High-dose Dual Therapy Research Articles

The Puzzle of Coccoid Forms of Helicobacter pylori: Beyond Basic Science.

Helicobacter pylori (H. pylori) may enter a non-replicative, non-culturable, low metabolically active state, the so-called coccoid form, to survive in extreme environmental conditions. Since coccoid forms are not susceptible to antibiotics, they could represent a cause of therapy failure even in the absence of antibiotic resistance, i.e., relapse within one year. Furthermore, coccoid forms may colonize and infect the gastric mucosa in animal models and induce specific antibodies in animals and humans. Their detection is hard, since they are not culturable. Techniques, such as electron microscopy, polymerase chain reaction, loop-mediated isothermal amplification, flow cytometry and metagenomics, are promising even if current evidence is limited. Among the options for the treatment, some strategies have been suggested, such as a very high proton pump inhibitor dose, high-dose dual therapy, N-acetycysteine, linolenic acid and vonoprazan. These clinical, diagnostic and therapeutic uncertainties will represent fascinating challenges in the future.

PPI-amoxicillin dual therapy for Helicobacter pylori infection: An update based on a systematic review and meta-analysis.

The efficacy of PPI-amoxicillin dual therapy (high-dose dual therapy) in the eradication of Helicobacter pylori is controversial. We aimed to investigate whether PPI-amoxicillin dual therapy is effective. We searched several publication databases for randomized controlled trials (RCTs) that compared PPI-amoxicillin dual therapy with controls up to March 2019. Meta-analyses of eradication rates were performed using random-effects models. Data from twelve RCTs including 2249 patients suggested that PPI-amoxicillin dual therapy and the current mainstream guidelines-recommended therapies achieved similar efficacy (83.2% vs 85.3%, risk ratio [RR]: 1.00, 95% CI 0.97-1.03, intention-to-treat analysis), (87.5% vs 90.1%, RR: 0.98, 95% CI 0.95-1.02, per-protocol analysis), and compliance (94.3% vs 93.5%, RR: 1.11, 95% CI 0.78-1.59), but side effects were less likely in the dual therapy (12.9% vs 28.0%, RR: 0.53, 95% CI 0.37-0.76). Further subgroup analyses showed that the seven RCTs (1302 patients) that reported antimicrobial susceptibility test results also showed that PPI-amoxicillin dual therapy and the current guidelines-recommended therapies achieved similar efficacy, and PPI-amoxicillin dual therapy was as effective for rescue therapy (RR: 0.97, 95% CI 0.89-1.05) as for first-line treatment (RR: 0.97, 95% CI 0.93-1.02). Compared with the current mainstream guidelines-recommended therapies, PPI-amoxicillin dual therapy has the same efficacy and compliance, and generally PPI-amoxicillin dual therapy causes fewer side effects.

High dose PPI-amoxicillin dual therapy for the treatment of Helicobacter pylori infection: a systematic review with meta-analysis.

Background:Helicobacter pylori resistance to amoxicillin remains rare in many regions. Proton pump inhibitor-amoxicillin-containing high dose dual therapy (HDDT) has been proposed to treat H. pylori infection. We aimed to assess the effectiveness and safety of PPI-amoxicillin HDDT for treatment of H. pylori infection in comparison with other regimens.Methods:Databases, including PubMed, Embase, and the Cochrane Register of Controlled Trials, were searched to find relevant publications. Randomized controlled trials comparing HDDT with control regimens for H. pylori eradication in adult patients were included. The primary outcome was eradication rate by intention-to-treat analysis. Adverse events were analyzed as second outcome.Results:A total of 15 trials with 3818 patients qualified for inclusion. The eradication rate of HDDT was neither significantly inferior nor superior to the recommended regimens such as triple therapy, bismuth quadruple therapy, and non-bismuth quadruple therapy [relative risk (RR): 1.00, 95% confidence interval (CI): 0.96–1.05, p = 0.870]. This finding was robust through subgroup analyses and sensitivity analyses. Trial sequential analysis showed that HDDT was equivalent to control regimens, and further similar trials were unlikely to alter the conclusions of this analysis. The frequency of adverse events was significantly lower in HDDT group (RR: 0.48, 95% CI: 0.37–0.64, p < 0.001).Conclusion:HDDT was equivalent to recommended first-line or rescue regimens with fewer adverse effects. The evidence from this meta-analysis supports the use of HDDT as first-line or rescue treatment for H. pylori infection.Trial registration:PROSPERO CRD42019133002

High prevalence of clarithromycin resistance and effect on Helicobacter pylori eradication in a population from Santiago, Chile: cohort study and meta-analysis

Helicobacter pylori (H. pylori) eradication using standard triple therapy (STT) with proton pump inhibitors (PPI), amoxicillin and clarithromycin (CLA) has been the standard in Latin America. However, CLA resistance is a rising problem affecting eradication rates. Genetic polymorphisms of CYP2C19, a PPI metabolizer may also affect eradication. The primary aims of this study were to evaluate the effect of clarithromycin resistance on H. pylori eradication in a population from Santiago, and to establish the pooled clarithromycin resistance in Santiago, Chile. Symptomatic adult patients attending a tertiary hospital in Santiago were recruited for this study. CLA resistance and the polymorphisms of CYP2C19 were determined on DNA extracted from gastric biopsies, using PCR. The STT was indicated for 14 days and eradication was determined by a urea breath test 4–6 weeks after therapy. A meta-analysis of CLA resistance studies among adult residents in Santiago was performed. Seventy-three out of 121 consecutive patients had positive rapid urease test (RUT) and received STT. Sixty-nine patients (95%) completed the study. The H. pylori eradication rate was 63% and the prevalence of CLA resistance was 26%. According to the CYP2C19 polymorphisms, 79.5% of the RUT-positive patients were extensive metabolizers. Multivariable analyses showed that only CLA resistance was significantly and inversely associated with failure of eradication (OR: 0.13; 95% confidence interval [95% CI], 0.04–0.49). A meta-analysis of two previous studies and our sample set (combined n = 194) yielded to a pooled prevalence of CLA resistance of 31.3% (95% CI 23.9–38.7). Our study shows that CLA resistance is associated with failure of H. pylori eradication. Given the high pooled prevalence of CLA resistance, consideration of CLA free therapies in Santiago is warranted. We could recommend bismuth quadruple therapy or high-dose dual therapy, according to bismuth availability. Further studies need to evaluate the best therapy.

Treatment of Helicobacter pylori.

Helicobacter pylori eradication has become more challenging over the past decade due to increasing antimicrobial resistance, especially to clarithromycin and levofloxacin. We identified 508 recent publications on H. pylori treatment (published between January 2018 and June 2019), focusing on the most highly clinically relevant for this review. Declining H. pylori eradication rates with clarithromycin triple therapy have led to most guidelines recommending 14 days bismuth-based quadruple therapy or concomitant therapy as the best initial empiric regimen. Substituting amoxicillin for tetracycline or metronidazole in quadruple therapy, and a three-in-one pill version of the regimen, also appear effective. Vonoprazan, a potent acid inhibitor, can overcome much clarithromycin resistance in triple therapy. High-dose dual therapy (proton pump inhibitor with amoxicillin) is a promising alternative approach. Reviewing resistance patterns to select suitable first-line empiric therapies is important in high resistance regions. Molecular methods to evaluate H. pylori antimicrobial susceptibility promise to be simpler than standard microbiological culture. The cost-effectiveness of antimicrobial susceptibility testing in refractory cases remains unproven. Updating clinicians treating H. pylori is important to combat the emerging problems of multidrug antimicrobial resistance in H. pylori strains. Truly novel approaches to H. pylori eradication are needed.

High-dose PPI-amoxicillin dual therapy with or without bismuth for first-line Helicobacter pylori therapy: A randomized trial.

A reliably highly effective high-dose proton-pump inhibitor plus amoxicillin (dual Helicobacter pylori therapy) has remained elusive. We compared whether the addition of bismuth to high-dose dual therapy would improve the efficacy of high-dose dual therapy as first-line treatment. This was an open-label, randomized single-center study of 160 treatment-naive patients with H.pylori infection who were randomly assigned to 14-day therapy with esomeprazole 40mg twice a day plus amoxicillin 1g three times a day with or without bismuth potassium citrate 600mg (elemental bismuth 220mg) twice a day. Antibiotic resistance was determined by agar dilution method and eradication by 13 C-urea breath test. The per-protocol eradication rates were 96.1%; 95% CI=88.9%-99.2% (73/76) without bismuth vs 93.3%; 95% CI=85.1%-97.8% (70/75) with bismuth (P=0.494). The intention-to-treat eradication rates were 92.5%; 95% CI=84.4%-97.2% (74/80) without bismuth and 88.8%; 95% CI=79.7%-94.7% (71/80) with bismuth (P=0.416). Resistance to amoxicillin, clarithromycin, metronidazole, and levofloxacin was 0%, 31.7%, 81.4%, and 40.7%, respectively. Smoking reduced treatment effectiveness limited to those not receiving bismuth. The per-protocol eradication rates were 70% (7/10) vs 100% (66/66) in smokers vs non-smokers without bismuth (P=0.002), and 100% (10/10) in smokers vs 92.3% (60/65) in non-smokers with bismuth (P=1.0). The adverse event rates were 7.5% (6/80) without bismuth vs 11.3% (9/80) with bismuth (P=0.416). Fourteen-day high-dose dual therapy was both effective and safe for first-line treatment in a region of high prevalence antibiotic resistance. Adding bismuth only improved treatment effectiveness among smokers.

436 – The Efficacy of Fourteen-Days Esomeprazole and Amoxicillin Containing High Dose Dual Therapy in the Treatment of First-Line Anti-H. Pylori Therapy: A Prospective Randomized Trial

436 – The Efficacy of Fourteen-Days Esomeprazole and Amoxicillin Containing High Dose Dual Therapy in the Treatment of First-Line Anti-H. Pylori Therapy: A Prospective Randomized Trial

Su1291 – Effectiveness of High Dose Dual Therapy in the Eradication of Helicobacter Pylori in a Public Hospital in Lima, Peru

Su1291 – Effectiveness of High Dose Dual Therapy in the Eradication of Helicobacter Pylori in a Public Hospital in Lima, Peru

Reconciliation of Recent Helicobacter pylori Treatment Guidelines in a Time of Increasing Resistance to Antibiotics.

Increasing resistance to antibiotics worldwide has adverse effects on the effectiveness of standard therapies to eradicate Helicobacter pylori infection. We reviewed guidelines developed by expert groups in Europe, Canada, and the United States for the treatment of H pylori infection. We compared the recommendations of these guidelines, reconciled them, and addressed the increasing resistance of H pylori to antibiotic therapy regimens. The guidelines recommend bismuth quadruple therapy for first-line treatment, replacing clarithromycin-based triple therapy. There is consensus for concomitant 4-drug therapy as an alternative, especially when bismuth is not available. When therapy is unsuccessful, it is likely due to resistance to clarithromycin, levofloxacin, and/or metronidazole; these drugs, if used previously, should be avoided in subsequent eradication attempts. Second-line therapies should be bismuth quadruple therapy or levofloxacin triple therapy, depending on suspected resistance, reserving rifabutin-based triple and high-dose dual amoxicillin proton pump inhibitor therapy for subsequent treatment attempts. The increasing resistance of H pylori to antibiotic therapy necessitates local availability of susceptibility tests for individuals, and establishment of regional and national monitoring programs to develop evidence-based locally relevant eradication strategies. Further studies into the development of more easily accessible methods of resistance testing, such as biomarker analysis of stool samples, are required. Options under investigation include substituting vonoprazan for proton pump inhibitors, adding probiotics, and vaccine development. Narrow-spectrum antibiotics and new therapeutic targets could be identified based on genomic, proteomic, and metabolomic analyses of H pylori.

A 14 day esomeprazole- and amoxicillin-containing high-dose dual therapy regimen achieves a high eradication rate as first-line anti-Helicobacter pylori treatment in Taiwan: a prospective randomized trial.

The first-line eradication rate of standard triple therapy for Helicobacter pylori infection has declined to <80%, and alternative therapies with >90% success rates are needed. Inconsistent eradication rates were reported for proton pump inhibitor- and amoxicillin-containing high-dose dual therapy. We performed a prospective, randomized controlled study to assess the efficacy of esomeprazole- and amoxicillin-containing high-dose dual therapy and investigated the influencing clinical factors. We recruited 240/278 eligible H. pylori-infected patients after exclusion. They were randomly assigned to 14 day high-dose dual therapy (esomeprazole 40 mg three times daily and amoxicillin 750 mg four times daily for 14 days; EA group) or 7 day non-bismuth quadruple therapy (esomeprazole 40 mg twice daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily and metronidazole 500 mg twice daily for 7 days; EACM group). Urea breath tests were followed up 8 weeks later. The eradication rates for the EA and EACM groups were 91.7% (95% CI = 85.3%-96.0%) and 86.7% (95% CI = 79.3%-92.2%) (P = 0.21) in ITT analysis; and 95.7% (95% CI = 90.2%-98.6%) and 92.0% (95% CI = 85.4%-96.3%) (P = 0.26) in PP analysis. The adverse event rates were 9.6% versus 23.0% in the two groups (P = 0.01). The H. pylori culture positivity rate was 91.8%. The antibiotic resistance rates were amoxicillin, 0%; clarithromycin, 14.6%; and metronidazole, 33.7%. A 14 day esomeprazole- and amoxicillin-containing high-dose dual therapy achieves a high eradication rate as first-line anti-H. pylori therapy, comparable to that with 7 day non-bismuth quadruple therapy but with fewer adverse events.

High dose dual therapy versus bismuth quadruple therapy for Helicobacter pylori eradication treatment: A systematic review and meta-analysis.

The aim of this study was to perform a systematic review and meta-analysis on high-dose dual therapy (HDDT) versus bismuth quadruple therapy (BQT) for Helicobacter pylori infection. Comparing HDDT to BQT were identified from PubMed, EMBASE, Cochrane library, CNKI, and Wanfang databases in Chinese up to March 2018. Statistical analyses were conducted using Review Manager 5.3 to compare the efficacy and side effects of these 2 therapies for H pylori infection. Dichotomous data were pooled to score the relative risk (RR) with 95% confidence intervals (CIs). Four randomized clinical trials (RCTs) including 829 patients with a diagnosis of H pylori infection were assessed. Overall the meta-analysis showed that both HDDT and BQT achieved similar efficacy of intention-to-treat (ITT) eradication rate, 85.5% versus 87.2%, RR 1.01 (95% CI: 0.96-1.06), P = .63, and of per-protocol (PP) eradication rate, 88.4% versus 91.5%, RR 1.00 (95% CI: 0.96-1.04), P = .99, and adherence 97.8% versus 95.0%, RR 1.01 (95% CI: 0.99-1.04), P = .32, but side effects were more likely in BQT (14.4% vs 40.4%, RR 0.42 (95% CI: 0.32-0.54), P <.00001). Both HDDT and BQT can achieve similar eradication rate for H pylori infection and adherence, and generally HDDT causes fewer side effects.

High-Dose PPI-Amoxicillin Dual Therapy with or Without Bismuth for First-Line &lt;i&gt;Helicobacter pylori &lt;/i&gt;Therapy: A Randomized Trial

Background A reliably highly effective high-dose proton-pump inhibitor plus amoxicillin (dual Helicobacter pylori therapy) has remained elusive. We compared whether the addition of bismuth to high-dose dual therapy would improve the efficacy of high-dose dual therapy as first-line treatment. Methods This was an open-label, randomized single-center study of 160 treatment-naive patients with H. pylori infection who were randomly assigned to 14-day therapy with esomeprazole 40 mg twice a day plus amoxicillin 1 g three times a day with or without bismuth potassium citrate 600 mg (elemental bismuth 220 mg) twice a day. Antibiotic resistance was determined by agar dilution method and eradication by 13 C-urea breath test. Results The per-protocol eradication rates were 96.1%; 95% CI = 88.9%-99.2% (73/76) without bismuth vs 93.3%; 95% CI = 85.1%-97.8% (70/75) with bismuth (P = 0.494). The intention-to-treat eradication rates were 92.5%; 95% CI = 84.4%-97.2% (74/80) without bismuth and 88.8%; 95% CI = 79.7%-94.7% (71/80) with bismuth (P = 0.416). Resistance to amoxicillin, clarithromycin, metronidazole, and levofloxacin was 0%, 31.7%, 81.4%, and 40.7%, respectively. Smoking reduced treatment effectiveness limited to those not receiving bismuth. The per-protocol eradication rates were 70% (7/10) vs 100% (66/66) in smokers vs non-smokers without bismuth (P = 0.002), and 100% (10/10) in smokers vs 92.3% (60/65) in non-smokers with bismuth (P = 1.0). The adverse event rates were 7.5% (6/80) without bismuth vs 11.3% (9/80) with bismuth (P = 0.416). Conclusions Fourteen-day high-dose dual therapy was both effective and safe for first-line treatment in a region of high prevalence antibiotic resistance. Adding bismuth only improved treatment effectiveness among smokers.

Second-line rescue treatment of Helicobacter pylori infection: Where are we now?

At present, the best rescue therapy for Helicobacter pylori (H. pylori) infection following failure of first-line eradication remains unclear. The Maastricht V/Florence Consensus Report recommends bismuth quadruple therapy, or fluoroquinolone-amoxicillin triple/quadruple therapy as the second-line therapy for H. pylori infection. Meta-analyses have shown that bismuth quadruple therapy and levofloxacin-amoxicillin triple therapy have comparable eradication rates, while the former has more adverse effects than the latter. There are no significant differences between the eradication rates of levofloxacin-amoxicillin triple and quadruple therapies. However, the eradication rates of both levofloxacin-containing treatments are suboptimal. An important caveat of levofloxacin-amoxicillin triple or quadruple therapy is poor eradication efficacy in the presence of fluoroquinolone resistance. High-dose dual therapy is an emerging second-line therapy and has an eradication efficacy comparable with levofloxacin-amoxicillin triple therapy. Recently, a 10-d tetracycline-levofloxacin (TL) quadruple therapy comprised of a proton pump inhibitor, bismuth, tetracycline and levofloxacin has been developed, which achieves a markedly higher eradication rate compared with levofloxacin-amoxicillin triple therapy (98% vs 69%) in patients with failure of standard triple, bismuth quadruple or non-bismuth quadruple therapy. The present article reviews current second-line anti-H. pylori regimens and treatment algorisms. In conclusion, bismuth quadruple therapy, levofloxacin-amoxicillin triple/quadruple therapy, high-dose dual therapy and TL quadruple therapy can be used as second-line treatment for H. pylori infection. Current evidence suggests that 10-d TL quadruple therapy is a simple and effective regimen, and has the potential to become a universal rescue treatment following eradication failure by all first-line eradication regimens for H. pylori infection.

52 - Efficacy of High-Dose Dual Therapy Versus Bismuth Quadruple Therapy for Rescue Treatment of Helicobacter Pylori — An Interim Report of Multi-Center, Randomized Control Study

52 - Efficacy of High-Dose Dual Therapy Versus Bismuth Quadruple Therapy for Rescue Treatment of Helicobacter Pylori — An Interim Report of Multi-Center, Randomized Control Study

972 - Efficacy of High-Dose Dual Therapy Versus Bismuthcontaining Quadruple Therapy for First-Line Treatment of Helicobacter Pylori Infection and an Interim Report of Multi-Center, Randomized Control Study

972 - Efficacy of High-Dose Dual Therapy Versus Bismuthcontaining Quadruple Therapy for First-Line Treatment of Helicobacter Pylori Infection and an Interim Report of Multi-Center, Randomized Control Study

Efficacy and safety of high-dose dual therapy for Helicobacter pylori rescue therapy: A systematic review and meta-analysis.

Although some studies have reported >90% success with high-dose dual proton pump inhibitor (PPI)-amoxicillin dual therapy for Helicobacter pylori (H. pylori) eradication, the efficacy of this therapy remains controversial. We aimed to re-evaluate the efficacy and safety of high-dose dual therapy on H. pylori eradication. We searched PubMed, the Cochrane Library, and EMBASE for randomized clinical trials (RCTs) evaluating the efficacy of high-dose PPI-amoxicillin dual therapy as the rescue therapy on H. pylori eradication. Treatment effect was determined with a fixed-effect model using the inverse variance method and was expressed as risk ratio (RR) with 95% confidence interval (CI). Because of significant statistical heterogeneity (χ2 15.98, I2 = 69%) among the six studies that qualified, four RCTs that included 473 patients with H. pylori infection after eradication failure were assessed. The meta-analysis showed that high-dose dual therapy and guideline-recommended rescue therapies achieved similar efficacy (81.3% vs 81.5%, RR 1.00 [95% CI 0.93-1.08], intention-to-treat analysis), compliance (95.3% vs 95.4%, RR 1.00 [95% CI 0.97-1.03]), and side effects (17.9% vs 19.7%, RR 0.88 [95% CI 0.62-1.25]). High-dose PPI-amoxicillin dual therapy is comparable to recommended rescue therapies for H. pylori infection. More researches are needed to determine the efficacy of high-dose dual therapy as a first-line therapy.

Doxycycline in Eradication Therapy of Helicobacter pylori - A Systematic Review and Meta-Analysis

Background: Since resistance of Helicobacter pylori is developing very fast all over the world, new treatment regimens for eradication are urgently needed. Aim: To compare eradication success rate of H. pylori treatment regimens with and without doxycycline. Methods: English medical literature searches were conducted for regimens including doxycycline for eradication of H. pylori. Searches were performed up to August 31, 2015, using MEDLINE, PubMed, EMBASE, Scopus and CENTRAL. Meta-analysis was performed by using comprehensive meta-analysis software. Pooled ORs and 95% CIs were calculated comparing treatment regimens for eradication of H. pylori infection with and without doxycycline. Results: The OR for eradication success rate in a fixed model was in favor for treatment regimens with doxycycline: 1.292, 95% CI 1.048-1.594, p = 0.016. There was no significant heterogeneity in the included studies: Q = 15.130, d.f. (Q) = 8, I² = 47.126, p > 0.10. When treatment regimens with doxycycline were compared only with treatment regimens with tetracycline, no significant difference was found in eradication success rate: OR 0.95, 95% CI 0.68-1.32, p = 0.77. But when treatment regimens with doxycycline were compared with treatment regimens without tetracycline, the OR in favor of doxycycline was even higher: OR 1.59, 95% CI 1.21-2.09, p < 0.001. Conclusion: In this meta-analysis, we confirmed doxycycline efficiency in the eradication of H. pylori. Thus, triple, quadruple or even high dose dual therapy with regimens containing doxycycline should be considered.

High Dose Ilaprazole/Amoxicillin as First-Line Regimen for Helicobacter pylori Infection in Korea.

Objective. The eradication rate of Helicobacter pylori (H. pylori) following standard triple therapy has declined over the past few decades. This study has determined whether high dose dual therapy (PPI and amoxicillin) is adequate for eradicating H. pylori in Korea. Methods. This was an open-labeled study of H. pylori infected treatment-naive patients. Subjects received dual therapy for 14 days: ilaprazole 40 mg tablets given twice a day and amoxicillin 750 mg tablets given 4 times a day. At the end of the therapy, the subjects visited the clinic to confirm compliance and monitor for any side effects. Subjects visited again after 4–6 weeks to confirm H. pylori status through a urea breath test. Results. The cure rate of H. pylori was 79.3% (23 of 29) (95% confidence interval: 61.6–90.2) in the intention-to-treat analysis and 82.1% (23 of 28) in the per-protocol analysis. Compliance rates were high (96.6%) and side effects were minimal and tolerable. Conclusion. A high dose of ilaprazole + amoxicillin was ineffective as the first-line therapy for eradicating H. pylori in Korea. Future studies should focus on intragastric pH measurements and assess amoxicillin resistance.

770 High Cumulative Eradication Rate in the First-Line and Rescue Therapies for Helicobacter pylori Infection by Repeated Optimized High Dose Dual Therapy

Background: The increased primary and acquired resistance rates of H. pylori to clarithromycin, metronidazole, and levofloxacin have resulted in a significant reduction in the efficacy of various anti-H. pylori regimens. We recently demonstrated that an optimized high-dose dual therapy (HDDT) is superior to the standard triple therapy (TT) or sequential therapy (ST) for H. pylori infection in a large-scale multi-hospital, randomized, comparative study (Clinical Gastro & Hepato, in press). Because the global prevalence of primary and acquired resistance to amoxicillin (AMO) is rare, we hypothesize that HDDT can be used repeatedly and empirically for H. pylori treatment without a reduction of eradication efficacy. Aim: To evaluated the cumulative efficacy of repeated HDDT treatment for first-line and rescue antiH. pylori therapy. Methods: A total of 618 patients with H. pylori infection diagnosed by endoscopy with biopsy for histology examination and bacterial culture were recruited in this multi-hospital study and were randomly allocated to receive HDDT, TT, or ST for therapy. As reported in our previous study, H. pylori was eradicated in 143 out of 150 (95.3%; 95% C.I. 92.9-97.8) treatment-naive patients receiving the first course of HDDT (rabeprazole 20 mg + AMO 750 mg, qid for 14 days). Six patients who failed in the first HDDT treatment received the second course of HDDT. For treatment-experienced patients, 68 out of 84 patients failed in TT and 25 out of 45 patients failed in ST received the first course of HDDT. The second course of HDDT was used again if the first course failed. Four to eight weeks after termination of each treatment, H. pylori infection status was examined by the C13-urea breath test. The E-test was used to evaluate the antibiotics resistances of H. pylori strains before and after failed treatment of repeated HDDT. Results: Five out of 6 treatment-naive patients had successfully H. pylori eradication by a second course of HDDT, resulting in a cumulative eradication rate of 98.7% (148/150; 95% C.I. 97.3-100.0) in the intention-to-treat (ITT) analysis, and 99.3% (148/149; 95% C.I. 98.4-100.3) in perprotocol (PP) analysis. For the treatment-experienced patients, H. pylori was successfully eradicated in 90.3% (84/93; 95% C.I. 85.9-94.7) of patients with first course of HDDT treatment. Seven out of 9 patients who failed in the first HDDT treatment achieved H. pylori eradication with a second course of HDDT. The cumulative eradication rate was 97.8% (91/ 93; 95% C.I. 95.7-100.0) in both ITT and PP analyses. The susceptibility of H. pylori to antibiotics did not significantly impact eradication rates. Conclusion: HDDT consisting of a PPI and AMO given four times daily is highly efficacious when it is used repeatedly for H. pylori eradication. Thus, H. pylori susceptibility testing may be avoided by using HDDT.

771 Seven-Day Rifabutin Containing Triple Therapy Versus Seven-Day Levofloxacin Containing Quadruple Therapy As Second-Line Treatment for Helicobacter pylori in Chinese Patients: An Open Label, Randomized Trial

Background: The increased primary and acquired resistance rates of H. pylori to clarithromycin, metronidazole, and levofloxacin have resulted in a significant reduction in the efficacy of various anti-H. pylori regimens. We recently demonstrated that an optimized high-dose dual therapy (HDDT) is superior to the standard triple therapy (TT) or sequential therapy (ST) for H. pylori infection in a large-scale multi-hospital, randomized, comparative study (Clinical Gastro & Hepato, in press). Because the global prevalence of primary and acquired resistance to amoxicillin (AMO) is rare, we hypothesize that HDDT can be used repeatedly and empirically for H. pylori treatment without a reduction of eradication efficacy. Aim: To evaluated the cumulative efficacy of repeated HDDT treatment for first-line and rescue antiH. pylori therapy. Methods: A total of 618 patients with H. pylori infection diagnosed by endoscopy with biopsy for histology examination and bacterial culture were recruited in this multi-hospital study and were randomly allocated to receive HDDT, TT, or ST for therapy. As reported in our previous study, H. pylori was eradicated in 143 out of 150 (95.3%; 95% C.I. 92.9-97.8) treatment-naive patients receiving the first course of HDDT (rabeprazole 20 mg + AMO 750 mg, qid for 14 days). Six patients who failed in the first HDDT treatment received the second course of HDDT. For treatment-experienced patients, 68 out of 84 patients failed in TT and 25 out of 45 patients failed in ST received the first course of HDDT. The second course of HDDT was used again if the first course failed. Four to eight weeks after termination of each treatment, H. pylori infection status was examined by the C13-urea breath test. The E-test was used to evaluate the antibiotics resistances of H. pylori strains before and after failed treatment of repeated HDDT. Results: Five out of 6 treatment-naive patients had successfully H. pylori eradication by a second course of HDDT, resulting in a cumulative eradication rate of 98.7% (148/150; 95% C.I. 97.3-100.0) in the intention-to-treat (ITT) analysis, and 99.3% (148/149; 95% C.I. 98.4-100.3) in perprotocol (PP) analysis. For the treatment-experienced patients, H. pylori was successfully eradicated in 90.3% (84/93; 95% C.I. 85.9-94.7) of patients with first course of HDDT treatment. Seven out of 9 patients who failed in the first HDDT treatment achieved H. pylori eradication with a second course of HDDT. The cumulative eradication rate was 97.8% (91/ 93; 95% C.I. 95.7-100.0) in both ITT and PP analyses. The susceptibility of H. pylori to antibiotics did not significantly impact eradication rates. Conclusion: HDDT consisting of a PPI and AMO given four times daily is highly efficacious when it is used repeatedly for H. pylori eradication. Thus, H. pylori susceptibility testing may be avoided by using HDDT.