A randomized controlled comparison of three quadruple therapy regimens in a population with low Helicobacter pylori eradication rates

BACKGROUND AND AIM: We sought to compare the efficacy and tolerability of an omeprazole/clarithromycin/bismuth/tetracycline-based quadruple therapy to that of a ranitidine/metronidazole/bismuth/tetracycline-based quadruple therapy of 2 or 3 weeks duration in a population with a high prevalence of metronidazole-resistant Helicobacter pylori and low triple therapy eradication rates. METHODS: Two hundred and twenty-one patients who presented endoscopically proven duodenal ulcers and a positive rapid urease test were randomized to receive either: (i) omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d., bismuth subcitrate 240 mg b.i.d. and tetracycline 500 mg b.i.d (OCBT) for 2 weeks; (ii) ranitidine 300 mg b.i.d., metronidazole 500 mg b.i.d, bismuth subcitrate 240 mg b.i.d. and tetracycline 500 mg b.i.d. (RMBT2) for 2 weeks; or (iii) ranitidine 300 mg b.i.d., metronidazole 500 mg b.i.d, bismuth subcitrate 240 mg b.i.d. and tetracycline 500 mg b.i.d. (RMBT3) for 3 weeks. Patients were interviewed 2 weeks after the completion of therapy to review compliance and side-effects. Eradication of H. pylori was assessed 8 weeks after the completion of therapy with the use of a 14C-urea breath test. RESULTS: The per-protocol eradication rate was significantly higher with OCBT (88%) than RMBT2 (73%) or RMBT3 (71%) (P<0.05). The intent-to-treat eradication rate was numerically higher with OCBT (80%) than RMBT2 (68%) or RMBT3 (68%), although this difference did not reach statistical significance (P=0.09). Per-protocol or intent-to-treat eradication rates were similar with RMBT2 and RMBT3. There were significantly greater side-effects with the RMBT2 regimen. CONCLUSIONS: The omeprazole/clarithromycin/bismuth/tetracycline-based quadruple therapy provides higher H. pylori eradication rates than the ranitidine/metronidazole/bismuth/tetracycline-based quadruple therapy when administered per protocol. The prolongation of the latter regimen from 2 to 3 weeks did not increase eradication rates.     

评估以泮托拉唑为基础的三联和四联疗法根除幽门螺杆菌的疗效

目的 比较以泮托拉唑为基础的7d标准三联疗法与泮托拉唑+铋剂+甲硝唑+四环素的10 d四联疗法根除Hp的疗效和安全性.方法 170例非溃疡性消化不良的Hp感染者随机入选三联、四联治疗组.三联治疗组实行PAC方案:泮托拉唑40 mg(2次/d)+阿莫西林1.0 g(2次/d)+克拉霉素500 mg(2次/d),口服7 d.四联治疗组实行PBMT方案:泮托拉唑40 mg(2次/d)+胶体次枸橼酸铋220 mg(2次/d)+四环素750 mg(2次/d)+甲硝唑400 mg(2次/d),口服10 d.治疗结束后至少停药4周后复查13C-尿素呼气试验,结果≤4%.为Hp阴性,表示根除成功.同时评估疗效及安全性.结果 166例患者按方案完成治疗.三联治疗组按意图治疗分析(ITT)根除率为63.53%(54/85),较四联治疗组低[89.41%(76/85),x2=17.168,P=0.000].三联治疗组按实验方案分析(PP)根除率为65.06%(54/83),亦较四联治疗组低[91.57%(76/83),x2=13.588,P=0.000].从年龄段分析,年龄＞30岁者三联治疗组根除失败率为22.22%(4/18),较四联治疗组高[3.84%(1/26),x2=19.884,P=0.000].三联和四联治疗组不良反应发生率分别为60.00%(51/85)和42.35%(36/85).结论 在7 d标准三联疗法Hp根除疗效降低的情况下,含泮托拉唑、铋剂、四环素和甲硝唑的10 d四联方案可考虑为首选方案.

Abstract：

Objective Compare the efficacy and safety of pantoprazole-based 7-day standard triple therapy with 10-day quadruple therapy including pantoprazole, bismuth, metronidazole and tetracycline in Helicobacter pylori (H.pylori) eradication.Methods A total of 170 H.pylori positive patients with non-ulcer dyspepsia were recruited and randomly assigned into triple and quadruple therapy groups.The triple therapy group was implemented with PAC program which included orally taking pantoprazole 40 mg twice per day, amoxicillin 1.0 g twice per day and clarithromycin 500 mg twice per day for seven days.The quadruple therapy group was implemented with PBMT program which consisted of orally taking pantoprazole 40 mg twice per day, colloidal bismuth subcitrate 220 mg twice per day, metronidazole 400 mg three times per day and tetracycline 750 mg twice per day for ten days.The 13C -urea breathe test was re-examined at least 4 weeks after the completion of treatment, the result lower than 4%.was H.pylori negative which indicated the success of H.pylori eradication.The efficacy and safety were also evaluated.Results A total of 166 patients completed the treatment.With intention-to-treat (ITT) analysis, the H.pylori eradication rate in the triple therapy group was 63.5% (54/85), lower than that of the quadruple therapy group (89.41%(76/85) ,x2= 17.168,P=0.000).With per protocol (PP) analysis, the eradication rate in the triple therapy group was 65.06% (54/83), also lower than that of the quadruple therapy group (91.57 % (76/83) ,x2 = 13.588 ,P=0.000).Through the age analysis, in patients over 30 years old,the eradication failed rate in the triple therapy group was 22.22% (4/18), higher than that of the quadruple therapy group (3.84% (1 / 26), x2 = 19.884, P=0.000).The incidence of adverse reaction rates of the triple and quadruple therapy group were 60.00% (51/85) and 42.35 % (36/85) respectively.Conclusion Since the reduction of eradication rate with seven day standard triple therapy,the 10-day pantoprazole, bismuth, metronidazole and tetracycline quadruple therapy may be considered as the first choice.     

The influence of pretreatment on cure rates of Helicobacter pylori eradication

BACKGROUND: Many patients treated for H. pylori infection have been taking a proton pump inhibitor beforehand. There is conflicting evidence whether pretreatment influences the efficacy of H. pylori eradication. The aim of this study was to investigate the influence of pretreatment on cure rates of H. pylori eradication. METHODS: Patients with H. pylori positive peptic ulcer disease or functional dyspepsia were treated with two-day quadruple therapy (lansoprazole 30 mg twice daily, and colloidal bismuth subcitrate 120 mg, tetracycline 250 mg and metronidazole 250 mg, all eight times a day). Patients were randomised to receive either three-day pretreatment with lansoprazole 30 mg twice daily or no pretreatment. H. pylori was diagnosed using CLO, histology and culture. RESULTS: Twenty-five (66%) of 38 patients with pretreatment and 32 (84%) of 38 patients without pretreatment were cured (p=0.06). After adjustment for diagnosis, smoking status and metronidazole resistance the influence of pretreatment became slightly less pronounced (OR 0.44, 95% CI 0.1-1.7). Nonsmokers and patients with peptic ulcer disease were more likely to achieve H. pylori eradication than smokers and patients with functional dyspepsia, respectively (adjusted odds ratios: 4.79 (1.2-19) and 4.32 (1.0-18)). CONCLUSIONS: This two-day quadruple therapy reached an overall cure rate of 75%. Nonsmokers and patients with peptic ulcer disease were more likely to achieve H. pylori eradication. Three-day pretreatment with a proton pump inhibitor may decrease cure rates of this two-day quadruple therapy.     

Comparison of the effectiveness of quadruple salvage regimen for Helicobacter pylori infection according to the duration of treatment]

BACKGROUND/AIMS: At present, triple therapy schemes are recommended by national and international consensus conferences for the treatment of Helicobacter pylori (H. pylori) infection. However, even with the most effective current treatment regimens, about 10-20% of patients fail to eradicate H. pylori, necessitating alternative strategy to eradicate H. pylori in primary treatment failure. Therefore, we performed this study to evaluate the efficacy of quadruple therapy and to compare 1 and 2-week quadruple regimen as a second-line therapy. METHODS: The hospital records of 155 patients who failed to the standard triple therapy (proton pump inhibitor, amoxicillin, clarithromycin) were reviewed retrospectively, and divided the 1 or 2 weeks OBMT regimen (omeprazole 20 mg bid, bismuth salt 120 mg qid, metronidazole 500 mg tid, tetracycline 500 mg qid). Presence of H. pylori infection and side-effects of the treatment regimen were assessed 4 weeks after the cessation of treatment. RESULTS: One hundred and eight male and 47 female (mean age, 52.2+/-15.4) patients were enrolled. The overall eradication rate of H. pylori with quadruple therapy was 83.9% and the eradication rate was similar between 1 and 2 weeks of OBMT regimen (76.8% in OBMT 1 week, 87.9% in OBMT 2 weeks, respectively p=0.110). CONCLUSIONS: Quadruple therapy is an effective salvage regimen for H. pylori eradication after the failure of standard triple therapy. One week quadruple therapy is not significantly different from 2-weeks regimen as the second-line option for H. pylori eradication.     

以泮托拉唑为基础的三联和四联疗法根除幽门螺杆菌疗效比较——一项单中心、随机、开放、平行对照研究

背景：近年质子泵抑制剂（PPI）＋阿莫西林＋克拉霉素标准三联疗法对幽门螺杆菌（H.pylori）的根除率有所降低,PPI＋铋剂＋甲硝唑＋四环素的四联疗法能否成为一线治疗的首选以及适当延长疗程能否提高根除率尚有待明确。目的：比较以泮托拉唑为基础的7d标准三联疗法与7d、10d四联疗法根除H.pylori的疗效。方法：133例非溃疡性消化不良的H.pylori感染患者随机分配至7d三联组（45例,泮托拉唑40mgbid＋阿莫西林1.0gbid＋克拉霉素500mgbid,PAC方案）以及7d、10d四联组（43例和45例,泮托拉唑40mgbid＋枸橼酸铋钾220mgbid＋甲硝唑400mgtid＋四环素750mgbid,PBMT方案）。治疗结束后至少间隔4周行13C-尿素呼气试验复查H.pylori,评估治疗结果。结果：共129例患者按方案完成治疗。三组H.pylori根除率按意图治疗（ITT）分析分别为73.3%、79.1%和88.9%,按方案（PP）分析分别为75.0%、82.9%和90.9%。7dPAC方案的PP根除率显著低于10dPBMT方案（P〈0.05）。除四联组中有2例患者分别因头晕和腹泻而未完成治疗外,其余患者的不良反应相似且均能耐受。结论：在7d标准三联疗法H.pylori根除疗效降低的情况下,含泮托拉唑、铋剂、甲硝唑和四环素的10d四联疗法可考虑作为根除治疗的首选方案。     

Effect of two different doses of metronidazole and tetracycline in bismuth triple therapy on eradication of Helicobacter pylori and its resistant strains.

BACKGROUND: Classic triple therapy with bismuth, tetracycline and metronidazole is one of the most economic and effective regimens for the eradication of Helicobacter pylori. The aim of the study was to assess the efficacy of two different doses of tetracycline (TET) and metronidazole (MET) on cure of H. pylori infection and its MET-resistant strains. MATERIAL AND METHODS: A total of 131 patients with duodenal ulcer were randomized into three groups and received the following medication for 2 weeks: group A, colloidal bismuth subcitrate (CBS) 3 x 120 mg + TET 3 x 500 mg + MET 3 x 250 mg/day; group B, CBS 3 x 120 mg + TET 3 x 500 mg + MET 3 x 125 mg/day; group C, CBS 3 x 120 mg + TET 3 x 250 mg + MET 3 x 125 mg/day. Control endoscopy was performed after 6 weeks. Two biopsy specimens from antral and three from corpus mucosa were taken for a urease test, histology and culture. Eradication was concluded if all three tests were negative for H. pylori. MET resistance was determined by the disc diffusion method. RESULTS: In total, 121 patients completed the study. Only two of the 43 patients in group A discontinued the therapy due to intolerance. Cure of H. pylori infection was achieved by per protocol analysis in 33 of 43 patients in group A (76.7%), in 20 of 40 patients in group B (50%) and in 20 of 38 patients in group C (52.6%) (P < 0.05 for A versus B or C). Forty-two out of 112 patients had H. pylori strains resistant to MET (42%). In each group, the cure rate of infection was higher in patients with MET-sensitive H. pylori than in MET-resistant H. pylori (80.7% versus 64.2% in group A, 60% versus 38.8% in group B and 52.6% versus 40% in group C, respectively). Increase of MET dose from 375 mg (in groups B and C) to 750 mg/day (in group A) seems to augment the eradication of MET-sensitive as well as MET-resistant strains (up from 52% to 84% and from 39% to 64%, respectively; P < 0.05). CONCLUSION: Cure rate of H. pylori infection under classic triple therapy remains unaffected by dose reduction of tetracycline but not of metronidazole. In countries with a high prevalence of metronidazole resistance, such as Iran, higher doses of metronidazole are probably needed to increase the cure rate of bismuth triple therapy.     

Bismuth-based triple therapy with bismuth subcitrate, metronidazole and tetracycline in the eradication of Helicobacter pylori: a randomized, placebo controlled, double-blind study.

OBJECTIVE: To determine the rate of Helicobacter pylori eradication following bismuth-based triple therapy with colloidal bismuth subcitrate, tetracycline hydrochloride and metronidazole. PATIENTS AND METHODS: One hundred and eleven patients were randomly assigned, in a two to one ratio, to colloidal bismuth subcitrate 120 mg qid plus metronidazole 250 mg qid plus tetracycline 500 mg qid (Gastrostat), or matching placebo tablets and capsules for 14 days. Presence or absence of H pylori was documented by histology at entry and at least 28 days after treatment. Patients had dyspeptic symptoms with or without a history of peptic ulcer. Patients with any previous attempt(s) at eradication of H pylori, who used bismuth, antibiotics, H2 receptor antagonists or proton pump inhibitors in the previous four weeks were excluded. RESULTS: Fifty-three of 59 (90%) patients on bismuth-based treatment and only one of 35 (3%) on placebo achieved eradication by per protocol analysis. Fifty-three of 65 (82%) patients on bismuth-based treatment achieved eradication, while only two of 34 (5%) achieved eradication on placebo by intention to treat analysis. Eradication rates for bismuth-based treatment across sites ranged from 83% to 100%. Only two patients in the bismuth-based treatment group (4%) and one in the placebo group (3%) discontinued treatment because of adverse events. CONCLUSIONS: Colloidal bismuth subcitrate plus metronidazole plus tetracycline, given in the doses studied for 14 days, is safe and highly effective against H pylori infection and would be appropriate as a first-line therapy for eradication.     

Azithromycin in one week quadruple therapy for H pylori eradication in Iran

AIM: To investigate eradication rates, patient compliance and tolerability of a 1-wk Azithromycin-based quadruple therapy versus the 2-wk conventional therapy. METHODS: A total of 129 H pylori-positive patients were randomized to either omeprazole 20 mg, bismuth subcitrate 240 mg, azithromycin 250 mg, and metronidazole 500 mg, all twice daily for 1-wk (B-OAzM) or omeprazole 20 mg, bismuth subcitrate 240 mg, amoxicillin 1g, and metronidazole 500 mg all twice daily for 2-wk (B-OAM). H pylori infection was defined at entry by histology and rapid urease test and cure of infection was determined by negative urea breath test. RESULTS: H pylori eradication rates produced by B-OAzM and B-OAM were 74.1% and 70.4% respectively based on an intention to treat analysis, and 78.1% versus 75.7% respectively based on a per-protocol analysis. The incidence of poor compliance was lower, although not significantly so, in patients randomized to B-OAzM than for B-OAM (3.5% versus 4.3%) but intolerability was similar in the two groups ( 35% versus 33.3%). CONCLUSION: 1-wk azithromycin based quadruple regimen achieves an H pylori eradication rate comparable to that of standard 2-wk quadruple therapy, and is associated with comparable patient compliance and complications.     

Colloidal bismuth subcitrate-based twice-a-day quadruple therapy as primary or salvage therapy for Helicobacter pylori infection

OBJECTIVE: Helicobacter pylori (H. pylori) eradication rates in northern Sardinia using standard 1-wk triple therapies (i.e., a proton pump inhibitor and two antibiotics) are typically <60%, primarily because of antibiotic resistance. The aim of this study was to test b.i.d. quadruple therapy as primary and as salvage therapy in this population. METHODS: This was a prospective, single center study of consecutive dyspeptic H. pylori-infected patients. Therapy consisted of omeprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate caplets 240 mg, all b.i.d. with the midday and evening meals for 14 days. H. pylori status was evaluated by 13C-urea breath test and histology before and 4-6 wk after therapy. Eradication was defined as no positive test. RESULTS: We enrolled 118 consecutive dyspeptic patients (mean age 46 yr; 73 men, including 15 with peptic ulcer disease). Of the patients, 42 (38%) had failed prior therapy: twice in 21 cases, three times in 12, and four or more times in nine. The intention-to-treat cure rate was 95% (110 of 116) (95% CI = 90-98%) overall, and 98% per protocol, irrespective of diagnosis, age, prior treatment failure, or smoking status. Moderate or severe side effects were experienced by only 5% of patients. CONCLUSIONS: Bismuth subcitrate-based b.i.d. quadruple therapy was an excellent primary and salvage therapy and should be considered as first line therapy.     

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。     

Standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori eradication

AIM: To compare the effectiveness of standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori (H. pylori ) eradication in a randomized, double-blinded, comparative clinical trial in China. METHODS: A total of 215 H. pylori -positive patients were enrolled in the study and randomly allocated into three groups: group A (n = 72) received a 10-d bismuth pectin quadruple therapy (20 mg rabeprazole bid , 1000 mg amoxicillin bid , 100 mg bismuth pectin qid , and 500 mg levofloxaci...     

幽门螺杆菌根除治疗失败后的补救治疗

幽门螺杆菌（H.pylori)对抗生素的耐药率上升是导致根除治疗失败率上升的主要原因，对经标准方案根除H.pylori失败的患者有必要进行补救治疗。目的：评估铋剂、质子泵抑制剂（PPI）联用呋喃唑酮和四环素组成的7天四联方案用于根除H.pylori治疗失败后补救治疗的疗效，以及H.pylori耐药对疗效的影响。方法：予35例经含克拉霉素根除H.pylori方案治疗、H.pylori仍为阳性的患者以为期7天的四联治疗：枸橼酸铋钾220mg bid 奥美拉唑20mg bid 呋喃唑酮100mg bid 四环素750mg bid。治疗前取胃窦黏膜活检标本进行快速尿素酶试验、组织学检查和培养检测H.pylori。用琼脂扩散法测定克拉霉素、呋喃唑酮和四环素的最低抑菌浓度（MIC）。治疗结束后至少4周，采用^13C-尿素呼气试验进行H.pylori感染状态评估。结果：33例患者完成治疗和随访，2例失访。根据意图治疗（ITT）和试验方案（PP）分析，该补救方案的H.pylori根除率分别为68．6％（24／35）和72．7％（24／33）。10例（28．6％）患者发生轻度副反应（9例发生恶心、中上腹不适，1例发生皮疹）。35例中有27例H.pylori培养成功，克拉霉素的耐药率为51．8％（14／27），呋喃唑酮为3．7％（1／27），四环素为7．4％（2／27）。各药物耐药菌株和敏感菌株的H.pylori根除率无显著差异。结论：铋剂、PPI联用呋喃唑酮和四环素组成的7天联方案作为根除H.pylori治疗失败后的补救治疗可获得较高的H.pylori根除率。     

Efficacy of levofloxacin-based triple therapy as second-line Helicobacter pylori eradication]

BACKGROUND/AIMS: Bismuth-based quadruple therapy for second-line eradication treatment achieves the eradication rate ranging from 70% to 81% due to antimicrobial resistance and poor compliance. The aim of this study was to compare the eradication rate of levofloxacin-based triple therapy with that of bismuth-based quadruple therapy in second-line Helicobacter pylori (H. pylori) eradication therapy. METHODS: Seventy-six outpatients with persistent H. pylori infection after first-line triple therapy were enrolled in this prospective randomized trial. The subjects were randomized to receive levofloxacin 300 mg, amoxicillin 1 g, and pantoprazole 20 mg, given twice daily for 7 days (LAP group), or metronidazole 500 mg twice, tetracycline 500 mg four times, and pantoprazole 20 mg twice, bismuth subcitrate 600 mg twice daily for 7 days (MTPB group). Eradication was confirmed with (13)C-urea breath test or rapid urease test 4 weeks after the cessation of therapy. RESULTS: Among Seventy-six patients initially included, eleven were lost during follow-up. The eradication rates, expressed as intention to treat (ITT) and per protocol (PP) analyses, were 51.6% and 53.3% in the LAP group, and 48.9% and 62.9% in the MTPB group, respectively. There was no significant difference in H. pylori eradication rates between the two groups (p=0.815 by ITT, p=0.437 by PP). LAP regimen was better tolerated than MTPB regimen with lower incidence of side effects (10.0% versus 31.4%, p=0.03). CONCLUSIONS: H. pylori eradication rates of levofloxacin-based triple therapy and bismuth-based quadruple therapy were not significantly different in second-line H. pylori eradication therapy, and low incidence of side effects was observed in levofloxacin-based triple therapy.     

Bismuth-based quadruple therapy with bismuth subcitrate, metronidazole, tetracycline and omeprazole in the eradication of Helicobacter pylori.

BACKGROUND: A previous study showed that 14 days of qid bismuth-based triple therapy with tetracycline 500 mg, metronidazole 250 mg and colloidal bismuth subcitrate 120 mg resulted in excellent Helicobacter pylori eradication rates (89.5%). The present study looked at a shorter treatment period by adding omeprazole and by reducing the dose of tetracycline. METHODS: One hundred sixty-one patients with H pylori confirmed by histology and (13)carbon urea breath test were included in the study. They were treated for seven days with bismuth subcitrate 120 mg plus metronidazole 250 mg plus tetracycline 250 mg qid plus omeprazole 20 mg bid (OBMT). Patients were 18 to 75 years of age and had dyspepsia with or without a history of peptic ulcer. Patients with irritable bowel syndrome, active ulcer or previous attempt at eradication, or those who had used antibiotics or antiulcer drugs in the previous 30 days were excluded. Eradication was determined by two (13)carbon urea breath tests done one and three months, respectively, after treatment. Strains with minimal inhibitory concentrations of 8 microg/mL or higher were considered to be resistant to metronidazole. RESULTS: The overall per protocol eradication rate was 84%-89.5% in metronidazole-sensitive and 70.8% in metronidazole-resistant strains. Modified intent-to-treat analysis resulted in a 80% eradication rate--82.5% in metronidazole-sensitive and 66.7% in metronidazole-resistant strains. Only one patient discontinued treatment because of adverse events. CONCLUSIONS: The OBMT regimen used in this study is safe and effective against metronidazole-sensitive H pylori strains.     

A 10-day levofloxacin-based therapy in patients with resistant Helicobacter pylori infection: a controlled trial.

BACKGROUND & AIMS: Antibiotic resistance is a major issue in anti- Helicobacter pylori treatment. This study was aimed at assessing the efficacy of 2 therapies in patients with resistant H pylori infection. METHODS: Patients who had failed 1 or more eradication regimens underwent upper gastrointestinal endoscopy and 2 antral and 2 corpus biopsy specimens were taken for histology and culture. Metronidazole, clarithromycin, and amoxicillin resistance were determined by E-test. Patients were randomly assigned to 2 therapies: 1 group received pantoprazole 40 mg, amoxicillin 1 g, levofloxacin 250 mg, all twice daily for 10 days, and the other group was treated with omeprazole 20 mg twice daily for the first week and omeprazole 20 mg twice daily, tetracycline 250 mg 4 times daily, metronidazole 500 mg twice daily, and bismuth subcitrate 240 mg twice daily for the second week. Therapeutic success was evaluated by 13C urea breath test after 4 weeks of treatment. RESULTS: We enrolled 44 patients in the levofloxacin-based regimen and 46 patients in the quadruple therapy. The former was successful in 31 of 44 (70%; 95% confidence interval: 53-87) and the latter in 17 of 46 (37%; 95% confidence interval: 23-47) patients, using intention-to-treat (ITT) analysis (P < .001). The rates of H pylori resistance to metronidazole, clarithromycin, and amoxicillin were 46%, 12%, and 0%, respectively. Resistance to both metronidazole and clarithromycin was found in 10% of cases. CONCLUSIONS: Triple therapy containing levofloxacin was better than quadruple therapy. The 70% success rate observed indicates that 10 days of pantoprazole, amoxicillin, and levofloxacin should be considered in patients who had failed 1 or more eradication regimens.     

Various durations of a standard regimen (amoxycillin, metronidazole, colloidal bismuth sub-citrate for 2 weeks or with additional ranitidine for 1 or 2 weeks) on eradication of Helicobacter pylori in Iranian peptic ulcer patients. A randomized controlled trial

INTRODUCTION: One of the most economical and effective therapeutic regimens for eradication of Helicobacter pylori is the classic triple therapy with amoxycillin or tetracycline, metronidazole and a bismuth derivative. Addition of H2-receptor antagonists to these drugs may heighten the rate of eradication and shorten the duration. We therefore performed a randomized controlled trial comparing twice daily metronidazole, bismuth derivative and amoxycillin for 2 weeks with additional ranitidine for 1 or 2 weeks. PATIENTS AND METHODS: In total, 240 adult patients with duodenal ulcer and H. pylori infection were randomly assigned to one of the following regimens: (1) amoxycillin 1 g bid, metronidazole 500 mg bid, bismuth sub-citrate 240 mg bid and ranitidine 300 mg bid for 1 week; (2) triple therapy without ranitidine for 2 weeks; or (3) triple therapy plus ranitidine 300 mg bid for 2 weeks. Side-effects of the drugs were evaluated two weeks after starting the treatment. The rapid urease test and histology from antrum and corpus, and/or 14C- urea breath test were used to determine H. pylori eradication six weeks after starting the treatment. RESULTS: In total, 195 patients were followed up for 6 weeks. The most frequent drug side-effects were unpleasant taste (46%), dry mouth (41%) and fatigue (26%), which had an equal distribution in all treatment groups. Endoscopy and 14C- urea breath test were performed for 178 and 123 patients, respectively. Eradication of H. pylori was documented in 19/64 (29.7%), 29/63 (46%) and 50/68 (73.5%) of patients in groups 1, 2 and 3, respectively (P < 0.000001 for group 1 versus group 3; P < 0.0014 for group 2 versus group 3; difference not significant for group 1 versus group 2). An intention-to-treat analysis showed eradication rates of 19/80 (23.75%), 29/80 (36.25%) and 50/80 (62.5%) for groups 1, 2 and 3, respectively. At four weeks post-treatment, the most sensitive test for evaluation of eradication of H. pylori was histology. CONCLUSION: Although combined use of an H2-receptor antagonist and twice daily triple therapy in a two-week regimen is more effective than two-week triple or one-week quadruple therapy in Iranian patients, none of these regimens is ideal in countries with a probable high rate of resistant and strongly toxic strains of H. pylori.     

One-week ranitidine bismuth citrate versus colloidal bismuth subcitrate-based anti-Helicobacter triple therapy: a prospective randomized controlled trial

OBJECTIVE: The efficacy of 1 wk bismuth triple therapy is adversely influenced by the presence of metronidazole resistance. In vitro studies suggest that ranitidine bismuth citrate (RBC) plus metronidazole exhibit synergistic activity against metronidazole resistant strains of Helicobacter pylori (H. pylori). Whether this confers a superior clinical efficacy remains unproven. This study compared the efficacy of RBC-based triple therapy with bismuth triple therapy in eradication of H. pylori. METHODS: Patients with H. pylori-related ulcer disease or gastritis were randomized to receive either 400/mg of RBC twice daily plus 400/mg of metronidazole and 500/mg of tetracycline four times daily for 1 wk (RMT) or 120/mg of colloidal bismuth subcitrate, 400/mg of metronidazole, and 500/mg of tetracycline, all given four times daily for 1 wk (BMT). Metronidazole susceptibility was determined by the E-test and pretreatment resistance was defined as minimum inhibitory concentration > or = 32/mg/L. RESULTS: Of 100 consecutive patients randomized, two patients were lost to follow-up in each group. Forty-three of 85 (51%) H. pylori isolates were metronidazole resistant. Per-protocol cure rate for RMT and BMT was 40 of 41 (98%) and 37 of 44 (84%), respectively (p = 0.058). Intent-to-treat cure rate for RMT and BMT was 46 of 50 and 41 of 50, respectively (92% vs 82%, p = 0.23). A significantly higher eradication of metronidazole resistant H. pylori was observed in the RMT group (25 of 25, 100%) than in the BMT group (12 of 16, 75%), (p = 0.018). Side effects observed in the two treatment groups were comparable. CONCLUSIONS: One week of RBC triple therapy with metronidazole and tetracycline is an effective anti-Helicobacter therapy. This regimen is more appropriate in areas of high prevalence of metronidazole resistance.     

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.     

Second-line bismuth-containing quadruple therapy for Helicobacter pylori eradication and impact of diabetes

AIM To investigate Helicobacter pylori (H. pylori) eradication rates using second-line bismuth-containing quadruple therapy and to identify predictors of eradication failure.METHODS This study included 636 patients who failed firstline triple therapy and received 7d of bismuthcontaining quadruple therapy between January 2005 and December 2015. We retrospectively demonstrated H. pylori eradication rates with respect to the year of therapy as well as demographic and clinical factors. H. pylori eradication was confirmed by a 13C-urea breath test or a rapid urease test at least 4 wk after the completion of bismuth-based quadruple therapy: proton pump inhibitor, metronidazole, bismuth, and tetracycline.RESULTS The overall eradication rates by intention-to-treat analysis and per-protocol analysis were 73.9%( 95% CI : 70.1 %- 77.4%) and 94.5% (95% CI : 92.4%-96.5%), respectively. Annual eradication rates from 2005 to 2015 were 100.0%, 92.9%, 100.0%, 100.0%, 100.0%, 97.4%, 100.0%, 93.8%, 84.4%, 98.9%, and 92.5%, respectively, by per-protocol analysis. A multivariate analysis showed that diabetes mellitus (OR=3.99, 95%CI: 1.56-10.20, P=0.004)was associated with H. pylori eradication therapy failure.CONCLUSION The second-line bismuth-containing quadruple therapy for H. pylori infection is still effective in Korea, and diabetes mellitus is suggested to be a risk factor for eradication failure.     

The efficacy of levofloxacin based triple therapy for Helicobacter pylori eradication]

BACKGROUND/AIMS: The failure rates of first and second line therapies of Helicobacter pylori (H. pylori) eradication range from 15 to 20%. This study was aimed to evaluate the efficacy and safety of levofloxacin based triple therapy compared with standard triple or quadruple therapy for H. pylori eradication in Korea. METHODS: We enrolled two hundred and sixty seven patients with presence of H. pylori infection. One hundred and forty-one patients were treated with levofloxacin based triple therapy (LAP; levofloxacin, amoxicillin, proton pump inhibitor; PPI), and 126 patients were treated with standard triple therapy (CAP; clarithromycin, amoxicillin, PPI). We retreated the patients who had failed in H. pylori eradication with standard quadruple second-line therapy (MTPB; metronidazole, tetracycline, PPI, bismuth subcitrate) or levofloxacin based therapy (LAP or LCP; levofloxacin, clarithromycin, PPI). RESULTS: In first line therapy of H. pylori eradication, the eradication rates of levofloxacin based triple therapy and standard triple therapy were 69.8% and 74.0% respectively (p=0.52). In second-line therapy, the eradication rate of levofloxacin based triple therapy and standard quadruple therapy were 62.5% and 40.0% respectively (p=0.34). CONCLUSIONS: Levofloxacin based triple therapy is effective as standard regimen to eradicate H. pylori infection and is useful for an alternative rescue therapy as well.