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.     

多药耐药基因MDR1 C3435T基因多态性对根除幽门螺杆菌疗效的影响

目的研究多药耐药基因MDR1 C3435T基因多态性对质子泵抑制剂联合阿莫西林与克拉霉素三联1周疗法根除幽门螺杆菌（砀,）治疗的影响。方法选取101例却阳性的慢性胃炎或消化性溃疡患者,分成2组,分别进入埃索美拉唑联合阿莫西林与克拉霉素方案（EAC）或奥美拉唑联合阿莫西林与克拉霉素方案（OAC）进行1周根除治疗。采用聚合酶链反应-限制性内切片段长度多态性（polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP）的方法检测MDR1 C3435T基因型,比较不同基因型患者之间埤,根除率的差异。结果MDR1 CC3435、C3435T和3435TT的却根除率分别为72．4％、88．2％和81．0％。MDR1 C3435T各基因型组间却根除率比较均元显著性差异。结论MDR1 C3435T基因多态性与却根除疗效无显著相关性。     

Comparative study of modified-release clarithromycin and immediate-release clarithromycin in the treatment of Helicobacter pylori-associated peptic ulcer disease

BACKGROUND/AIMS: Proton pump inhibitor-based triple therapy containing immediate-release clarithromycin is an important regimen for the eradication of Helicobacter pylori (H. pylori). However, the efficacy of modified-release clarithromycin for the treatment of H. pylori-associated peptic ulcer disease is still unknown. The aims of the study were to compare the efficacy of modified-release clarithromycin and immediate-release clarithromycin on the rates of ulcer healing and eradication of H. pylori. METHODOLOGY: One hundred and sixty-one patients with Helicobacter pylori-associated peptic ulcer were randomized to receive one-week triple therapy with either modified-release clarithromycin 1000mg once daily (AECMR) or immediate-release clarithromycin 500mg twice daily (AECIR) in combination with amoxicillin 1,000mg twice daily (A) and esomeprazole 40mg once daily (E). Post-treatment ulcer healing status and Helicobacter pylori status was determined by endoscopy and 13C urea-breath test at 16 weeks and 8 weeks after completion of triple therapy, respectively. RESULTS: Helicobacter pylori eradication rates were 87.5% and 87.7% for AECMR and AECIR, respectively, in the intent-to-treat analysis. Eradication rates in the per-protocol groups were 90.3% and 91.4% for AECMR and AECIR, respectively. In both the intent-to-treat and per-protocol analyses, the eradication rates were comparable in the AECMR and AECIR groups (p= 1.0 and 1.0, respectively). Ulcer healing rates in the intention-to-treat analysis were 81.3% and 77.8% for AECMR and AECIR, respectively. Ulcer healing rates in the per-protocol analysis were 90.3% and 90.0% for AECMR and AECIR groups, respectively. In both the intention-to-treat and per-protocol analyses, the ulcer healing rates were comparable in the AECMR and AECIR groups (p=0.645 and 0.584, respectively). CONCLUSIONS: Modified-release clarithromycin 1000mg once daily can be used as an alternative to immediate-release clarithromycin 500mg twice daily for the treatment of Helicobacter pylori-associated peptic ulcer disease.     

Ten-day sequential therapy is more effective than proton pump inhibitor-based therapy in Korea: a prospective, randomized study

Background and Aims: The eradication rate of proton pump inhibitor (PPI)‐based triple therapy for Helicobacter pylori (H. pylori) infection has decreased, mainly due to increasing antibiotic resistance, especially against clarithromycin. It has been reported that a 10‐day sequential strategy can produce good outcomes. The aim of this prospective study was to assess the efficacy of sequential therapy as the first‐line treatment for the eradication of H. pylori in Korea. Methods: A total of 116 patients with proven H. pylori infection received 10‐day sequential therapy (20 mg rabeprazole and 1 g amoxicillin, twice daily for the first 5 days, followed by 20 mg rabeprazole, 500 mg clarithromycin, and 500 mg metronidazole, twice daily for the remaining 5 days); 130 patients received 7‐day triple therapy (20 mg rabeprazole, 500 mg clarithromycin, and 1 g amoxicillin, twice daily for 7 days). Eradication was evaluated by the ¹³C‐urea breath test, 4 weeks after the completion of treatment. Compliance and adverse events were assessed. Results: The eradication rates of 10‐day sequential therapy and PPI‐based triple therapy were 79.3% (92/116) and 63% (82/130) by intention‐to‐treat analysis, respectively (P = 0.005), and 81.9% (91/111) and 64.5% (82/127) by per protocol analysis, respectively (P = 0.003). Mild adverse events occurred in both therapy groups (27.5% vs 23.8%), but both treatments were well tolerated. Conclusion: The eradication rate of the 10‐day sequential therapy regimen was significantly higher than that of PPI‐based triple therapy in the Korean population. Ten‐day sequential therapy might be effective as a first‐line treatment for H. pylori infection in Korea.     

Update on clarithromycin resistance in Helicobacter pylori in Hong Kong and its effect on clarithromycin-based triple therapy

AIM: To determine the antibiotic susceptibility of Helicobacter pylori and evaluate the efficacy of a clarithromycin-based triple therapy in relation to antibiotic resistance. METHODS: Consecutive patients referred for upper endoscopy due to dyspeptic symptoms were recruited. Gastric biopsies were obtained for the CLO test, histology and culture. Antibiotic susceptibility was assessed by the E-test. Patients with H. pylori infection received rabeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg, all twice daily for 7 days. RESULTS: Of 234 patients recruited, 124 were H. pylori-positive and culture was successful in 102 patients. The updated prevalences of resistance to clarithromycin, amoxicillin and metronidazole were 7.8, 0 and 39.2%, respectively. A total of 86 patients received 1-week triple therapy with rabeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg, all twice daily, and 81 patients attended the follow-up test. Eradication rates by per-protocol and intention-to-treat analysis were 92.6 and 87.2%, respectively. The eradication rate by per protocol was significantly higher in patients with clarithromycin-susceptible strains than in those with clarithromycin-resistant strains (98.6 vs. 28.6%, p < 0.001). CONCLUSION: Clarithromycin resistance reduces the clinical efficacy of clarithromycin-based triple therapy. However, due to the low prevalence of clarithromycin resistance, clarithromycin-based therapy is still the first choice for clinical use.     

Efficacy of omeprazole and amoxicillin with either clarithromycin or metronidazole on eradication of Helicobacter pylori in Chinese peptic ulcer patients

AIM: One-week triple therapy with proton pump inhibitors, clarithromycin and amoxicillin has recently been proposed as the first-line treatment for Helicobacter pylori (H pylori) infection; however, data regarding the effects of this regimen in China are scarce. The aim of this prospective and randomized study was to compare the efficacy of clarithromycin and metronidazole when they were combined with omeprazole and amoxicillin on eradication of H pylori and ulcer healing in Chinese peptic ulcer patients. METHODS: A total of 103 subjects with Hpylori-positive peptic ulcer were randomly divided into two groups, and accepted triple therapy with omeprazole 20 mg, amoxicillin 1 000 mg and either clarithromycin 500 mg (OAC group, n = 58) or metronidazole 400 mg (0AM group, n - 45). All drugs were given twice daily for 7 d. Patients with active peptic ulcer were treated with omeprazole 20 mg daily for 2-4 wk after anti-H pylori therapy. Six to eight weeks after omeprazole therapy, all patients underwent endoscopies and four biopsies (two from the antrum and two others from the corpus of stomach) were taken for rapid urease test and histological analysis (with modified Giemsa staining) to examine H pylori. Successful eradication was defined as negative results from both examination methods. RESULTS: One hundred patients completed the entire course of therapy and returned for follow-up. The eradication rate of H pylori for the per-protocol analysis was 89.3% (50/56) in OAC group and 84.1% (37/44) in 0AM group. Based on the intention-to-treat analysis, the eradication rate of H pylori was 86.2% (50/58) in OAC group and 82.2% (37/45) in 0AM group. There were no significant differences in eradication rates between the two groups on either analysis. The active ulcer-healing rate was 96.7% (29/30) in OAC group and 100% (21/21) in 0AM group (per-protocol analysis, P>0.05). Six patients in OAC group (10.3%) and five in OAM group (11.1%) reported adverse events (P>0.05). CONCLUSION: One-week triple therapy with omeprazole and amoxicillin in combination with either clarithromycin or metronidazole is effective for the eradication of H pylori. The therapeutic regimen comprising metronidazole with low cost, good compliance and mild adverse events may offer a good choice for the treatment of peptic ulcers associated with H pylori infection in China.     

High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin

BACKGROUND/AIMS: Some patients are refractory to the usual triple therapy for eradication of Helicobacter pylori, consisting of a proton pump inhibitor, amoxicillin and clarithromycin, so there needs to be an alternative strategy for retreatment after failure to eradicate the infection. METHODOLOGY: The study group comprised 17 H. pylori-positive patients who had failed to clear H. pylori infection after 1 week of treatment with usual doses of proton pump inhibitor, amoxicillin and clarithromycin. The sensitivity of H. pylori to clarithromycin and amoxicillin, and the CYP2C19 genotype status of each patient were determined and treatment with rabeprazole (10 mg qid) and amoxicillin (500 mg qid) for 2 weeks was started. RESULTS: Eleven patients were infected with a clarithromycin-resistant strain of H. pylori. Twelve patients had the homozygous extensive metabolizer genotype, 5 had the heterozygous extensive metabolizer genotype and there were none with the poor metabolizer genotype of CYP2C19. All patients were successfully cleared of their H. pylori infection without any adverse effects, irrespective of CYP2C19 genotype status (100%, 95% confidence interval: 76-100%). CONCLUSIONS: High-dose dual therapy with rabeprazole (10 mg qid) and amoxicillin (500 mg qid) for 2 weeks appears useful treatment strategy after failure of eradication of H. pylori by the usual triple proton pump inhibitor/amoxicillin/clarithromycin therapy.     

One-year follow-up study of Helicobacter pylori eradication rate with 13C-urea breath test after 3-d and 7-d rabeprazole-based triple therapy

AIM: To investigate the long-term role of a 3-d rabeprazole-based triple therapy in patients with Helicobacter pylori (H pylori)-infected active peptic ulcers. METHODS: We prospectively studied 115 consecutive patients with H pylori-infected active peptic ulcers. H pylori infection was confirmed if any two of H pylori DNA, histology, and rapid urease test were positive. Patients were assigned to either an open-labeled 3-d course of oral amoxicillin 1 000 mg b.i.d., clarithromycin 500 mg b.i.d., and rabeprazole 20 mg b.i.d., or 7-d course of oral amoxicillin 1 000 mg b.i.d., clarithromycin 500 mg b.i.d., and rabeprazole 20 mg b.i.d. Subsequently, all patients received oral rabeprazole 20 mg once daily until the 8th wk. Three months after therapy, all patients were followed-up endoscopically for the peptic ulcer, H pylori DNA, histology, and rapid urease test. One year after therapy, H pylori infection was tested using the 13C-urea breath test. RESULTS: The ulcer healing rates 3 mo after therapy were 81.0% vs 75.4% for the 3-d and 7-d groups [intention-to-treat (ITT) analysis, P=0.47] respectively, and 90.4% vs 89.6% for the 3-d and 7-d groups [per-protocol (PP) analysis, P=0.89] respectively. The eradication rates 3 mo after therapy were 75.9% vs 73.7% for the 3-d and 7-d groups (ITT, P=0.79) respectively, and 84.6% vs 87.5% for the 3-d and 7-d groups (PP, P=0.68) respectively. One year after therapy, seventy-five patients returned to receive the 13C-urea breath test, and the eradication rates were 78.4% vs 81.6% in 3-d and 7-d groups (PP, P=0.73) respectively. CONCLUSION: Our study showed the eradication rates against H pylori infection 3 and 12 mo after triple therapy were not different between the 3-d and 7-d rabeprazole-based groups. Therefore, the 3-d rabeprazole-based triple therapy may be an alternative treatment for peptic ulcers with H pylori infection.     

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.     

Symptom-based tendencies of Helicobacter pylori eradication in patients with functional dyspepsia

AIM： To investigate whether there were symptom-based tendencies in the Helicobacter pylori （H. pylori） eradication in functional dyspepsia （FD） patients. METHODS： A randomized, single-blind, placebo-controlled study of H. pylori eradication for FD was conduct- ed. A total of 195 FD patients with H. pylori infection were divided into two groups： 98 patients in the treatment group were treated with rabeprazole 10 mg twice daily for 2 wk, amoxicillin 1.0 g and clarithromycin 0.5 g twice daily for 1 wk; 97 patients in the placebo group were given placebos as control. Symptoms of FD, such as postprandial fullness, early satiety, nausea, belching,epigastric pain and epigastric burning, were assessed 3 mo after H. pylori eradication. RESULTS： By per-protocol analysis in patients with successful H. pylori eradication, higher effective rates of 77.2% and 82% were achieved in the patients with epigastric pain and epigastric burning than those in the placebo group （P 〈 0.05）. The effective rates for postprandial fullness, early satiety, nausea and belching were 46%, 36%, 52.5% and 33.3%, respectively, and there was no significant difference from the placebo group （39.3%, 27.1%, 39.1% and 31.4%） （P 〉 0.05）. In 84 patients who received H. pylori eradication therapy, the effective rates for epigastric pain （73.8%） and epigastric burning （80.7%） were higher than those in the placebo group （P 〈 0.05）. The effective rates for postprandial fullness, early satiety, nausea and belch- ing were 41.4%, 33.3%, 50% and 31.4%, respective- ly, and did not differ from those in the placebo group （P 〉 0.05）. By intention-to-treat analysis, patients with epigastric pain and epigastric burning in the treatment group achieved higher effective rates of 60.8% and 65.7% than the placebo group （33.3% and 31.8%） （P 〈 0.05）. The effective rates for postprandial fullness, early satiety, nausea and belching were 34.8%, 27.9%, 41.1% and 26.7% respectively in the treatment group, with no significant difference from those in the placebo group （34.8%, 23.9%, 35.3% and 27.1%） （P 〉 0.05）. CONCLUSION： The efficacy of H. pylori eradication has symptom-based tendencies in FD patients. It may be effective in the subgroup of FD patients with epigastric pain syndrome.     

Eradication therapy with rabeprazole versus omeprazole in the treatment of active duodenal ulcer

BACKGROUND: Rabeprazole has been demonstrated to be a potent antisecretory agent and has been shown to be clinically effective in the treatment of acid-related diseases. AIMS: It was to determine the efficacy of rabeprazole at 20 and 40 mg in addition to amoxicillin and clarithromycin in the treatment of active Helicobacter pylori-positive duodenal ulcers compared with omeprazole 40 mg. PATIENTS AND METHODS: One hundred and twenty-seven patients were randomised into three treatment groups: 40 patients were treated with rabeprazole 40 mg daily, 42 patients with rabeprazole 20 mg daily and 45 patients with omeprazole 40 mg daily for 10 days. All patients received amoxicillin 1 g twice a day and clarithromycin 500 mg twice a day for 5 days. All patients were re-assessed at least 4 weeks after the end of the treatment. RESULTS: According to the intention-to-treat (ITT) protocol, ulcer healing was observed in 90% of patients in the rabeprazole 40 group, in 85.7% in the rabeprazole 20 group and in 93.3% in the omeprazole 40 group. We observed H. pylori eradication in 90% ITT in the rabeprazole 40 group, in 80.9% ITT in the rabeprazole 20 group and in 88.8% ITT in the omeprazole 40 group. Statistical analysis did not show significant differences among the three groups. CONCLUSIONS: A 10-day rabeprazole 20 mg regimen represents an efficacious and safe regimen for H. pylori eradication and ulcer healing.     

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.     

4-day triple therapy with rabeprazole, amoxicillin and clarithromycin in the eradication of Helicobacter pylori in patients with peptic ulcer disease--A pilot study

BACKGROUND: It is well established that a 7-day triple therapy achieves eradication rates of Helicobacter pylori between 90% and 95%. Due to a lack of highly effective short-term eradication studies the aim of the present pilot study was to investigate the effect of a 4-day triple therapy with the new proton pump inhibitor rabeprazole (20 mg b. i. d.) in combination with clarithromycin (500 mg b. i. d.) and amoxicillin (1 g b. i. d.) without acid-suppressive pre-treatment in patients with H. pylori-related peptic ulcer disease. METHODS: 20 patients (11 men, 9 women) with endoscopically diagnosed peptic ulcers (gastric ulcer: n = 5; duodenal ulcer: n = 9; combined gastric and duodenal ulcer: n = 2, gastric or duodenal ulcer scars: n = 4) and H. pylori infection were consecutively recruited. The Helicobacter pylori status was assessed by means of histology, CLO (urea-) test and C13-urea breath test (C13-UBT) at entry. Treatment success was determined by C13-UBT 35-42 days after end of treatment. RESULTS: In 18 out of the 20 patients (90%) [77-100%, 95%-CI] a negative test result was found in C13-UBT 35-42 days after treatment. The 2 patients who remained H. pylori-positive had a duodenal ulcer. CONCLUSION: A 4-day triple therapy of rabeprazole in combination with clarithromycin and amoxicillin seems to be highly effective in eradicating H. pylori and well tolerated in patients with gastric and duodenal ulcer disease. The achieved eradication rate of 90% is comparable with the established 7-day triple therapy regimens. On the basis of these results and considering costs, side effects and compliance a large number of patients should be enrolled in a confirmatory 4-day eradication trial.     

Randomized open trial for comparison of proton pump inhibitors in triple therapy for Helicobacter pylori infection in relation to CYP2C19 genotype

BACKGROUND AND AIMS: Genetic polymorphism of cytochrome P450 (CYP) 2C19 influences the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin. However, in triple therapy (PPI plus amoxicillin and clarithromycin), little is known about the impact of CYP2C19 polymorphism, or the use of rabeprazole, which is not well metabolized by CYP2C19. The efficacy of three PPI (omeprazole, lansoprazole, and rabeprazole) in a 1-week triple regimen were compared in relation to CYP2C19 polymorphism. METHOD: One hundred and eighty-three patients were randomized to receive one of the following regimens: amoxicillin 500 mg t.i.d., clarithromycin 200 mg t.i.d., and PPI (omeprazole 20 mg, lansoprazole 30 mg, or rabeprazole 10 mg) b.i.d. CYP2C19 polymorphism was analyzed by PCR restriction fragment length polymorphism. RESULTS: Intention-to-treat-based overall cure rates for omeprazole, lansoprazole or rabeprazole regimens were 83.1% (95% confidence interval (CI): 69-89%), 86.7% (CI: 75-93%), and 76.6% (CI: 64-85%), respectively, without significant difference. The cure rate of the rabeprazole regimen (but not the lansoprazole or omeprazole regimens) tended to be correlated with CYP2C19 genotypes (P = 0.076). In patients with a homozygous extensive metabolizer genotype, the per protocol-based cure rate with rabeprazole (62.5%) was significantly lower than that with lansoprazole (90.0%; P = 0.038). CONCLUSION: The overall cure rate of 1-week triple therapy for H. pylori eradication was not significantly different between regimens with omeprazole, lansoprazole or rabeprazole, but the impact of CYP2C19 genetic polymorphism on the cure rate appeared to differ between these PPI.     

Quadruple therapy for initial eradication of Helicobacter pylori in peptic ulcer: comparison with triple therapy.

BACKGROUND: Quadruple therapy appears to be more effective than standard triple therapy in the management of patients with Helicobacter pylori infection who harbor drug-resistant organisms. No data are available on the relative efficacies of triple and quadruple drug regimens from India. METHODS: Consecutive patients with peptic ulcer and H. pylori infection were randomized to receive lansoprazole 30 mg twice daily along with either amoxycillin (500 mg four times daily) and clarithromycin (500 mg twice a day) (Group A), or tri-potassium dicitrato bismuthate (120 mg four times daily), metronidazole (400 mg thrice daily) and tetracycline (500 mg 4 times daily) (Group B) for 10 days. Presence of H. pylori infection was looked for using an in-house urease test and histology before starting treatment, and 30 days after completion of treatment. RESULTS: Twenty-nine of 35 patients in Group A and 24 of 33 in Group B had eradication of infection (82.8% and 72.7% by intention-to-treat analysis, and 87.9% and 85.7% by per protocol analysis, respectively; p = ns). Side-effects occurred in 4 (12%) and 5 (18%) patients in Groups A and B, respectively (p = ns); discontinuation of drugs was required in two patients in group B. CONCLUSIONS: Quadruple therapy for initial treatment of H. pylori infection does not offer any advantage over standard triple therapy in Indian patients.     

克拉霉素、甲硝唑和兰索拉唑联合治疗幽门螺杆菌感染的临床疗效观察

目的：本文报道克拉霉素与甲硝唑及兰索拉唑联合应用治疗ＨＰ阳性的十二指肠溃疡。方法：５９例符合条件的病人随机分成两个治疗组，其中３０例口服充拉霉素２５０ｍｇ，甲硝唑４００ｍｇ，兰索拉唑３０ｍｇ。另一组２９例口服克拉霉素５００ｍｇ，甲硝唑４００ｍｇ．兰索拉唑３０ｍｇ，用法均为每日２次，疗程１周，继而口服兰索拉唑３０ｍｇ，每日１次，共１周。疗程结束后１个月复查胃镜。结果：克拉霉素１０００ｍｇ组ＨＰ根除率及溃疡愈合率分别为９３．１％及８９．７％，稍高于克拉霉素５００ｍｇ组的７６．７％及８０．０％，但差异无显著性（Ｐ＞０．０５）。体外检测。克拉霉素ＨＰ耐药发生率仅４．８％，而甲硝唑ＨＰ耐药发生率则达３３．３％，且甲硝唑耐药对ＨＰ根除率有较大影响。两组病人副反应总发生率为１５．３％，克拉霉素两个剂量组间副反应发生率无明显差别，未发现严重副反应。病人依从性良好。结论：克拉霉素与甲硝唑及兰索拉唑合用１周疗法有较理想的溃疡愈合率与ＨＰ根除率；克拉霉素用量以每日１０００ｍｇ为佳。     

Seven-day proton pump inhibitor, amoxicillin and clarithromycin triple therapy. factors that influence Helicobacter pylori eradications success.

AIM: To evaluate which factors influence eradication success with standard triple therapy for Helicobacter pylori. PATIENTS AND METHODS: A prospective study was made of 891 patients infected by H. pylori and diagnosed with duodenal ulcer (n=422), gastric ulcer (n=221), or functional dyspepsia (n=248). Initially, an endoscopy with biopsies of antrum and body (haematoxylin-eosin stain), and a 13C-urea breath test were performed. All patients were treated for seven days with either omeprazole 20 mg twice daily in 442 patients (OCA) or pantoprazole 40 mg twice daily in 449 patients (PCA), associated to clarithromycin (500 mg twice a day) and amoxicillin (1 g twice a day). Two months after completing therapy urea breath test was repeated to confirm eradication. RESULTS: Mean age +/- SD was 51.6 +/- 15 years, 61% were male. Overall eradication rate was 73.7% (95% CI 69-77%) and 80.8% (77-84%) with OCA and PCA therapy, respectively, showing significant difference between treatment regimens (chi 2 =6.3; p= 0.01). As refers to underlying diseases, H. pylori eradication was achieved in 77.4% (74-80%) of peptic ulcers and 77% (71-82%) of functional dyspepsia (p=n.s.). With our two treatment regimens (OCA/PCA) eradication success was 74/81% in peptic ulcer (p=0.03), and 72/80% in functional dyspepsia (p=0.1). In the multivariate analysis, type of therapy was the only variable that correlated with eradication success (odds ratio 1.5; 95% CI: 1.1-2.1) (chi2 model: 6,4; p=0.01). CONCLUSIONS: Standard triple therapy containing a proton pump inhibitor, clarithromycin and amoxicillin for seven days achieves in our community a moderate eradication success; this result could improve by using pantoprazole instead of omeprazole. This therapy is equally effective in patients with peptic ulcer and functional dyspepsia.     

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.     

Effectiveness of 10 day-sequential therapy for Helicobacter pylori eradication in Korea

BACKGROUND/AIMS: Antibiotic resistance and poor compliance are the main causes of Helicobacter pylori (H. pylori) eradication failure. Proton pump inhibitor (PPI)-based triple therapy is the most preferred regimen in clinical practice. However, a critical fall in the H. pylori eradication rate has been observed in the recent years. A novel 10 day-sequential therapy consists of five days of dual therapy followed by five days of triple therapy regimen has recently been described. We aimed to evaluate whether 10 day-sequential therapy eradicated H. pylori infection better than the PPI-based triple therapy in Korea. METHODS: 158 patients with proven H. pylori infection were randomized to receive either 10 day-sequential therapy (20 mg of omeprazole, 1.0 g of amoxicillin, each administered twice daily for the first 5 days, followed by 20 mg of omeprazole, 500 mg of clarithromycin, 500 mg of metronidazole, each administered twice daily for the remaining 5 days) or PPI-based triple therapy (20 mg of omeprazole, 1.0 g of amoxicillin, 500 mg of clarithromycin, each administered twice daily for 1 week). Outcome of eradication therapy was assessed 8 weeks after the cessation of treatment. RESULTS: Eradication rates of 10 day-sequential therapy and PPI-based triple therapy were 77.9% (60/77) and 71.6% (58/81) by intention to treat analysis, respectively (p=0.361). By per protocol analysis, eradication rates of 10 day-sequential therapy and triple therapy were 85.7% (60/70) and 76.6% (58/76), respectively (p=0.150). There were no significant differences in adverse event rates and treatment compliance between two groups. CONCLUSIONS: The 10 day-sequential therapy regimen failed to achieve significantly higher eradication rates than PPI-based triple therapy.     

Recent success of pantoprazole -or lansoprazole- based clarithromycin plus amoxicillin treatment in the eradication of Helicobacter pylori.

BACKGROUND/AIMS: There are some reports showing that resistance of Helicobacter pylori (H. pylori) to clarithromycin has increased in recent years. We aimed to investigate the current success of a most popular first-line eradication regimen by using two different proton pump inhibitors: lansoprazole and pantoprazole. METHODS: Ninety patients with H. pylori-positive functional dyspepsia were randomized to receive pantoprazole 40 mg b.i.d. or lansoprazole 30 mg b.i.d. in addition to amoxicillin 1,000 mg and clarithromycin 500 mg twice daily for 14 days in a multicenter study. H. pylori infection was determined by histological examination and a rapid urease test. A follow-up endoscopy was performed to assess the H. pylori eradication six weeks after the end of therapy. RESULTS: Seventy-nine patients completed the study protocol properly. The H. pylori eradication rates according to per protocol analysis were 70% in group pantoprazole, amoxicillin and clarithromycin (28/40) and 69.2% in group pantoprazole, amoxicillin and clarithromycin (27/39). The eradication rates according to intention to treat analysis were 62.2% and 60% in lansoprazole, amoxicillin, clarithromycin, pantoprazole, amoxicillin, clarithromycin groups, respectively. The eradication rates were similar in both protocols (p>0.05). CONCLUSIONS: The most popular first-line eradication protocols of H. pylori achieved only a moderate success in the current study. Alternative therapy options are needed instead of clarithromycin-based triple treatment for eradication of H. pylori. The choice of proton pump inhibitor is not important in the eradication rate of H. pylori.