Quinolone-Based Third-Line Therapy for Helicobacter pylori Eradication

Currently, a standard third-line therapy for Helicobacter pylori (H. pylori) eradication remains to be established. Quinolones show good oral absorption, no major side effects, and marked activity against H. pylori. Several authors have studied quinolone-based third-line therapy and reported encouraging results, with the reported H. pylori cure rates ranging from 60% to 84%. Resistance to quinolones is easily acquired, and the resistance rate is relatively high in countries with a high consumption rate of these drugs. We recently reported a significant difference in the eradication rate obtained between patients infected with gatifloxacin-susceptible and gatifloxacin-resistant H. pylori, suggesting that the selection of quinolones for third-line therapy should be based on the results of drug susceptibility testing. As other alternatives of third-line rescue therapies, rifabutin-based triple therapy, high-dose proton pump inhibitor/amoxicillin therapy and furazolidone-based therapy have been suggested.     

Eradication of Helicobacter pylori in Japan]

Twenty five years has passed since the re-discovery of Helicobacter pylori. Many people have studied on this organism since that time. Some mechanisms about gastric mucosal inflammation have been clarified, and pathogenesis of peptic ulcer formation and gastric cancer have been solved. H. pylori infection is related to chronic gastritis, peptic ulcer, gastric carcinoma, and MALToma. In 1998, it was reported that gastric cancer occurred in H. pylori infected mongolian gerbils. In Japan, the prevalence of peptic ulcer and gastric cancer is very high. Therefore, the treatment for H. pylori infection is necessary to prevent occurrence of these diseases. To treat H. pylori infection, various regimen have been tried. Triple therapy with PPI and two antibiotics is recommended for cure of H. pylori infection in European and US guidelines. Some guidelines for management of H. pylori infection and regimen were shown in this part.     

New Options in Eradication of Helicobacter pylori

Better treatment options to eradicate Helicobacter pylori are needed, while we await a possible effective vaccine against the world's most common infection. The goals of therapy for H. pylori infection should be an effective and low-cost therapy with a low frequency of side-effects. The currently available eradication regimens are cumbersome, which can lead to a reduction of compliance and a lower efficacy. More recent studies have shown, however, that the duration of antimicrobial treatment may be shortened, which also makes the treatment more cost-effective and more tolerable. At this point it seems relevant to treat H. pylori infection first with some antisecretory modification of triple therapy, while the therapeutic failures can be treated with other more relevant and suitable alternatives. Metronidazole is still a cornerstone of triple therapy and the more expensive clarithromycin is an alternative second-line treatment. Time will show the effectiveness and suitability of the latest topical 1-day treatments.     

Eradication therapy of Helicobacter pylori for elderly patients in Japan

In Japan, an eradication therapy of Helicobacter pylori(H. pylori) for peptic ulcers of stomach and duodenum was approved by a health insurance since November 1, 2000. A method of an eradication therapy is as follows. Adult patients are received lansoprazole 30 mg, amoxicillin 750 mg, clarithromycin 200-400 mg at the same time twice daily for seven days. This therapy is based on a guideline of a Japanese association of Helicobacter Research. Many elderly patients have complications such as hypertension, cerebral vascular disturbance, heart failure and so on. Moreover, they often take a several medicine including NSAIDs(non-steroidal anti-inflammatory drugs). Therefore, you should pay attention especially to interaction of drugs when planning an eradication therapy of H. pylori for elderly patients.     

Clarithromycin Resistance and Eradication of Helicobacter pylori in Children

Outcome of Helicobacter pylori infection was analyzed in 61 children treated with a triple therapy including clarithromycin. Bacterial eradication was obtained in all children with clarithromycin-susceptible strains but not in children with clarithromycin-resistant ones (P = 0.0001). H. pylori antimicrobial susceptibility is mandatory before choosing a treatment, and clarithromycin should be avoided in case of resistance.     

含左氧氟沙星的序贯疗法对根除幽门螺杆菌的疗效观察

目的 探讨含左氧氟沙星的10 d序贯疗法根除幽门螺杆菌(HP)的疗效.方法 将胃镜检查确诊为慢性胃炎和消化性溃疡伴HP阳性的86例患者采用随机数字表法分为两组,每组43例.治疗组前5d给予埃索美拉唑20 ng+阿莫西林1000 mg,2次/d,后5d给予埃索美拉唑20rg2次/d+左氧氟沙星500 mg 1次/d+呋喃唑酮100 mg2次/d;对照组三联疗法为埃索美拉唑20 mg+阿莫西林1000mg+克拉霉素500 mg,2次/d,疗程7d.用药方法均为口服,比较治疗后两组患者的HP根除率.结果 治疗组HP根除率为93.0％ (40/43),对照组为74.4％( 32/43),两组HP根除率差异有统计学意义(x2 =4.18,P＜0.05).结论 含左氧氟沙星的10 d序贯疗法治疗HP感染具有较高的根除率.     

含左氧氟沙星序贯疗法根除幽门螺杆菌的疗效观察

目的观察由雷贝拉唑、左氧氟沙星、阿莫西林、呋喃唑酮组成的10日序贯疗法根除幽门螺杆菌（Hp）的疗效。方法将经胃镜检查确诊为慢性胃炎和消化性溃疡且Hp阳性的患者88例随机分为两组,治疗组（44例）方案为前5d给予雷贝拉唑、阿莫西林,后5d给予雷贝拉唑、左氧氟沙星、呋喃唑酮;对照组（44例）三联疗法为雷贝拉唑、阿莫西林、克拉霉素,疗程7d。比较治疗后两组患者Hp根除率。结果治疗组Hp根除率为90．9％,对照组为75．0％,两组患者Hp根除率间差异有统计学意义（P〈0．05）。结论以雷贝拉唑、左氧氟沙星等组成的10日序贯疗法治疗Hp感染具有较高的根除率。     

Eradication of Helicobacter pylori: recent advances in treatment

Helicobacter pylori plays a key role in dyspepsia, peptic ulcer disease, and gastric neoplasia and eradication of the infection has become an important treatment goal in clinical practice. Seven-day proton-pump inhibitor-amoxicillin-clarithromycin triple therapy is the current first-line therapy for H. pylori but eradication rates are compromised by poor compliance and antibiotic resistance. Ten-day sequential treatment may emerge as an alternative first-line therapy. Bismuth-based quadruple therapy is the second-line regimen of choice. Antimicrobial sensitivity testing is not recommended in the routine management of H. pylori infection. Novel triple-therapy regimens containing rifabutin, levofloxacin, or furazolidone may be useful alternatives as second- or third-line therapy.     

含阿莫西林/克拉维酸的三联疗法根治幽门螺杆菌的临床疗效观察

目的:探讨含阿莫西林/克拉维酸的三联疗法(泮托拉唑、克拉霉素、阿莫西林/克拉维酸)根治幽门螺杆菌(HP)的临床疗效.方法:将14C-尿素呼气试验确诊HP感染且胃镜证实为消化性溃疡的250例患者随机分为A、B两组各125例,A组采用泮托拉唑、克拉霉素、阿莫西林/克拉维酸三联方案;B组采用泮托拉唑、克拉霉素、阿莫西林三联方案.疗程结束4周后复查14C-尿素呼气试验.结果:A组HP根治率为82.4%,明显高于B组的71.2%(P<0.05);两组之间药物不良反应无统计学差异(P>0.05).结论:含阿莫西林/克拉维酸的三联疗法(泮托拉唑、克拉霉素、阿莫西林/克拉维酸)较传统三联疗法(泮托拉唑、克拉霉素、阿莫西林)根治HP的疗效更好.     

含左氧氟沙星序贯疗法根除幽门螺杆菌的疗效和安全性

[目的]评价含左氧氟沙星序贯疗法根除幽门螺杆菌(Hp)的疗效和安全性.[方法]将145例Hp感染患者随机分为治疗组76例和对照组69例.治疗组在前7 d应用兰索拉唑30 mg、阿莫西林1 000 mg,每日早晚两次口服,在接下来的7 d中,应用兰索拉唑30 mg、左氧氟沙星500 mg、替硝唑500 mg,每日早晚两次...     

以雷贝拉唑与加替沙星为基础的三联疗法根除幽门螺杆菌的效果观察

目的比较两种三联疗法根治幽门螺杆菌（Hp）的疗效及安全性。方法选择快速尿素酶及14C-尿素呼气试验确诊的80例Hp感染患者,随机分为两组,每组40例。其中雷贝拉唑组采用雷贝拉唑、克拉霉素、加替沙星三联方案;枸橼酸铋钾（CBS）组用枸橼酸铋钾（CBS）、克拉霉素、加替沙星三联方案。疗程结束4周后复查快速尿素酶及14C-尿素呼气试验。结果奥美拉唑组与枸橼酸铋钾组Hp根除率分别为93.33%（40/56）和75.00%（40/45）,两种根除Hp的治疗方案比较差异有统计学意义（χ2=7.5664,P〈0.05）;两组不良反应发生率比较差异无统计学意义（P〉0.05）。结论雷贝拉唑、克拉霉素、加替沙星三联疗法在两种方案中Hp根治率高,值得临床推广。     

序贯疗法和三联疗法治疗幽门螺杆菌阳性溃疡的疗效观察

目的观察由奥关拉唑联合阿莫西林、克拉霉素、替硝唑组成的10日序贯疗法根除幽门螺杆菌（Hp）的疗效。方法210例Hp阳性的消化性溃疡患者,随机分为两组。治疗组采用前5d应用奥美拉唑20mg加阿莫西林1000mg,2次／d,后5d用奥美拉唑20mg加克拉霉素500mg加替硝唑500mg,2次／d,对照组采用10d奥美拉唑20mg加阿莫西林1000mg加克拉霉素500mg,2次／d。4周后复查Hp。结果治疗组Hp根除率92．4％,对照组78．1％,差异有统计学意义（P〈0．05）。结论以奥美拉唑、阿莫西林、克拉霉素、替硝唑组成的10日序贯疗法治疗成人Hp感染具有疗效高、耐受性和依从性好等优点。     

Mechanism of drug resistance in Helicobacter pylori

Clarithromycin is one of the most important antibiotics for H. pylori eradication. However, 5-10% was reported to be resistant. It has been shown that one point mutation in the 23S rRNA gene is associated with resistance to clarithromycin. To detect H. pylori infection and the mutation simultaneously, we have designed PCR primers specific for H. pylori, and established assays of PCR-RFLP and PCR-preferential homo-duplex formation (PHFA). Using this assay, we can detect mixed infections with wild and mutant-strains. The prevalence of mutant infection increased through clarithromycin-based eradication. However, the existence of mutant strains had been confirmed before therapy in most cases who 'converted' to mutant after therapy. Metronidazole is also one of the most important antibiotics for eradication. However, 5-50% was reported to be resistant. It has been shown that rdx gene mutation is associated with resistance. It is reported that inactivation of the rdx gene is frequently, but not always, associated with resistance to metronidazole. Amoxicillin resistant strains were rare (1.2% in Japanese strains). It is reported that penicillin-binding protein might play a role in the resistance. By detecting of the resistance based on the molecular mechanism, patients can be treated with adequate antibiotics with information about resistance.     

Nitazoxanide, a Potential Drug for Eradication of Helicobacter pylori with No Cross-Resistance to Metronidazole

Nitazoxanide, a thiazolide compound, and its desacetyl derivative, tizoxanide, have antimicrobial properties against anaerobic bacteria, as well as against helminths and protozoa. Because the treatment of Helicobacter pylori infection may be jeopardized by metronidazole resistance, nitazoxanide and tizoxanide were tested in vitro against these bacteria. The MICs of these two compounds were determined by agar dilution and were compared to those of metronidazole. Exposure to subinhibitory concentrations of nitazoxanide was also carried out by the method of Szybalski (W. Szybalski and V. Bryson, J. Bacteriol. 64:489–499, 1952). The MICs of nitazoxanide and tizoxanide for 103 strains ranged from 0.25 to 8 μg/ml, with the MIC at which 50% of strains are inhibited (MIC₅₀) being 1 μg/ml and the MIC₉₀ being 4 μg/ml, and no resistant strain was detected, whereas strains resistant to metronidazole were detected. When 10 strains were successively subcultured on medium containing nitazoxanide, no significant change in the MICs of this compound was observed. A pilot study of nitazoxanide for the treatment of H. pylori infection was carried out with 86 patients in association with 20 mg of omeprazole. An eradication rate of 83% (95% confidence interval, 64% to 94%) was obtained in a per-protocol analysis in the group receiving 1 g of nitazoxanide orally twice daily, and a few side effects were observed. The failures could not be explained by the selection of resistant strains since the MICs of nitazoxanide were similar for six pairs of isolates (proven to be the same strain by random amplified polymorphic DNA analysis in four cases) cultured before and after the treatment failure. Nitazoxanide exhibits good antimicrobial activity against H. pylori without the problem of acquired resistance which is encountered with metronidazole and has been demonstrated to have a satisfactory effect in a dose-ranging pilot study. It is therefore a good candidate to be included in treatment regimens aimed at the eradication of H. pylori.     

根治幽门螺杆菌对功能性消化不良的影响

目的：评估功能性消化不良合并幽门螺杆菌（H．pyloN）感染患者在根治H．pylon治疗后的疗效。方法：符合罗马Ⅱ的功能性消化不良的诊断标准，且胃镜病理和^14C呼气试验H．pylon阳性者为研究对象，随机分为治疗组和对照组。治疗组88例，予以奥美拉唑，阿莫西林，痢特灵，对照组86例予以安慰剂奥美拉唑。参考Glasgow消化不良严重程度积分标准，1年后作疗效评价。结果：1年后，治疗组88例中有23例消化不良症状消失，占26．13％；而对照组86例中有9例消化功能不良症状消失，占10．46％，两组差异显著（P〈0．05）。治疗组88例中有55例症状缓解，占62．50％，对照组86例中有34例症状缓解，占39．53％，两组差异显著（P〈0．05）。结论：功能性消化不良合并H．pylon感染的患者，予以奥美拉唑，抗生素根治H．pylon感染后，消化不良症状的改善优于单用奥美拉唑。