达2×104～3.2×105。其中2株单抗属IgG1亚类,3株单抗属IgG2a亚类。8株单抗分属于3种不同的抗原决定簇。结论:获得了IgG1和IgG2a类型的针对3种不同抗原决定簇的特异性幽门螺杆菌尿素酶B的mAb,为进一步用于幽门螺杆菌的临床诊断和实验研究创造了条件。     

A Novel Design of Multi-epitope Vaccine Against Helicobacter pylori by Immunoinformatics Approach

International Journal of Peptide Research and Therapeutics - Helicobacter pylori (H. pylori) is a gram-negative spiral bacterium that caused infections in half of the world’s population and...     

Systemic Immunization with Unadjuvanted Whole Helicobacter pylori Protects Mice Against Heterologous Challenge

Background: Adjuvant‐free vaccines have many benefits, including decreased cost and toxicity. We examined the protective effect of systemic vaccination with adjuvant‐free formalin‐fixed Helicobacter pylori or bacterial lysate and the ability of this vaccine to induce protection against heterologous challenge. Materials and Methods: Mice were vaccinated subcutaneously with H. pylori 11637 lysate or formalin‐fixed bacteria, with or without ISCOMATRIX^TM adjuvant, then orally challenged with H. pylori SS1. Serum was taken prior to challenge to examine specific antibody levels induced by the vaccinations, and protection was assessed by colony‐forming assay. Results: Vaccination with H. pylori 11637 lysate or formalin‐fixed bacteria delivered systemically induced significantly higher levels of Helicobacter‐specific serum IgG than the control, unvaccinated group and orally vaccinated group. After heterologous challenge with H. pylori SS1, all vaccinated groups had significantly lower levels of colonization compared with unvaccinated, control mice, regardless of the addition of adjuvant or route of delivery. Protection induced by systemic vaccination with whole bacterial preparations, without the addition of adjuvants, was only associated with a mild cellular infiltration into the gastric mucosa, with no evidence of atrophy. Conclusions: Subcutaneous vaccination using unadjuvanted formalin‐fixed H. pylori has the potential to be a simple, cost‐effective approach to the development of a Helicobacter vaccine. Importantly, this vaccine was able to induce protection against heterologous challenge, a factor that would be crucial in any human Helicobacter vaccine. Further studies are required to determine mechanisms of protection and to improve protective ability.     

Conventional, regulatory, and unconventional T cells in the immunologic response to Helicobacter pylori

Infection by the gastroduodenal pathogen Helicobacter pylori elicits a complex immunologic response in the mucosa involving neutrophils, plasma cells, eosinophils, and lymphocytes, of which T cells are the principal orchestrators of immunity. While so-called classical T cells (e.g. T-helper cells) that are activated by peptide fragments presented on antigen-presenting cells have received much attention in H. pylori infection, there exists a diverse array of other T cell populations that are potentially important for the outcome of the ensuing immune response, some of which have not been extensively studied in H. pylori infection. Pathogen-specific regulatory T cells that control and prevent the development of immunopathology associated with H. pylori infection have been investigated, but these cells can also benefit the bacterium in helping to prolong the chronicity of the infection by suppressing protective immune responses. An overlooked T cell population, the more recently described Th17 cells, may play a role in H. pylori-induced inflammation, due to triggering responses that ultimately lead to the recruitment of polymorphs, including neutrophils. The so-called innate or unconventional T cells, that include two conserved T cell subsets expressing invariant antigen-specific receptors, the CD1d-restricted natural killer T cells which are activated by glycolipids, and the mucosal-associated invariant T cells which play a role in defense against orally acquired pathogens in the intestinal mucosa, have only begun to receive attention. A greater knowledge of the range of T cell responses induced by H. pylori is required for a deeper understanding of the pathogenesis of this bacterium and its ability to perpetuate chronic infection, and could reveal new strategies for therapeutic exploitation.     

应用生物信息学方法筛选幽门螺杆菌疫苗候选抗原

目的：应用生物信息学分析方法筛选幽门螺杆菌新的疫苗候选抗原。方法：从TIGRCMR下载幽门螺杆菌26695和J99株全基因组序列,应用生物信息学SignalP、PredTMBB、LipoP、TMHMM、Phobius、PSORT-B和SubLoc等分析软件,筛选幽门螺杆菌新的外膜蛋白和分泌蛋白疫苗候选抗原。结果：从幽门螺杆菌26695株筛选得到54个编码β-桶型跨膜蛋白、脂蛋白或分泌表达蛋白的疫苗候选蛋白抗原,从幽门螺杆菌J99株得到61个呈现上述表达方式的疫苗候选蛋白抗原;且这2株细菌的疫苗候选蛋白呈现良好的交集状况,即有43个候选疫苗蛋白是相同的。结论：用生物信息学分析方法可以从全基因组范围内快速筛选到保守的分泌或表面暴露的疫苗候选抗原,为疫苗抗原的快速筛选与鉴定奠定了基础。     

Comparative Analysis of Different Typing Methods for Helicobacter pylori Clinical Isolates

The goal of the present work was to compare different techniques of molecular typing using as an example clinical isolates of Helicobacter pylori obtained from patients in different regions of Russia. DNA-macroarray genome scanning using individual genes was employed to set up our basic classification of isolates that did or did not contain pathogenicity islands. In parallel, DNA of the same isolates was used in the conventional random amplified polymorphic DNA (RAPD) PCR analysis, and the isolates were also genotyped (cagA, vacA, iceA, and babA status) and their proteomic maps were obtained by means of unidimensional SDS polyacrylamide gel electrophoresis (1D-SDS-PAGE) coupled with identification using peptide mass fingerprinting by MALDI-TOF mass spectrometry. A statistically significant correlation (coefficient of correlation r = 0.25, p = 0.005) was observed between the results of genome scanning and 1D-SDS-PAGE. No correlation was found between RAPD-PCR typing and genome scanning.     

Helicobacter pylori and dyspepsia

It is clear that non-ulcer (or functional) dyspepsia is a heterogeneous syndrome that includes a subset of patients with unrecognized gastroesophageal reflux. Patient heterogeneity combined with inadequate study methodology has led to enormous confusion in interpreting the relationship between Helicobacter pylori and non-ulcer dyspepsia. The possibility that H. pylori is associated with gastroesophageal reflux disease may explain, in part, the difficulty in establishing a link between non-ulcer dyspepsia and H. pylori infection. It is unclear whether the prevalence of H. pylori is increased in non-ulcer dyspepsia over and above the background population. H. pylori does not appear to be linked to heartburn or other specific upper gastrointestinal tract symptoms. The results of eradication trials in H. pylori-infected patients with non-ulcer dyspepsia have been equivocal and generally flawed. There is no doubt that H. pylori is not a sufficient cause of non-ulcer dyspepsia, because it is well documented in the literature that dyspepsia can occur in the absence of infection and infection can occur in the absence of symptoms. At this stage, there is insufficient evidence to support the hypothesis that H. pylori is etiologically linked to non-ulcer dyspepsia, but data from well designed large randomized controlled trials of eradication therapy, are awaited with great interest.     

Efficacy of two rabeprazole/gatifloxacin-based triple therapies for Helicobacter pylori infection

OBJECTIVES: To evaluate the efficacy of two novel treatment regimens consisting of gatifloxacin (400 mg daily), amoxicillin (1 g twice daily), and rabeprazole 20 mg once (RAG20) or twice daily (RAG40) given for 7 days in the eradication of Helicobacter pylori. METHODS: Eligible patients undergoing endoscopy and having a positive rapid urease assay for H. pylori were enrolled in this open-label trial. Gastric biopsies from a random cohort of patients were cultured for H. pylori and in vitro susceptibility to gatifloxacin and amoxicillin was performed using the E-test. Compliance and side-effects were evaluated by phone calls. (14)C-urea breath tests were performed a minimum of 4 weeks after therapy and 3 weeks after any acid suppressive therapy. RESULTS: A total of 104 patients, 52 in each group (40 females and 64 males; mean age 45.7 years) were enrolled sequentially. Eradication occurred in 43 out of 52 patients in RAG20 group (both per-protocol and intention-to-treat analysis: 83%; 95% CI: 72-93%) and in 48 of 52 patients in the RAG40 group (both per-protocol and intention-to-treat analysis: 92%; 95% CI: 85-99%). Seven patients in the RAG40 group who had previously failed one or more treatment regimens for H. pylori were cured. No significant adverse effects were reported. All 50 recovered H. pylori strains were susceptible to amoxicillin and gatifloxacin in vitro. CONCLUSIONS: A 7-day regimen of gatifloxacin-rabeprazole-amoxicillin is effective eradication therapy for H. pylori. The use of rabeprazole twice daily results in superior eradication rates including cases of failed primary therapy. This new regimen is simple, well-tolerated, and may lead to higher compliance and lower costs.     

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.     

黄连素四联方案补救治疗幽门螺杆菌感染的有效性和安全性

目的:探索黄连素四联方案用于幽门螺杆菌感染根除失败患者补救治疗的有效性及安全性。方法:将经四联方案初次根除治疗失败并自愿接受补救治疗的130例患者按纳入顺序,以1:1的比例分配治疗,随机接受14天黄连素四联(埃索美拉唑20mg+胶体果胶铋200 mg+阿莫西林1000 mg,2/d+黄连素300 mg 3/d)或四环素四联(埃索美拉唑20 mg+胶体果胶铋200 mg+四环素750 mg+呋喃唑酮100 mg,2/d)方案的治疗。所有患者均于治疗14天及治疗结束至少28天后随诊,详细记录患者症状及不良反应情况。治疗结束至少28天后进行13C尿素呼气试验来判断幽门螺杆菌根除情况。结果:65例接受黄连素四联根除治疗,65例接受四环素四联方案治疗。两组分别有6例和4例患者因不良反应服药依从性小于80%,其余患者均完成了14天的治疗。黄连素组和四环素组的幽门螺杆菌根除率ITT分析分别为76.9%(50/65)和81.5%(53/65),P=0.520;PP分析分别为84.7%(50/59)和86.9%(53/61),P=0.739。黄连素组和四环素组不良事件总体发生率分别为49.2%和41.5%,P=0.370。结论:黄连素四联疗法用于幽门螺杆菌感染的二次根除治疗,根除率较高,未明显增加不良事件发生率,是有效及安全的补救治疗方案。