Helicobacter pylori eradication with doxycycline-metronidazole-bismuth subcitrate triple therapy.

Triple therapy containing tetracycline HCl is currently among the most efficient combination therapies for eradication of Helicobacter pylori. Substitution of doxycycline for tetracycline HCl offers advantages of less frequent dosing and extrarenal excretion. In this study patients with duodenal ulcer or non-ulcer dyspepsia positive for H. pylori were randomized to either doxycycline or tetracycline HCl triple therapy in conjunction with bismuth subcitrate and metronidazole. Of the 34 patients taking doxycycline, only 22 (65%) achieved H. pylori eradication at the 4-week rebiopsy, compared with 36 of 39 (92%) taking tetracycline HCl (p = 0.004). We conclude that doxycycline-containing triple therapy is less effective for H. pylori eradication and offers no clinical advantage over tetracycline HCl-containing triple therapy.     

Low efficacy of levofloxacin-doxycycline-based third-line triple therapy for Helicobacter pylori eradication in Italy

AIM: To evaluate a levofloxacin-doxycycline-based triple therapy with or without a susceptibility culture test in non-responders to Helicobacter pylori (H. pylori) eradication.METHODS: A total of 142 (99 women, 43 men; mean 53.0 ± 12.7 years) non-responders to more than two H. pylori eradication therapies underwent susceptibility culture tests or were treated with a seven-day triple therapy consisting of esomeprazole, 20 mg b.i.d., levofloxacin, 500 mg b.i.d., and doxycycline, 100 mg b.i.d., randomly associated with (n = 71) or without (n = 71) Lactobacillus casei DG. H. pylori status was checked in all patients at enrollment and at least 8 wk after the end of therapy. Compliance and tolerability of regimens were also assessed.RESULTS: H. pylori eradication was achieved in < 50% of patients [per prototol (PP) = 49%; intention to treat (ITT) = 46%]. Eradication rate was higher in patients administered probiotics than in those without (PP = 55% vs 43%; ITT = 54% vs 40%). Estimated primary resistance to levofloxacin was 18% and multiple resistance was 31%. Therapy was well tolerated, and side effects were generally mild, with only one patient experiencing severe effects.CONCLUSION: Third-line levofloxacin-doxycycline triple therapy had a low H. pylori eradication efficacy, though the success and tolerability of this treatment may be enhanced with probiotics.     

Dual versus triple therapy in eradication of Helicobacter pylori

BACKGROUND/AIMS: Duodenal ulcers should be treated by eradication of Helicobacter pylori. This study compared the efficacy of a proton pump inhibitor together with one or two antibiotics in eradication therapy. METHODOLOGY: 177 patients who were H. pylori positive were randomized to receive 14 days of either: lansoprazole 30 mg bd and amoxicillin 1 g bd (LA), omeprazole 20 mg bd and amoxicillin 1 g bd (OA) or lansoprazole 30 mg bd, amoxicillin 1 g bd and clarithromycin 500 mg bd (LAC). The efficacy was assessed at four weeks and at six months after the end of treatment. Biopsies were taken for culture and bacterial sensitivity testing at inclusion and at four weeks after the end of treatment. RESULTS: 149 patients were evaluated for efficacy. The eradication rate was significantly higher in LAC (96%) compared to LA (51%) and OA (64%) treatments (P < 0.001). At baseline 17%, 21% and 19% of the patients in the LA, OA and LAC groups, respectively, were resistant to metronidazole and only one patient was resistant to clarithromycin. Post-treatment, four patients had acquired metronidazole resistance. CONCLUSIONS: LAC is more effective than LA and OA for eradication of H. pylori in duodenal ulcer disease.     

Influence of Helicobacter pylori genotype on triple eradication therapy

BACKGROUND: The efficiency of Helicobacter pylori eradication varies geographically, as do many parameters that might affect therapeutic efficiency. The aims of this study were to investigate the relationship between different genotypes of H. pylori and bacterium-related histopathological lesions in patients with duodenal ulcer and to determine the effect of genotype on triple eradication therapy. METHODS: Helicobacter pylori infections were analyzed in 78 duodenal ulcer patients. The cytotoxin-associated gene (cagA) and vacuolating cytotoxin gene (vacA) subtype status of cultured strains were studied by PCR. Histopathological findings were graded using a described grading system. The patients were treated with triple-therapy regimens consisting of a proton pump inhibitor and two antibiotics twice daily for 7 days. Endoscopy was repeated at 4 weeks post-therapy to monitor ulcer healing and H. pylori eradication. RESULTS: The bacteria were genotyped from 66 patients, 57 of whom had H. pylori eradicated. The absence of cagA was associated with unsuccessful treatment. No difference was found with regard to vacA subtype between the successful and unsuccessful eradication groups. On histopathological examination, high H. pylori colonization density and intestinal metaplasia were associated with low eradication rate, while a high grade of neutrophil infiltration was associated with a significantly higher eradication rate. CONCLUSIONS: The data confirm the importance of cagA positivity as a predictor of successful eradication. When high H. pylori colonization density and intestinal metaplasia are present, therapy appears to be less effective. Therefore, these histopathological features may be involved in an unsuccessful therapeutic outcome.     

序贯疗法和标准三联疗法根除幽门螺杆菌的疗效比较

目的:观察10d序贯疗法治疗幽门螺杆菌(Helicobacter pylori,H.pylori)的疗效及不良反应,与14d三联标准疗法比较H.pylori根除情况及经济学上有无优越性.方法:将103例经胃镜检查确诊为慢性胃炎或消化性溃疡且H.pylori阳性的患者随机分为两组,治疗组(10d序贯疗法)52例,前5d埃索美拉唑、阿莫西林,后5d埃索美拉唑、克拉霉素、替硝唑.对照组(14d标准三联疗法)51例,埃索美拉唑、阿莫西林、克拉霉素14d.所有患者停药4wk后复查13C呼气试验或胃镜检查,判断H.pylori根除情况.结果:治疗组H.pylori根除率为90.4%,与对照组(90.2%)比较无统计学差异(P=1.000);两组不良反应发生率分别为12/52(23.1%)、18/51(35.3%),两组比较无统计学差异(P=0.172);治疗组费用为380.6元,较对照组(677.88元)明显减低.结论:10d序贯疗法的H.pylori根除率不低于标准14d三联疗法,2组不良反应发生率相似,但10d序贯疗法根除H.pylori的效价比更高.     

Factors influencing the eradication of Helicobacter pylori with triple therapy.

Helicobacter pylori infection has been associated with gastritis, duodenal ulcer, gastric ulcer, and the epidemic form of gastric carcinoma. Eradication of H. pylori infection has proven to be difficult. Recently, combinations of antimicrobial drugs have been shown to eradicate greater than 50% of infections; however, the results have proven variable, and the factors influencing effectiveness of therapy are unclear. In the present study, the effectiveness of a triple therapy for eradication of H. pylori infection was evaluated. Triple therapy consisted of 2 g tetracycline, 750 mg metronidazole, and five or eight tablets of bismuth subsalicylate daily in 93 patients (70 with duodenal ulcer, 17 with gastric ulcer, and 6 with simple H. pylori gastritis). Combinations of a sensitive urea breath test, serology, culture, and histology were used to confirm the presence of infection, eradication, or relapse. Eradication was defined as inability to show H. pylori greater than or equal to 1 month after ending therapy. The overall eradication rate was 87%. The factors evaluated for their effect on predicting eradication included age, gender, type of disease, duration of therapy, amount of bismuth subsalicylate [five or eight Pepto-Bismol tablets daily (Procter & Gamble, Cincinnati, OH)], and compliance with the prescribed medications. Stepwise regression showed that compliance was the most important factor predicting success; the success rate was 96% for patients who took greater than 60% of the prescribed medications and 69% for patients who took less. For those taking greater than 60% of the prescribed therapy, the eradication rates were similar (a) for patients receiving therapy for 14 days or when tetracycline and bismuth subsalicylate were taken for an additional 14 days; (b) for patients with duodenal ulcer, gastric ulcer, and simple H. pylori gastritis; and (c) whether five or eight bismuth subsalicylate tablets were taken. It is concluded that triple therapy is effective for eradication of H. pylori and that future studies need to take compliance into account for comparisons between regimens.     

Levofloxacin-azithromycin combined triple therapy for Helicobacter pylori eradication]

BACKGROUND/AIMS: Antibiotic resistance and poor compliance are the main causes of Helicobacter pylori (H. pylori) eradication failure. This study evaluated the eradication rate, tolerability, and compliance of levofloxacin- azithromycin combined triple therapy for H. pylori eradication. METHODS: 1) First-line eradication: A total of 78 H. pylori-positive patients were enrolled. Seventeen military men in Armed Forces Capital Hospital were treated with 7 days of levofloxacin-azithromycin combined triple therapy (omeprazole 20 mg bid, levofloxacin 500 mg od, and azithromycin 500 mg od), and 61 patients in Kangbuk Samsung Hospital were treated with standard PPI-based triple therapy (omeprazole 20 mg bid, amoxicillin 1.0 g bid, and clarithromycin 500 mg bid) for 7 days. 2) Second-line eradication: A consecutive series of 59 patients who failed H. pylori eradication with standard PPI-based triple therapy in Kangbuk Samsung Hospital were randomized to two groups. Thirty patients were retreated with 7 days of bismuth-based quadruple therapy (omeprazole 20 mg bid, bismuth 120 mg qid, metronidazole 500 mg tid, and tetracycline 500 mg qid), and remaining 29 patients were retreated with levofloxacin-azithromycin combined triple therapy. Patient's compliance and tolerability were evaluated at the end of treatment. The status of H. pylori infection was assessed 8 weeks later then. The successful eradication of H. pylori was defined as negative results from histology and CLO test, or 13C-urea breath test. RESULTS: First-line eradication rate of levofloxacin-azithromycin triple therapy was lower than that of standard PPI-based triple therapy, but there was no statistically significant difference (70.6% vs. 80.3%, p=0.390). Second-line eradication rate of levofloxacin-azithromycin combined triple therapy was significantly lower than that of bismuth-based quadruple therapy (ITT/PP 65.5%/73.1% vs. 90%/90%, p<0.0001). The compliances of all patients were more than 85%. Two of patients with levofloxacin-azithromycin combined triple therapy complained self-limiting side effects (mild dizziness; mild insomnia with general weakness). CONCLUSIONS: Levofloxacin-azithromycin combined triple therapy should not be recommended as the first-line or second-line H. pylori eradication regimen in Korea.     

Furazolidone-based triple and quadruple eradication therapy for Helicobacter pylori infection

AIM: To evaluate the efficacy of furazolidone-based triple and quadruple therapy in eradicating Helicobacter pylori (H. pylori) in a multi-center randomized controlled trial.METHODS: A total of 720 H. pylori positive patients with duodenal ulcer disease were enrolled at 10 different hospitals in Jiangxi province in China. The patients were randomly assigned to four treatment groups as follows: patients in Groups 1 and 3 received rabeprazole (10 mg), amoxicillin (1000 mg) and furazolidone (100 mg) twice daily for 7 and 10 d, respectively; patients in Groups 2 and 4 received rabeprazole (10 mg), bismuth (220 mg), amoxicillin (1000 mg) and furazolidone (100 mg) twice daily for 7 and 10 d, respectively. The primary outcome measure was H. pylori eradication rate 4 wk after treatment by intention-to-treat and per protocol analysis, while the secondary outcome measures were symptom and sign changes at the end of treatment and 4 wk after the end of treatment, as well as the proportion of patients who developed adverse events.RESULTS: The demographic data of the four groups were not significantly different. Overall, 666 patients completed the scheme and were re-assessed with the ¹³C-urea breath test. The intention-to-treat analysis of the H. pylori eradication rates in Groups 1, 2, 3 and 4 were 74.44%, 82.78%, 78.89% and 86.11%, respectively. The H. pylori eradication rate in Group 4 was significantly higher than that in Group 1. According to the per protocol analysis, the H. pylori eradication rates in Groups 1, 2, 3 and 4 were 81.21%, 89.22%, 85.54% and 92.26%, respectively. The H. pylori eradication rate in Group 4 was significantly higher than that in Group 1. The number of adverse events was 15 (8.3%), 16 (8.9%), 15 (8.3%) and 17 (9.4%) in Groups 1, 2, 3 and 4, respectively, including dizziness, vomiting, diarrhea, nausea, skin rash, itchy skin, and malaise. The symptoms were relieved without special treatment in all of the patients.CONCLUSION: Both 7- and 10-d quadruple furazolidone-based therapies achieve satisfactory H. pylori eradication rates.     

Pseudomembranous colitis associated with a triple therapy for Helicobacter pylori eradication

Helicobacter pylori(H.pylori)is one of the most common chronic bacterial infections in humans,affecting half of world’s population.Therapy for H.pylori infection has proven to be both effective and safe.The oneweek triple therapy including proton pump inhibitor,clarithromycin,and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H.pylori infection in countries with low clarithromycin resistance.Generally,this therapy is well-tolerated,with only a few and usually minor side effects.However,rare but severe adverse effects such as pseudomembranous colitis have been reported,Clostridium difficile(C.difficile)infection being the main causative factor in all cases.We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid,clarithromycin 500 mg bid,and amoxicillin 1 g bid to eradicate H.pylori infection.A limited colonoscopy showed typical appearance of pseudomembranous colitis,and the stool test for C.difficile toxins was positive.Rapid resolution of symptoms and negative C.difficile toxins were obtained in both patients with oral vancomycin.No relapse occurred during a four and eleven-month,respectively,follow up.These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H.pylori eradication therapy.     

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.     

Efficacy of 14-d vs 7-d moxifloxacin-based triple regimens for second-line Helicobacter pylori eradication

AIM: To evaluate the efficacy of the 14-d moxifloxacinbased triple therapy for the second-line eradication of Helicobacter pylori(H. pylori) infection.METHODS: Between 2011 and 2013, we conducted a retrospective review of the medical records of 160 patients who had experienced failure of their first-line proton pump inhibitor-based eradication therapy and subsequently received the moxifloxacin-based triple therapy as a second-line eradication treatment regimen. The patients who were treated with the moxifloxacinbased triple therapy(oral 20 mg rabeprazole b.i.d., 1000 mg amoxicillin b.i.d., and 400 mg moxifloxacin q.d.) for 7 d were assigned to the RAM-7 group(n = 79) while those who took them for 14 days were assigned to RAM-14 group(n = 81). The eradication rates for both groups were determined by intentionto-treat(ITT) and per-protocol(PP) analyses. ITT analysis compared the treatment groups as originally allocated while the PP analysis including only those patients who had completed the treatment as originally allocated. Successful eradication therapy for H. pylori infection was defined as the documentation of a negative 13C-urea breath test 4 wk after the end of the eradication treatment.RESULTS: The overall ITT eradication rate was 76.2%(122/160). The final ITT eradication rates were 70.8%(56/79; 95%CI: 63.3%-77.1%) in the RAM-7 group and 81.4%(66/81; 95%CI: 74.6%-88.3%) in the RAM-14 group(P = 0.034). The overall PP eradication rate was 84.1%(122/145), and the final PP eradication rates were 77.7%(56/72; 95%CI: 70.2%-85.3%) in the RAM-7 group and 90.4%(66/73; 95%CI: 82.8%-98.1%) in the RAM-14 group(P = 0.017). The H. pylori-eradication rates in the RAM-14 group were significantly higher compared with that of the RAM-7 group according to both the ITT(P = 0.034) and the PP analyses(P = 0.017). Both groups exhibited good treatment compliance(RAM-7/RAM-14 group: 100%/100%). The adverse event rates were19.4%(14/72)and 20.5%(15/73)in the RAM-7 and RAM-14 groups,respectively(P=0.441).Adverse events occurred in 14 of the 72 patients(19.4)in the RAM-7 group and in 15 of the 73 patients(20.5)in the RAM-14 group.No statistically significant differences(P=0.441)were observed.CONCLUSION:The 14-d moxifloxacin-based triple therapy is a significantly more effective secondline eradication treatment as compared to the 7-d alternative for H.pylori infection in South Korea.     

10天序贯和标准三联疗法根除幽门螺杆菌的疗效比较

目的评估新的序贯疗法对幽门螺杆菌的根除率。方法我院91例慢性胃炎患者纳入研究。幽门螺杆菌感染由组织学、尿素酶和尿素酶呼气试验评估。序贯疗法包括埃索美拉唑、阿莫西林治疗5天,随后以埃索美拉唑、克拉霉素和替硝唑治疗另外的5天。对照组标准三联疗法包括埃索美拉唑、阿莫西林和克拉霉素治疗10天。幽门螺杆菌的根除率以意向性分析(ITT)和完成治疗分析(PP)表示。根除疗效的判断根据治疗后6周的尿素酶呼气试验结果。结果序贯治疗对慢性胃炎患者的幽门螺杆菌感染获得86.36%(95%CI=81.19%-91.53%)和92.68%(95%CI=88.62%-96.74%)的根除率,但是和10天标准三联治疗相比较差异没有统计学意义。结论序贯治疗能获得较高的幽门螺杆菌根除率,但和10天标准三联治疗比较未获得显著的统计学差异。     

Effectiveness of triple therapy and quadruple therapy for Helicobacter pylori eradication]

BACKGROUND/AIMS: Quadruple therapy can be considered as a first-line therapy in areas where the resistance rate to clarithromycin is high. Comparison study of triple therapy and quadruple therapy for Helicobacter pylori (H. pylori) eradication is still lacking in Korea despite the increasing prevalence of antibiotic resistance. This study was conducted to compare the efficacy of triple and quadruple therapy as a first-line treatment in H. pylori infected patients with peptic ulcer. METHODS: Consecutive 149 cases of peptic ulcer disease associated with H. pylori infection were randomized either to proton pump inhibitor (PPI, bid), amoxicillin (1,000 mg, bid), and clarithromycin (500 mg, bid) (PAC group) or to PPI (bid), bismuth subcitrate (300 mg, qid), metronidazole (500 mg, tid), and tetracycline (500 mg, qid) (PBMT group) eradication treatments for 7 days. Outcome of eradication therapy was assessed by 13C-urea breath test performed 4-6 weeks after eradication. RESULTS: Eradication rates in PAC and PBMT group were 78.7% (59/75) and 71.6% (53/74) by intention to treat analysis, respectively (p=0.424). By per protocol analysis, eradication rates of PAC and PBMT group were 85.5% (59/69) and 85.5% (53/62), respectively (p=1.012). Adverse reactions occurred in 5 (6.6%) and 7 (9.5%) patients in PAC and PBMT group, respectively (p=0.346). CONCLUSIONS: One week-quadruple therapy as a first-line treatment for H. pylori infection does not offer any advantage over PPI-based triple therapy in Korean patients.     

亚洲人群中序贯疗法与三联疗法根除幽门螺旋杆菌临床疗效的Meta分析

目的评价在亚洲人群中序贯疗法与三联疗法根除幽门螺旋杆菌(Helicobacter pylori,H.pylori)临床疗效的差异。方法计算机检索中文数据库和外文数据库包括万方数据库、中国知网、维普数据库、中国生物医学文献数据库(CBM)、Medline/Pubmed、Embase、Wiley、Springer和Elsevier;手工检索《中华消化杂志》、《世界华人消化杂志》和会议记录。查找与此研究相关的临床随机对照试验(RCT)文献,采用Cochrane系统评价员手册5.0.2版推荐的方法纳入文献,并对其进行Meta分析。结果共纳入19篇临床随机对照(RCT)文献,纳入患者2 854例,其中采用序贯疗法的患者1 282例,采用三联疗法的患者1 572例。对19篇RCT研究进行Meta分析的结果显示:序贯疗法根除幽门螺旋杆菌(H.pylori)的疗效优于三联疗法,差异具有统计学意义(P0.05)。序贯疗法和三联疗法根除率的意向处理(ITT)分析分别为86.91%和73.47%(OR=2.43,95%CI:1.83~3.22,P0.05),序贯疗法与三联疗法根除率的试验方案(PP)分析分别为89.85%和77.32%(OR=2.51,95%CI:1.91~3.30,P0.05)。对于溃疡显效情况、疼痛缓解情况和不良反应发生情况等,由于条件所限未能进行Meta分析,仅进行了描述性分析。结论在亚洲人群中,序贯疗法较传统三联疗法具有较高的H.pylori根除率,为当前由于H.pylori抗生素耐药性提高而引起的三联疗法治疗成功率降低提供了一种新的选择,在临床上具有很好的应用前景。但目前相关RCT研究样本量少,且普遍质量较低。上述结论尚需要高质量、多中心、大样本量的随机双盲试验加以证实。     

Comparison of sequential and 7-, 10-, 14-d triple therapy for Helicobacter pylori infection

AIM: To compare the effectiveness of sequential therapy for Helicobacter pylori (H. pylori) infection with that of triple therapy of varying durations.METHODS: The 460 patients enrolled in this study had H. pylori-associated gastritis or a gastric or duodenal ulcer. After screening, H. pylori-infected patients were randomly assigned to receive either conventional triple therapy for 7, 10 or 14 d, or a new 10-d sequential therapy. Each of the 4 treatment groups included 115 patients. The outcomes of eradication therapy were assessed 4 wk after treatment by the urea breath test and histology.RESULTS: The overall eradication rate was 81.0%, and eradication rates were 75.7% for 7-d conventional triple therapy, 81.9% for 10-d conventional triple therapy, 84.4% for 14-d conventional triple therapy, and 82.0% for 10-d sequential therapy. Neither intention-to-treat analysis nor per protocol analysis showed significant differences in eradication rates using sequential therapy or the standard triple therapy (P = 0.416 and P = 0.405, respectively).CONCLUSION: There are no significant differences between 10-d sequential eradication therapy for H. pylori and any duration of standard triple treatment in Korean patients.