含铋剂和克拉霉素的四联根除方案在幽门螺杆菌一线治疗中的作用

背景：近年经典三联方案对幽门螺杆菌（H.pylori）感染的根除疗效明显下降,建立新型、安全和高效的一线标准治疗方案是临床工作的当务之急。目的：评估含铋剂和克拉霉素的四联方案作为H.pylori一线治疗方案的疗效和安全性。方法：120例胃镜诊断为非溃疡性消化不良的H.pylori感染患者随机分为3组：7 d三联组（奥美拉唑20 mgbid＋阿莫西林1000 mg bid＋克拉霉素500 mg bid,疗程7 d）、7 d四联组（7 d三联方案＋枸橼酸铋钾220 mg bid,疗程7 d）和2周四联组（方案同7 d四联组,疗程2周）。治疗结束后至少4周行13C-尿素呼气试验以评估根除疗效。H.pylori分离菌株行克拉霉素、甲硝唑和阿莫西林药敏试验。结果：115例患者按方案完成治疗。7 d三联组、7 d四联组和2周四联组按意向治疗（ITT）分析H.pylori根除率分别为70.0%、75.0%和90.0%,按方案（PP）分析分别为73.7%、76.9%和94.7%。2周四联组ITT和PP根除率均显著高于7 d三联组（P〈0.05）,PP根除率显著高于7 d四联组（P=0.026）,而7 d三联组ITT和PP根除率与7 d四联组相比均无明显差异。H.pylori对克拉霉素、甲硝唑和阿莫西林的耐药率分别为24.2%、48.3%和0%,7 d三联组、7 d四联组和2周四联组对克拉霉素耐药菌株的根除率逐渐升高（37.5%、55.6%、80.0%）,但差异无统计学意义。除2周四联组中1例患者因皮肤过敏而未完成治疗外,其余患者的不良反应相似且轻微,耐受性良好。结论：含铋剂和克拉霉素的2周四联方案可明显提高H.pylori根除疗效,且安全性较高,可作为H.pylori一线治疗的标准方案。     

Comparison of 1 and 2 weeks of omeprazole, amoxicillin and clarithromycin treatment for Helicobacter pylori eradication: the HYPER Study

BACKGROUND: Triple therapy is recommended for Helicobacter pylori eradication, yet consensus on the duration of treatment is lacking. AIM: To compare the efficacy and safety of 1- and 2-week regimens of omeprazole, amoxicillin and clarithromycin in a large, multicentre, double-blind and randomised study. METHODS: A total of 909 H pylori-positive patients with duodenal ulcer, enrolled in 81 endoscopy units in Italy, were randomised to receive omeprazole, amoxicillin and clarithromycin for either 1 week (OAC1W) or 2 weeks (OAC2W) or omeprazole and amoxicillin for 2 weeks. H pylori eradication was assessed by histological examination and carbon-13 urea breath test 4 weeks after treatment. RESULTS: Both the intention-to-treat (ITT; n = 907) and per protocol (PP; n = 661) analyses showed no significant differences between the eradication rates of OAC1W (ITT 79.7%; PP 83.6%) and OAC2W (ITT 81.7%; PP 84.9%; ITT p = 0.53; PP p = 0.71). Both triple omeprazole, amoxicillin and clarithromycin regimens gave significantly higher eradication rates compared with omeprazole and amoxicillin treatment (ITT 44.6%; PP 42.8%; p<0.001). Poor compliance was reported in 18.6%, 17.3% and 15.1% (p = 0.51) of patients for OAC2W, OAC1W and omeprazole and amoxicillin, respectively. Adverse events occurred in 9.9% and 9.6% (p = 0.88) of patients for OAC2W and OAC1W, respectively, and in 5.9% for omeprazole and amoxicillin (p = 0.11). CONCLUSIONS: 1-week and 2-week triple treatments for H pylori eradication are similar in terms of efficacy, safety and patient compliance.     

Esomeprazole versus omeprazole for the eradication of Helicobacter pylori infection: results of a randomized controlled study

BACKGROUND: Esomeprazole has higher oral bioavailability and increased antimicrobial activity against Helicobacter pylori than omeprazole. GOALS: To compare 7 days esomeprazole with 7 days of omeprazole based triple therapies for the eradication of H. pylori, and to assess whether the administration of higher dose of esomeprazole leads to improved eradication rates. STUDY: One hundred and fifty-six dyspeptic patients with H. pylori received either: (1) 1-week treatment including esomeprazole 40 mg once daily, amoxicillin 1 g, and clarithromycin 500 mg, both twice daily (EAC1 group, n = 52); (2) 1-week treatment of omeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg, all administered twice daily (OAC group, n = 52); or (3) 1-week treatment with esomeprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily (EAC2 group, n = 52). RESULTS: H. pylori was eradicated in 37 of 52 patients in the OAC group (Intension to treat [ITT] 71%), and in 42 patients in the EAC1 group (ITT 81%). High eradication rate was achieved by the EAC2 regimen (ITT; 96%), but more patients reported unwanted effects. CONCLUSION: Seven days of esomeprazole based triple therapy is a satisfactory eradication regimen for H. pylori infection. Higher doses of esomeprazole have excellent eradication rates, but they may lead to increased side effects.     

十二指肠溃疡患者根除幽门螺杆菌后抑酸维持治疗的疗效研究

背景：对感染幽门螺杆菌（H.pylori）的消化性溃疡患者成功根除且H.ylori后,是否应继续行抑酸治疗,目前尚存在争议。目的：探讨合并H.pylori感染的十二指肠溃疡（DU）患者根除H.pylori后抑酸维持治疗的疗效。方法：112例合并H.pylori感染的DU患者随机分为A组和B组,A组给予10d四联疗法：兰索拉唑30mg＋阿莫西林1g＋克拉霉素0．5gbid＋枸橼酸铋钾110mg qid,疗程10d。B组：在A组方案的基础上,疗程结束后再予兰索拉唑30mg,1次／d,维持4周。治疗结束4周后复查胃镜,评估H.pylori根除疗效、溃疡愈合率和腹痛缓解率。结果：109例患者完成方案。A、B两组按意向治疗（ITT）和按方案（PP）分析的H.pylori根除率（ITT：85．7％对87．5％;PP：88．9％对89．1％）和溃疡愈合率（ITT：87．5％对94．6％;PP：90．7％对96．4％）以及腹痛缓解率（95．6％对95．7％）相比差异均无统计学意义（P〉0．05）。结论：以10d四联疗法根除H.pylori后,可使多数DU患者的溃疡愈合,无需进一步行维持抑酸治疗。     

A randomized trial comparing seven-day ranitidine bismuth citrate and clarithromycin dual therapy to seven-day omeprazole, clarithromycin and amoxicillin triple therapy for the eradication of Helicobacter pylori.

OBJECTIVE: To assess Helicobacter pylori eradication after one week dual ranitidine bismuth citrate-clarithromycin (RBC-C) or triple omeprazole, clarithromycin and amoxicillin (OCA) therapy. METHODS: In this multicentre Canadian trial, H pylori-positive patients with functional dyspepsia or inactive peptic ulcer disease were randomized to open-label treatment with RBC-C (ranitidine bismuth citrate 400 mg plus clarithromycin 500 mg) or OCA (omezaprole 20 mg, clarithromycin 500 mg and amoxicillin 1000 mg), given twice a day for seven days. Treatment allocation was randomly assigned. H pylori infection was confirmed by positive 13C-urea breath test (13C-UBT). H pylori status was reassessed by UBT at least four and 12 weeks after treatment (negative: d13CO2 below 3.5 per mil). Intention-to-treat (ITT) eradication rates were determined for all patients with confirmed H pylori infection. Per protocol (PP) rate was determined for all patients treated with at least two evaluable follow-up visits. RESULTS: Three hundred five patients were included in the ITT and 222 in the PP analysis. The ITT eradication rates were 66% for RBC-C and 78% for OCA. The PP success rates were 84% for RBC-C and 96% for OCA. The difference for both ITT 12% (95% CI 2 to 22) and PP 12% (95% CI 4 to 19) were statistically significant, P=0.030 and P=0.007, respectively. Treatment was generally well tolerated. CONCLUSION: The eradication rate for the seven-day dual RBC-C regimen was lower than that for OCA.     

序贯疗法与标准四联疗法对幽门螺杆菌根除失败后补救治疗的疗效分析

近年经典三联疗法的幽门螺杆菌（11．pylori）根除疗效明显降低,选择有效补救疗法对Hpylori根除失败者有重要意义。目的：比较序贯疗法与标准四联疗法对且pylori根除失败者的疗效。方法：将98例Hpylori根除失败者随机分为序贯疗法组（前5d予奥美拉唑20mg＋阿莫西林1000mgbid,后5d予奥美拉唑20mg＋左氧氟沙星200mg＋克拉霉素500mgbid）和标准四联疗法组（予奥美拉唑20mg＋胶体次枸橼酸铋钾220mg＋阿莫西林1000mg＋克拉霉素500mgbid,疗程7d）。停药4周后复查”C一尿素呼气试验,评估Hpylori根除疗效。结果：共95例患者完成方案,序贯疗法组11Tr和PP分析的Hpylori根除率均显著高于标准四联疗法组（ITF：89．8％对71,4％,PP：91．7％对74。5％,P〈0．05）,序贯疗法组临床症状改善的总有效率亦显著高于标准四联疗法组（95．8％对80．9％,P〈0．05）,两组不良反应发生率无明显差异（P〉0．05）。结论：对Hpylori根除治疗失败的患者,序贯疗法和标准四联疗法均可作为有效的补救治疗方案,但10d序贯疗法的疗效优于7d标准四联疗法。     

High-dose versus low-dose clarithromycin in 1-week triple therapy, including rabeprazole and levofloxacin, for Helicobacter pylori eradication

GOALS: To compare high-dose versus low-dose clarithromycin in 1-week triple therapy including rabeprazole and levofloxacin. BACKGROUND: Regimens containing rabeprazole and levofloxacin have proved to be effective against H. pylori infection. STUDY: One-hundred H. pylori-positive patients were randomly assigned to one of the following 1-week regimens: rabeprazole 20 mg o.d. plus levofloxacin 500 mg o.d. and clarithromycin 250 mg b.d. (RLC-1 group); rabeprazole 20 mg o.d. plus levofloxacin 500 mg o.d. and clarithromycin 500 mg b.d. (RLC-2 group). H. pylori status was assessed at entry and after the treatment. Patients who experienced treatment failure underwent antibiotic susceptibility testing. RESULTS: Forty-two patients in RLC-1 group (both PP and ITT analysis: 84%; 95%CI: 71-93%) and 47 in RLC2 group (both PP and ITT analysis: 94%; 95% CI: 83-98%) became H. pylori negative. Clarithromycin resistance was detected in all of 8 (100%) RLC-1 failures and in 1 out of 3 (33%) RLC-2 failures. Side effects occurred in 8% of patients in RLC-1 group and in 12% in RLC-2. CONCLUSIONS: Regimens tested are competitive with other PPI-based treatments. One-week triple therapy containing rabeprazole plus, levofloxacin, and high-dose clarithromycin yielded a higher eradicating rate than the one containing low-dose clarithromycin and may be considered as a first-line therapy option.     

影响慢性胃炎患者幽门螺杆菌根除的临床因素分析

背景:幽门螺杆菌(H.pylori)感染与慢性胃炎和消化性溃疡密切相关,然而,目前临床普遍采用的三联疗法对相当一部分患者的H.pylori根除无效。目的:探讨影响慢性胃炎患者H.Pylori根除的主要临床因素。方法:取128例H.pylori阳性的慢性胃炎患者的内镜活检标本行H.pylori培养和药敏试验,以奥美拉唑+克拉霉素+甲硝唑的7 d三联疗法行H.pylori根除治疗,以PCR-RFLP法检测CYP2C19基因型。分析不同因素对H.pylori根除率的影响。结果:共123例完成治疗,H.pylori根除率按ITT和按PP分析分别为66.4%和69.1%。H.pylori对甲硝唑和克拉霉素的耐药率分别为48.4%和14.1%。有吸烟史者的H.pylori根除率显著低于无吸烟史者(37.0%对88.3%,P0.01)。甲硝唑敏感菌株和克拉霉素敏感菌株的根除率均显著高于相应的耐药菌株(90.5%对46.7%,P0.01;76.6%对18.8%,P0.01)。CYP2C19强代谢型的根除率显著低于弱代谢型(63.4%对 86.7%,P0.05)。不同性别、年龄以及是否饮酒的患者之间H.pylori根除率差异均无统计学意义(P0.05)。结论:H.pylori对抗生素耐药和宿主CYP2C19强代谢型是导致H.pylori根除失败的主要原因,吸烟史对根除失败亦具有一定的意义。     

Effects of a specially designed fermented milk product containing probiotic Lactobacillus casei DN-114 001 and the eradication of H. pylori in children: a prospective randomized double-blind study

GOALS: To determine the efficacy of triple therapy supplemented with a specially designed fermented milk product containing specific probiotic Lactobacillus casei (L. casei) DN-114 001 strain on Helicobacter pylori eradication in children. BACKGROUND: Lactobacillus species possess in vitro activity against H. pylori. There are no consistent data on the impact of eradication therapy supplemented with probiotics on H. pylori cure rates in childhood in vivo. STUDY: Multicenter, prospective, randomized, double-blind controlled study. Eighty-six symptomatic H. pylori-positive children were randomized either to receive the control treatment of omeprazole, amoxicillin, and clarithromycin (OAC) for 7 days or the test treatment of omeprazole, amoxicillin, and clarithromycin for 7 days supplemented with fermented milk (Actimel) containing L. casei DN-114 001 (OAC-LC), for 14 days. H. pylori status was assessed at 4 weeks following therapy using two noninvasive tests. RESULTS: Intention-to-treat (ITT) based eradication rates for the OAC-LC group were 84.6% (95% CI, 71.2%-95.5%), and 91.6% (95% CI, 76.9%-98.2%) by per-protocol (PP) analysis. Eradication in the OAC group was 57.5% (95% CI, 42.2%-72.3%) in the ITT set and 61.3% (95% CI, 44.4%-75.0%) in the PP group. Eradication success was higher in the OAC-LC group compared with the OAC group in both ITT (P=0.0045) and PP analysis (P=0.0019). Primary resistance for clarithromycin could be determined in 21.2%. Side effects were infrequent. Drug compliance was good throughout the study. CONCLUSION: Supplementation with fermented milk, containing live special probiotic L. casei DN-114 001, confers an enhanced therapeutic benefit on H. pylori eradication in children with gastritis on triple therapy.     

Hybrid vs sequential therapy for eradication of Helicobacter pylori in Taiwan: a prospective randomized trial

AIM: To evaluate the efficacy of sequential vs hybrid therapy in patients with Helicobacter pylori(H. pylori) infection.METHODS: From March 2013 to May 2014,one hundred and seventy-five H. pylori infected patients who had not been treated for H. pylori before wererandomized to receive either sequential therapy(rabeprazole 20 mg and amoxicillin 1 g twice daily for 5 d,followed by rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg twice daily for 5 d) or hybrid therapy(rabeprazole 20 mg and amoxicillin 1 g for 7 d,followed by rabeprazole 20 mg,amoxicillin 1 g,clarithromycin 500 mg and metronidazole 500 mg twice daily for 7 d). H. pylori status was confirmed by positive results of both rapid urease test and histology examination or a positive result of culture. Eradication efficacy was assessed by follow-up endoscopy with rapid urease test and histological examination 8 wk after the end of anti-H. pylori therapy,or 13C-urea breath test at least 4 wk after completion of treatment. The primary outcome was H. pylori eradication by intension-to-treat(ITT) and per-protocol(PP) analyses.RESULTS: One hundred and sixty-seven patients(83 patients in the sequential group and 84 patients in the hybrid group) completed the study. The compliance rates were 97.6% and 97.7% for the two groups,respectively. The eradication rate was 78.2% for the sequential group and 92% for the hybrid group by ITT analysis(P = 0.01). The eradication rate was 81.9% for the sequential group and 96.4% for the hybrid group by PP analysis(P = 0.01). Univariate analysis for the clinical and bacterial factors did not identify any risk factors associated with treatment failure. Severe adverse events were observed in 2.3% of patients in the sequential group and 2.4% of those in the hybrid group.CONCLUSION: Due to a grade A( 95%) success rate for H. pylori eradication by PP analysis,similar compliance and adverse events,hybrid therapy seems to be an appropriate eradication regimen in Taiwan.     

Impact of clarithromycin resistance and CYP2C19 genetic polymorphism on treatment efficacy of Helicobacter pylori infection with lansoprazole- or rabeprazole-based triple therapy in Japan

OBJECTIVE: Helicobacter pylori treatment failure is thought to be due mainly to polymorphic cytochrome P450 2C19 (CPY2C19) genetic polymorphism, associated with proton pump inhibitor metabolism, and antimicrobial susceptibility. This report has ascertained which was more important, CPY2C19 polymorphism or antimicrobial susceptibility, when using 1-week lansoprazole-based or rabeprazole-based triple therapy in Japan. DESIGN: An open, randomized, parallel group study. SETTING: One hundred and forty-five subjects with H. pylori-positive gastritis or peptic ulcers were randomly assigned to receive 30 mg lansoprazole twice daily (LAC group), 10 mg rabeprazole twice daily (RAC20 group), or 20 mg rabeprazole twice daily (RAC40 group), with 1000 mg amoxicillin twice daily and 400 mg clarithromycin twice daily for 1 week. Antimicrobial resistance testing was performed by E-test. More than 4 weeks after completion of treatment, H. pylori status was assessed by 13C-urea breath test, histology, and culture. RESULTS: Cure rates expressed as intention-to-treat and per-protocol analyses, respectively, were 79.6 and 83.0% with LAC, 85.4 and 89.1% with RAC20, and 83.3 and 88.9% with RAC40. In the case of clarithromycin-sensitive strains, the cure rates were more than 97%, regardless of CPY2C19 polymorphism. However, treatment succeeded in only one out of 16 clarithromycin-resistant strains. CONCLUSIONS: The key to successful eradication of H. pylori, using lansoprazole or rabeprazole with clarithromycin and amoxicillin, is clarithromycin susceptibility, not CPY2C19 polymorphism.     

益生菌联合四联疗法治疗老年人幽门螺杆菌感染的临床观察

目的探讨益生菌在治疗老年人幽门螺杆菌(H.pylori)感染中的价值。方法入选2014年1月至10月解放军总医院南楼临床部消化内科120例老年H.pylori感染患者,根据年龄性别进行随机区组设计,分为益生菌治疗组和对照组,各60例。对照组给予阿莫西林+克拉霉素+雷贝拉唑+胶体果胶铋标准四联疗法,治疗组给予酪酸梭菌肠球菌三联活菌片+四联疗法,两组疗程均为14 d,治疗结束4周后复查~(13)C尿素呼气试验(~(13)C UBT),观察并比较两组患者H.pylori根除率及不良反应发生情况。结果 117例患者按方案完成治疗。治疗组和对照组按意向治疗(ITT)分析H.pylori根除率分别为83.33%和71.67%,按方案(PP)分析H.pylori根除率分别为86.21%和72.88%,治疗组ITT和PP根除率均明显高于对照组,但差异无统计学意义(P0.05),随访1年后复查,治疗组H.pylori根除率仍显著高于对照组,差异有统计学意义(P0.05);治疗组不良反应发生率为10.34%,明显低于对照组的27.12%,差异有统计学意义(P0.05)。治疗组对药物的耐受程度显著优于对照组(P0.05)。结论益生菌联合标准四联疗法能有效提高H.pylori根除率,并且能显著降低药物不良反应。     

细胞色素P450 2C19基因多态性对以质子泵抑制剂为基础的三联疗法根除幽门螺杆菌疗效的影响

目的 研究以质子泵抑制剂(PPI)、左氧氟沙星、羟氨苄青霉素作为一线疗法对幽门螺杆菌(Hp)根除的影响,以及Hp根除率与CYP2C19基因多态性的相关性.方法 205例Hp阳性的患者被分为4组:埃索美拉唑20 mg 2次/d(E_(20)组),埃索美拉唑40 mg 2次/d(E_(40)组),雷贝拉唑10 mg 2次/d(R组),兰索拉唑30 mg 2次/d(L组),4组均加左氧氟沙星500 mg 1次/d和羟氨苄青霉素1000 mg 2次/d,疗程1周.其中有161例患者进行了CYP2C19基因型的检测,对Hp根除率分别按意愿治疗(intention-to-treat,ITT)分析和按方案(per protocol,PP)分析进行评估.结果 Hp总根除率为83.4%(PP)和79.0%(ITT).各组的根除率为:E_(20)组86.7%,E_(40)组88.5%,R组73.5%,L组78.1%.其中完成基因型检测的161例患者中,各基因型的根除率分别为:纯合子弱代谢型(PM)90%,杂合子强代谢型(HetEM)81.5%,纯合子强代谢型(HomEM)82.1%.CYP2C19各基因型间Hp根除率、各治疗方案间的根除率及各方案内各基因型间的根除率差异均无统计学意义(P>0.05).结论 以PPI为基础包含左氧氟沙星的三联疗法是目前根除Hp的有效方案,且该方案对Hp的根除率不受CYP2C19基因多态性的影响.     

Levofloxacin-based triple therapy in first-line treatment for Helicobacter pylori eradication

BACKGROUND:  The standard first-line therapies for Helicobacter pylori eradication are based on clarithromycin and amoxicillin or metronidazole. Recent studies suggested levofloxacin as an alternative option for both first-and second-line H. pylori eradication treatment.
AIMS:  To compare efficacy and tolerability of two different 7-day standard triple therapies versus 7-day levofloxacin-based triple therapy in first-line treatment for H. pylori infection.
METHODS:  Three hundred consecutive H. pylori positive patients were randomized to receive: clarithromycin, amoxicillin, esomeprazole (Group A: N = 100); clarithromycin, metronidazole, esomeprazole (Group B: N = 100); or clarithromycin, levofloxacin, esomeprazole (Group C: N = 100). H. pylori status was rechecked by ¹³C urea breath test 6 wk after the end of therapy.
RESULTS:  Sixteen out of 300 patients discontinued treatment because of the occurrence of side effects (Group A, 5; Group B, 7; Group C, 4). The eradication rates in intention to treat (ITT) and per protocol (PP) analyses were: Group A, 75% and 79%; Group B, 72% and 77.4%; and Group C, 87% and 90.6%. The eradication rate achieved with levofloxacin-based triple therapy was significantly higher than that with standard therapies in either ITT (87% vs 75%, p <0.05; 87% vs 72%, p <0.01;) or PP analysis (90.6% vs 79%, p <0.05; 90.6 vs 77.4, p <0.05). No difference was found between standard triple therapies. The incidence of side effects was similar among groups.
CONCLUSIONS:  A 7-day levofloxacin-based triple therapy can achieve higher H. pylori eradication rates than standard regimens. These data suggest levofloxacin-based regimens can be the most effective in first-line anti- H. pylori therapy, at least in the Italian population.     

Quadruple therapy with lactoferrin for Helicobacter pylori eradication: A randomised, multicentre study

BACKGROUND: Helicobacter pylori eradication rate with standard triple therapies is decreasing. Recently, lactoferrin administration has been shown to significantly increase the cure rate of 7-day rabeprazole, clarithromycin and tinidazole triple therapy. We assessed whether lactoferrin also increases the eradication rate of 7-day esomeprazole, clarithromycin and amoxycillin triple therapy as first-line treatment. METHODS: Overall, 133 consecutive patients with non-ulcer dyspepsia and H. pylori infection were randomised to receive either a standard 7-day triple therapy with esomeprazole 20mg b.i.d., clarithromycin 500 mg b.i.d. and amoxycillin 1g b.i.d. (68 patients) or a quadruple therapy comprising of the same regimen plus lactoferrin 200mg b.i.d. (65 patients). H. pylori at entry was assessed by endoscopy, while bacterial eradication was checked by (13)C urea breath test 4-6 weeks after treatment. RESULTS: H. pylori eradication following standard triple therapy was achieved in 53/68 (77.9%; 95% CI = 68-88) and in 53/66 (80.3%; 95% CI = 71-89) patients at ITT and PP analyses, respectively. Following the quadruple regimen, the infection was cured in 50/65 (76.9%; 95% CI = 67-87) and 50/64 (78.1%; 95% CI = 68-88) patients at ITT and PP analyses, respectively. No statistically significant difference emerged between the two therapeutic regimens, both at ITT (p = 0.9) and PP analyses (p = 0.9). Side effects were complained by seven (10.3%) patients and six (9.2%) patients following the triple and quadruple regimens, respectively (p = 0.9), with only one patient in the quadruple group interrupting the treatment due to side effects. CONCLUSIONS: Quadruple therapy with lactoferrin did not significantly increase the H. pylori cure rate of standard 7-day clarithromycin-amoxycillin based triple therapy in non-ulcer dyspepsia patients.     

Is a 7-day Helicobater pylori treatment enough for eradication and inactivation of gastric inflammatory activity？

AIM： To compare the efficacy of a 7-d vs 10-d triple therapy regarding H pylori eradication, endoscopic findings and histological gastric inflammatory inactivation in the Ecuadorian population.
METHODS： 136 patients with dyspepsia and H pylori infection were randomized in 2 groups （68 per group）： group 1, 7-d therapy; group 2, 10-d therapy. Both groups received the same medication and daily dosage： omeprazole 20 mg bid, clarithromycin 500 mg bid and amoxicillin 1 g bid. Endoscopy was performed for histological assessment and H pylori infection status before and 8 wk after treatment.
RESULTS： H pylori was eradicated in 68% of group 1 vs 83.8% of group 2 for the intention-to-treat analysis （ITT） （P = 0.03; OR = 2.48; 95% CI, 1.1-5.8）, and 68% in group 1 vs 88% in group 2 for the per-protocol analysis （PP） （P = 0.008; OR = 3.66; 95% CI, 1.4-10）. Endoscopic gastric mucosa normalization was observed in 56.9% in group 1 vs 61.2% in group 2 for ITT, with similar results for the PP, the difference being statistically not significant. The rate of inflammatory inactivation was 69% in group 1 vs 88.7% in group 2 for ITT （P = 0.007; OR = 3.00; 95% CI, 1.2-7.5）, and 69% in group 1 vs96% in group 2 for PP （P = 0.0002; OR = 7.25; 95% CI, 2-26）.
CONCLUSION： In this Ecuadorian population, the 10-d therapy was more effective than the 7-d therapy for H pylori eradication as well as for gastric mucosa inflammatory inactivation.     

细胞色素P450 2C19基因多态性对埃索美拉唑三联疗法根除幽门螺杆菌疗效的影响

目的 前瞻性对比埃索美拉唑和奥美拉唑三联疗法根除幽门螺杆菌(Hp)的疗效,及细胞色素P450(CYP)2C19基因多态性对根除Hp疗效的影响.方法 240例Hp阳性消化性溃疡患者,随机分为EAC组(埃索美拉唑、阿莫西林和克拉霉素)和OAC组(奥美拉唑、阿莫西林和克拉霉素),每组120例,疗程7 d.继后埃索美拉唑或奥美拉唑巩固治疗3周.胃镜观察2周溃疡愈合情况,结束治疗4周后进行13C尿素呼气试验.利用聚合酶链反应(PCR)及限制片段长度多态性(RFLP)分析技术,测定所有患者的CYP2C19基因型,分为强代谢型(Ems)和弱代谢型(PMs),强代谢型包括纯合子(homEM)和杂合子(hetEM).结果 240例患者中225例完成疗效观察.Hp根除率按意向处理分析(ITT),EAC组为88.3%,OAC组为79.2%(P>0.05);按方案分析(PP)EAC组为91.4%,OAC组为87.2 oA(P>0.05).ITT分析显示,在CYP2C19 homEM基因型中,EAC和OAC组Hp根除率分别为91.9%和71.8%,两组间差异有统计学意义(P=0.037).PP分析显示,在homEM基因型中,EAC组和OAC组Hp根除率分别为97.1%和77.8%,两组间差异也有统计学意义(P=0.028).ITT分析显示,EAC组和OAC组2周溃疡愈合率分别为79.2%和69.2%(P>0.05);PP分析显示分别为81.9%和76.1%(P>0.05).EAC组和OAC组不良反应均较少(分别为3.3%和7.5%,P>0.05).结论 EAC方案Hp根除率较高,尤其在CYP2C19 homEM基因型患者,埃索美拉唑优于奥美拉唑.     

细胞色素P450 2C19基因多态性对埃索美拉唑三联疗法根除幽门螺杆菌疗效的影响

目的 前瞻性对比埃索美拉唑和奥美拉唑三联疗法根除幽门螺杆菌(Hp)的疗效,及细胞色素P450(CYP)2C19基因多态性对根除Hp疗效的影响.方法 240例Hp阳性消化性溃疡患者,随机分为EAC组(埃索美拉唑、阿莫西林和克拉霉素)和OAC组(奥美拉唑、阿莫西林和克拉霉素),每组120例,疗程7 d.继后埃索美拉唑或奥美拉唑巩固治疗3周.胃镜观察2周溃疡愈合情况,结束治疗4周后进行13C尿素呼气试验.利用聚合酶链反应(PCR)及限制片段长度多态性(RFLP)分析技术,测定所有患者的CYP2C19基因型,分为强代谢型(Ems)和弱代谢型(PMs),强代谢型包括纯合子(homEM)和杂合子(hetEM).结果 240例患者中225例完成疗效观察.Hp根除率按意向处理分析(ITT),EAC组为88.3%,OAC组为79.2%(P>0.05);按方案分析(PP)EAC组为91.4%,OAC组为87.2 oA(P>0.05).ITT分析显示,在CYP2C19 homEM基因型中,EAC和OAC组Hp根除率分别为91.9%和71.8%,两组间差异有统计学意义(P=0.037).PP分析显示,在homEM基因型中,EAC组和OAC组Hp根除率分别为97.1%和77.8%,两组间差异也有统计学意义(P=0.028).ITT分析显示,EAC组和OAC组2周溃疡愈合率分别为79.2%和69.2%(P>0.05);PP分析显示分别为81.9%和76.1%(P>0.05).EAC组和OAC组不良反应均较少(分别为3.3%和7.5%,P>0.05).结论 EAC方案Hp根除率较高,尤其在CYP2C19 homEM基因型患者,埃索美拉唑优于奥美拉唑.     

Changing patterns of antibiotic resistance of Helicobacter pylori in patients with peptic ulcer disease]

BACKGROUND/AIMS: Antibiotic resistance of Helicobacter pylori (H. pylori) is a significant clinical problem because it reduces the efficacy of eradication therapy. The aims of this study were to assess the changing patterns of antibiotic resistance of H. pylori in patients with peptic ulcer diseases and to evaluate the eradication rate in antibiotic resistant H. pylori strains. METHODS: One hundred forty four H. pylori isolates obtained from 466 patients with peptic ulcer disease between June 2001 and December 2005 were examined for antimicrobial resistance. The minimum inhibitory concentration (MIC) of metronidazole was determined by modified broth microdilution method (mBMD) and E test. MICs of clarithromycin and amoxicillin were determined by mBMD, E test, and disc diffusion test. The breakpoints for metronidazole, clarithromycin, and amoxicillin resistance were defined as >8 microg/mL, >1 microg/mL, and > or =1 microg/mL, respectively. RESULTS: Resistance to metronidazole and clarithromycin was detected in 34.7% and 16.7% of H. pylori isolates, respectively. During the recent 5-year study period, amoxicillin-resistant rate of H. pylori was 11.8%, and multi-drug resistance rate of H. pylori was 16.7%. The eradication rate of clarithromycin containing triple therapies was low (7.8%) in clarithromycin-resistant H. pylori strains. CONCLUSIONS: The proportions of clarithromycin-resistant H. pylori strains have increased significantly over the last 5-years. There is an increasing tendency for the emergence of strains with multi-drug resistance. The increase in clarithromycin-resistant strains results in a decrease in eradication rate for H. pylori. In areas with high clarithromycin resistance, new alternative first-line treatment combination should be considered.     

Helicobacter pylori eradication: a randomized prospective study of triple therapy versus triple therapy plus lactoferrin and probiotics

OBJECTIVES: Helicobacter pylori is causally associated with gastritis and peptic ulcer diseases. Recent data (meta-analysis) have demonstrated that triple therapy with amoxicillin, clarithromycin, and a proton pump inhibitor has an eradication rate of only 74-76% and new therapeutic protocols may be necessary. The aim of this study was to examine whether adding bovine lactoferrin (bLf) and probiotics (Pbs) to the standard triple therapy for H. pylori infection could improve the eradication rate and reduce side effects. METHODS: H. pylori infection was diagnosed in 206 patients: in 107 based on an upper endoscopy exam and a rapid urease test, and in 99 by means of the H. pylori stool antigen-test and the C(13) urea breath test (C(13) UBT). The patients were randomized into two groups: 101 patients (group A) underwent standard triple eradication therapy (esomeprazole, clarithromycin, amoxicillin), while 105 patients (group B) underwent a modified eradication therapy (standard triple eradication therapy plus bLf and Pb). Successful eradication therapy was defined as a negative C(13) UBT 8 wk after completion of the treatment. Results were evaluated by intention-to-treat (ITT) and per-protocol (PP) analysis. Data were evaluated and considered positive when P<0.05. RESULTS: At the end of the study 175/206 patients showed negative C(13) UBT results. According to intention-to-treat analysis, the infection was eradicated in 73/101 patients from Group A and in 93/105 from Group B. PP analysis showed 73/96 patients from Group A and 93/101 from Group B to have been successfully treated. More patients from group A than from group B reported side effects from their treatment (P<0.05). CONCLUSIONS: The results of our study suggest that the addition of bLf and Pbs could improve the standard eradication therapy for H. pylori infection--bLf serving to increase the eradication rate and Pbs to reduce the side effects of antibiotic therapy.