奥美拉唑、左氧氟沙星、阿莫西林三联疗法治疗幽门螺杆菌感染

[摘要]目的：探讨奥美拉唑、左氧氟沙星、阿莫西林三联一周疗法治疗幽门螺杆菌(Hp)感染的疗效及安全性。方法：选择90例Hp阳性慢性胃炎和消化性溃疡患者，随机分为两组。治疗观察组采用奥美拉唑(20 mg，2次／天)，左氧氟沙星(200mg，2次／天)，阿莫西林(1000 mg，2 次／天)，治疗7天。对照组采用奥美拉唑(20mg，2次／天)和克拉霉素(250 mg，2次／天)，阿莫西林(1000 mg，2次／天)，治疗7天；溃疡患者继用奥美拉唑20 mg，1 次／天，3周。疗程结束4周后复查Hp，观察症状缓解率、Hp根除率、溃疡治愈率、不良反应发生率等。结果：治疗组和对照组的症状缓解率、Hp根除率、溃疡治愈率、不良反应发生率分别为92.6％、90.2％ 、90.2％ 、4.8％ 和88．1％ 、85.7％ 、92.9％ 、4.8％ 。两组差异无显著性(P>0．05)。结论：奥美拉唑、左氧氟沙星、阿莫西林三联一周疗法是根除Hp的理想方案，可被作为根除Hp一线治疗方案。     

幽门螺杆菌根除治疗方案比较

目的 对本院门诊患者根除幽门螺杆菌的常规疗法进行比较。方法 选择2002年11月至2004年10月于我院门诊由胃镜活检病理诊断幽门螺杆菌感染行根除治疗且资料完整的患者789例,质子泵抑制剂组376例,铋剂组303例,质子泵抑制剂＋铋剂组110例。其中,国产奥美拉唑组140例,进口奥美拉唑组197例;质子泵抑制剂＋阿莫西林组327例,铋剂＋阿莫西林组270例;质子泵抑制剂＋克拉霉素组174例,铋剂＋克拉霉素组61例;质子泵抑制剂＋甲硝唑组82例,铋剂＋甲硝唑组98例;质子泵抑制剂＋替硝唑组163例,铋剂＋替硝唑组152例。停药1个月以上行13C-呼气试验,比较各根除方案的根除率。结果789例患者的研究结果显示铋剂＋两种抗生素与质子泵抑制剂＋两种抗生素的根除率分别为63.7％和71.0％,两组间差异有统计学意义（P=0．043）;铋剂＋阿莫西林＋另一种抗生素与质子泵抑制剂＋阿莫西林＋另一种抗生素的根除率分别为65．2％和75,8％,两组间差异有统计学意义（P=0.004）。结论 以质子泵抑制剂为基础的根除方案优于以铋剂为基础的方案。     

Proton-pump inhibitors versus H2-receptor antagonists in triple therapy for Helicobacter pylori eradication

Triple therapy with two antibiotics and acid-suppressing drugs is widely accepted for H. pylori eradication. Both H2-receptor antagonist and proton-pump inhibitor are reported to enhance the eradication rate when antibiotics are administered together. Comparative studies using H2-receptor antagonist or proton-pump inhibitor in triple therapy were reviewed. The efficacy of H. pylori eradication regimens with H2-receptor antagonist or proton-pump inhibitor with two antibiotics is not significantly different.     

Antibiotic therapy for Helicobacter pylori

Helicobacter pylori is one of the most common bacterial infections in the world. H pylori infection of the gastric mucosa is the most common cause of peptic ulcers and is believed to be responsible for 50% to 60% of all gastric carcinomas. This infection is difficult to treat because the bacterium is located within the gastric lumen in the mucus and not within the gastric tissue. Antimicrobial therapy for H pylori includes two or three antibiotics plus either a proton pump inhibitor or a histamine receptor antagonist. H pylori readily develops resistance to antibiotics; therefore, if the initial treatment is unsuccessful, repeat treatment should include different antibiotics.     

Treatment of Helicobacter pylori infections

The available literature on the relationship between severaldiseases and Helicobacter pylori (H. pylori) is reviewed. Duodenalulcer, gastric ulcer, complicated peptic ulcer, abdominal symptomsand gastroduodenal mucosal damage during the use of non-steroidalanti-inflammatory drugs (NSAIDs), non-ulcer dyspepsia (NUD)and gastric malignancy are discussed. The case for and againsteradication is critically discussed. Eradication of H. pylorishould be pursued in all patients with peptic ulcer disease,whether they are using NSAIDs or not. Eradication of H. pyloriin the treatment of NUD should be considered experimental. Treatmentaimed at the eradication of H. pylori should be considered inall patients with low-grade malignant mucosaassociated lymphoidtissue (MALT) lymphoma and in all patients with Menetrier'sdisease. Finally, this treatment should be considered in a subsetof H. pylori-infected patients who possibly are at an increasedrisk of gastric cancer: patients with a strong family historyof gastric carcinoma and patients in need of long-term treatmentwith a proton-pump inhibitor. In view of the importance of patientcompliance, the risk of side-effects and the possibility ofinducing metronidazole resistance when treatment with a metronidazole-containingregimen is used, treatment aimed at the eradication of H. pylorishould be carefully implemented and monitored.     

Role of metronidazole resistance in therapy of Helicobacter pylori infections.

Susceptibility to metronidazole was determined by disk diffusion tests for 559 strains of Helicobacter pylori isolated from patients. The overall metronidazole resistance was 26%. In males metronidazole-resistant strains made 18% of all H. pylori strains, and in females the corresponding figure was 40% (P less than 0.001). MICs of metronidazole were determined for H. pylori strains from 86 patients undertaking triple therapy, i.e., treatment with colloidal bismuth subcitrate, amoxicillin, and metronidazole. Of the nonresponders who remained culture positive despite the therapy, 69% had strains with metronidazole MICs of greater than or equal to 32 micrograms/ml before the therapy, and all nonresponders had metronidazole-resistant strains after the therapy. Metronidazole resistance was, however, also found in 27% of responders before therapy. To find whether the MICs of metronidazole for H. pylori strains remained constant for longer periods, consecutive isolates sampled several years apart from the same patients were tested in parallel and no changes in the MICs were found. H. pylori was successfully eradicated by the triple therapy from 91% of patients with metronidazole-susceptible pretreatment strains and from 63% of patients with metronidazole-resistant strains before the therapy (P less than 0.01). Although resistance to metronidazole has a significant role in treatment failures in H. pylori infections, high eradication rates can be achieved with the use of the present triple therapy even in populations with a high overall metronidazole resistance rate.     

A randomized comparison of triple therapy Helicobacter pylori eradication regimens in children with peptic ulcers

An open, randomized trial was performed to compare the efficacy of three Helicobacter pylori eradication regimens in children with peptic ulcer disease. A total of 106 children (5 - 15 years) were treated for 1 week with metronidazole, 30 - 40 mg/kg per day depending on age, amoxycillin, 750 mg/day, and one of three anti-secretory agents: proprietary omeprazole, 20 - 40 mg/day depending on age; generic omeprazole, 20 - 40 mg/day; or ranitidine, 150 mg twice daily. The H. pylori eradication rate was significantly higher in patients receiving proprietary omeprazole (88.9%) than in those receiving generic omeprazole (80.0%) or ranitidine (74.3%), and this was associated with a trend towards faster ulcer healing. It is concluded that triple therapy consisting of an anti-secretory agent and two antimicrobials produces effective eradication of H. pylori and ulcer healing in children with peptic ulcer disease, and that proprietary omeprazole is more effective than both ranitidine and the generic formulation used in this study.     

Laboratory tests for the evaluation of Helicobacter pylori infections.

Helicobacter pylori is a highly motile bacterium with multiple unipolar flagella, and it produces the urease enzyme. The flagella and urease are the virulence factors of H. pylori. H. pylori often establishes a chronic infection in the stomach that may lead to gastric and duodenal ulcers, gastric cancers, gastric lymphomas, and other gastrointestinal diseases. There are several different invasive and noninvasive clinical laboratory tests for H. pylori. Laboratory testing is not indicated in asymptomatic patients and should be considered only if treatment of H. pylori infection is planned. Invasive tests for H. pylori, such as tissue histology, culture, and rapid urease tests, are used if an endoscopy is performed on the patient. The noninvasive tests for H. pylori, such as enzyme antibody and urea breath tests, are recommended in patients whose symptoms do not warrant endoscopy. The urea breath test is very useful and is recommended to evaluate effectiveness in the eradication and treatment of H. pylori infections. Nucleic acid tests can complement other diagnostic procedures, and are useful in evaluating fixed biopsy tissue, environmental samples, gastric juices, oral secretions, and stool samples.     

Evaluation of nitrofurantoin combination therapy of metronidazole-sensitive and -resistant Helicobacter pylori infections in mice

The main objectives of this study were to determine whether the nitroreductase enzyme encoded by the rdxA gene of Helicobacter pylori was responsible for reductive activation of nitrofurantoin and whether a triple-therapy regimen with nitrofurantoin was able to eradicate metronidazole-sensitive and -resistant H. pylori infections from mice. The susceptibilities to nitrofurantoin of parent and isogenic rdxA mutant strains (three pairs), as well as a series of matched metronidazole-sensitive and -resistant strains isolated from mice (30) and patients (20), were assessed by agar dilution determination of the MIC. Groups of mice colonized with the metronidazole-sensitive H. pylori SS1 strain or a metronidazole-resistant rdxA SS1 mutant were treated with either metronidazole or nitrofurantoin as part of a triple-therapy regimen. One month after the completion of treatment the mice were sacrificed and their stomachs were cultured for H. pylori. The nitrofurantoin MICs for all strains tested were between 0.5 and 4.0 microg/ml. There was no significant difference between the susceptibility to nitrofurantoin of the parental strains and those of respective rdxA mutants or between those of matched metronidazole-sensitive and -resistant H. pylori isolates. The regimen with metronidazole eradicated infection from all eight SS1-infected mice and from one of eight mice inoculated with the rdxA mutant (P < or =0.001). The regimen with nitrofurantoin failed to eradicate infection from any of the six SS1-infected mice (P < or =0.001) and cleared infection from one of seven mice inoculated with the rdxA mutant. These results demonstrate that, despite the good in vitro activity of nitrofurantoin against H. pylori and the lack of cross-resistance between metronidazole and nitrofurantoin, eradication regimens involving nitrofurantoin are unable to eradicate either metronidazole-sensitive or -resistant H. pylori infections from mice.     

以加替沙星为基础的三联疗法治疗幽门螺杆菌感染

目的分析以加替沙星、呋喃唑酮、兰索拉唑为基础的三联疗法作为一线治疗方案治疗幽门螺杆菌(Hp)感染的疗效。方法将200例Hp感染者,随机分为2组,每组100例。治疗组给予加替沙星、呋喃唑酮、兰索拉唑治疗,对照组给予克拉霉素、呋喃唑酮、兰索拉唑治疗,疗程均为7 d。停药4周后复查Hp,分析Hp的根除率、副反应发生率及成本/效果比(C/E)。结果治疗组、对照组Hp根除率分别为90.53%、81.52%,差异有统计学意义(P<0.05)。不良反应发生率治疗组为12.63%,对照组为20.65%,两组间差异有统计学意义(P<0.05)。治疗组与对照组成本/效果比(C/E)分别为1.48和2.71。结论以加替沙星为基础的三联疗法能有效、安全地根除Hp感染且费用较低。     

四联方案根除幽门螺杆菌的疗效及药物经济学评价

目的　从疗效和药物经济学两方面观察质子泵抑制剂 (PPIs)四联 1周疗法与 2周疗法的临床疗效及药物经济学评价。方法　 86例十二指肠球部溃疡或慢性胃炎阳性患者随机分为两组 ,给予奥美拉唑2 0mg、枸橼酸铋钾 2 2 0mg、克拉霉素 2 5 0mg、替硝唑 5 0 0mg组成的四联每日 2次 ,疗程分别为 1周和 2周。结果　无论按意向性 (ITT)分析还是按方案 (PP)分析幽门螺杆菌 (H pylori)根除率 1周疗法与 2周疗法比较 ,两组差异无显著性意义 (P >0 0 5 ) ;1周疗法的费用 疗效比 (5 0 3)明显低于 2周疗法 (9 6 1)。结论　四联 2周疗法的Hpylori根除率较 1周疗法并未显示出明显优势 ;而且 1周疗法费用相对低廉     

儿童幽门螺杆菌相关性胃十二指肠疾病的三联治疗临床研究

目的分别用以雷尼替丁和胶体枸橼酸铋为主,另外加两种抗生素的2组低剂量短疗程三联疗法治疗儿童幽门螺杆菌(HP)相关性胃炎,评价不同治疗方案的疗效并探讨根除HP感染与胃炎好转的关系。方法HP相关性胃十二指肠疾病患儿55例,随机分为A、B2组,接受三联治疗。A组用胶体枸橼酸铋6～8mg/(kg·d),每日2次;阿莫西林30mg/(kg·d),每日3次;克拉霉素10～15mg/(kg·d),每日2次。B组用雷尼替丁3～5mg/(kg·d),每日睡前服1次;阿莫西林30mg/(kg·d),每日3次;克拉霉素10～15mg/(kg·d),每日2次。2组均治疗2周停药,停药满4周以上行13C尿素呼气试验及血清抗HPIgG抗体检测。结果治疗后HP根除率A组为63.3%,B组为88%(χ2=4.373,P<0.05)。两组患儿腹痛症状缓解时间A组为(5.1±3.0)d,B组为(4.3±3.5)d(P>0.05)。两组副反应均较轻,如腹泻、腹胀、恶心、纳差等胃肠症状,个别患者出现皮疹,均无肝肾、造血系统副作用,且于停药后均很快缓解,未影响治疗。2组血清抗HPIgG抗体阴转情况:A组1个月为56.7%,3个月73.3%,6个月90.0%,12个月96.7%;B组1个月为88%,3个月96.0%,6个月100.0%。结论儿童HP相关性胃炎经根除HP的治疗,可使胃炎好转。以雷尼替丁为主的联合克拉霉素和阿莫西林组成的三联疗法治疗儿童HP相关性胃十二指肠疾病具有疗程短、疗效高、副反应小和HP根除率高等优点。血清抗HPIgG抗体检测可以作为监测HP根除效果的观测指标。