Helicobacter Pylori Eradication Regimens Research Articles

Selection of an Appropriate Helicobacter Pylori Eradication Regimen in an Urban Population: A Quality Improvement Project

Helicobacter pylori (H pylori) infection is one of the most common chronic bacterial infection. H pylori infection is associated with peptic ulcer disease and gastric cancer. In the US, most commonly used therapies for H pylori eradication include clarithromycin-based triple therapy (PPI, clarithromycin, and amoxicillin) and quadruple therapy (PPI, bismuth, metronidazole, and tetracycline). According to the 2017 ACG Clinical Guidelines for treatment of H pylori infection, quadruple therapy is preferred in patients with any previous macrolide exposure or high local clarithromycin resistance (>15% failure rate).

Prospective comparative study between two first-line regimens for Helicobacter pylori eradication: Non-bismuth quadruple versus bismuth quadruple therapy

The Maastricht V Consensus recommends quadruple therapies as first-line Helicobacter pylori treatment in high clarithromycin (CLA) resistance areas. To compare efficacy, side effects and compliance between quadruple concomitant non-bismuth vs bismuth quadruple therapy. Prospective study enrolling H. pylori -positive patients. Omeprazol and a three-in-one formulation of bismuth–metronidazol–tetracycline (OBMT-3/1) for 10 days, or combination of omeprazol–clarithromycin–amoxicillin–metronidazol (OCAM) for 14 days, were prescribed. Eradication outcome was assessed by urea breath test or histology. Side effects and compliance were recorded during the treatment period with specific questionnaires. 404 patients were recruited (median age 53 years; 62.87% women). In 382 (183 with OCAM, 199 with OBMT-3/1) the post-treatment test result was available. The eradication rates were 85.94% (CI95%: 80.20–90.52) with OCAM and 88.21% (CI95%: 83.09–92.22) with OBMT-3/1 ( p = 0.595) in intention-to-treat analysis, whilst in per protocol analysis they were 91.12% (CI95%: 85.78–94.95) and 96.17% (CI95%: 92.28–98.45) respectively ( p = 0.083). Compliance over 90% was 91.35% with OCAM and 92.04% with OBMT-3/1 ( p = 0.951). Some side effect was present in 94.02% with OCAM and in 88.89% with OBMT-3/1 ( p = 0.109), being longer (12 vs 7 days, p < 0.0001) and more severe ( p < 0.0001) with OCAM. In a high CLA-resistance area, there are no differences between OBMT-3/1 and OCAM in H. pylori eradication and compliance rates, but OBMT-3/1 achieves a higher safety profile. El Consenso de Maastricht V recomienda tetraterapias como tratamiento de primera línea de Helicobacter pylori en áreas con elevada resistencia a claritromicina (CLA). Comparar la eficacia, los efectos secundarios y el cumplimiento terapéutico entre la tetraterapia sin bismuto y la tetraterapia con bismuto. Estudio prospectivo que incluyó a pacientes con H. pylori . Se prescribió omeprazol y una formulación 3 en uno de bismuto-metronidazol-tetraciclina (OBMT-3/1) durante 10 días, o una combinación de omeprazol-claritromicina-amoxicilina-metronidazol (OCAM) durante 14 días. El resultado de la erradicación se evaluó mediante una prueba de aliento con urea o histología. Los efectos secundarios y el cumplimiento terapéutico se registraron durante el período de tratamiento empleando cuestionarios específicos. Se incluyeron 404 pacientes (mediana de edad de 53 años; un 62,87% de mujeres). El resultado de la prueba posterior al tratamiento estuvo disponible en 382 pacientes (183 con OCAM, 199 con OBMT-3/1). Las tasas de erradicación fueron del 85,94% (IC 95%: 80,20-90,52) con OCAM y del 88,21% (IC 95%: 83,09-92,22) con OBMT-3/1 ( p = 0,595) en el análisis por intención de tratar, mientras que en el análisis por protocolo fueron del 91,12% (IC 95%: 85,78-94,95) y del 96,17% (IC 95%: 92,28-98,45), respectivamente ( p = 0,083). El cumplimiento terapéutico superior al 90% fue del 91,35% con OCAM y del 92,04% con OBMT-3/1 ( p = 0,951). Se observaron efectos secundarios en el 94,02% de los pacientes tratados con OCAM y en el 88,89% de los tratados con OBMT-3/1 ( p = 0,109), y fueron más prolongados (12 frente a 7 días, p < 0,0001) y más graves ( p < 0,0001) con OCAM. En un área con elevada resistencia a la CLA no se observan diferencias entre OBMT-3/1 y OCAM en la erradicación de H. pylori ni en las tasas de cumplimiento, pero OBMT-3/1 presenta un perfil de seguridad superior.

Prospective comparative study between two first-line regimens for Helicobacter pylori eradication: Non-bismuth quadruple versus bismuth quadruple therapy

BackgroundThe Maastricht V Consensus recommends quadruple therapies as first-line Helicobacter pylori treatment in high clarithromycin (CLA) resistance areas. AimsTo compare efficacy, side effects and compliance between quadruple concomitant non-bismuth vs bismuth quadruple therapy. MethodProspective study enrolling H. pylori-positive patients. Omeprazol and a three-in-one formulation of bismuth–metronidazol–tetracycline (OBMT-3/1) for 10 days, or combination of omeprazol–clarithromycin–amoxicillin–metronidazol (OCAM) for 14 days, were prescribed. Eradication outcome was assessed by urea breath test or histology. Side effects and compliance were recorded during the treatment period with specific questionnaires. Results404 patients were recruited (median age 53 years; 62.87% women). In 382 (183 with OCAM, 199 with OBMT-3/1) the post-treatment test result was available. The eradication rates were 85.94% (CI95%: 80.20–90.52) with OCAM and 88.21% (CI95%: 83.09–92.22) with OBMT-3/1 (p=0.595) in intention-to-treat analysis, whilst in per protocol analysis they were 91.12% (CI95%: 85.78–94.95) and 96.17% (CI95%: 92.28–98.45) respectively (p=0.083). Compliance over 90% was 91.35% with OCAM and 92.04% with OBMT-3/1 (p=0.951). Some side effect was present in 94.02% with OCAM and in 88.89% with OBMT-3/1 (p=0.109), being longer (12 vs 7 days, p<0.0001) and more severe (p<0.0001) with OCAM. ConclusionsIn a high CLA-resistance area, there are no differences between OBMT-3/1 and OCAM in H. pylori eradication and compliance rates, but OBMT-3/1 achieves a higher safety profile.

A Comparison between 10-day and 12-day Concomitant Regimens for Helicobacter Pylori Eradication: A Randomized Clinical Trial.

BACKGROUND Helicobacter pylori (H. pylori) infection is one of the most common bacterial infections worldwide, which is associated with peptic ulcer disease and gastric cancer. In this study, we compared the efficacy of 10-day versus 12-day concomitant therapy as the first-line treatment for H. pylori eradication in Iran. METHODS 218 patients with peptic ulcer disease and naïve H. pylori infection, were randomly divided into two groups to receive either 10-day or 12-day concomitant regimens, composed of pantoprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily. Eight weeks after treatment, H. pylori eradication was assessed by 14C- urea breath test. The trial was registered in the Iranian Registry of Clinical Trials (code: IRCT20170521034070N2). RESULTS 212 patients completed the study. According to the intention to treat analysis, the eradication rates were 83.6% (95% CI: 76.6-90.5) and 88.8% (95% CI: 82.8-94.7) in 10-day and 12-day concomitant therapy groups, respectively (p = 0.24). Per-protocol eradication rates were 85.9% (95% CI: 79.3–92.4) and 92.6% (95% CI: 87.6–97.5), respectively (p = 0.19). The rates of severe side effects were not statistically different between the two groups (3.6% vs. 8.1%; p = 0.428). CONCLUSION 12-day concomitant therapy could achieve ideal eradication rates by both intention to treat and perprotocol analyses. In order to reduce the cost of drugs and the rate of adverse effects of therapy, among 10-day and 12day regimens, 12-day concomitant therapy seems to be a good alternative to 14-day concomitant therapy that has been suggested by international guidelines.

Efficacy of a bismuth-based quadruple therapy regimen for Helicobacter pylori eradication in Saudi Arabia.

Background/Aim:The treatment efficacy of Helicobacter pylori (H. pylori) has been decreasing over time due to resistance to multiple antimicrobial therapies. The most effective treatment regimen for Saudi Arabian patients infected with H. pylori is still unknown. We aimed to study the eradication rate of 10 days of quadruple therapy; bismuth subcitrate potassium 140 mg, metronidazole 125 mg, and tetracycline 125 mg for H. pylori infection in a Saudi population.Patients and Methods:This was a prospective, open-label, non-randomized controlled trial. Patients with H. pylori infection were diagnosed by upper gastrointestinal (GI) endoscopy and rapid urease test (RUT) or histology. Patients who tested positive were recruited. Eligible patients were prescribed a 10-day course of quadruple therapy and received three capsules 4 times daily for 10 days along with omeprazole 20 mg twice daily. H. pylori was considered eradicated if the urea breath test (UBT) was negative after 6 weeks of completing the treatment.Results:Ninety-two patients with H. pylori infection were recruited. Three patients withdrew from the trial and another seven patients lost follow-up. We analyzed 82 patient's data as per-protocol analysis, of whom 66 (80%) were naive to H. pylori treatment. Four patients had failed previous treatment with the sequential regimen and 12 patients had treatment with clarithromycin-based triple therapy. The post-treatment UBT for H. pylori infection was negative by per-protocol analysis in 72/82 patients (87.8%), and 72/92 (78.3%) by intention-to-treat analysis. There was no correlation between previous treatment failure and treatment response to the bismuth-based quadruple therapy (P value = 0.28).Conclusions:Treatment with a bismuth-based quadruple therapy was effective in eradicating H. pylori infection in 78.3% of Saudi patients with an ITT analysis and in 87.8% as per-protocol analysis.

Safety and Efficacy of Nitazoxanide-Based Regimen for the Eradication of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis

BackgroundHelicobacter pylori (HP) is the most common cause of gastritis worldwide. Clarithromycin-based triple therapy or bismuth-based quadruple therapy is usually considered the first-line treatment, however with around 30% failure rate for both regimens. Drug resistance of clarithromycin and metronidazole is a growing concern in some parts of the world. Therefore, there is a need for effective eradication regimen for HP. Nitazoxanide, a bactericidal thiazolide antibiotic, has been shown to be effective in HP infection. We conducted a systematic review and meta-analysis to evaluate the efficacy of nitazoxanide-based regimen for the eradication of HP.MethodsWe have searched PubMed, Embase, Ovid Medline and Cochrane library database from inception to December 9, 2020 to identify studies that utilized nitazoxanide in the treatment regimen for HP eradication. Our primary outcome was pooled eradication rate of HP.ResultsThirteen studies including 1,028 patients met our inclusion criteria and were analyzed in a meta-analysis. HP eradication was successful in 867 patients with a pooled eradication rate of 86% (95% confidence interval (CI): 79-90%) with 84% heterogeneity. A subgroup analysis that included 230 patients who failed other prior eradication regimens revealed a pooled eradication rate of 85% (95% CI: 69-94%) without heterogeneity. In a subgroup analysis, highest eradication rates were achieved with levofloxacin, doxycycline, nitazoxanide and proton pump inhibitor with a pooled eradication rate of 92% (88-95%).ConclusionNitazoxanide-based regimen is safe and effective in the eradication of HP infection. It is also successful as a salvage therapy in patients who have failed prior treatments.

Clinical pharmacology of antisecretory drugs. Focus on H2-histamine receptor blockers

The purpose of the review is to illuminate the physiology of hydrochloric acid secretion and the clinical pharmacology of H2-histamine receptor blockers, also known as H2-histamine receptor antagonists, H2-histamine blockers, and H2-blockers.The main provisions. Antagonists of H2-histamine receptors (cimetidine, ranitidine, famotidine, nizatidine, lafutidin) selectively block the histamine receptors of parietal cells, preventing the activation of acid secretion by histamine secreted by enterochromaffin-like cells of the stomach. When using the means of this pharmacological group, both the total amount of gastric juice and its acidity decrease. H2-histamine blockers are rapidly absorbed after oral administration and for a long time inhibit the basal and stimulated acidity of the gastric mucosa. This class of drugs is approved by the FDA for short-term use in the treatment of uncomplicated gastroesophageal reflux disease, peptic ulcer or duodenal ulcer, hypersecretion of the stomach and mild infrequent heartburn. Off-label H2-histamine receptor blockers can also be used to prevent stress ulcers, esophagitis, gastritis, and gastrointestinal bleeding. Sometimes H2-histamine blockers are included in the Helicobacter pylori eradication regimen. Due to their safety, H2-histamine blockers are sold over the counter. However, they are gradually replaced by even more effective drugs - inhibitors of H+,K+-ATPase (PPI).Conclusion. H2-histamine receptor antagonists inhibit basal, nocturnal and stimulated secretion. Despite the presence of powerful antisecretory drugs in the doctor’s arsenal, such as proton pump inhibitors, H2-histamine blockers have not lost their importance in clinical practice. The knowledge of the clinical pharmacology of H2-histamine receptor blockers allows a competent approach to the choice of a treatment strategy and monitoring the safety and effectiveness of treatment of patients with acid-dependent diseases.

Clarithromycin versus levofloxacin-based regimens for Helicobacter pylori eradication in the Kurdistan Region of Iraq: A randomized clinical trial

Helicobacter pylori infection is a predisposing factor for gastric cancer. This prospective, randomized clinical trial aimed to compare H. pylori eradication rates associated with a clarithromycin-based regimen and levofloxacin-based regimen. H. pylori infection was confirmed by a rapid urease test during endoscopy and its eradication by a urea breath test. In this study, 192 patients were recruited; 93 patients received a clarithromycin- based regimen and 99 a levofloxacin- based regimen. Sixty-four patients completed the clarithromycinbased regimen and 60 the levofloxacinbased regimen. The eradication success rate of the clarithromycin-based regimen was 52/64 (81.25%), while that of the levofloxacin- based regimen was 49/60 (81.6%) (P=0.9524; odds ratio [OR]=1.0280; confidence interval [CI]=0.4153-2.5447). Investigation of the risk factors associated with treatment failure showed that the overall efficacy of the regimens was influenced by body mass index (BMI), with a high failure rate observed in patients with a high BMI (P=0.0174; OR=1.1116; CI=1.0187- 1.2129). Age, sex, endoscopic diagnosis and smoking did not influence treatment outcomes. Further studies are needed to monitor H. pylori antibiotic resistance rates.

Пробиотики в схемах эрадикации Helicobacter pylori: современные данные и результаты собственного исследования

Пробиотики в схемах эрадикации Helicobacter pylori: современные данные и результаты собственного исследования

The efficacy of first-line regimens for Helicobacter pylori eradication in different continents: A systematic review and network meta-analysis protocol.

Background:Striking prevalence of Helicobacter pylori infection has been convoluted with considerable resistance to various antibiotics worldwide. Although many eradication regimens have been introduced as the first-line therapies against H pylori, lack of appropriate multiple comparison studies makes hard to implement such results to the clinical practice. This project attempts to utilize a comprehensive network meta-analysis to pool the results of clinical trial comparing various first-line eradication therapies simultaneously in different continents.Methods:We will include all randomized controlled trials assessing the first-line regimens for treatment of H pylori published in last 10 years. We will search the databases of PubMed, EMBASE, Scopus, Web of Science and Cochrane Central Register of Controlled Trials, International Standard Randomised Controlled Trial Number registry, World Health Organisation International Clinical Trials Registry Platform, and ClinicalTrials.gov for randomized controlled trials published since January 2009 without language limitation. The primary and secondary outcomes will be H pylori eradication rate and adverse events, respectively. Subgroup analyses will be conducted for different continents. Two reviewers will independently contribute in study selection and data extraction. For evaluating quality of studies, Cochrane Collaboration tool score will be used. We will conduct network meta-analysis for treatment comparisons using STATA software version 13.Results:These findings will be submitted to a peer-reviewed journal for publication.Conclusion:Our results will provide the guidance for clinicians in deferent regions to select the best possible therapeutic regimen for treatment of H pylori infected patients.Registration number:This systematic review and network meta-analysis has been registered in the PROSPERO International Prospective Register of Systematic Reviews, with registration number CRD42017077061.

Oral metronidazole use and risk of acute pancreatitis: a population-based case-control study.

ObjectiveOral metronidazole used in combined regimens for Helicobacter pylori eradication has been associated with an increased risk of acute pancreatitis; however, it is less clear whether a similar association exists for single-regimen metronidazole. We, therefore, examined the association of single and combined regimens of oral metronidazole with risk of acute pancreatitis.MethodsIn this population-based case-control study, all individuals in Sweden (aged 40–84 years) hospitalized with acute pancreatitis between January 2006 and December 2008 were identified from a national hospital register (n=5,996). Controls, matched for calendar year, age, and sex, were randomly sampled from a national population register (n=60,681). Data on oral metronidazole and covariates were extracted from national health and prescription registers. Odds ratios (ORs) of acute pancreatitis, according to timing of the latest metronidazole prescription before hospitalization, were estimated using logistic regression models. Confounding by indication was examined by contrasting the main results with the association when amoxicillin was used as exposure. The robustness of results was examined by calculating incidence rate ratios using a self-controlled case series approach.ResultsAfter adjustment for potential confounders, there was a substantially increased risk of acute pancreatitis within 30 days of oral metronidazole exposure, both for single (OR: 4.06; 95% confidence interval [CI]: 1.90–8.64) and combined (OR: 11.80; 95% CI: 6.86–20.28) regimens, compared to nonexposure. In contrast, the adjusted OR was 1.79 (95% CI: 1.25–2.54) for current use of amoxicillin compared to nonexposure. These results were supported by the self-controlled cases series analysis (incidence rate ratio: 3.30; 95% CI: 2.69–4.06, for single and combined regimens of oral metronidazole pooled). There was no strong association between oral metronidazole and acute pancreatitis more than 30 days after exposure.ConclusionThere was an increased risk of acute pancreatitis within 30 days of exposure to single and combined regimens of oral metronidazole. While reverse causality and confounding by indication cannot be entirely excluded, they are unlikely to fully explain the association. These results warrant an increased awareness among physicians.

Efficacy of Helicobacter pylori eradication regimens in Rwanda: a randomized controlled trial

BackgroundSuccessful H. pylori treatment requires the knowledge of local antimicrobial resistance. Data on the efficacy of H. pylori eradication regimens available in sub-Saharan Africa are scant, hence the optimal treatment is unknown.Our goals were to determine the efficacy of available regimens in Rwanda as well as evaluate the effect of treatment on health-related quality of life (HRQoL) in patients undergoing esophagogastroduodenoscopy.MethodsThis is a randomized controlled trial conducted from November 2015 to October 2016 at a tertiary hospital in Rwanda. Enrollees were 299 patients (35% male, age 42 ± 16 years (mean ± SD)) who had a positive modified rapid urease test on endoscopic biopsies. After a fecal antigen test (FAT) and HRQoL assessment by the Short Form Nepean Dyspepsia Index (SF-NDI) questionnaire, patients were randomized 1:1:1:1 to either a triple therapy combining omeprazole, amoxicillin and one of clarithromycin/ciprofloxacin/metronidazole or a quadruple therapy combining omeprazole, amoxicillin, ciprofloxacin and doxycycline. All therapies were given for a duration of 10 days. The outcome measures were the persistence of positive FAT (treatment failure) 4 to 6 weeks after treatment and change in HRQoL scores.ResultsThe treatment success rate was 80% in the total population and 78% in patients with a history of prior triple therapy. Significant improvement in HRQoL in the total group (HRQoL mean scores before and after treatment respectively: 76 ± 11 and 32 ± 11, p < 0.001) and the group with functional dyspepsia (HRQoL mean scores before and after treatment respectively: 73 ± 11 and 30 ± 9, P < 0.001) was observed across all treatment groups.Using clarithromycin based triple therapy (standard of care) as a reference, the group treated with metronidazole had worse HRQoL (p = 0.012) and had a trend towards worse treatment outcome (p = 0.086) compared to the ciprofloxacin based combination therapies.ConclusionClarithromycin and ciprofloxacin based combination therapies are effective and safe to use alternatively for H. pylori eradication and improve HRQoL. Among the regimens studied, metronidazole based triple therapy is likely to be clinically inferior.Trial registrationThe clinical trial was retrospectively registered (PACTR201804003257400) with the Pan African Clinical Trial Registry database, on April 6th, 2018 in South Africa.

Comparison of Helicobacter pylori eradication regimens in patients with end stage renal disease.

The aim of this study was to compare the Helicobacter pylori (HP) eradication regimens in patients with end stage renal disease. In patients undergoing hemodialysis, the pathologic changes seen in the stomach may be the result of high serum levels of gastrin, delayed gastric emptying or HP infection. Our study was a randomized clinical trial in which 120 patients with ESRD (Patients who undergo hemodialysis) confirmed HP infection, were divided to four groups having 2-week eradication regimens; Group I: LCA (lansoprazole 30 mg-BD,clarithromycin 250 mg-BD, amoxicillin 500 mg-BD), Group II: LCM (lansoprazole 30 mg-BD,clarithromycin 250 mg-BD, metronidazole 500 mg-BD), Group III: LCAM (lansoprazole 30 mg-BD,clarithromycin 250 mg-BD,amoxicillin 500 mg-BD, metronidazole 500 mg-BD) and Group IV: Sequential (lansoprazole 30 mg-BDfor two weeks; first week: amoxicillin 500 mg-BD and second week: clarithromycin 250 mg-BD, metronidazole 500 mg-BD).6 weeks after treatment, Urea Breath Test (UBT) was performed for all patients. The mean age of patients was 43.1±11.2 years. 55.8% of patients were male. The success rates of HP eradication in 4 groups were76.7%, 70%, 90% and 90%, respectively. HP eradication rates were not statistically different among the regimens (p=0.11). There were not significant differences among the groups regarding demographic and anthropometric variables. The results showed there was no significant difference between the success rates of HP eradication regimens for ESRD patients. According to approved regimen for 90% eradication rate, with a lower number of medications and given the less risk of side effects and drug interactions, the sequential regimen is the best.

Comparison of the efficacy of six different Helicobacter pylori eradication regimens: greater than or equal to another

Objective: This study aimed to compare H. pylori eradication rates of different therapy regimens that are commonly used and investigated. Methods: The study included 210 patients with H. pylori positive nonulcer dyspepsia, who were randomised into 6 groups. Group 1: Rabeprazole 20 mg BID+amoxicillin 1000 mg BID for the first 7 d and rabeprazole 20 mg BID+amoxicillin 1000 mg BID+clarithromycin 500 mg BID+metronidazole 500 mg TID for the second 7 d. Group 2: Rabeprazole 20 mg BID+amoxicillin 1000 mg BID for the first 5 d and rabeprazole 20 mg BID+clarithromycin 500 mg BID+metronidazole 500 mg TID for the second 5 d. Group 3: Rabeprazole 20 mg BID+metranidazole 500 mg TID+tetracycline 500 mg QID+bismuth QID for 14 d. Group 4: Rabeprazole 20 mg BID+clarithromycin 500 mg BID+amoxicillin 1000 mg BID for 14 d. Group 5: Rabeprazole 20 mg BID+amoxicillin 1000 mg BID+clarithromycin 500 mg BID +metronidazole 500 mg TID for 7 d. Group 6: Rabeprazole 20 mg BID+amoxicillin 1000 mg BID +clarithromycin 500 mg BID+metronidazole 500 mg TID for 14 d. Results: H. pylori eradication rates were 65.6%, 68.6%, 56.7%, 51.4%, 65.6% and 62.9% respectively, included in the ITT analysis, and 68.6%, 68.6%, 62.9%, 51.4%, 68.6% and 62.9% respectively, included in the PP analysis for all groups. There was no significant difference between the groups with regard to eradication rates. Conclusion: Although H. pylori eradication rates of hybrid, sequential and concomitant therapy regimens were higher than those of quadruple and standard triple therapy regimens, they were also far from the ideal rate.

Comparison of efficacy and pharmacoeconomics of two Helicobacter pylori eradication regimens in peptic ulcer disease.

Background:Helicobacter pylori, the cause of most peptic ulcer diseases, infects approximately 50% of the population worldwide. Indian data on cost and effectiveness of the standard first-line therapies for H. pylori eradication are scarce. Thus, the present study was aimed at comparing the cost and efficacy of two standard first-line therapies: Regimen I comprising pantoprazole (40 mg) plus amoxicillin (750 mg) plus clarithromycin (500 mg) (PAC) and Regimen II comprising rabeprazole (20 mg) plus amoxicillin (625 mg) plus metronidazole (200 mg) (RAM).Methodology:This prospective, observational, bottom-up study collected demographic, economic, diagnostic, and therapeutic data from 60 H. pylori-positive patients. The study was carried out for 6 months in the Gastroenterology Department of a Tertiary Care Hospital in Hyderabad, Telangana, India.Results:Health-care system perspective was used to account for direct costs. Average cost per patient for complete H. pylori eradication was Rs. 10,221 and Rs. 8568 for Regimen I and Regimen II, respectively. Inpatient cost was considerably higher than the outpatient cost. Diagnostic costs ranked first in direct costs, followed by hospitalization costs, medication costs, and finally, physician's office visit cost. Individual patient's costs difference between two regimens was found to be statistically significant. Overall, Regimen I proved to be more efficacious than Regimen II, but Regimen II proved to be more cost-effective than Regimen I. Furthermore, incremental cost-effectiveness analysis revealed additional cost of Rs. 127 per patient if the patient was treated with Regimen I instead of Regimen II.Conclusion:Our study showed that Regimen II (RAM) was more cost-effective than Regimen I (PAC), but PAC achieved faster H. pylori eradication than RAM. We assume that this study provides local clinical data as to which regimen may be useful in a particular patient. National Level Clinical Trials are required to further ascertain this conclusion.

Impact of amoxicillin resistance on the efficacy of amoxicillin-containing regimens for Helicobacter pylori eradication: analysis of five randomized trials.

The impact of amoxicillin resistance on the efficacy of regimens containing amoxicillin for Helicobacter pylori eradication remains unknown. To investigate whether the efficacy of an amoxicillin-containing regimen is affected by amoxicillin resistance and to identify the optimal breakpoint for amoxicillin resistance. This was a pooled analysis of five randomized trials conducted in Taiwan from 2007 to 2016. Patients who received amoxicillin-containing regimens were recruited. MICs were determined by agar dilution testing. Meta-analysis was performed to assess the risk ratio of eradication failure in amoxicillin-resistant strains compared with susceptible strains of seven different regimens. We performed further the pooled analysis and logistic regression in patients treated with clarithromycin triple therapy to identify the optimal breakpoint for amoxicillin resistance. A total of 2339 patients with available amoxicillin MICs were enrolled. Meta-analysis showed that the presence of amoxicillin resistance was consistently associated with increased risk of treatment failure of amoxicillin-containing regimens at different breakpoints (risk ratio: 1.41, 95% CI 1.12-1.78, P = 0.004 when the cut-off was 0.5 mg/L). The heterogeneity was low (I2 = 0%, P = 0.615). Pooled analysis also showed that amoxicillin resistance was an independent risk factor for treatment failure of clarithromycin triple therapy at different breakpoints. The best correlation was observed when the breakpoint of amoxicillin resistance was ≥0.125 mg/L (kappa coefficient 0.298), at which the resistance rate was 11.1% (110 of 990). The efficacies of amoxicillin-containing regimens are affected by amoxicillin resistance and the optimal breakpoint MIC is ≥ 0.125 mg/L.

Hybrid therapy as first-line regimen for Helicobacter pylori eradication in a high clarithromycin resistance area: a prospective open-label trial.

BackgroundHybrid therapy is a promising first-line regimen for Helicobacter pylori (H. pylori) eradication. We evaluated a hybrid therapy, assessing the impact of antibiotic resistance on eradication outcome.MethodsThis was a prospective study that included 155 treatment-naïve patients diagnosed with H. pylori infection by positive CLO-test, confirmed with histology and/or culture. The hybrid therapy consisted of 40 mg esomeprazole and 1 g amoxicillin for 14 days, with the addition of 500 mg clarithromycin and 500 mg metronidazole for the final 7 days (all b.i.d.). Eradication was defined by negative 13C-urea breath test or histology.ResultsThe eradication rates were 85.8% (133/155; 95% confidence interval [CI] 79.4-90.5%) by intention-to-treat and 90.2% (129/143; 95%CI 84.1-94.2%) by per-protocol analysis in a setting of high antibiotic resistance (clarithromycin 25.9%, metronidazole 31.1%, dual resistance 8.9%). Adverse events occurred in 29.7% and 1.3% discontinued treatment because of adverse events. Adherence >90% was achieved in 96.6%. The eradication rate in patients with dual clarithromycin/metronidazole resistance (50%) was markedly lower compared to those with single clarithromycin resistance (91.4%), single metronidazole resistance (90.5%) or dual susceptibility (97.8%). Dual resistance was the only factor to correlate with the failure of hybrid therapy (odds ratio 14.4, 95%CI 3.8-54.9, P=0.0003).ConclusionsHybrid therapy is an effective and safe first-line regimen in populations with relatively high rates of antibiotic resistance. However, dual clarithromycin/metronidazole resistance may significantly compromise its efficacy.

Randomized Controlled Trial Comparing Standard Triple and Sequential Regimens for Helicobacter pylori Eradication

Objectives: The aim of this study was to compare effectiveness of sequential therapy to the standard triple therapy to eradicate Helicobacter pylori (H. pylori) in Mongolia. Methods: From September 2014 to February 2016, 140 patients with confirmed H. pylori infection (upper gastrointestinal tract (GI) endoscopy, rapid urease test, histology, H. pylori stool antigen test (HpStAg)) randomly received 10 days standard triple therapy (20 mg pantoprazole, 1 g amoxicillin, 500 mg clarithromycin, all twice daily for 10 days; STT group, n = 70), and sequential therapy (20 mg pantoprazole, 1 g amoxicillin twice daily for 5 days followed by 20 mg pantoprazole, 500 mg clarithromycin, 500 mg metronidazole twice daily for 5 days; SQT group, n = 70). Successful eradication therapy for H. pylori infection was defined as a negative HpStAg test 4 weeks after the end of eradication treatment. Results: The eradication rates by intention to treat (ITT) analysis were 71.4% (50/70) and 50% (35/70) in the STT and SQT groups, respectively (p = 0.033). The eradication rates by per-protocol (PP) analysis were 72.5% (50/69) and 51.5% (35/68) in the STT and SQT groups, respectively (p = 0.018). The adverse event rates were 7.6% (5/70) and 18.6% (13/70) in the STT and SQT groups, respectively (p = 0.043). Conclusion: The eradication rate was significantly higher in the STT group compared with the SQT group. But the eradication efficacies of both STT and SQT for H. pylori infection in Mongolia are unacceptable.

Efficacy of Triple Therapy of Vonoprazan, Amoxicillin, and Sitafloxacin as the Third-Line Regimen for Helicobacter pylori Eradication in Japan

Introduction: In Japan, the increase in bacterial resistance to clarithromycin caused a decline in the eradication rate of first-line therapy. Although second-line therapy using metronidazole has higher eradication rate until now, increase of the number of patients who receive H. pylori eradication therapy resulting in the increase of patients who failed to respond to both first- and second-line therapy. Triple therapy of PPI, amoxicillin (AMOX) and sitafloxacin (STFX) has been shown as a preferable third-line therapy. Vonoprazan (VPZ), a novel oral potassium-competitive acid blocker, has higher acid-inhibitory effects comparing with PPIs. The aim of this study was to investigate the efficacy of the triple therapy of VPZ, AMOX and STFX for the treatment of H. pylori infection in patients who failed both first- and second-line therapy. Methods: 49 H. pylori-positive patients who had failed both first-line therapy (PPI or VPZ + AMOX + clarithromycin) and second-line therapy (PPI or VPZ + AMOX + metronidazole) were enrolled into the study. Prior to the third-line therapy, patients underwent endoscopy to obtain H. pylori strains to test the susceptibility to antibiotics if they agreed. VPZ (20 mg bid), AMOX (750 mg bid) and STFX (100 mg bid) were administered for 1 week and the result was tested by one of 13C-UBT or stool antigen test 6-10 week after finishing the treatment. Results: One patient did not hope third-line therapy after she was told about the low susceptibility to STFX. No major adverse effects were seen and all the 48 patients completed the one-week regimen. The eradication rate of PCAB-AMOX-STFX was 85.7% (42/49; 95% CI, 75.9-95.5%) by intention-to-treat analysis and 87.5% (42/48; 78.4-96.9%) by per protocol analysis. H. pylori was isolated from 19 patients before starting the triple therapy of PCAB, AMOX and STFX. Eradication was unsuccessful in one of two patients whose strains had low sensitivity to AMOX (MIC 0.25≤ mg/mL) and three patients whose strains showed STFX MICs of 0.5≤ mg/mL. In contrast, eradication therapy was successful in 13 patients infected with strains which were sensitive to both AMOX and STFX. Conclusion: Triple therapy of VPZ, AMOX and STFX would be an effective third-line H. pylori eradication therapy in Japan. Bacterial low susceptibility to AMOX and STFX would be a major cause of the treatment failure.

Reply to letter to the editor: “The dosage of rifabutin in H. pylori eradication regimen should be appropriately determined in each area of the world”

We appreciate the interest of Losurdo et al.1 in our paper entitled “Rifabutin-based 10-day and 14-day triple therapy as a third-line and fourth-line regimen for Helicobacter pylori eradication: A pilot study.”2 We agree with them in terms of the importance of confirming tuberculosis status before starting rifabutin therapy, including the regimen, and the assurance of empirical rescue regimens especially in third- or fourth-line treatment. Losurdo et al.1 raised concerns regarding the accuracy of the eradication rates we reported (83.3% in the 10-day group and 94.1% in the 14-day group with intention to treat) because recent studies show lower success rates (60%–80%) in relation to drug dose and treatment duration. There are few reports of rifabutin-containing regimen from Asia, while most of the reports are from Europe.3 Meanwhile, Wong et al.4 showed a 91% eradication rate and a 58% adverse-events rate with a rifabutin-containing regimen in China.4 Both of the Asian eradication rates are higher than those in previous reports.3 Rifabutin is metabolized and eliminated mainly by the CYP3A pathway and is a moderate inducer of CYP3A4 activity.5 Yamaori et al.6 revealed the difference between Japanese and Caucasian populations in the expression levels of messenger RNA (mRNA) for CYP3A4. Thus, we should determine the appropriate dosage of rifabutin because 300 mg per day may be a very high dose for Asian patients. Although Losurdo et al.1 described rifabutin 150 mg b.i.d. as low dose in their quadruple therapy, the daily dose was the same as that in our clinical trial (300 mg q.d.).2 Furthermore, Perri et al.7 also showed that the triple therapy (pantoprazole 40 mg b.i.d., amoxicillin 1 g b.i.d., and rifabutin 300 mg q.d. for 10 days) was more effective and well tolerated than the quadruple therapy (pantoprazole 40 mg b.i.d., metronidazole 250 mg t.i.d., bismuth citrate 240 mg b.i.d., and tetracycline 500 mg q.i.d. for 10 days) (eradication rates: 86.6% vs. 66.6%, respectively). Therefore, it could not be determined whether the quadruple therapy is better than the rifabutin plus amoxicillin triple therapy. Losurdo et al.1 indicated that the amoxicillin resistance rate of our study (55%) is higher than the global rate.8 Although a broad international consensus has been formed about the cut-off points for antimicrobial resistance of clarithromycin and metronidazole, the cut-off point of amoxicillin has not been determined. In addition, the cut-off point of amoxicillin differs in each report (minimum inhibitory concentration (MIC) range 0.06–8 µg/ml).8–10 Therefore, the amoxicillin resistance rate of our clinical data is simply not designated as high because most of the MICs of amoxicillin in our report were less than 1 µg/ml.2 We previously reported about the enhancement of amoxicillin resistance after unsuccessful eradication.11 Therefore, we can partially understand the opinion of Losurdo et al.1 that it would be reasonable to avoid drugs that have already been used in previously unsuccessful regimens.